[{"chunk_id": "40952411_0", "pmid": "40952411", "title": "Exploring precision medicine by utilizing individual genetic information for the management of Alzheimer's disease.", "authors": "Kanda A, Rani A, Mazumder A", "year": "2025", "journal": "Pharmacogenomics", "keywords": "Alzheimer\u2019s disease, biomarkers, neurology, patent technologies, precision medicine", "chunk": "Alzheimer's Disease (AD) represents a formidable challenge in neurology, characterized by progressive neurodegeneration and cognitive decline. Traditional therapeutic approaches have failed to deliver significant outcomes, underscoring the need for innovative paradigms such as precision medicine. The review explores integrating genomic, biomarker-driven, and individualized therapeutic strategies to tackle AD. It examines the role of key genetic factors, including <i>APOE</i> and <i>MTHFR</i> polymorphisms, in influencing disease susceptibility and treatment responses. Advances in biomarker technologies, such as blood-based and imaging biomarkers, are highlighted for their potential in early diagnosis and patient stratification. Additionally, the review underscores the importance of tailoring interventions across different stages of AD, incorporating lifestyle modifications and emerging tools like artificial intelligence & recent patented technologies. Precision medicine offers a transformative pathway, aiming to deliver personalized, effective care that addresses the complex and multifactorial nature of AD. The paradigm shift promises improved clinical outcomes and enhanced patient quality of life.", "source": "PubMed"}, {"chunk_id": "40952411_1", "pmid": "40952411", "title": "Exploring precision medicine by utilizing individual genetic information for the management of Alzheimer's disease.", "authors": "Kanda A, Rani A, Mazumder A", "year": "2025", "journal": "Pharmacogenomics", "keywords": "Alzheimer\u2019s disease, biomarkers, neurology, patent technologies, precision medicine", "chunk": "transformative pathway, aiming to deliver personalized, effective care that addresses the complex and multifactorial nature of AD. The paradigm shift promises improved clinical outcomes and enhanced patient quality of life.", "source": "PubMed"}, {"chunk_id": "41710570_0", "pmid": "41710570", "title": "Arabic Translation & Validation of Strength, Ambulation, Rising from A Chair, Stair Climbing and History of Falling Scale (SARC-F).", "authors": "Alothman SA, AlMasud AA, Altalhi AS et al.", "year": "2026", "journal": "International journal of general medicine", "keywords": "SARC-F, aging, arabic translation, reliability, sarcopenia, screening tool, validity", "chunk": "Sarcopenia, characterized by a progressive decline in muscle mass and function associated with aging, impacts around 10% of older adults worldwide and leads to heightened morbidity, increased hospitalization, and escalating healthcare costs. Early detection is crucial for timely intervention. The SARC-F questionnaire is a brief and validated screening tool utilized globally to identify individuals at risk of sarcopenia. Nevertheless, a validated Arabic version is currently unavailable. The SARC-F questionnaire was translated into Arabic employing a forward-backward translation method, followed by cultural adaptation, including the conversion of metric units. Content validity was evaluated by two domain experts using a 4-point relevance scale. Face validity was assessed through cognitive interviews conducted in a sample of 15 Arabic-speaking participants (range = 25-40). Internal consistency was measured using Cronbach's alpha in a sample of 120 adults (31.76 years (SD = 10.43, range = 20-68)). Test-retest reliability was analyzed utilizing the Intraclass Correlation Coefficient (ICC)", "source": "PubMed"}, {"chunk_id": "41710570_1", "pmid": "41710570", "title": "Arabic Translation & Validation of Strength, Ambulation, Rising from A Chair, Stair Climbing and History of Falling Scale (SARC-F).", "authors": "Alothman SA, AlMasud AA, Altalhi AS et al.", "year": "2026", "journal": "International journal of general medicine", "keywords": "SARC-F, aging, arabic translation, reliability, sarcopenia, screening tool, validity", "chunk": "consistency was measured using Cronbach's alpha in a sample of 120 adults (31.76 years (SD = 10.43, range = 20-68)). Test-retest reliability was analyzed utilizing the Intraclass Correlation Coefficient (ICC) in a sample of 86 participants over an interval of 10 to 14 days. Inter-item associations were examined using Spearman's rank-order correlations. Following an expert review and gender-inclusive modifications, the content validity index improved from 2.0 to 4.0. Face validity testing demonstrated high clarity and acceptability across all items. The internal consistency analysis yielded a Cronbach's alpha of 0.648, indicating moderate reliability. Furthermore, the test-retest reliability displayed a commendable ICC value of 0.767 (95% CI: 0.663-0.841). The strongest inter-item correlation was found between assistance in walking and stair climbing (<i>\u03c1</i> = 0.419, p <0.001). The Arabic version of the SARC-F exhibits acceptable content and face validity, moderate internal consistency, and good test-retest reliability. This tool is poised to enhance the", "source": "PubMed"}, {"chunk_id": "41710570_2", "pmid": "41710570", "title": "Arabic Translation & Validation of Strength, Ambulation, Rising from A Chair, Stair Climbing and History of Falling Scale (SARC-F).", "authors": "Alothman SA, AlMasud AA, Altalhi AS et al.", "year": "2026", "journal": "International journal of general medicine", "keywords": "SARC-F, aging, arabic translation, reliability, sarcopenia, screening tool, validity", "chunk": "= 0.419, p <0.001). The Arabic version of the SARC-F exhibits acceptable content and face validity, moderate internal consistency, and good test-retest reliability. This tool is poised to enhance the early detection of sarcopenia in Arabic-speaking populations and support clinical decision-making for preventative strategies.", "source": "PubMed"}, {"chunk_id": "41341425_0", "pmid": "41341425", "title": "Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.", "authors": "Rubaiat R, Templeton JM, Schneider SL et al.", "year": "2025", "journal": "JMIR neurotechnology", "keywords": "ALS, Parkinson's disease, amyotrophic lateral sclerosis, concussion, detection, diagnosis, digital health, machine learning, mobile device, mobile health, mobile phone, neurodegenerative disease, neurological, speech, speech biosignatures, speech feature analysis, traumatic brain injury", "chunk": "Speech features are increasingly linked to neurodegenerative and mental health conditions, offering the potential for early detection and differentiation between disorders. As interest in speech analysis grows, distinguishing between conditions becomes critical for reliable diagnosis and assessment. This pilot study explores speech biosignatures in two distinct neurodegenerative conditions: (1) mild traumatic brain injuries (eg, concussions) and (2) Parkinson disease (PD) as the neurodegenerative condition. The study included speech samples from 235 participants (97 concussed and 94 age-matched healthy controls, 29 PD and 15 healthy controls) for the PaTaKa test and 239 participants (91 concussed and 104 healthy controls, 29 PD and 15 healthy controls) for the Sustained Vowel (/ah/) test. Age-matched healthy controls were used. Young age-matched controls were used for concussion and respective age-matched controls for neurodegenerative participants (15 healthy samples for both tests). Data augmentation with noise was applied to balance small datasets for neurodegenerative and healthy controls.", "source": "PubMed"}, {"chunk_id": "41341425_1", "pmid": "41341425", "title": "Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.", "authors": "Rubaiat R, Templeton JM, Schneider SL et al.", "year": "2025", "journal": "JMIR neurotechnology", "keywords": "ALS, Parkinson's disease, amyotrophic lateral sclerosis, concussion, detection, diagnosis, digital health, machine learning, mobile device, mobile health, mobile phone, neurodegenerative disease, neurological, speech, speech biosignatures, speech feature analysis, traumatic brain injury", "chunk": "for concussion and respective age-matched controls for neurodegenerative participants (15 healthy samples for both tests). Data augmentation with noise was applied to balance small datasets for neurodegenerative and healthy controls. Machine learning models (support vector machine, decision tree, random forest, and Extreme Gradient Boosting) were employed using 37 temporal and spectral speech features. A 5-fold stratified cross-validation was used to evaluate classification performance. For the PaTaKa test, classifiers performed well, achieving <i>F</i> <sub>1</sub>-scores above 0.9 for concussed versus healthy and concussed versus neurodegenerative classifications across all models. Initial tests using the original dataset for neurodegenerative versus healthy classification yielded very poor results, with <i>F</i> <sub>1</sub>-scores below 0.2 and accuracy under 30% (eg, below 12 out of 44 correctly classified samples) across all models. This underscored the need for data augmentation, which significantly improved performance to 60%-70% (eg, 26-31 out of 44 samples) accuracy. In contrast, the Sustained Vowel test showed", "source": "PubMed"}, {"chunk_id": "41341425_2", "pmid": "41341425", "title": "Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.", "authors": "Rubaiat R, Templeton JM, Schneider SL et al.", "year": "2025", "journal": "JMIR neurotechnology", "keywords": "ALS, Parkinson's disease, amyotrophic lateral sclerosis, concussion, detection, diagnosis, digital health, machine learning, mobile device, mobile health, mobile phone, neurodegenerative disease, neurological, speech, speech biosignatures, speech feature analysis, traumatic brain injury", "chunk": "across all models. This underscored the need for data augmentation, which significantly improved performance to 60%-70% (eg, 26-31 out of 44 samples) accuracy. In contrast, the Sustained Vowel test showed mixed results; <i>F</i> <sub>1</sub>-scores remained high (more than 0.85 across all models) for concussed versus neurodegenerative classifications but were significantly lower for concussed versus healthy (0.59-0.62) and neurodegenerative versus healthy (0.33-0.77), depending on the model. This study highlights the potential of speech features as biomarkers for neurodegenerative conditions. The PaTaKa test exhibited strong discriminative ability, especially for concussed versus neurodegenerative and concussed versus healthy tasks, whereas challenges remain for neurodegenerative versus healthy classification. These findings emphasize the need for further exploration of speech-based tools for differential diagnosis and early identification in neurodegenerative health.", "source": "PubMed"}, {"chunk_id": "41341425_3", "pmid": "41341425", "title": "Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.", "authors": "Rubaiat R, Templeton JM, Schneider SL et al.", "year": "2025", "journal": "JMIR neurotechnology", "keywords": "ALS, Parkinson's disease, amyotrophic lateral sclerosis, concussion, detection, diagnosis, digital health, machine learning, mobile device, mobile health, mobile phone, neurodegenerative disease, neurological, speech, speech biosignatures, speech feature analysis, traumatic brain injury", "chunk": "in neurodegenerative health.", "source": "PubMed"}, {"chunk_id": "41332987_0", "pmid": "41332987", "title": "Diabetic encephalopathy: metabolic reprogramming as a potential driver of accelerated brain aging and cognitive decline.", "authors": "Huai JX, Chang EE, Zhu YR et al.", "year": "2025", "journal": "Frontiers in cell and developmental biology", "keywords": "GLP-1 receptor agonists, NAD\u207a boosters, brain insulin resistance, diabetic encephalopathy, glycolytic flux, metabolic reprogramming, mitophagy, oxidative stress", "chunk": "Diabetic encephalopathy (DE) is a serious neurological complication of diabetes and is expressed as progressive decline in cognitive function, emotional disorders, and changes in brain structure. This review brings together the relevant evidence and demonstrates that metabolic reprogramming, the adaptive reconfiguration of the core metabolic pathway in response to hyperglycemia, is a potential driver of accelerated brain aging in DE. The main pathological characteristics are: abnormal brain insulin signaling, resulting in a decrease in neuronal glucose intake and a decrease in mitochondrial oxidative phosphorylation, oxidative stress and neuroinflammation caused by high blood sugar, in which excess reactive oxygen species (ROS), impairs mitochondrial integrity and leads to activation of microglia cells. The impaired mitophagy and the macrophages remove defects and cause the accumulation and energy collapse of the dysfunctional organelles. In addition, it promotes excessive glycolytic flux, lipolysis disorder, lactic acid accumulation, and ceramide-dependent synaptic damage. We further examine shared metabolic", "source": "PubMed"}, {"chunk_id": "41332987_1", "pmid": "41332987", "title": "Diabetic encephalopathy: metabolic reprogramming as a potential driver of accelerated brain aging and cognitive decline.", "authors": "Huai JX, Chang EE, Zhu YR et al.", "year": "2025", "journal": "Frontiers in cell and developmental biology", "keywords": "GLP-1 receptor agonists, NAD\u207a boosters, brain insulin resistance, diabetic encephalopathy, glycolytic flux, metabolic reprogramming, mitophagy, oxidative stress", "chunk": "the accumulation and energy collapse of the dysfunctional organelles. In addition, it promotes excessive glycolytic flux, lipolysis disorder, lactic acid accumulation, and ceramide-dependent synaptic damage. We further examine shared metabolic mechanisms between DE and neurodegenerative diseases such as alzheimer's disease (AD) and treatment strategies for pathological metabolic reprogramming including GLP-1 receptor agonists, NAD<sup>+</sup> boosters, and AMPK activators. This analysis laid the foundation for new intervention measures against the development of DE.", "source": "PubMed"}, {"chunk_id": "36371232_0", "pmid": "36371232", "title": "Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.", "authors": "Wilson EN, Young CB, Ramos Benitez J et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Phospho-tau, Plasma", "chunk": "The recent promise of disease-modifying therapies for Alzheimer's disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation. We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer's Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association", "source": "PubMed"}, {"chunk_id": "36371232_1", "pmid": "36371232", "title": "Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.", "authors": "Wilson EN, Young CB, Ramos Benitez J et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Phospho-tau, Plasma", "chunk": "longitudinal Stanford University Alzheimer's Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid \u03b2 peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change. The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF A\u03b242/A\u03b240 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in A\u03b2+ and A\u03b2- groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years.", "source": "PubMed"}, {"chunk_id": "36371232_2", "pmid": "36371232", "title": "Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease.", "authors": "Wilson EN, Young CB, Ramos Benitez J et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Phospho-tau, Plasma", "chunk": "age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years. This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.", "source": "PubMed"}, {"chunk_id": "37071449_0", "pmid": "37071449", "title": "MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease.", "authors": "Kumar A, Su Y, Sharma M et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarker, brain cells, extracellular vesicles, microRNA", "chunk": "Brain cell-derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment. Total sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI-AD; n = 6), and AD dementia (n = 11). Various brain cell-derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs. miRNAs in sEV subtypes differentially expressed in MCI, MCI-AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI). miRNA", "source": "PubMed"}, {"chunk_id": "37071449_1", "pmid": "37071449", "title": "MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease.", "authors": "Kumar A, Su Y, Sharma M et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarker, brain cells, extracellular vesicles, microRNA", "chunk": "the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI). miRNA analyses in specific sEVs could serve as a novel blood-based molecular biomarker for AD. Multiple brain cell-derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEV<sup>CD31</sup> and sEV<sup>PDGFR\u03b2</sup> suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.", "source": "PubMed"}, {"chunk_id": "41436338_0", "pmid": "41436338", "title": "Intranasal insulin for mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Silva AMP, Gon\u00e7alves OR, Tudella GCN et al.", "year": "2026", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Cognitive function, Diabetes mellitus, Intranasal insulin, Meta-analysis, Mild cognitive impairment, Neurodegeneration", "chunk": "Central insulin resistance has been implicated in the pathophysiology of Alzheimer's disease (AD), supporting the hypothesis that, in some individuals, AD may represent \"type 3 diabetes.\" Intranasal insulin has been proposed as a non-invasive approach to enhance brain insulin signaling while minimizing peripheral metabolic effects, but clinical evidence remains inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intranasal insulin with placebo in patients with mild cognitive impairment (MCI) or mild-to-moderate AD. Primary outcomes included changes in cognitive performance (ADAS-Cog13, CDR-SB, DSRS, delayed recall) and functional ability (ADCS-ADL). Secondary outcomes included cerebrospinal fluid (CSF) biomarkers (A\u03b242, total tau, phosphorylated tau) and safety endpoints. Literature searches were performed in PubMed, Embase, and Cochrane Central up to April 2025. Random-effects models were used to pool effect estimates, and risk of bias was assessed using the Cochrane RoB 2 tool. Five RCTs enrolling 540 participants met the inclusion", "source": "PubMed"}, {"chunk_id": "41436338_1", "pmid": "41436338", "title": "Intranasal insulin for mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Silva AMP, Gon\u00e7alves OR, Tudella GCN et al.", "year": "2026", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Cognitive function, Diabetes mellitus, Intranasal insulin, Meta-analysis, Mild cognitive impairment, Neurodegeneration", "chunk": "April 2025. Random-effects models were used to pool effect estimates, and risk of bias was assessed using the Cochrane RoB 2 tool. Five RCTs enrolling 540 participants met the inclusion criteria. Pooled analyses showed no significant differences between intranasal insulin and placebo for ADAS-Cog13 (mean difference: -1.09 [95% CI: -4.89; 2.71]), ADCS-ADL (mean difference 0.06 [-0.33; 0.45]), CDR-SB, DSRS, or delayed recall. No significant effects were observed on CSF A\u03b242, total tau, or p-tau181. Gastrointestinal adverse events were more frequent with insulin (risk ratio: 1.57; [95% CI: 1.15; 2.14]), whereas cardiovascular events were less frequent (risk ratio: 0.30 [0.12; 0.79]). No differences were found for other safety outcomes, and discontinuation rates were comparable between groups. Intranasal insulin was generally well tolerated but did not produce meaningful improvements in cognitive, functional, or biomarker outcomes in patients with MCI or mild-to-moderate AD. Current evidence does not support its routine clinical use, and", "source": "PubMed"}, {"chunk_id": "41436338_2", "pmid": "41436338", "title": "Intranasal insulin for mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.", "authors": "Silva AMP, Gon\u00e7alves OR, Tudella GCN et al.", "year": "2026", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Cognitive function, Diabetes mellitus, Intranasal insulin, Meta-analysis, Mild cognitive impairment, Neurodegeneration", "chunk": "tolerated but did not produce meaningful improvements in cognitive, functional, or biomarker outcomes in patients with MCI or mild-to-moderate AD. Current evidence does not support its routine clinical use, and further trials with standardized dosing, longer follow-up, and biomarker-stratified designs are warranted to clarify its therapeutic potential.", "source": "PubMed"}, {"chunk_id": "41591089_0", "pmid": "41591089", "title": "The Multifaceted Role of Irisin in Neurological Disorders: A Systematic Review Integrating Preclinical Evidence with Clinical Observations.", "authors": "Alzoughool F, Alanagreh L, Aljawarneh Y et al.", "year": "2026", "journal": "Neurology international", "keywords": "Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), irisin, neurological diseases", "chunk": "<b>Background:</b> Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin's association with neurological diseases and its underlying mechanisms. <b>Methods:</b> Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson's disease (PD), Alzheimer's disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle-Ottawa Scale, and RoB 2, where disagreements between reviewers", "source": "PubMed"}, {"chunk_id": "41591089_1", "pmid": "41591089", "title": "The Multifaceted Role of Irisin in Neurological Disorders: A Systematic Review Integrating Preclinical Evidence with Clinical Observations.", "authors": "Alzoughool F, Alanagreh L, Aljawarneh Y et al.", "year": "2026", "journal": "Neurology international", "keywords": "Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), irisin, neurological diseases", "chunk": "and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle-Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. <b>Results:</b> Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher \u03b1-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-\u03b2 pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker", "source": "PubMed"}, {"chunk_id": "41591089_2", "pmid": "41591089", "title": "The Multifaceted Role of Irisin in Neurological Disorders: A Systematic Review Integrating Preclinical Evidence with Clinical Observations.", "authors": "Alzoughool F, Alanagreh L, Aljawarneh Y et al.", "year": "2026", "journal": "Neurology international", "keywords": "Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), irisin, neurological diseases", "chunk": "analyses within studies suggested a closer association with amyloid-\u03b2 pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin \u03b1V\u03b25/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. <b>Conclusions:</b> Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance", "source": "PubMed"}, {"chunk_id": "41591089_3", "pmid": "41591089", "title": "The Multifaceted Role of Irisin in Neurological Disorders: A Systematic Review Integrating Preclinical Evidence with Clinical Observations.", "authors": "Alzoughool F, Alanagreh L, Aljawarneh Y et al.", "year": "2026", "journal": "Neurology international", "keywords": "Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), irisin, neurological diseases", "chunk": "it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation.", "source": "PubMed"}, {"chunk_id": "41317534_0", "pmid": "41317534", "title": "Cognition in schizophrenia across phases of illness: A systematic review and meta-analysis.", "authors": "Howie JH, Fielden CR, Rempfer MV", "year": "2026", "journal": "Psychiatry research", "keywords": "Cognition, Meta-analysis, Phase of illness, Schizophrenia, Systematic review", "chunk": "Cognitive deficits among individuals with schizophrenia spectrum disorders are a well-documented feature of the syndrome associated with a variety of adverse functional outcomes. While cross sectional research comparing clinical to control populations has proliferated in the field, the trajectory of cognitive functioning in schizophrenia across the lifespan is less clear. Improved understanding of the progression of cognitive symptoms may help to inform optimal treatment planning and identify effective periods for intervention. A systematic review and meta-analysis was conducted to examine cognition across phases of illness in schizophrenia. A search for peer-reviewed journal articles published prior to July 1st, 2025, was performed using the PRISMA guidelines. Sixty-nine studies met inclusion criteria for the current review. Results were reported for six cognitive domains (complex attention, executive function, perceptual-motor function, language, learning and memory, and social cognition) and for two comparisons of illness phases: prodrome - first-episode psychosis (FEP), and FEP - multi-episode/chronic", "source": "PubMed"}, {"chunk_id": "41317534_1", "pmid": "41317534", "title": "Cognition in schizophrenia across phases of illness: A systematic review and meta-analysis.", "authors": "Howie JH, Fielden CR, Rempfer MV", "year": "2026", "journal": "Psychiatry research", "keywords": "Cognition, Meta-analysis, Phase of illness, Schizophrenia, Systematic review", "chunk": "domains (complex attention, executive function, perceptual-motor function, language, learning and memory, and social cognition) and for two comparisons of illness phases: prodrome - first-episode psychosis (FEP), and FEP - multi-episode/chronic (ME). Meta-analysis results suggest a progression of small to moderate decline in cognitive functioning from prodrome to FEP in all domains, and a negligible to small decline from FEP to ME in all domains except for language. Conclusions, limitations, and future directions are discussed.", "source": "PubMed"}, {"chunk_id": "36149090_0", "pmid": "36149090", "title": "Complement dysregulation and Alzheimer's disease in Down syndrome.", "authors": "Veteleanu A, Pape S, Davies K et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, complement system, dementia, immune dysregulation", "chunk": "Down syndrome (DS) is associated with immune dysregulation and a high risk of early onset Alzheimer's disease (AD). Complement is a key part of innate immunity and driver of pathological inflammation, including neuroinflammation in AD. Complement dysregulation has been reported in DS; however, the pattern of dysregulation and its relationship to AD risk is unclear. Plasma levels of 14 complement biomarkers were measured in 71 adults with DS and 46 controls to identify DS-associated dysregulation; impact of apolipoprotein E (APOE) \u03b54 genotype, single nucleotide polymorphisms (SNPs) in CLU and CR1, and dementia on complement biomarkers was assessed. Plasma levels of complement activation products (TCC, iC3b), proteins (C1q, C3, C9), and regulators (C1 inhibitor, factor H, FHR4, clusterin) were significantly elevated in DS versus controls while FI and sCR1 were significantly lower. In DS with AD (n = 13), C3 and FI were significantly decreased compared to non-AD DS (n =", "source": "PubMed"}, {"chunk_id": "36149090_1", "pmid": "36149090", "title": "Complement dysregulation and Alzheimer's disease in Down syndrome.", "authors": "Veteleanu A, Pape S, Davies K et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, complement system, dementia, immune dysregulation", "chunk": "in DS versus controls while FI and sCR1 were significantly lower. In DS with AD (n = 13), C3 and FI were significantly decreased compared to non-AD DS (n = 58). Neither APOE genotype nor CLU SNPs impacted complement levels, while rs6656401 in CR1 significantly impacted plasma sCR1 levels. Complement is dysregulated in DS, likely reflecting the generalized immune dysregulation state; measurement may help identify inflammatory events in individuals with DS. Complement biomarkers differed in DS with and without AD and may aid diagnosis and/or prediction. Complement is significantly dysregulated in plasma of people with DS who show changes in levels of multiple complement proteins compared to controls. People with DS and dementia show evidence of additional complement dysregulation with significantly lower levels of C3 and factor I compared to those without dementia. rs6656401 in CR1 was associated with significantly elevated sCR1 plasma levels in DS.", "source": "PubMed"}, {"chunk_id": "36149090_2", "pmid": "36149090", "title": "Complement dysregulation and Alzheimer's disease in Down syndrome.", "authors": "Veteleanu A, Pape S, Davies K et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, complement system, dementia, immune dysregulation", "chunk": "significantly lower levels of C3 and factor I compared to those without dementia. rs6656401 in CR1 was associated with significantly elevated sCR1 plasma levels in DS.", "source": "PubMed"}, {"chunk_id": "35644416_0", "pmid": "35644416", "title": "Spatial navigation in older adults with mild cognitive impairment and dementia: A systematic review and meta-analysis.", "authors": "Pl\u00e1cido J, de Almeida CAB, Ferreira JV et al.", "year": "2022", "journal": "Experimental gerontology", "keywords": "Aging, Allocentric reference frame, Egocentric reference frame, Route learning, Spatial memory, Wayfinding", "chunk": "In this systematic review and meta-analysis, we compared the spatial navigation performance of older adults with mild cognitive impairment (MCI), Alzheimer's Disease (AD), and other dementias, using healthy older adults as controls. In addition, we evaluated the possible influence of the environment type (virtual and real), protocol (object- or environment-based), and the navigation mode (active and passive navigation) on spatial navigation task performance. In total, 1372 articles were identified and 24 studies were included in the meta-analysis. We found a large effect size on the spatial navigation performance of patients with cognitive decline (standardized mean difference (SMD) = 0.87, confidence interval (CI<sub>95%</sub>) = 0.62-1.09, p < 0.001), especially amnestic MCI (SMD = 1.10, CI<sub>95%</sub> = 0.71-1.49, p < 0.001) and patients with AD (SMD = 1.60, CI<sub>95%</sub> = 1.25-1.95, p < 0.001). However, the tasks did not identify mixed and vascular dementia (SMD = 0.92, CI<sub>95%</sub> = -0.33-2.18, p =", "source": "PubMed"}, {"chunk_id": "35644416_1", "pmid": "35644416", "title": "Spatial navigation in older adults with mild cognitive impairment and dementia: A systematic review and meta-analysis.", "authors": "Pl\u00e1cido J, de Almeida CAB, Ferreira JV et al.", "year": "2022", "journal": "Experimental gerontology", "keywords": "Aging, Allocentric reference frame, Egocentric reference frame, Route learning, Spatial memory, Wayfinding", "chunk": "patients with AD (SMD = 1.60, CI<sub>95%</sub> = 1.25-1.95, p < 0.001). However, the tasks did not identify mixed and vascular dementia (SMD = 0.92, CI<sub>95%</sub> = -0.33-2.18, p = 0.15 and SMD = 0.65, CI<sub>95%</sub> = -0.67-1.97, p = 0.33, respectively). Spatial navigation ability assessed using the Floor Maze Test showed the largest effect size in differentiating healthy older adults and patients with cognitive decline (SMD = 1.98,CI<sub>95%</sub> = 1.00-2.97, p < 0.001). In addition, tasks that require walking showed the greatest differences between the two groups. These results suggest that spatial navigation impairment is important, but disease-specific behavioral biomarker of the dementia pathology process that can be identified even in the early stages.", "source": "PubMed"}, {"chunk_id": "41673341_0", "pmid": "41673341", "title": "Resting-state motor network connectivity as a biomarker of Levodopa response in Parkinson's disease.", "authors": "Russo EE, Simmatis LER, Kadak K et al.", "year": "2026", "journal": "Brain imaging and behavior", "keywords": "Functional connectivity, Levodopa, Neuroimaging, Parkinson\u2019s disease, Resting-state networks", "chunk": "Parkinson's disease (PD), the second most common neurodegenerative disorder, affects over 10 million people and leads to progressive motor and non-motor decline. Levodopa (L-DOPA) remains the primary treatment, yet long-term use causes motor fluctuations and dyskinesias, and tools to optimize therapy remain limited. This review systematically evaluates studies assessing how L-DOPA affects functional connectivity within the motor network, to inform more precise and personalized treatment strategies. A systematic search of PubMed and Web of Science was performed using terms related to PD, L-DOPA, and resting-state connectivity. Included studies examined L-DOPA-induced changes in resting-state functional connectivity within motor network-related regions in humans. L-DOPA broadly modulates connectivity within motor and cognitive resting-state networks. In 28/32 comparisons, L-DOPA increased striatal connectivity with cortical motor regions, basal ganglia nuclei, the cerebellum, and the brainstem. In 21/26 comparisons, connectivity increased between motor cortical areas, the basal ganglia, thalamus, and cerebellum. In 9/16 comparisons, intracerebral connectivity", "source": "PubMed"}, {"chunk_id": "41673341_1", "pmid": "41673341", "title": "Resting-state motor network connectivity as a biomarker of Levodopa response in Parkinson's disease.", "authors": "Russo EE, Simmatis LER, Kadak K et al.", "year": "2026", "journal": "Brain imaging and behavior", "keywords": "Functional connectivity, Levodopa, Neuroimaging, Parkinson\u2019s disease, Resting-state networks", "chunk": "motor regions, basal ganglia nuclei, the cerebellum, and the brainstem. In 21/26 comparisons, connectivity increased between motor cortical areas, the basal ganglia, thalamus, and cerebellum. In 9/16 comparisons, intracerebral connectivity decreased. In all 9 comparisons, L-DOPA increased cerebellar connectivity with the globus pallidus, midbrain, and brainstem. In all 6 comparisons, connectivity increased within the midbrain and between the midbrain, thalamus, and brainstem. This review consolidates ON/OFF L-DOPA findings to characterize how L-DOPA modulates motor network connectivity. These insights may advance precision therapies, guide individualized dose titration, and support the development of treatments with improved side-effect profiles.", "source": "PubMed"}, {"chunk_id": "41396773_0", "pmid": "41396773", "title": "Abnormal Large-Scale Dynamic Brain Networks in Parkinson's Disease With Cognitive Impairment: Insights From EEG Co-Activation Patterns.", "authors": "Xie P, Lv H, Wang P et al.", "year": "2026", "journal": "IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society", "keywords": "None", "chunk": "This study investigated the large-scale dynamic brain network mechanisms underlying cognitive decline in Parkinson's disease (PD) by integrating high-density Electroencephalography (EEG) signal source localization and co-activation pattern (CAP) analysis to track transient network states during cognitive tasks. Twenty patients with PD and fourteen healthy controls (HC) underwent simultaneous EEG acquisition while performing Chinese character reading, color recognition, and Stroop tasks; cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). High-density EEG signals were reconstructed using standardized low-resolution brain electromagnetic tomography (sLORETA), yielding six CAPs representing whole-brain transient dynamic activation. Results indicated that the decoupling between the default mode network (DMN) and the task-related network (TRN) is impaired in PD patients. Specifically, during the Stroop task, PD patients showed reduced dwell time in CAP4 (TRN activation/DMN inhibition), prolonged DMN activation, and increased transitions from TRN to DMN states. CAP fraction of time correlated positively with MoCA scores, suggesting DMN-TRN decoupling", "source": "PubMed"}, {"chunk_id": "41396773_1", "pmid": "41396773", "title": "Abnormal Large-Scale Dynamic Brain Networks in Parkinson's Disease With Cognitive Impairment: Insights From EEG Co-Activation Patterns.", "authors": "Xie P, Lv H, Wang P et al.", "year": "2026", "journal": "IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society", "keywords": "None", "chunk": "dwell time in CAP4 (TRN activation/DMN inhibition), prolonged DMN activation, and increased transitions from TRN to DMN states. CAP fraction of time correlated positively with MoCA scores, suggesting DMN-TRN decoupling efficiency predicts cognitive performance. PD patients also exhibited compensatory overactivation of the anterior cingulate cortex (ACC) and salience network (SN). In conclusion, PD is characterized by disrupted dynamic DMN-TRN interactions, frequent state switching, and compensatory hyperactivation, directly contributing to cognitive decline. This study maps large-scale dynamic brain networks in PD with millisecond resolution, revealing new insights into transient network states and compensatory mechanisms, identifying potential biomarkers, and informing interventions targeting network uncoupling efficiency.", "source": "PubMed"}, {"chunk_id": "39665604_0", "pmid": "39665604", "title": "A Six-Gene Signature Related to Liquid-Liquid Phase Separation for Diagnosis of Alzheimer's Disease.", "authors": "Qiu C, Xu H", "year": "2024", "journal": "Actas espanolas de psiquiatria", "keywords": "None", "chunk": "Liquid-liquid phase separation (LLPS) has been increasingly recognized as a crucial mechanism in the pathogenesis of various neurodegenerative disorders, including Alzheimer's disease (AD). There remains a paucity of effective diagnostic biomarkers for this condition. This study aims to develop and validate a novel LLPS-related molecular signature to enhance the diagnostic accuracy and early detection of AD. LLPS-related genes were identified from online databases and subjected to bioinformatic analyses, including protein-protein interaction (PPI) network analysis and least absolute shrinkage and selection operator (LASSO) regression. Based on the optimal LLPS-related genes, a diagnosis risk model was constructed, and the diagnostic ability was evaluated using a receiver operator characteristic (ROC) curve. To elucidate the biological functions of the identified LLPS-related genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. A total of 149 LLPS-related genes were screened, which were found to be involved in functions related to", "source": "PubMed"}, {"chunk_id": "39665604_1", "pmid": "39665604", "title": "A Six-Gene Signature Related to Liquid-Liquid Phase Separation for Diagnosis of Alzheimer's Disease.", "authors": "Qiu C, Xu H", "year": "2024", "journal": "Actas espanolas de psiquiatria", "keywords": "None", "chunk": "(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. A total of 149 LLPS-related genes were screened, which were found to be involved in functions related to oxidative stress, apoptosis, and cancer progression. The 149 genes were refined to six optimal candidates through PPI network analysis and LASSO regression: Activator of HSP90 ATPase Activity 1 (AHSA1), Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2 (EIF2AK2), Heat Shock Protein Family A (Hsp70) Member 4 (HSPA4), Notch Receptor 1 (NOTCH1), Superoxide Dismutase 1 (SOD1), and Thioredoxin (TXN). Based on the six optimal genes, a diagnostic risk model was constructed, and the diagnostic ability was verified to be promising in AD both in training, internal validation, and two external validation datasets, with area under ROC curve (AUC) above 0.8. Furthermore, significant correlations were observed between the expression of these genes and tumor immune cell infiltration. A six-gene diagnosis model was", "source": "PubMed"}, {"chunk_id": "39665604_2", "pmid": "39665604", "title": "A Six-Gene Signature Related to Liquid-Liquid Phase Separation for Diagnosis of Alzheimer's Disease.", "authors": "Qiu C, Xu H", "year": "2024", "journal": "Actas espanolas de psiquiatria", "keywords": "None", "chunk": "datasets, with area under ROC curve (AUC) above 0.8. Furthermore, significant correlations were observed between the expression of these genes and tumor immune cell infiltration. A six-gene diagnosis model was constructed and verified to exhibit robust diagnostic ability in AD.", "source": "PubMed"}, {"chunk_id": "40976962_0", "pmid": "40976962", "title": "Redefining insomnia: from neural dysregulation to personalized therapeutics.", "authors": "Arias-Carri\u00f3n O", "year": "2025", "journal": "Expert review of neurotherapeutics", "keywords": "Insomnia disorder, cognitive-emotional regulation, hyperarousal, personalized therapeutics, precision sleep medicine, salience network", "chunk": "Insomnia disorder (ID) affects nearly one in three individuals across the lifespan and confers elevated risk for cognitive decline, psychiatric illness, cardiometabolic disease, and neurodegeneration. Despite its recognition as a distinct clinical entity, ID remains underdiagnosed and undertreated. Current diagnostic frameworks fail to capture its neurobiological complexity, and available models inadequately reflect its chronic, heterogeneous, and hyperarousal-driven nature. We advance the view that ID is fundamentally a disorder of arousal regulation. Converging evidence implicates persistent hyperactivity in salience and executive networks, heightened cortical excitability, and disrupted emotional processing. Genetic susceptibility-most notably polymorphisms in MEIS1, CLOCK, and PER2-interacts with environmental exposures such as prenatal stress and early-life adversity. These gene-environment interactions recalibrate stress-regulatory systems through epigenetic mechanisms, shaping enduring vulnerability. Existing treatments, including CBT-I, pharmacotherapy, neuromodulation, and digital therapeutics, remain limited in their mechanistic precision and generalizability. The field requires a decisive shift from symptom-based classification toward precision neuroscience. Integrating circuit-level", "source": "PubMed"}, {"chunk_id": "40976962_1", "pmid": "40976962", "title": "Redefining insomnia: from neural dysregulation to personalized therapeutics.", "authors": "Arias-Carri\u00f3n O", "year": "2025", "journal": "Expert review of neurotherapeutics", "keywords": "Insomnia disorder, cognitive-emotional regulation, hyperarousal, personalized therapeutics, precision sleep medicine, salience network", "chunk": "treatments, including CBT-I, pharmacotherapy, neuromodulation, and digital therapeutics, remain limited in their mechanistic precision and generalizability. The field requires a decisive shift from symptom-based classification toward precision neuroscience. Integrating circuit-level dysfunction, stress responsivity, and genetic architecture with advanced EEG, neuroimaging, and machine learning will enable biologically grounded subtyping. Such an approach is essential to deliver personalized interventions, identify novel therapeutic targets, and ultimately redefine care in insomnia disorder.", "source": "PubMed"}, {"chunk_id": "41503900_0", "pmid": "41503900", "title": "Current Perspectives on Oxytocin and Alzheimer's Disease-Related Symptoms.", "authors": "Modaffari A, Dixon S, Alshehri MSA et al.", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease, LIT-001, dementia., neuroinflammation, neuroprotection, oxidative stress, oxytocin", "chunk": "Alzheimer's Disease (AD) is a neurodegenerative disorder accounting for 60-80% of dementia cases globally. Several risk factors are associated with increased AD onset, including genetics, physical activity, and varying levels of social interaction. Extensive research has explored potential treatments for AD, among which oxytocin (OX) has shown beneficial effects on memory-related neurological processes. OX has been suggested to modulate neuroplasticity within the hippocampus in rat and mouse AD models. Further studies indicate that intranasal administration of OX may lead to significant improvements in memory and cognition. In addition, a non-peptide agonistic analogue, LIT-001, has been investigated. This review aims to provide insight into the potential of OX as a therapeutic target for AD and to explore alternatives that activate similar cellular signaling pathways.", "source": "PubMed"}, {"chunk_id": "41503900_1", "pmid": "41503900", "title": "Current Perspectives on Oxytocin and Alzheimer's Disease-Related Symptoms.", "authors": "Modaffari A, Dixon S, Alshehri MSA et al.", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease, LIT-001, dementia., neuroinflammation, neuroprotection, oxidative stress, oxytocin", "chunk": "cellular signaling pathways.", "source": "PubMed"}, {"chunk_id": "39546981_0", "pmid": "39546981", "title": "IGUANe: A 3D generalizable CycleGAN for multicenter harmonization of brain MR images.", "authors": "Roca V, Kuchcinski G, Pruvo JP et al.", "year": "2025", "journal": "Medical image analysis", "keywords": "Alzheimer, Brain MRI, Brain age, Harmonization, Image synthesis, Multisite", "chunk": "In MRI studies, the aggregation of imaging data from multiple acquisition sites enhances sample size but may introduce site-related variabilities that hinder consistency in subsequent analyses. Deep learning methods for image translation have emerged as a solution for harmonizing MR images across sites. In this study, we introduce IGUANe (Image Generation with Unified Adversarial Networks), an original 3D model that leverages the strengths of domain translation and straightforward application of style transfer methods for multicenter brain MR image harmonization. IGUANe extends CycleGAN by integrating an arbitrary number of domains for training through a many-to-one architecture. The framework based on domain pairs enables the implementation of sampling strategies that prevent confusion between site-related and biological variabilities. During inference, the model can be applied to any image, even from an unknown acquisition site, making it a universal generator for harmonization. Trained on a dataset comprising T1-weighted images from 11 different scanners, IGUANe", "source": "PubMed"}, {"chunk_id": "39546981_1", "pmid": "39546981", "title": "IGUANe: A 3D generalizable CycleGAN for multicenter harmonization of brain MR images.", "authors": "Roca V, Kuchcinski G, Pruvo JP et al.", "year": "2025", "journal": "Medical image analysis", "keywords": "Alzheimer, Brain MRI, Brain age, Harmonization, Image synthesis, Multisite", "chunk": "be applied to any image, even from an unknown acquisition site, making it a universal generator for harmonization. Trained on a dataset comprising T1-weighted images from 11 different scanners, IGUANe was evaluated on data from unseen sites. The assessments included the transformation of MR images with traveling subjects, the preservation of pairwise distances between MR images within domains, the evolution of volumetric patterns related to age and Alzheimer's disease (AD), and the performance in age regression and patient classification tasks. Comparisons with other harmonization and normalization methods suggest that IGUANe better preserves individual information in MR images and is more suitable for maintaining and reinforcing variabilities related to age and AD. Future studies may further assess IGUANe in other multicenter contexts, either using the same model or retraining it for applications to different image modalities. Codes and the trained IGUANe model are available at https://github.com/RocaVincent/iguane_harmonization.git.", "source": "PubMed"}, {"chunk_id": "39546981_2", "pmid": "39546981", "title": "IGUANe: A 3D generalizable CycleGAN for multicenter harmonization of brain MR images.", "authors": "Roca V, Kuchcinski G, Pruvo JP et al.", "year": "2025", "journal": "Medical image analysis", "keywords": "Alzheimer, Brain MRI, Brain age, Harmonization, Image synthesis, Multisite", "chunk": "contexts, either using the same model or retraining it for applications to different image modalities. Codes and the trained IGUANe model are available at https://github.com/RocaVincent/iguane_harmonization.git.", "source": "PubMed"}, {"chunk_id": "36448771_0", "pmid": "36448771", "title": "Effect of APOE \u03b54 genotype on amyloid-\u03b2, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.", "authors": "Li W, Li R, Yan S et al.", "year": "2023", "journal": "European journal of neurology", "keywords": "amyloid-\u03b2, apolipoprotein E \u03b54, glucose metabolism, mild cognitive impairment, positron emission tomography", "chunk": "The presence of apolipoprotein E \u03b54 (APOE \u03b54) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE \u03b54 on amyloid-\u03b2 (A\u03b2) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1-weighted magnetic resonance imaging, <sup>18</sup> F-florbetapir positron emission tomography (PET), and <sup>18</sup> F-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24-month scans were included for follow-up study. Voxelwise analysis revealed that APOE \u03b54 carriers exhibited greater baseline A\u03b2 deposition than APOE \u03b54 noncarriers in both diagnostic groups. However, there was no significant difference between APOE \u03b54 noncarriers and APOE \u03b54 carriers in terms of <sup>18</sup> F-FDG PET", "source": "PubMed"}, {"chunk_id": "36448771_1", "pmid": "36448771", "title": "Effect of APOE \u03b54 genotype on amyloid-\u03b2, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.", "authors": "Li W, Li R, Yan S et al.", "year": "2023", "journal": "European journal of neurology", "keywords": "amyloid-\u03b2, apolipoprotein E \u03b54, glucose metabolism, mild cognitive impairment, positron emission tomography", "chunk": "A\u03b2 deposition than APOE \u03b54 noncarriers in both diagnostic groups. However, there was no significant difference between APOE \u03b54 noncarriers and APOE \u03b54 carriers in terms of <sup>18</sup> F-FDG PET standardized uptake value ratio and GM volume. Region of interest-based analysis showed statistically significant greater A\u03b2 deposition in APOE \u03b54 carriers than APOE \u03b54 noncarriers only in aMCI patients. Furthermore, APOE \u03b54 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in A\u03b2 deposition than APOE \u03b54 noncarriers in both diagnostic groups. Our findings suggest a differential effect of APOE \u03b54 on A\u03b2 pathology, glucose metabolism, and GM volume. Studying APOE \u03b54-related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.", "source": "PubMed"}, {"chunk_id": "36448771_2", "pmid": "36448771", "title": "Effect of APOE \u03b54 genotype on amyloid-\u03b2, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.", "authors": "Li W, Li R, Yan S et al.", "year": "2023", "journal": "European journal of neurology", "keywords": "amyloid-\u03b2, apolipoprotein E \u03b54, glucose metabolism, mild cognitive impairment, positron emission tomography", "chunk": "of the pathophysiology of AD at an early stage.", "source": "PubMed"}, {"chunk_id": "41428086_0", "pmid": "41428086", "title": "Associations of pathologic Parkinson's disease (PD) and co-pathologies with cognitive decline and progression of parkinsonian signs in decedents with subclinical disease.", "authors": "Buchman AS, Yu L, Oveisgharan S et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "Cognitive decline, Lewy bodies, Lewy body dementia, Nigral neuronal loss, Parkinsonism, Parkinson\u2019s disease", "chunk": "To advance the nosology of pathologic Parkinson's disease (PD), we examined the associations of Lewy bodies (LBs), nigral neuronal loss (NNL), and co-pathologies with cognitive decline and progression of parkinsonian signs in older decedents without clinical PD during life. Nineteen cognitive tests and 26 Unified Parkinson's Disease Rating Scale items were measured annually. We measured both elements of pathologic PD, i.e., LBs and NNL, and eight other Alzheimer's disease and related dementias (ADRD) co-pathologies in 1717 brains. A semiquantitative scale (0-3) was used to assess NNL. Pathologic PD was based on the presence of LBs plus moderate or severe NNL. Possible pathologic PD was based on LBs alone or LBs with mild NNL. A series of bivariate linear mixed effect models jointly quantified cognitive decline and progressive parkinsonian signs in each decedent. Almost 30% of decedents without a diagnosis of clinical PD showed elements of pathologic PD [pathologic PD (8%);", "source": "PubMed"}, {"chunk_id": "41428086_1", "pmid": "41428086", "title": "Associations of pathologic Parkinson's disease (PD) and co-pathologies with cognitive decline and progression of parkinsonian signs in decedents with subclinical disease.", "authors": "Buchman AS, Yu L, Oveisgharan S et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "Cognitive decline, Lewy bodies, Lewy body dementia, Nigral neuronal loss, Parkinsonism, Parkinson\u2019s disease", "chunk": "models jointly quantified cognitive decline and progressive parkinsonian signs in each decedent. Almost 30% of decedents without a diagnosis of clinical PD showed elements of pathologic PD [pathologic PD (8%); possible pathologic PD (19%)]. On average, pathologic PD accounted for 4.9% of the variance of cognitive decline and 9.4% of the variance of progression of parkinsonian signs controlling for ADRD pathologies. Adding another term for possible pathologic PD accounted for an additional 1.8% variance of cognitive decline but did not account for additional variance of progressive parkinsonian signs. Co-pathologies accounted for an additional 19% of cognitive decline and 7% of progressive parkinsonism. Thirty-three percent of the association of LBs with cognitive decline was attributable to NNL. In contrast, more than 70% of its association with progressive parkinsonism was attributable to NNL. Subclinical pathologic PD in older adults is heterogeneous. The associations of LBs with cognition and parkinsonism may vary with", "source": "PubMed"}, {"chunk_id": "41428086_2", "pmid": "41428086", "title": "Associations of pathologic Parkinson's disease (PD) and co-pathologies with cognitive decline and progression of parkinsonian signs in decedents with subclinical disease.", "authors": "Buchman AS, Yu L, Oveisgharan S et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "Cognitive decline, Lewy bodies, Lewy body dementia, Nigral neuronal loss, Parkinsonism, Parkinson\u2019s disease", "chunk": "70% of its association with progressive parkinsonism was attributable to NNL. Subclinical pathologic PD in older adults is heterogeneous. The associations of LBs with cognition and parkinsonism may vary with the severity of NNL and together with its co-pathologies account for a minority of late-life progressive parkinsonism and cognitive decline. Synucleinopathies in older adults without clinical PD may be underestimated.", "source": "PubMed"}, {"chunk_id": "35912746_0", "pmid": "35912746", "title": "Diagnostic Utility of Cerebrospinal Fluid \u03b1-Synuclein in Creutzfeldt-Jakob Disease: A Systematic Review and Meta-Analysis.", "authors": "Kong Y, Chen Z, Wang X et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CSF biomarkers, Creutzfeldt-Jakob disease, meta-analysis, systematic review, \u03b1-synuclein", "chunk": "Creutzfeldt-Jakob disease (CJD) can be difficult to distinguish clinically from some non-prion neurological diseases. Previous studies have reported markedly increased levels of \u03b1-synuclein in cerebrospinal fluid (CSF) of CJD patients, indicating that it is a potential diagnostic biomarker. The aim of this study was to assess the diagnostic power of CSF \u03b1-synuclein in discriminating CJD from non-prion disorders. The Ovid MEDLINE, Cochrane, and Embase databases were searched for articles published on or before February 25, 2022, using the search term (prion diseases OR Creutzfeldt-Jakob syndrome) AND (synuclein OR \u03b1-synuclein). The difference in CSF \u03b1-synuclein levels between CJD and non-prion diseases was calculated using random-effects models (I2 &gt; 50%) or fixed-effects models (I2 &lt; 50%) in terms of standardized mean difference (SMD) and 95% confidence interval (CI). The publication bias was estimated using funnel plots and the Egger's test. Ten studies were included in this study. The concentrations of CSF \u03b1-synuclein", "source": "PubMed"}, {"chunk_id": "35912746_1", "pmid": "35912746", "title": "Diagnostic Utility of Cerebrospinal Fluid \u03b1-Synuclein in Creutzfeldt-Jakob Disease: A Systematic Review and Meta-Analysis.", "authors": "Kong Y, Chen Z, Wang X et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CSF biomarkers, Creutzfeldt-Jakob disease, meta-analysis, systematic review, \u03b1-synuclein", "chunk": "(SMD) and 95% confidence interval (CI). The publication bias was estimated using funnel plots and the Egger's test. Ten studies were included in this study. The concentrations of CSF \u03b1-synuclein were significantly higher in CJD patients compared to total non-prion controls (SMD = 1.98, 95% CI 1.60 to 2.36, p &lt; 0.00001), tauopathies (SMD = 1.34, 95% CI 0.99 to 1.68, p &lt; 0.00001), synucleinopathies (SMD = 1.78, 95% CI 1.11 to 2.44, p &lt; 0.00001), or Alzheimer's (SMD = 1.14, 95% CI 0.95 to 1.33, p &lt; 0.00001). CSF \u03b1-synuclein could distinguish CJD from non-prion diseases with overall sensitivity of 89% (95% CI 80-95%), specificity of 92% (95% CI 86-95%), and AUC of 0.96 (95% CI: 0.94-0.97). CSF \u03b1-synuclein has excellent diagnostic value in discriminating CJD from non-prion neurological diseases. Given the high heterogeneity among the included studies, further studies are needed to confirm its clinical utility.", "source": "PubMed"}, {"chunk_id": "35912746_2", "pmid": "35912746", "title": "Diagnostic Utility of Cerebrospinal Fluid \u03b1-Synuclein in Creutzfeldt-Jakob Disease: A Systematic Review and Meta-Analysis.", "authors": "Kong Y, Chen Z, Wang X et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CSF biomarkers, Creutzfeldt-Jakob disease, meta-analysis, systematic review, \u03b1-synuclein", "chunk": "has excellent diagnostic value in discriminating CJD from non-prion neurological diseases. Given the high heterogeneity among the included studies, further studies are needed to confirm its clinical utility.", "source": "PubMed"}, {"chunk_id": "35401412_0", "pmid": "35401412", "title": "Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer's Disease.", "authors": "Withington CG, Turner RS", "year": "2022", "journal": "Frontiers in neurology", "keywords": "ARIA-E, ARIA-H, Alzheimer's disease, aducanumab, amyloid related imaging abnormalities", "chunk": "Second-generation anti-amyloid monoclonal antibodies are emerging as a viable therapeutic option for individuals with prodromal and mild dementia due to Alzheimer's disease (AD). Passive immunotherapy with aducanumab (Aduhelm), lecanemab, donanemab, and gantenerumab all lower CNS amyloid (A\u03b2) burden but come with a significant risk of amyloid-related imaging abnormality (ARIA)-the most common side effect of this class of drugs. While usually asymptomatic and detected only on brain MRI, ARIA may lead to new signs and symptoms including headache, worsening confusion, dizziness, visual disturbances, nausea, and seizures. In addition, one fatality related to ARIA-E (edema) with aducanumab and one fatality due to ARIA-H (hemorrhage) with donanemab are reported to date. ARIA-E may be associated with excessive neuroinflammation and saturation of perivascular clearance pathways, while ARIA-H may be related to vascular amyloid clearance with weakening and rupture of small blood vessels. The risk of ARIA-E is higher at treatment initiation, in ApoE4 carriers,", "source": "PubMed"}, {"chunk_id": "35401412_1", "pmid": "35401412", "title": "Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer's Disease.", "authors": "Withington CG, Turner RS", "year": "2022", "journal": "Frontiers in neurology", "keywords": "ARIA-E, ARIA-H, Alzheimer's disease, aducanumab, amyloid related imaging abnormalities", "chunk": "pathways, while ARIA-H may be related to vascular amyloid clearance with weakening and rupture of small blood vessels. The risk of ARIA-E is higher at treatment initiation, in ApoE4 carriers, with higher dosage, and with >4 of microhemorrhages on a baseline MRI. The risk of ARIA-H increases with age and cerebrovascular disease. Dose titration mitigates the risk of ARIA, and contraindications include individuals with >4 microhemorrhages and those prescribed anti-platelet or anti-coagulant drugs. A brain MRI is required before aducanumab is initiated, before each scheduled dose escalation, and with any new neurologic sign or symptom. Management of ARIA ranges from continued antibody treatment with monthly MRI monitoring for asymptomatic individuals to temporary or permanent suspension for symptomatic individuals or those with moderate to severe ARIA on MRI. Controlled studies regarding prevention and treatment of ARIA are lacking, but anecdotal evidence suggests that a pulse of intravenous corticosteroids may be of", "source": "PubMed"}, {"chunk_id": "35401412_2", "pmid": "35401412", "title": "Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer's Disease.", "authors": "Withington CG, Turner RS", "year": "2022", "journal": "Frontiers in neurology", "keywords": "ARIA-E, ARIA-H, Alzheimer's disease, aducanumab, amyloid related imaging abnormalities", "chunk": "with moderate to severe ARIA on MRI. Controlled studies regarding prevention and treatment of ARIA are lacking, but anecdotal evidence suggests that a pulse of intravenous corticosteroids may be of benefit, as well as a course of anticonvulsant for seizures.", "source": "PubMed"}, {"chunk_id": "40982847_0", "pmid": "40982847", "title": "RELATIONSHIP BETWEEN COGNITIVE IMPAIRMENT AND LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PATIENTS WITH HEART ARRHYTHMIAS.", "authors": "Germanova O, Reshetnikova Y, Ermolayeva K et al.", "year": "2025", "journal": "Psychiatria Danubina", "keywords": "MoCA, atrial fibrillation, cognitive function, heart arrhythmia, premature ventricular contractions", "chunk": "To estimate the relationship between cognitive function of patients with heart arrhythmias and left ventricle (LV) diastolic function. In a one-center cross-control study we recruited 28 patients with heart arrhythmias, of whom 14 had 1800 or more premature ventricular contractions (PVCs) per 24 hours and more (group 1), and 14 had paroxysmal AF (group 2). All patients were asymptomatic for heart arrhythmias. Laboratory and instrumental methods included standard investigations: lipidograms, 24 hours ECG monitoring, transthoracic echocardiography (TTE), and, if prescribed, coronary angiography. In the TTE protocol, we followed current clinical recommendations in assessing the LV diastolic function. For cognitive function evaluation, we used the standard Montreal Cognitive Assessment (MoCA) test, with the following scoring: maximum possible score - 30 points; mild cognitive impairment - 22-27 points; moderate cognitive impairment - 10-21 points; severe cognitive impairment - 0-9 points. The most common heart arrhythmias (frequent PVCs, paroxysmal AF) were associated with", "source": "PubMed"}, {"chunk_id": "40982847_1", "pmid": "40982847", "title": "RELATIONSHIP BETWEEN COGNITIVE IMPAIRMENT AND LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PATIENTS WITH HEART ARRHYTHMIAS.", "authors": "Germanova O, Reshetnikova Y, Ermolayeva K et al.", "year": "2025", "journal": "Psychiatria Danubina", "keywords": "MoCA, atrial fibrillation, cognitive function, heart arrhythmia, premature ventricular contractions", "chunk": "mild cognitive impairment - 22-27 points; moderate cognitive impairment - 10-21 points; severe cognitive impairment - 0-9 points. The most common heart arrhythmias (frequent PVCs, paroxysmal AF) were associated with cognitive impairment in the preponderance of patients (mean score here). LV diastolic dysfunction is a predictor for cognitive impairment in patients with frequent PVCs and paroxysmal AF. The MoCA test can be an additional tool for this category of patients to detect the early cognitive impairment.", "source": "PubMed"}, {"chunk_id": "40672878_0", "pmid": "40672878", "title": "A comprehensive method of isolating proteins from serum, cerebrospinal fluid, and hippocampal neurons in rats for proteomic profiling using the LC-MS/MS platform.", "authors": "Sharma P, Dhamija RK", "year": "2025", "journal": "Biochemistry and biophysics reports", "keywords": "None", "chunk": "Neurology research largely utilizes rat brains due to their structural and functional similarities to humans, making them valuable models for studying various neurological conditions. There is growing interest in investigating diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), cognition, and other mental health-related disorders. This has created a need for a comprehensive, combined, and easy-to-follow method to isolate serum, cerebrospinal fluid (CSF), and hippocampal neurons. The hippocampus, responsible for learning and memory, is affected by various neurological and psychiatric disorders. However, obtaining samples like CSF and hippocampal neurons is challenging, especially from small animals like rats. Currently, there is no efficient method for isolating these samples altogether from a single animal, and its use in downstream applications has not been thoroughly tested. We have developed a comprehensive and streamlined method for isolating serum, CSF, and hippocampal neurons from a single animal, suitable for downstream applications such as proteomics and", "source": "PubMed"}, {"chunk_id": "40672878_1", "pmid": "40672878", "title": "A comprehensive method of isolating proteins from serum, cerebrospinal fluid, and hippocampal neurons in rats for proteomic profiling using the LC-MS/MS platform.", "authors": "Sharma P, Dhamija RK", "year": "2025", "journal": "Biochemistry and biophysics reports", "keywords": "None", "chunk": "been thoroughly tested. We have developed a comprehensive and streamlined method for isolating serum, CSF, and hippocampal neurons from a single animal, suitable for downstream applications such as proteomics and biomarker research. This method involves using high-speed centrifugation instruments and density gradient centrifugation, which are easy to follow. The isolated proteins were identified through mass spectrometry. Our method has been successfully tested for high-throughput applications with small sample volumes, demonstrating its clinical utility. With our simplified approach, proteins in serum, CSF, and neural cells can be studied simultaneously. The method achieves ease of use, cost-effectiveness, and reproducibility, thereby facilitating a better understanding of neurological disorders.", "source": "PubMed"}, {"chunk_id": "40551395_0", "pmid": "40551395", "title": "The Impact of APOE \u03b54 on Neuropsychological Test Performance in Hispanics: The Panama Aging Research Initiative - Health Disparities Study.", "authors": "Villarreal AE, Rangel GA, Tratner AE et al.", "year": "2026", "journal": "Dementia and geriatric cognitive disorders", "keywords": "Aging, Alzheimer\u2019s disease, Apolipoprotein E \u03b54, Cognition, Hispanics, Mild cognitive impairment", "chunk": "The apolipoprotein E (APOE) gene is a well-established risk factor for Alzheimer's disease, with the APOE \u03b54 allele being the most strongly associated genetic variant. Research has suggested that the influence of APOE \u03b54 on cognitive decline may vary across different populations. This study aimed to investigate the relationship between APOE genotype and cognitive aging in Hispanics. A diverse sample of Hispanic adults was recruited for a study on cognitive aging. Data were analyzed for n = 725 participants from the Panama Aging Research Initiative - Health Disparities (PARI-HD) study. Participants were divided into 2 groups, an outpatient cohort (n = 269) and a community cohort (n = 456) and underwent comprehensive neuropsychological assessments. A greater number of participants in the outpatient cohort were cognitively impaired than the community cohort, and the outpatient cohort had a significantly higher frequency of \u03b54 (33.8% vs. 25.7%). Results showed that carrying at least", "source": "PubMed"}, {"chunk_id": "40551395_1", "pmid": "40551395", "title": "The Impact of APOE \u03b54 on Neuropsychological Test Performance in Hispanics: The Panama Aging Research Initiative - Health Disparities Study.", "authors": "Villarreal AE, Rangel GA, Tratner AE et al.", "year": "2026", "journal": "Dementia and geriatric cognitive disorders", "keywords": "Aging, Alzheimer\u2019s disease, Apolipoprotein E \u03b54, Cognition, Hispanics, Mild cognitive impairment", "chunk": "the outpatient cohort were cognitively impaired than the community cohort, and the outpatient cohort had a significantly higher frequency of \u03b54 (33.8% vs. 25.7%). Results showed that carrying at least one copy of the APOE \u03b54 allele was a significant predictor of cognitive impairment in the community cohort (OR = 2.06, 95% CI = 1.14-3.72, p = 0.017) but was not significantly associated with performance on cognitive tests for either cohort. These findings suggest that APOE \u03b54 confers risk for cognitive deterioration in the Panamanian population, highlighting the importance of considering genetic and demographic factors in understanding the heterogeneity of cognitive impairment.", "source": "PubMed"}, {"chunk_id": "38451820_0", "pmid": "38451820", "title": "Protocol to measure apoptosis-associated speck-like protein containing a CARD specks in human cerebrospinal fluid via imaging flow cytometry.", "authors": "S\u00e1nchez KE, Jiang S, Palencia Desai S et al.", "year": "2024", "journal": "STAR protocols", "keywords": "Clinical Protocol, Flow Cytometry, Molecular Biology, Neuroscience", "chunk": "Apoptosis-associated speck-like protein containing a c-terminal caspase activation and recruitment domain (ASC) specks are elevated in the cerebrospinal fluid (CSF) of Alzheimer's disease and related dementias (AD/ADRDs) patients. Here, we present a flow cytometry protocol to quantify ASC specks. We describe steps for fluorescently labeling ASC specks using antibody technology, visualizing with imaging flow cytometry, and gating based on physical characteristics. CSF ASC specks levels positively correlate with phosphorylated tau (Thr181) and negatively correlate with amyloid \u03b2 ratio (42/40), thus serving as a neuroinflammatory biomarker for diagnosing AD/ADRDs. For complete details on the use and execution of this protocol, please refer to Jiang et al.<sup>1</sup>.", "source": "PubMed"}, {"chunk_id": "33082443_0", "pmid": "33082443", "title": "Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.", "authors": "P\u00e9rez-Cord\u00f3n A, Mont\u00e9-Rubio G, Sanabria A et al.", "year": "2020", "journal": "Scientific reports", "keywords": "None", "chunk": "To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (A\u03b2) deposition and regional volumetric reduction in areas of interest for Alzheimer's disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests", "source": "PubMed"}, {"chunk_id": "33082443_1", "pmid": "33082443", "title": "Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.", "authors": "P\u00e9rez-Cord\u00f3n A, Mont\u00e9-Rubio G, Sanabria A et al.", "year": "2020", "journal": "Scientific reports", "keywords": "None", "chunk": "magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between A\u03b2 deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral A\u03b2 deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.", "source": "PubMed"}, {"chunk_id": "33082443_2", "pmid": "33082443", "title": "Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.", "authors": "P\u00e9rez-Cord\u00f3n A, Mont\u00e9-Rubio G, Sanabria A et al.", "year": "2020", "journal": "Scientific reports", "keywords": "None", "chunk": "our results may contribute to the early detection of AD in individuals with SCD.", "source": "PubMed"}, {"chunk_id": "39222645_0", "pmid": "39222645", "title": "Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies.", "authors": "Kobayashi LC, Peterson RL, Yu X et al.", "year": "2024", "journal": "The lancet. Healthy longevity", "keywords": "None", "chunk": "Intersectionality has rarely been considered in research studies of cognitive ageing. We investigated whether life-course financial mobility is differentially associated with later-life memory function and decline across intersectional identities defined by gender, and race and ethnicity. Data were from two harmonised multiethnic cohorts (the Kaiser Healthy Aging and Diverse Life Experiences cohort and the Study of Healthy Aging in African Americans cohort) in northern California, USA (n=2340). Life-course financial mobility, measured using a combination of self-reported financial capital measures in childhood (from birth to age 16 years) and later adulthood (at the cohort baseline) was defined as consistently high, upwardly mobile, downwardly mobile, or consistently low. We clustered individuals into 32 strata representing intersectional identities defined by life-course financial mobility combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017 to 2023. Adjusted mixed-effects linear", "source": "PubMed"}, {"chunk_id": "39222645_1", "pmid": "39222645", "title": "Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies.", "authors": "Kobayashi LC, Peterson RL, Yu X et al.", "year": "2024", "journal": "The lancet. Healthy longevity", "keywords": "None", "chunk": "combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017 to 2023. Adjusted mixed-effects linear regression models were estimated with and without fixed effects of gender, race and ethnicity, and financial mobility, to evaluate whether the random effects of the intersectional identity strata contributed variance to memory beyond individual fixed effects. Mean age was 73\u00b76 years (SD 8\u00b71). Of 2340 individuals, 1460 (62\u00b74%) were women, 880 (37\u00b76%) were men, 388 (16\u00b76%) were Asian, 1136 (48\u00b75%) were Black, 334 (14\u00b73%) were Latinx, and 482 (20\u00b76%) were White. Consistently low and downwardly mobile financial capital were strongly negatively associated with later-life memory at baseline (-0\u00b7162 SD units [95% CI -0\u00b7273 to -0\u00b7051] for consistently low and -0\u00b7171 [-0\u00b7250 to -0\u00b7092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0\u00b72% of memory variance", "source": "PubMed"}, {"chunk_id": "39222645_2", "pmid": "39222645", "title": "Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies.", "authors": "Kobayashi LC, Peterson RL, Yu X et al.", "year": "2024", "journal": "The lancet. Healthy longevity", "keywords": "None", "chunk": "[95% CI -0\u00b7273 to -0\u00b7051] for consistently low and -0\u00b7171 [-0\u00b7250 to -0\u00b7092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0\u00b72% of memory variance after accounting for the fixed effects of gender, race and ethnicity, and financial mobility. Consistently low and downward life-course financial mobility are associated with lower later-life memory function. Intersectional identities defined by financial mobility in addition to gender, and race and ethnicity, contribute negligible additional variance to later-life memory in this study setting. US National Institute on Aging, US National Institutes of Health.", "source": "PubMed"}, {"chunk_id": "35843356_0", "pmid": "35843356", "title": "RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons.", "authors": "van der Linden RJ, Gerritsen JS, Liao M et al.", "year": "2022", "journal": "Progress in neurobiology", "keywords": "Alzheimer\u2019s disease (AD), ELAVL4, HuD, RNA-binding protein", "chunk": "The RNA binding protein ELAVL4/HuD regulates the translation and splicing of multiple Alzheimer's disease (AD) candidate genes. We generated ELAVL4 knockout (KO) human induced pluripotent stem cell-derived neurons to study the effect that ELAVL4 has on AD-related cellular phenotypes. ELAVL4 KO significantly increased the levels of specific APP isoforms and intracellular phosphorylated tau, molecular changes that are related to the pathological hallmarks of AD. Overexpression of ELAVL4 in wild-type neurons and rescue experiments in ELAVL4 KO cells showed opposite effects and also led to a reduction of the extracellular amyloid-beta (A\u03b2)42/40 ratio. All these observations were made in familial AD (fAD) and fAD-corrected neurons. To gain insight into the molecular cascades involved in neuronal ELAVL4 signaling, we conducted pathway and upstream regulator analyses of transcriptomic and proteomic data from the generated neurons. These analyses revealed that ELAVL4 affects multiple biological pathways linked to AD, including those involved in synaptic function,", "source": "PubMed"}, {"chunk_id": "35843356_1", "pmid": "35843356", "title": "RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons.", "authors": "van der Linden RJ, Gerritsen JS, Liao M et al.", "year": "2022", "journal": "Progress in neurobiology", "keywords": "Alzheimer\u2019s disease (AD), ELAVL4, HuD, RNA-binding protein", "chunk": "upstream regulator analyses of transcriptomic and proteomic data from the generated neurons. These analyses revealed that ELAVL4 affects multiple biological pathways linked to AD, including those involved in synaptic function, as well as gene expression downstream of APP and tau signaling. The analyses also suggest that ELAVL4 expression is regulated by insulin receptor-FOXO1 signaling in neurons. Taken together, ELAVL4 expression ameliorates AD-related molecular changes in neurons and affects multiple synaptic pathways, making it a promising target for novel drug development.", "source": "PubMed"}, {"chunk_id": "37950362_0", "pmid": "37950362", "title": "Cognitive deficits among people with schizophrenia and prediabetes or diabetes.", "authors": "John AP, Mya T, Haywood D", "year": "2024", "journal": "Acta psychiatrica Scandinavica", "keywords": "cognitive deficits, diabetes, prediabetes, schizophrenia", "chunk": "Both type 2 diabetes mellitus (T2DM) and schizophrenia are known to be associated with cognitive deficits. The impact of the comorbidities of T2DM or prediabetes (PD) on cognition among people with schizophrenia has been poorly researched. We evaluated the cognitive functioning of patients with schizophrenia and PD or T2DM and compared them to patients with schizophrenia with normal blood sugar. We retrospectively collated data on cognition, fasting blood glucose (FBG), lipids and other selected demographic and clinical variables of 171 patients with schizophrenia and 16 patients with schizoaffective disorder who were admitted to an inpatient rehabilitation facility in Western Australia from 2011 to 2018. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive functioning. Parametric and non-parametric analyses were used to examine the study's aims. Sixty-six percent of the patients had normal blood sugar, 25% had PD and 9% had T2DM. The BACS composite score revealed", "source": "PubMed"}, {"chunk_id": "37950362_1", "pmid": "37950362", "title": "Cognitive deficits among people with schizophrenia and prediabetes or diabetes.", "authors": "John AP, Mya T, Haywood D", "year": "2024", "journal": "Acta psychiatrica Scandinavica", "keywords": "cognitive deficits, diabetes, prediabetes, schizophrenia", "chunk": "non-parametric analyses were used to examine the study's aims. Sixty-six percent of the patients had normal blood sugar, 25% had PD and 9% had T2DM. The BACS composite score revealed an increasing gradient of cognitive deficits, ranging from mild to severe, between the normal, PD and T2DM groups, respectively. The T2DM group had a significantly lower composite score compared with the PD (p = 0.026) and normal groups (p < 0.001). On the BACS subtests, the scores of T2DM and PD patients were similar except for the token motor task, in which the T2DM group had significantly lower scores (p < 0.001). The T2DM group also had lower scores on the subtests of BACS, except memory tests, compared with those with normal blood sugar. There was no significant difference in the composite and subtest cognitive scores between the PD and normal groups. Our study revealed more pronounced cognitive deficits among", "source": "PubMed"}, {"chunk_id": "37950362_2", "pmid": "37950362", "title": "Cognitive deficits among people with schizophrenia and prediabetes or diabetes.", "authors": "John AP, Mya T, Haywood D", "year": "2024", "journal": "Acta psychiatrica Scandinavica", "keywords": "cognitive deficits, diabetes, prediabetes, schizophrenia", "chunk": "with normal blood sugar. There was no significant difference in the composite and subtest cognitive scores between the PD and normal groups. Our study revealed more pronounced cognitive deficits among patients with schizophrenia and dysglycaemia, particularly those with T2DM, compared with those with schizophrenia with normal blood sugar.", "source": "PubMed"}, {"chunk_id": "41378779_0", "pmid": "41378779", "title": "An updated patent review of acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (2021-present).", "authors": "Begines P, Fern\u00e1ndez-Bola\u00f1os JG, L\u00f3pez \u00d3", "year": "2026", "journal": "Expert opinion on therapeutic patents", "keywords": "AChE inhibitors, Alzheimer\u2019s disease, multitarget agents, natural products, prodrugs", "chunk": "Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex and not fully elucidated etiology. An exponential rise in its incidence underscores the urgent need for effective therapeutic strategies. AD imposes a significant economic burden on public healthcare systems and on patient's families. This manuscript focuses on the review of potent acetylcholinesterase (AChE) inhibitors, either through chemical synthesis or isolation from natural sources, aimed at restoring acetylcholine levels. Most of the compounds discussed act as multitarget agents and are categorized into four groups: drug derivatives (9 patents), heterocyclic scaffolds (16 patents), natural products from plant extracts (12 patents), and synthetic compounds inspired by natural templates (18 patents). AChE inhibition remains a compelling target in AD drug design, as it enhances acetylcholine levels and can alleviate cognitive decline. Furthermore, inhibitors that interact with the peripheral anionic site (PAS) of AChE may reduce \u03b2-amyloid self-aggregation, thereby preventing the deposition of neurotoxic", "source": "PubMed"}, {"chunk_id": "41378779_1", "pmid": "41378779", "title": "An updated patent review of acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (2021-present).", "authors": "Begines P, Fern\u00e1ndez-Bola\u00f1os JG, L\u00f3pez \u00d3", "year": "2026", "journal": "Expert opinion on therapeutic patents", "keywords": "AChE inhibitors, Alzheimer\u2019s disease, multitarget agents, natural products, prodrugs", "chunk": "enhances acetylcholine levels and can alleviate cognitive decline. Furthermore, inhibitors that interact with the peripheral anionic site (PAS) of AChE may reduce \u03b2-amyloid self-aggregation, thereby preventing the deposition of neurotoxic peptides in the brain. However, targeting AChE alone is insufficient for the development of effective therapeutics. A multitarget approach, combining AChE inhibition with pharmacophores addressing \u03b2-amyloid aggregation, neuroinflammation, oxidative stress, and other pathological hallmarks, holds greater promise for the development of more efficient anti-Alzheimer's agents.", "source": "PubMed"}, {"chunk_id": "37244436_0", "pmid": "37244436", "title": "Magnetic resonance imaging detects cerebral gray and white matter injury correlated with cognitive impairments in diabetic db/db mice.", "authors": "Li MZ, Zhang L, Shi ZY et al.", "year": "2023", "journal": "Behavioural brain research", "keywords": "Db/db mice, Diabetes, Gray matter, Magnetic resonance imaging, White matter", "chunk": "Type-2 diabetes not only causes gray matter injury but also induces widespread white matter damages, which may contribute the cognitive impairments. This study aimed to assess the structural alterations of the gray and white matter in 20-week-old diabetic db/db mice using magnetic resonance imaging including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), and to correlate them with the cognitive performance detected by Morris water maze (MWM). The results revealed impaired spatial learning and memory in db/db mice. T2WI detected severe brain atrophy involving the hippocampus and cortex after diabetes. DTI showed reduced fractional anisotropy (FA) in the cortex, hippocampus, corpus callosum/external capsule, and increased radial diffusivity in the corpus callosum/external capsule of the db/db mice. The immunostaining confirmed the MRI findings showing decreased cell density in the cortex, hippocampus, and reduced integrated optical density of Luxol fast blue staining in the corpus callosum/external capsule. The correlational analysis revealed that", "source": "PubMed"}, {"chunk_id": "37244436_1", "pmid": "37244436", "title": "Magnetic resonance imaging detects cerebral gray and white matter injury correlated with cognitive impairments in diabetic db/db mice.", "authors": "Li MZ, Zhang L, Shi ZY et al.", "year": "2023", "journal": "Behavioural brain research", "keywords": "Db/db mice, Diabetes, Gray matter, Magnetic resonance imaging, White matter", "chunk": "MRI findings showing decreased cell density in the cortex, hippocampus, and reduced integrated optical density of Luxol fast blue staining in the corpus callosum/external capsule. The correlational analysis revealed that the T2WI-derived tissue atrophy and DTI-derived FA in the relevant gray matter and white matter significantly correlated with the behavior performance in the MWM test. Collectively, the present in vivo MRI detected varying degrees of structural abnormalities in the gray and white matter of db/db mice, which might be favorable predictors of diabetic cognitive dysfunction. Our findings might provide new clues for identifying gray and white matter damages associated with cognitive decline, which is imperative for the evaluation of potential pharmacological therapies in preclinical phase.", "source": "PubMed"}, {"chunk_id": "39729132_0", "pmid": "39729132", "title": "Differences in Blood and Cerebrospinal Fluid Between Parkinson's Disease and Related Diseases.", "authors": "Ma J, Tang Z, Wu Y et al.", "year": "2024", "journal": "Cellular and molecular neurobiology", "keywords": "Atypical Parkinsonian disorders, Biomarkers, Dementia and movement disorders, Differential diagnosis, Parkinson\u2019s disease", "chunk": "It is difficult to distinguish Parkinson's disease (PD) in the early stage from those of various disorders including atypical Parkinson's syndrome (APS), vascular parkinsonism (VP), and even essential tremor (ET), because of the overlap of symptoms. Other, more challenging problems will arise when Parkinson's disease develops into Parkinson's disease dementia (PDD) in the middle and late stages. At this time, the differential diagnosis of PDD and DLB becomes thorny. These complicate the diagnostic process for PD, which traditionally heavily relies on symptomatic assessment and treatment response. Recent advances have identified several biomarkers in the blood and cerebrospinal fluid (CSF), including \u03b1-synuclein, lysosomal enzymes, fatty acid-binding proteins, and neurofilament light chain, whose concentration differs in PD and the related diseases. However, not all these molecules can effectively discriminate PD from related disorders. This review advocates for a paradigm shift toward biomarker-based diagnosis to effectively distinguish between PD and similar conditions. These", "source": "PubMed"}, {"chunk_id": "39729132_1", "pmid": "39729132", "title": "Differences in Blood and Cerebrospinal Fluid Between Parkinson's Disease and Related Diseases.", "authors": "Ma J, Tang Z, Wu Y et al.", "year": "2024", "journal": "Cellular and molecular neurobiology", "keywords": "Atypical Parkinsonian disorders, Biomarkers, Dementia and movement disorders, Differential diagnosis, Parkinson\u2019s disease", "chunk": "not all these molecules can effectively discriminate PD from related disorders. This review advocates for a paradigm shift toward biomarker-based diagnosis to effectively distinguish between PD and similar conditions. These biomarkers may reflect the diversity that exist among different diseases and provide an effective way to accurately understand their mechanisms. This review focused on blood and CSF biomarkers of PD that may have differential diagnostic value and the related molecular measurement methods with high diagnostic performance due to emerging technologies.", "source": "PubMed"}, {"chunk_id": "41720701_0", "pmid": "41720701", "title": "Perioperative Neurocognitive Disorders in Elderly Patients Undergoing Cardiac Surgery: Mechanisms, Biomarkers, and Prevention.", "authors": "Xu X, Zhu D, Wu Y et al.", "year": "2026", "journal": "Journal of cardiothoracic and vascular anesthesia", "keywords": "cardiac surgery, elderly population, perioperative neurocognitive disorders", "chunk": "Perioperative neurocognitive disorders (PNDs), which primarily encompass postoperative delirium and postoperative cognitive dysfunction, represent common and severe complications in elderly patients undergoing cardiac surgery. These disorders not only lengthen hospital stays and increase morbidity but also significantly impact long-term cognitive status and overall quality of life. The pathophysiology of PNDs is multifactorial, involving mechanisms such as neuroinflammation, cerebral hypoperfusion, and neurodegenerative changes. Older age, prior cognitive impairment, cerebrovascular comorbidities, and genetic influences are major risk factors. Current evidence has shown that biomarkers, ranging from peripheral blood to neuroimaging detection, enable early detection and individualized risk assessment. Prevention and management strategies, such as preoperative cognitive assessment, intraoperative cerebral oxygenation monitoring, and postoperative multimodal analgesia, have shown promise. Despite these developments, the pathophysiology of PNDs remains incompletely understood. This review was designed to provide a concise summary of the literature on PNDs, including mechanisms, biomarkers, and prevention, and to offer insights into", "source": "PubMed"}, {"chunk_id": "41720701_1", "pmid": "41720701", "title": "Perioperative Neurocognitive Disorders in Elderly Patients Undergoing Cardiac Surgery: Mechanisms, Biomarkers, and Prevention.", "authors": "Xu X, Zhu D, Wu Y et al.", "year": "2026", "journal": "Journal of cardiothoracic and vascular anesthesia", "keywords": "cardiac surgery, elderly population, perioperative neurocognitive disorders", "chunk": "pathophysiology of PNDs remains incompletely understood. This review was designed to provide a concise summary of the literature on PNDs, including mechanisms, biomarkers, and prevention, and to offer insights into directions for future research. By highlighting knowledge gaps and delivering evidence-based prevention strategies, this review seeks to improve patient outcomes and reduce societal costs associated with cognitive impairment among elderly cardiac surgery patients.", "source": "PubMed"}, {"chunk_id": "41449005_0", "pmid": "41449005", "title": "The roles of biomarkers in Alzheimer's disease clinical trials.", "authors": "Cummings J, Sharma S, DeAndrea G et al.", "year": "2026", "journal": "Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics", "keywords": "Alzheimer's disease, Amyloid imaging, Biomarker, Clinical trials, Context of use, p-Tau 217", "chunk": "Biomarkers are essential to guide decision making in Alzheimer's disease (AD) clinical trials where they have a variety of contexts of use (COUs) including diagnosis, risk, pharmacodynamic response, prognosis, prediction, monitoring, and safety. The COU of biomarkers may differ by phase of drug development with Phase 1, 2, and 3 emphasizing different types of information for decision making. A variety of biomarkers are currently serving as pharmacodynamic outcomes in clinical trials including amyloid and tau PET and fluid measures of amyloid, tau, neurodegeneration, inflammation, and synaptic plasticity. Biomarker strategies are integrated throughout drug development programs from collection and assay performance to statistical analysis and data interpretation. Data interrogation approaches using artificial intelligence and machine learning may enhance the value of biomarker observations through integration of multimodal data. Emerging biomarkers that may play a role in future AD trials include proteomics, exosome assays of co-pathology occurring in AD, EEG, ocular measures,", "source": "PubMed"}, {"chunk_id": "41449005_1", "pmid": "41449005", "title": "The roles of biomarkers in Alzheimer's disease clinical trials.", "authors": "Cummings J, Sharma S, DeAndrea G et al.", "year": "2026", "journal": "Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics", "keywords": "Alzheimer's disease, Amyloid imaging, Biomarker, Clinical trials, Context of use, p-Tau 217", "chunk": "biomarker observations through integration of multimodal data. Emerging biomarkers that may play a role in future AD trials include proteomics, exosome assays of co-pathology occurring in AD, EEG, ocular measures, and digital biomarkers. Biomarkers inform drug development decision-making including termination of candidate agents without sufficient biomarker effects, resourcing of promising therapies impacting the fundamental features of AD, and accelerating the development of new therapies for those with or at risk for AD.", "source": "PubMed"}, {"chunk_id": "40739848_0", "pmid": "40739848", "title": "APOE4 Exacerbates Cerebral Tau Pathology Through Cholesterol-Induced Degradation of Phosphatase in Atherosclerosis.", "authors": "Ding J, Sun B, Gao Y et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "APOE4, Alzheimer's disease, atherosclerosis, cholesterol, tau protein", "chunk": "Apolipoprotein epsilon4 allele (APOE4) is a common risk factor for atherosclerosis (AS) and neurodegenerative diseases like Alzheimer's disease (AD), but whether and how APOE4 induces AD-like neuropathies in the brain of AS pathology remains poorly characterized. By combining postmortem AS human brains and APOE4 knock-in mice, we examined the effects of APOE4 on tau and related neuropathological changes in the brain of AS. Behavioral and pathological observations were used to evaluate the protective effects of facilitating cholesterol transport in APOE4 AS mice. Here, we showed that APOE4 carriers exhibited higher AD-like phosphorylated Tau (p-Tau) levels in AS postmortem brains. Knocking in human APOE4 in high fat diet-fed mice induced AS pathology and coupled AS and AD. APOE4 promoted cerebral cholesterol content, which could trigger protein phosphatase 2A (PP2A) degradation. We further demonstrated cholesterol could facilitate the ubiquitination of PP2A B and PP2A C, which were regulatory and catalytic subunits of", "source": "PubMed"}, {"chunk_id": "40739848_1", "pmid": "40739848", "title": "APOE4 Exacerbates Cerebral Tau Pathology Through Cholesterol-Induced Degradation of Phosphatase in Atherosclerosis.", "authors": "Ding J, Sun B, Gao Y et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "APOE4, Alzheimer's disease, atherosclerosis, cholesterol, tau protein", "chunk": "content, which could trigger protein phosphatase 2A (PP2A) degradation. We further demonstrated cholesterol could facilitate the ubiquitination of PP2A B and PP2A C, which were regulatory and catalytic subunits of PP2A respectively, leading to PP2A B and PP2A C degradation through the ubiquitin-proteasome system. Reduced PP2A B and PP2A C resulted in cerebral Tau hyperphosphorylated at multiple AD-associated sites. The APOE4 AS mice exhibited an AD-like phenotype, including synaptic degeneration, blood-brain barrier breakdown, glial activation, and cognitive impairment simultaneously. Pharmacologically facilitating cholesterol transport alleviated neuropathologies in APOE4 AS mice. Altogether, these results suggested a role of the APOE4 in linking AS with Tau neuropathology, which might increase the risk of related neurodegenerative diseases for AS patients.", "source": "PubMed"}, {"chunk_id": "41282097_0", "pmid": "41282097", "title": "Sex Differences in the Relationship of Biomarker Change to Memory Decline in Early Alzheimer's Disease: an Observational Cohort Study.", "authors": "Sundermann EE, Banks SJ, Bondi MW et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, Alzheimer\u2019s pathology, Sex/gender, clinical presentation, cognitive reserve, mild cognitive impairment, preclinical Alzheimer\u2019s disease, verbal memory", "chunk": "Alzheimer's disease (AD) exhibits sex differences in pathology and cognitive trajectories. Understanding how these differences manifest across the Alzheimer's continuum can improve early detection, diagnostics, and interventions. We examined sex differences in how cerebrospinal fluid pTau181/A\u03b242 ratio changes relate to verbal memory decline across the preclinical and mild cognitive impairment (MCI) stages of AD. In this retrospective, longitudinal, observational study, data were extracted from 404 participants (age range: 55-87.8, 98% non-Hispanic White) of the Alzheimer's Disease Neuroimaging Initiative cohort study who were classified as either preclinical AD (69 females, 68 males) or MCI (113 females, 151 males) at baseline and had CSF pTau181/A\u03b242 ratio and cognitive assessment data at at-least two timepoints. Using regression models, we examined the relationship between changes in CSF pTau181/A\u03b242 and verbal memory and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a", "source": "PubMed"}, {"chunk_id": "41282097_1", "pmid": "41282097", "title": "Sex Differences in the Relationship of Biomarker Change to Memory Decline in Early Alzheimer's Disease: an Observational Cohort Study.", "authors": "Sundermann EE, Banks SJ, Bondi MW et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, Alzheimer\u2019s pathology, Sex/gender, clinical presentation, cognitive reserve, mild cognitive impairment, preclinical Alzheimer\u2019s disease, verbal memory", "chunk": "changes in CSF pTau181/A\u03b242 and verbal memory and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a composite z-score averaging Immediate and Delayed Recall z-scores of the Rey Auditory Verbal Learning Test. Covariates included baseline age, education, and apolipoprotein E genotype. A significant sex x diagnostic group x biomarker change interaction (\u03b2 = -17.47, 95%CI = 27.60 to -7.33, <i>p</i> = .001) indicated that sex differences in the relationship between changes in CSF pTau181/A\u03b242 ratio and verbal memory differed by disease stage. While males in the preclinical AD stage showed steeper memory decline than females with increasing pTau181/A\u03b242 ratios, this difference was not statistically significant. In contrast, in the mild cognitive impairment stage, a significant sex X biomarker change interaction (\u03b2 = 10.17, 95% CI = 4.94 to 15.40, p < .001) in the MCI stage indicated", "source": "PubMed"}, {"chunk_id": "41282097_2", "pmid": "41282097", "title": "Sex Differences in the Relationship of Biomarker Change to Memory Decline in Early Alzheimer's Disease: an Observational Cohort Study.", "authors": "Sundermann EE, Banks SJ, Bondi MW et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, Alzheimer\u2019s pathology, Sex/gender, clinical presentation, cognitive reserve, mild cognitive impairment, preclinical Alzheimer\u2019s disease, verbal memory", "chunk": "in the mild cognitive impairment stage, a significant sex X biomarker change interaction (\u03b2 = 10.17, 95% CI = 4.94 to 15.40, p < .001) in the MCI stage indicated that females exhibited significantly steeper memory decline associated with increasing pTau181/A\u03b242 ratios compared to males. Sex differences in the relationship between AD biomarker levels and cognitive decline vary by disease stage. Although not statistically significant, females demonstrated resilience to memory decline in the preclinical stage, whereas, in the MCI stage, they experienced significantly steeper memory loss compared to males. Results suggest that accounting for sex in biomarker-based methods of disease detection and tracking can improve early detection and intervention in both sexes.", "source": "PubMed"}, {"chunk_id": "41716662_0", "pmid": "41716662", "title": "Case Report: Distinctive features of cognitive dysfunction and amelioration by antiseizure medication in neuronal intranuclear inclusion disease.", "authors": "Ohara H, Yamanaka M, Okada F et al.", "year": "2026", "journal": "Frontiers in neuroscience", "keywords": "agraphia, antiseizure medications, cognitive dysfunction, dementia, neuronal intranuclear inclusion disease, nonconvulsive status epilepticus, skin biopsy, visuospatial execution", "chunk": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. We investigated a role of nonconvulsive status epilepticus (NCSE) in cognitive dysfunction in pathologically confirmed NIID. We also analyzed distinctive factors to differentiate NIID from Alzheimer's disease (AD). A 63-year-old man presented with transient consciousness disturbance (Day 1). For previous 6 years he had been suffering from similar episodes and gradually progressive cognitive decline. Clinical characteristics and response to antiseizure medications (ASM) were analyzed with a narrative literature review. Neurological examination showed disorientation, memory disturbance, aphasia, agraphia, and impaired visuospatial ability. On Day 27, his MMSE scored 10. Diffusion-weighted MRI showed high intensity signal in the corticomedullary junction of the frontal lobe, which could not explain his neurological manifestations. EEG showed seizure patterns arising from the bilateral occipital areas. ASM improved MMSE score to 23. Skin biopsy confirmed his diagnosis as dementia-dominant sporadic NIID. He died on Day 77. Cognitive", "source": "PubMed"}, {"chunk_id": "41716662_1", "pmid": "41716662", "title": "Case Report: Distinctive features of cognitive dysfunction and amelioration by antiseizure medication in neuronal intranuclear inclusion disease.", "authors": "Ohara H, Yamanaka M, Okada F et al.", "year": "2026", "journal": "Frontiers in neuroscience", "keywords": "agraphia, antiseizure medications, cognitive dysfunction, dementia, neuronal intranuclear inclusion disease, nonconvulsive status epilepticus, skin biopsy, visuospatial execution", "chunk": "showed seizure patterns arising from the bilateral occipital areas. ASM improved MMSE score to 23. Skin biopsy confirmed his diagnosis as dementia-dominant sporadic NIID. He died on Day 77. Cognitive dysfunction in visuospatial execution, manifested by impaired pentagon drawing and agraphia of both kanji (Japanese morphograms) and kana (Japanese syllabograms), its fluctuating course, and reactivity to ASM were clear distinction from AD. NCSE can accelerate cognitive decline and ASM can improve cognitive function in NIID. Cognitive evaluation using pentagon drawing and handwriting of both morphograms and syllabograms can be useful to differentiate NIID from AD.", "source": "PubMed"}, {"chunk_id": "38788080_0", "pmid": "38788080", "title": "Pimavanserin's Safety Profile: Insights from a Phase 3b Clinical Trial.", "authors": "Yunusa I", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019 disease, pimavanserin, safety", "chunk": "The recent Alva et al. Phase 3b study on pimavanserin use in older adults with neurodegenerative diseases (NDDs), specifically including Alzheimer's disease, vascular dementia, Parkinson's disease (with or without dementia), frontotemporal dementia, and dementia with Lewy bodies, provides important new data on its safety for managing neuropsychiatric symptoms in this population. This commentary on the study further examines the findings within the broader context of antipsychotic therapy as it has evolved from chlorpromazine to pimavanserin in a continuous search for greater safety. Comparing pimavanserin's safety and efficacy profile with historical data and regulatory milestones provides a nuanced perspective for clinicians regarding the significance of the drug's known advantages over prior antipsychotic treatments. More research is needed to determine the full potential of pimavanserin to improve neuropsychiatric symptoms in older adults with NDDs.", "source": "PubMed"}, {"chunk_id": "38788080_1", "pmid": "38788080", "title": "Pimavanserin's Safety Profile: Insights from a Phase 3b Clinical Trial.", "authors": "Yunusa I", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019 disease, pimavanserin, safety", "chunk": "potential of pimavanserin to improve neuropsychiatric symptoms in older adults with NDDs.", "source": "PubMed"}, {"chunk_id": "37314655_0", "pmid": "37314655", "title": "Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3\u03b2/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.", "authors": "Ramires J\u00fanior OV, Silveira JS, Dos Santos TM et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "GLUT1, Glucose metabolism, Homocysteine, Ibuprofen, Rivastigmine, via Akt/GSK3\u03b2", "chunk": "Homocysteine (Hcy) is a risk factor for neurodegenerative diseases, such as Alzheimer's Disease, and is related to cellular and tissue damage. In the present study, we verified the effect of Hcy on neurochemical parameters (redox homeostasis, neuronal excitability, glucose, and lactate levels) and the Serine/Threonine kinase B (Akt), Glucose synthase kinase-3\u03b2 (GSK3\u03b2) and Glucose transporter 1 (GLUT1) signaling pathway in hippocampal slices, as well as the neuroprotective effects of ibuprofen and rivastigmine alone or in combination in such effects. Male Wistar rats (90 days old) were euthanized and the brains were dissected. The hippocampus slices were pre-treated for 30 min [saline medium or Hcy (30 \u00b5M)], then the other treatments were added to the medium for another 30 min [ibuprofen, rivastigmine, or ibuprofen + rivastigmine]. The dichlorofluorescein formed, nitrite and Na+, K+-ATPase activity was increased by Hcy at 30 \u00b5M. Ibuprofen reduced dichlorofluorescein formation and attenuated the effect of Hcy.", "source": "PubMed"}, {"chunk_id": "37314655_1", "pmid": "37314655", "title": "Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3\u03b2/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.", "authors": "Ramires J\u00fanior OV, Silveira JS, Dos Santos TM et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "GLUT1, Glucose metabolism, Homocysteine, Ibuprofen, Rivastigmine, via Akt/GSK3\u03b2", "chunk": "rivastigmine, or ibuprofen + rivastigmine]. The dichlorofluorescein formed, nitrite and Na+, K+-ATPase activity was increased by Hcy at 30 \u00b5M. Ibuprofen reduced dichlorofluorescein formation and attenuated the effect of Hcy. The reduced glutathione content was reduced by Hcy. Treatments with ibuprofen and Hcy + ibuprofen increased reduced glutathione. Hcy at 30 \u00b5M caused a decrease in hippocampal glucose uptake and GLUT1 expression, and an increase in Glial Fibrillary Acidic Protein-protein expression. Phosphorylated GSK3\u03b2 and Akt levels were reduced by Hcy (30 \u00b5M) and co-treatment with Hcy + rivastigmine + ibuprofen reversed these effects. Hcy toxicity on glucose metabolism can promote neurological damage. The combination of treatment with rivastigmine + ibuprofen attenuated such effects, probably by regulating the Akt/GSK3\u03b2/GLUT1 signaling pathway. Reversal of Hcy cellular damage by these compounds may be a potential neuroprotective strategy for brain damage.", "source": "PubMed"}, {"chunk_id": "37314655_2", "pmid": "37314655", "title": "Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3\u03b2/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.", "authors": "Ramires J\u00fanior OV, Silveira JS, Dos Santos TM et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "GLUT1, Glucose metabolism, Homocysteine, Ibuprofen, Rivastigmine, via Akt/GSK3\u03b2", "chunk": "Reversal of Hcy cellular damage by these compounds may be a potential neuroprotective strategy for brain damage.", "source": "PubMed"}, {"chunk_id": "41277295_0", "pmid": "41277295", "title": "Neuronal GSK3\u03b2 Protects Against Amyloid Pathology by Regulating APP Degradation.", "authors": "Zhang Y, Zhang Y, Ge C et al.", "year": "2025", "journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "keywords": "Alzheimer's disease, GSK3\u03b2, amyloid precursor protein, neuroinflammation, protein degradation", "chunk": "Glycogen synthase kinase 3\u03b2 (GSK3\u03b2) exhibits dysregulated activity in Alzheimer's disease (AD), yet its cell type-specific roles in driving disease pathogenesis remain poorly understood. To explore the neuronal role of GSK3\u03b2 in \u03b2-amyloid (A\u03b2) pathogenesis, we conditionally deleted Gsk3\u03b2 in 5 \u00d7 FAD mice using CaMKII\u03b1-Cre-mediated recombination. Neuronal Gsk3\u03b2 deletion exacerbated AD pathology, including increased A\u03b2 deposition, pronounced gliosis, and enhanced neuroinflammatory responses. Loss of GSK3\u03b2 impaired amyloid precursor protein (APP) degradation, leading to its accumulation and subsequent A\u03b2 overproduction. These findings identify neuronal GSK3\u03b2 as a critical modulator of APP turnover and A\u03b2 pathology, revealing a protective role against AD progression. These findings suggest that broad inhibition of GSK3\u03b2 may not be an optimal therapeutic strategy for AD, highlighting the importance of cell type-specific targeting.", "source": "PubMed"}, {"chunk_id": "41277295_1", "pmid": "41277295", "title": "Neuronal GSK3\u03b2 Protects Against Amyloid Pathology by Regulating APP Degradation.", "authors": "Zhang Y, Zhang Y, Ge C et al.", "year": "2025", "journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "keywords": "Alzheimer's disease, GSK3\u03b2, amyloid precursor protein, neuroinflammation, protein degradation", "chunk": "the importance of cell type-specific targeting.", "source": "PubMed"}, {"chunk_id": "41537461_0", "pmid": "41537461", "title": "The Gwangju Alzheimer's & Related Dementias (GARD) cohort: Over a decade of Asia's largest longitudinal multimodal study.", "authors": "Choi KY, Kang S, Cook S et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Korean population, cohort study, early diagnosis, longitudinal study, multi\u2010modal data, multi\u2010omics, neuroimaging", "chunk": "Alzheimer's disease (AD) is a major public health concern in Korea, with a high prevalence among older adults. A community-based longitudinal study is essential for tracking disease progression, identifying biomarkers, and developing targeted prevention and treatment strategies. The Gwangju Alzheimer's & Related Dementias (GARD) cohort was established to address these needs through a multimodal approach. Participants aged \u226560 years undergo comprehensive clinical evaluations, neuroimaging, and biospecimen collection for multi-omics analyses (genomics, transcriptomics, proteomics, and metagenomics) at baseline and systematic follow-up visits. From over 17,000 screened individuals, 12,877 were enrolled. Baseline diagnoses include 5,123 cognitively unimpaired (CU), 3,250 mild cognitive impairment (MCI), and 2,125 AD dementia. The resource includes magnetic resonance imaging scans (n = 10,843) and extensive multi-omics data: genomic (n = 10,775), proteomic (n = 116), and microbiome (n = 595). The integrated GARD dataset provides a powerful and scalable resource for identifying novel biomarkers, understanding disease heterogeneity, and", "source": "PubMed"}, {"chunk_id": "41537461_1", "pmid": "41537461", "title": "The Gwangju Alzheimer's & Related Dementias (GARD) cohort: Over a decade of Asia's largest longitudinal multimodal study.", "authors": "Choi KY, Kang S, Cook S et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Korean population, cohort study, early diagnosis, longitudinal study, multi\u2010modal data, multi\u2010omics, neuroimaging", "chunk": "(n = 10,775), proteomic (n = 116), and microbiome (n = 595). The integrated GARD dataset provides a powerful and scalable resource for identifying novel biomarkers, understanding disease heterogeneity, and advancing precision medicine for AD. Gwangju Alzheimer's & Related Dementias (GARD) is a large-scale, longitudinal, community-based cohort study in South Korea. The study focuses on early detection and monitoring of dementia progression. GARD includes cognitive testing, imaging, biospecimens, and multi-omics data. We aim to identify Korean-specific biomarkers predictive of cognitive decline. Supports East Asian insights and fills gaps in global Alzheimer's research.", "source": "PubMed"}, {"chunk_id": "39667646_0", "pmid": "39667646", "title": "Mitochondrial protective properties exerted by JM-20 in a dementia model induced by intracerebroventricular administration of streptozotocin in mice.", "authors": "Wong-Guerra M, Montano-Peguero Y, Hern\u00e1ndez-Ense\u00f1at D et al.", "year": "2025", "journal": "Behavioural brain research", "keywords": "Brain mitochondria, Dementia, JM-20, Neuroprotection, STZ icv", "chunk": "Mitochondrial dysfunction and brain insulin resistance have been related to Alzheimer's disease (AD) development. Streptozotocin (STZ) is commonly employed to disrupt glucose and insulin metabolism, even causing cognitive impairment in animal models. We aimed at studying the protective effect of JM-20 on STZ-induced memory impairment and brain mitochondrial dysfunction. Male C57Bl6 mice received 3 mg/kg STZ intracerebroventricularly and JM-20 (0.25 mg/kg or 4 mg/kg) was administered daily by gastric gavage. Episodic memory was evaluated through Y-maze, novel object recognition, and Morris water maze. Endogenous antioxidant systems (catalase and superoxide dismutase activities), total sulfhydryl groups, malondialdehyde levels were also studied and acetylcholinesterase (AChE) activity were assessed in the prefrontal cortex (PC) and hippocampus (HO). demonstrated that STZ injection impaired recognition and spatial learning and memory and oxygen flow in all mitochondrial respiration states. Additionally, STZ increased AChE, superoxide dismutase, and catalase activity in the PC but not in HO tissue. A", "source": "PubMed"}, {"chunk_id": "39667646_1", "pmid": "39667646", "title": "Mitochondrial protective properties exerted by JM-20 in a dementia model induced by intracerebroventricular administration of streptozotocin in mice.", "authors": "Wong-Guerra M, Montano-Peguero Y, Hern\u00e1ndez-Ense\u00f1at D et al.", "year": "2025", "journal": "Behavioural brain research", "keywords": "Brain mitochondria, Dementia, JM-20, Neuroprotection, STZ icv", "chunk": "spatial learning and memory and oxygen flow in all mitochondrial respiration states. Additionally, STZ increased AChE, superoxide dismutase, and catalase activity in the PC but not in HO tissue. A neuroprotective effect of JM-20 on STZ-induced memory decline, and mitochondrial dysfunction was observed, suggesting an important causal interaction. In addition, JM-20 was able to decreased AChE enzyme hyperactivity, rescued endogenous antioxidant systems, and prevented histologically observed neuronal damage CONCLUSION: Our results indicate that JM-20 protects against STZ-induced impairment in brain bioenergetic metabolism and memory, confirming its potential as a candidate for treating neurodegenerative disorders associated with mitochondrial dysfunction like AD.", "source": "PubMed"}, {"chunk_id": "37171575_0", "pmid": "37171575", "title": "Investigating the Synergistic Potential of Low-Dose HDAC3 Inhibition and Radiotherapy in Alzheimer's Disease Models.", "authors": "Ricciardi NR, Modarresi F, Lohse I et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Cognition, HDAC inhibitor, Low-dose, Radiation", "chunk": "We have previously shown that histone deacetylase (HDAC) inhibition and cranial radiotherapy (RT) independently improve molecular and behavioral Alzheimer's disease (AD)-like phenotypes. In the present study, we investigate the synergistic potential of using both RT and HDACi as a low-dose combination therapy (LDCT) to maximize disease modification (reduce neuroinflammation and amyloidogenic APP processing, increase neurotrophic gene expression) while minimizing the potential for treatment-associated side effects.LDCT consisted of daily administration of the HDAC3 inhibitor RGFP966 and/or bi-weekly cranial x-irradiation. Amyloid-beta precursor protein (APP) processing and innate immune response to LDCT were assessed in vitro and in vivo using human and murine cell models and 3xTg-AD mice. After 2 months of LDCT in mice, behavioral analyses as well as expression and modification of key AD-related targets (A\u03b2, tau, Csf1r, Bdnf, etc.) were assessed in the hippocampus (HIP) and prefrontal cortex (PFC).LDCT induced a tolerant, anti-inflammatory innate immune response in microglia and increased", "source": "PubMed"}, {"chunk_id": "37171575_1", "pmid": "37171575", "title": "Investigating the Synergistic Potential of Low-Dose HDAC3 Inhibition and Radiotherapy in Alzheimer's Disease Models.", "authors": "Ricciardi NR, Modarresi F, Lohse I et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Cognition, HDAC inhibitor, Low-dose, Radiation", "chunk": "of key AD-related targets (A\u03b2, tau, Csf1r, Bdnf, etc.) were assessed in the hippocampus (HIP) and prefrontal cortex (PFC).LDCT induced a tolerant, anti-inflammatory innate immune response in microglia and increased non-amyloidogenic APP processing in vitro. Both RT and LDCT improved the rate of learning and spatial memory in the Barnes maze test. LDCT induced a unique anti-AD HIP gene expression profile that included upregulation of neurotrophic genes and downregulation of inflammation-related genes. RT lowered HIP A\u03b2<sub>42/40</sub> ratio and Bace1 protein, while LDCT lowered PFC p-tau181 and HIP Bace1 levels.Our study supports the rationale for combining complementary therapeutic approaches at low doses to target multifactorial AD pathology synergistically. Namely, LDCT with RGFP966 and cranial RT shows disease-modifying potential against a wide range of AD-related hallmarks.", "source": "PubMed"}, {"chunk_id": "37171575_2", "pmid": "37171575", "title": "Investigating the Synergistic Potential of Low-Dose HDAC3 Inhibition and Radiotherapy in Alzheimer's Disease Models.", "authors": "Ricciardi NR, Modarresi F, Lohse I et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Cognition, HDAC inhibitor, Low-dose, Radiation", "chunk": "range of AD-related hallmarks.", "source": "PubMed"}, {"chunk_id": "41211317_0", "pmid": "41211317", "title": "Cognitive domain-specific impairments and associated risk factors in type 2 diabetes mellitus: a cross-sectional observational study based on neuropsychological assessment from Xiamen, China.", "authors": "Xiao X, Chen L, Liu J et al.", "year": "2025", "journal": "PeerJ", "keywords": "Cognitive domain, Cognitive impairment, Influencing factor, T2DM", "chunk": "Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment, yet limited research has been conducted in subtropical regions of China. To examine the characteristics of cognitive impairment and identify the potential risk factors in patients with T2DM in Xiamen. This cross-sectional observational study included 84 patients with T2DM from Zhongshan Hospital Xiamen University. Patients were grouped based on their Montreal Cognitive Assessment (MoCA) scores into a cognitively impaired group (T2DM-CI group, <i>n</i> = 52) and a cognitively normal group (T2DM-NCI group, <i>n</i> = 32). Multivariate logistic regression was used to identify independent risk factors. Among the 52 patients in the T2DM-CI group, the most commonly affected cognitive domains were executive function (82.7%), language (75.0%), memory (61.5%), and attention (48.1%), with 59.6% exhibiting impairments in three or more domains. Compared with the T2DM-NCI group, the T2DM-CI group showed poorer performance in most MoCA subdomains-including visuospatial/executive function,", "source": "PubMed"}, {"chunk_id": "41211317_1", "pmid": "41211317", "title": "Cognitive domain-specific impairments and associated risk factors in type 2 diabetes mellitus: a cross-sectional observational study based on neuropsychological assessment from Xiamen, China.", "authors": "Xiao X, Chen L, Liu J et al.", "year": "2025", "journal": "PeerJ", "keywords": "Cognitive domain, Cognitive impairment, Influencing factor, T2DM", "chunk": "(61.5%), and attention (48.1%), with 59.6% exhibiting impairments in three or more domains. Compared with the T2DM-NCI group, the T2DM-CI group showed poorer performance in most MoCA subdomains-including visuospatial/executive function, language, delayed recall, abstraction, and orientation-as well as in individual cognitive domain tests (all <i>P</i> < 0.05), except for the Clock Drawing Test. Older age (OR = 1.167, 95% CI [1.045-1.303], <i>P</i> = 0.006) and higher lipoprotein (a) levels (OR = 1.109, 95% CI [1.020-1.205], <i>P</i> = 0.015) were independently associated with cognitive impairment in T2DM patients. Cognitive impairment in T2DM affects multiple domains, with executive dysfunction most prominent. Age and elevated lipoprotein(a) may increase risk. Routine cognitive screening is warranted, particularly in older patients and those with vascular risk factors.", "source": "PubMed"}, {"chunk_id": "41211317_2", "pmid": "41211317", "title": "Cognitive domain-specific impairments and associated risk factors in type 2 diabetes mellitus: a cross-sectional observational study based on neuropsychological assessment from Xiamen, China.", "authors": "Xiao X, Chen L, Liu J et al.", "year": "2025", "journal": "PeerJ", "keywords": "Cognitive domain, Cognitive impairment, Influencing factor, T2DM", "chunk": "factors.", "source": "PubMed"}, {"chunk_id": "41059738_0", "pmid": "41059738", "title": "Diagnostic potential of near-infrared spectroscopy in mild cognitive impairment and neurodegenerative disorders: Implications for resource-limited settings.", "authors": "Osei GN, Bockarie A, Akpalu A et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, functional connectivity, mild cognitive impairment, near\u2010infrared spectroscopy, neurodegenerative diseases, oxyhemoglobin", "chunk": "Near-infrared spectroscopy (NIRS) is emerging as a promising tool for early detection of mild cognitive impairment (MCI) and neurodegenerative diseases, especially where advanced imaging is limited. This systematic review investigates NIRS's diagnostic capabilities. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive review of studies using NIRS for cognitive assessment in MCI and neurodegenerative conditions. NIRS effectively assesses cognitive function, identifying reduced prefrontal connectivity in MCI and subjective cognitive decline (SCD). Interestingly, while SCD patients maintain stronger brain network integrity, NIRS reveals decreased oxyhemoglobin levels in Alzheimer's disease (AD) patients' dorsolateral prefrontal cortex. Combining NIRS with graph analysis, cognitive tasks, and machine learning significantly boosts diagnostic accuracy. Moreover, NIRS can differentiate between neurodegenerative disorders and, with concurrent electroencephalography, offers enhanced understanding of brain connectivity issues in AD. Our findings emphasize NIRS's considerable potential to improve cognitive assessment and neurodegeneration diagnosis. Mild cognitive impairment (MCI)", "source": "PubMed"}, {"chunk_id": "41059738_1", "pmid": "41059738", "title": "Diagnostic potential of near-infrared spectroscopy in mild cognitive impairment and neurodegenerative disorders: Implications for resource-limited settings.", "authors": "Osei GN, Bockarie A, Akpalu A et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, functional connectivity, mild cognitive impairment, near\u2010infrared spectroscopy, neurodegenerative diseases, oxyhemoglobin", "chunk": "and, with concurrent electroencephalography, offers enhanced understanding of brain connectivity issues in AD. Our findings emphasize NIRS's considerable potential to improve cognitive assessment and neurodegeneration diagnosis. Mild cognitive impairment (MCI) individuals show disruptions in neurovascular coupling and functional connectivity, particularly in the dorsolateral prefrontal cortex during near-infrared spectroscopy (NIRS) assessments. Significant reductions in oxyhemoglobin (HbO<sub>2</sub>) levels are observed in the dorsolateral prefrontal cortex of amnestic MCI (aMCI) individuals compared to healthy controls. Individuals with subjective cognitive decline (SCD) show lower HbO<sub>2</sub> levels than healthy individuals, while aMCI individuals show even more pronounced reductions. The dorsolateral prefrontal cortex is identified as a critical area for Alzheimer's disease (AD) assessment using NIRS, correlating with cognitive performance. Differences in Broca's area activation during language tasks help distinguish behavioral variant frontotemporal dementia from AD, revealing unique cognitive profiles through NIRS.", "source": "PubMed"}, {"chunk_id": "41059738_2", "pmid": "41059738", "title": "Diagnostic potential of near-infrared spectroscopy in mild cognitive impairment and neurodegenerative disorders: Implications for resource-limited settings.", "authors": "Osei GN, Bockarie A, Akpalu A et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, functional connectivity, mild cognitive impairment, near\u2010infrared spectroscopy, neurodegenerative diseases, oxyhemoglobin", "chunk": "language tasks help distinguish behavioral variant frontotemporal dementia from AD, revealing unique cognitive profiles through NIRS.", "source": "PubMed"}, {"chunk_id": "39708217_0", "pmid": "39708217", "title": "Linking metabolic syndrome, cerebral small vessel disease, and cognitive health: insights from a subclinical population study using TriNetX.", "authors": "Gosalia J, Spicuzza JMD, Bowlus CK et al.", "year": "2025", "journal": "GeroScience", "keywords": "ADRDs, Cognitive decline, EHR, Metabolic syndrome, VCID", "chunk": "Metabolic syndrome (MetS) has been linked to accelerated cognitive decline and Alzheimer's disease and related dementias (ADRDs) via cerebral small vessel disease (CSVD); however, this relation in MetS without overt cardiometabolic disease comorbidities is unknown and may represent a population amenable to preventative strategies. Our study aimed to determine risk profiles for neurocognitive decline and ADRDs in early-stage MetS with evidence of CSVD using the TriNetX electronic health records (EHR) research network. Patients aged 50 to 80 years old meeting MetS criteria were identified utilizing TriNetX data from 76 healthcare organizations. Propensity score matching controlled for demographic and confounding factors. Cohorts included MetS-only, non-MetS, and a MetS subset with evidence of CSVD (MetS-CSVD) created by clustering relevant ICD-codes for diagnoses, imaging, and lab work. Contingency analyses determined odds of developing neurocognitive decline, ADRDs, and CSVD in MetS vs non-MetS and MetS-CSVD vs. MetS-only, using odd ratios with 95% confidence intervals", "source": "PubMed"}, {"chunk_id": "39708217_1", "pmid": "39708217", "title": "Linking metabolic syndrome, cerebral small vessel disease, and cognitive health: insights from a subclinical population study using TriNetX.", "authors": "Gosalia J, Spicuzza JMD, Bowlus CK et al.", "year": "2025", "journal": "GeroScience", "keywords": "ADRDs, Cognitive decline, EHR, Metabolic syndrome, VCID", "chunk": "imaging, and lab work. Contingency analyses determined odds of developing neurocognitive decline, ADRDs, and CSVD in MetS vs non-MetS and MetS-CSVD vs. MetS-only, using odd ratios with 95% confidence intervals (p-value < 0.05). After propensity score matching, there were 57,347 men and 52,259 women in each of the MetS and non-MetS cohorts and 2,810 men and 2,862 women in each of the MetS-CSVD and MetS-only cohorts. Compared to non-MetS, the MetS cohort exhibited higher odds of developing neurocognitive decline (men: RR = 1.82, p < 0.001; women: RR = 1.34, p = 0.015) and CSVD (men: RR = 2.83, p < 0.001; women: RR = 2.14, p < 0.001), but only women exhibited significantly higher odds of developing ADRDs (men: RR = 1.13, p = 0.38; women: RR = 1.52, p < 0.001). Compared to MetS-only, the MetS-CSVD showed elevated odds in developing neurocognitive decline (men: RR = 1.81, p", "source": "PubMed"}, {"chunk_id": "39708217_2", "pmid": "39708217", "title": "Linking metabolic syndrome, cerebral small vessel disease, and cognitive health: insights from a subclinical population study using TriNetX.", "authors": "Gosalia J, Spicuzza JMD, Bowlus CK et al.", "year": "2025", "journal": "GeroScience", "keywords": "ADRDs, Cognitive decline, EHR, Metabolic syndrome, VCID", "chunk": "RR = 1.13, p = 0.38; women: RR = 1.52, p < 0.001). Compared to MetS-only, the MetS-CSVD showed elevated odds in developing neurocognitive decline (men: RR = 1.81, p = 0.040; women: RR = 1.87, p = 0.018) and ADRDs (men: RR = 2.39, p = 0.009; women: RR = 1.65, p = 0.041). A large, predominantly US, sample of subclinical MetS demonstrated heightened odds for developing neurocognitive decline and ADRDs, with even higher odds when evidence of CSVD was also present. TriNetX facilitated a robust exploration of these associations, and our findings warrant further investigation of interventions that target this subclinical at-risk population.", "source": "PubMed"}, {"chunk_id": "41792369_0", "pmid": "41792369", "title": "Interaction between transient receptor potential vanilloid 4 and glutamate NMDA receptor subunit 1 mediates endoplasmic reticulum stress and neuroinflammation in postoperative delirium.", "authors": "Huang S, Zhang T, Wang Y et al.", "year": "2026", "journal": "Molecular biomedicine", "keywords": "Endoplasmic reticulum stress, GluN1, Neuroinflammation, Postoperative delirium, TRPV4", "chunk": "Postoperative delirium (POD) is a serious and prevalent neurocognitive complication that poses a major clinical challenge because its mechanism is unclear. This study identifies a pathogenic pathway centred on the direct interaction between transient receptor potential vanilloid 4 (TRPV4) and the essential N-methyl-D-aspartate receptor (NMDAR) subunit GluN1. Using a murine POD model, the neuron-centric glutamatergic dysfunction in the hippocampus was initially confirmed through ex vivo metabolic kinetic analysis. Transcriptomic analysis revealed upregulation of Trpv4, predominantly in neurons. Co-immunoprecipitation coupled with mass spectrometry revealed that TRPV4 directly interacts with GluN1. This enhanced TRPV4-GluN1 coupling promoted GluN1 phosphorylation at serine 896 and hyperactivated NMDAR signalling. We subsequently observed the concurrent induction of endoplasmic reticulum (ER) stress, as evidenced by a dilated ER ultrastructure and the upregulation of the expression of UPR markers (ATF6, p-PERK, p-IRE1\u03b1, and CHOP), as well as neuroinflammation, characterized by microglial activation and elevated expression of proinflammatory mediators (IL-6,", "source": "PubMed"}, {"chunk_id": "41792369_1", "pmid": "41792369", "title": "Interaction between transient receptor potential vanilloid 4 and glutamate NMDA receptor subunit 1 mediates endoplasmic reticulum stress and neuroinflammation in postoperative delirium.", "authors": "Huang S, Zhang T, Wang Y et al.", "year": "2026", "journal": "Molecular biomedicine", "keywords": "Endoplasmic reticulum stress, GluN1, Neuroinflammation, Postoperative delirium, TRPV4", "chunk": "ultrastructure and the upregulation of the expression of UPR markers (ATF6, p-PERK, p-IRE1\u03b1, and CHOP), as well as neuroinflammation, characterized by microglial activation and elevated expression of proinflammatory mediators (IL-6, IL-1\u03b2, and ICAM-1). These molecular pathologies were associated with decreased neuronal activity and the characteristic cognitive-affective deficits associated with POD. Critically, both pharmacological inhibition of TRPV4 (HC067047) and hippocampal CA3-specific Trpv4 knockdown reversed these pathologies and rescued the behaviour. Inhibiting NMDAR with MK801 recapitulated these therapeutic benefits. Furthermore, TRPV4 was significantly upregulated in early-onset Alzheimer's disease patients. Our study defines a novel TRPV4-GluN1 axis that drives POD pathogenesis, suggesting that it is a promising therapeutic target.", "source": "PubMed"}, {"chunk_id": "40524264_0", "pmid": "40524264", "title": "Independent validation and outlier analysis of EuroPOND alzheimer's disease staging model using ADNI and real-world clinical data.", "authors": "Wittens MMJ, Sima DM, Brys A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Automated volumetry, Biomarkers, Event-based modelling, Magnetic resonance imaging", "chunk": "Event-based modeling (EBM) traces sequential progression of events in complex processes like neurodegenerative diseases, adept at handling uncertainties. This study validated an EBM for Alzheimer's disease (AD) staging designed by EuroPOND, an EU-funded Horizon 2020 project, using research and real-world datasets, a crucial step towards application in multi-center trials. The training dataset comprised 1737 subjects from ADNI-1/GO/2, using the EuroPOND EBM toolbox. Testing datasets included a research cohort from University of Antwerp (controls, CN (n = 46), subjective cognitive decline, SCD (n = 10), mild cognitive impairment, MCI (n = 47), AD dementia, ADD (n = 16)) and a real-world cohort from 9 Belgian Dementia Council memory clinics (CN (n = 91), SCD (n = 66), (non-amnestic) naMCI (n = 54), aMCI (n = 255), and ADD (n = 220). Biomarkers included: 2 clinical scores (Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT)); 3 CSF-biomarkers (A\u03b2<sub>1-42</sub>, P-tau<sub>181</sub>,", "source": "PubMed"}, {"chunk_id": "40524264_1", "pmid": "40524264", "title": "Independent validation and outlier analysis of EuroPOND alzheimer's disease staging model using ADNI and real-world clinical data.", "authors": "Wittens MMJ, Sima DM, Brys A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Automated volumetry, Biomarkers, Event-based modelling, Magnetic resonance imaging", "chunk": "54), aMCI (n = 255), and ADD (n = 220). Biomarkers included: 2 clinical scores (Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT)); 3 CSF-biomarkers (A\u03b2<sub>1-42</sub>, P-tau<sub>181</sub>, total-Tau); and 4 magnetic resonance imaging (MRI) biomarkers (volumes of the hippocampi, temporal, parietal, and frontal cortices) computed with icobrain dm. The naMCI and aMCI groups were compared by EBM stage proportions, and the model's effectiveness at patient level was evaluated. The research cohort's maximum likelihood event sequence comprised CSF A\u03b2<sub>1-42</sub>, P-tau<sub>181</sub>, T-tau, RAVLT, MMSE, and cortical volumes. The clinical cohort's order was frontal cortex volume, MMSE, and remaining cortical regions. aMCI subjects showed higher staging than naMCI, with 54% in the two most advanced stages compared to 38% in naMCI. In the research cohort, 10 outliers were identified with potential mismatches between assigned stages and clinical or biomarker profiles, with CN (n = 4) and SCD (n = 2)", "source": "PubMed"}, {"chunk_id": "40524264_2", "pmid": "40524264", "title": "Independent validation and outlier analysis of EuroPOND alzheimer's disease staging model using ADNI and real-world clinical data.", "authors": "Wittens MMJ, Sima DM, Brys A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Automated volumetry, Biomarkers, Event-based modelling, Magnetic resonance imaging", "chunk": "naMCI. In the research cohort, 10 outliers were identified with potential mismatches between assigned stages and clinical or biomarker profiles, with CN (n = 4) and SCD (n = 2) subjects assigned in stage 4, one control in stage 9 with abnormal imaging, and three aMCI cases in stage 0 despite clinical or volumetric signs of impairment. This study highlights the generalizability of EuroPOND's AD EBM model across research and real-world clinical datasets, supporting its use in multi-center trials. aMCI subjects generally reside in more advanced stages than naMCI, who may not necessarily have AD, demonstrating utility for precision recruitment/screening.", "source": "PubMed"}, {"chunk_id": "36562884_0", "pmid": "36562884", "title": "Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders.", "authors": "Kaur P, Khera A, Alajangi HK et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Biomarkers, Neurodegeneration, Tau, Tauopathy", "chunk": "A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3\u03b2) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies", "source": "PubMed"}, {"chunk_id": "36562884_1", "pmid": "36562884", "title": "Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders.", "authors": "Kaur P, Khera A, Alajangi HK et al.", "year": "2023", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Biomarkers, Neurodegeneration, Tau, Tauopathy", "chunk": "nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease. Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.", "source": "PubMed"}, {"chunk_id": "32176641_0", "pmid": "32176641", "title": "Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.", "authors": "Alifier M, Olsson B, Andreasson U et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Cardiac surgery, cognitive impairment, dementia, extracorporeal circulation, neurofilament light protein, plasma, tau", "chunk": "Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, A\u03b240, and A\u03b242 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. Tau increased during surgery (1752%, p = 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients", "source": "PubMed"}, {"chunk_id": "32176641_1", "pmid": "32176641", "title": "Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.", "authors": "Alifier M, Olsson B, Andreasson U et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Cardiac surgery, cognitive impairment, dementia, extracorporeal circulation, neurofilament light protein, plasma, tau", "chunk": "= 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for A\u03b240 and A\u03b242. Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.", "source": "PubMed"}, {"chunk_id": "40028849_0", "pmid": "40028849", "title": "Cerebrospinal Fluid Beta-Amyloid Concentration and Clinical and Radiographic Manifestations of Cerebral Amyloid Angiopathy.", "authors": "Alten B, Gokcal E, Warren A et al.", "year": "2025", "journal": "Journal of the American Heart Association", "keywords": "amyloid, cerebral amyloid angiopathy, cerebrospinal fluid biomarkers, cortical superficial siderosis, intracerebral hemorrhage, perivascular spaces in centrum semiovale, tau", "chunk": "Cerebral amyloid angiopathy (CAA) is driven by vascular A\u03b2 (amyloid-beta) deposition, which can be detected as reduced A\u03b2 species in cerebrospinal fluid (CSF). We sought to identify relationships between CSF A\u03b2 and tau concentrations and various manifestations of CAA. This is a retrospective cross-sectional single-center study of patients diagnosed with CAA per Boston Criteria version 2.0, had magnetic resonance imaging brain scans, and underwent CSF testing for A\u03b2 and tau concentrations between 2008 and 2022. Associations between clinical/magnetic resonance imaging features and CSF biomarker concentrations were investigated with univariate and multivariate models. We identified 31 patients aged 69.6\u00b18.4 years, of whom 20 presented with cognitive complaints, 9 with CAA-related macrohemorrhage (lobar intraparenchymal or convexity subarachnoid hemorrhage), and 2 with transient focal neurological episodes. Presence of macrohemorrhage (301.8\u00b1112 pg/mL versus 400.9\u00b1123 pg/mL, <i>P</i>=0.029), cortical superficial siderosis (309.6\u00b1131 mg/dL versus 412.3\u00b1100 pg/mL, <i>P</i>=0.021), and severe enlarged perivascular spaces in centrum semiovale (285.8\u00b191", "source": "PubMed"}, {"chunk_id": "40028849_1", "pmid": "40028849", "title": "Cerebrospinal Fluid Beta-Amyloid Concentration and Clinical and Radiographic Manifestations of Cerebral Amyloid Angiopathy.", "authors": "Alten B, Gokcal E, Warren A et al.", "year": "2025", "journal": "Journal of the American Heart Association", "keywords": "amyloid, cerebral amyloid angiopathy, cerebrospinal fluid biomarkers, cortical superficial siderosis, intracerebral hemorrhage, perivascular spaces in centrum semiovale, tau", "chunk": "focal neurological episodes. Presence of macrohemorrhage (301.8\u00b1112 pg/mL versus 400.9\u00b1123 pg/mL, <i>P</i>=0.029), cortical superficial siderosis (309.6\u00b1131 mg/dL versus 412.3\u00b1100 pg/mL, <i>P</i>=0.021), and severe enlarged perivascular spaces in centrum semiovale (285.8\u00b191 pg/mL versus 428.3\u00b1117 pg/mL, <i>P</i><0.001) were associated with lower A\u03b242 concentrations. A\u03b242 concentrations inversely correlated with the number of these manifestations, being lowest in patients having all three. Patients with cognitive complaints had higher t-tau (total tau; 551\u00b1320 pg/mL versus 317.2\u00b1141 pg/mL, <i>P</i>=0.03) and trended toward having higher p-tau (phosphorylated tau at threonine 181) concentrations (75.69\u00b139 pg/mL versus 49.24\u00b122 pg/mL, <i>P</i>=0.05). Lower CSF A\u03b242, suggesting higher amyloid burden, is associated with CAA-related macrohemorrhages and severe enlarged perivascular spaces in centrum semiovale, suggesting potential mechanistic links and CSF A\u03b242 as a potential biomarker for progression of CAA. CSF tau concentrations are linked to cognitive complaints, likely representing comorbid Alzheimer disease pathology.", "source": "PubMed"}, {"chunk_id": "40028849_2", "pmid": "40028849", "title": "Cerebrospinal Fluid Beta-Amyloid Concentration and Clinical and Radiographic Manifestations of Cerebral Amyloid Angiopathy.", "authors": "Alten B, Gokcal E, Warren A et al.", "year": "2025", "journal": "Journal of the American Heart Association", "keywords": "amyloid, cerebral amyloid angiopathy, cerebrospinal fluid biomarkers, cortical superficial siderosis, intracerebral hemorrhage, perivascular spaces in centrum semiovale, tau", "chunk": "potential biomarker for progression of CAA. CSF tau concentrations are linked to cognitive complaints, likely representing comorbid Alzheimer disease pathology.", "source": "PubMed"}, {"chunk_id": "41561816_0", "pmid": "41561816", "title": "AI agents in Alzheimer's disease management: challenges and future directions.", "authors": "Grammenos G, Vrahatis AG, Lazaros K et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, autonomous AI agents, clinical decision, explainable AI, large language models", "chunk": "Neurodegenerative diseases such as Alzheimer's and Parkinson's disease pose a major global healthcare challenge, with cases projected to rise sharply as populations age and effective treatments remain limited. AI has shown promise in supporting diagnostics, predicting disease progression, and exploring biomarkers, yet most current tools are narrowly focused, unimodal, and lack longitudinal reasoning or interpretability. By enabling context-aware analysis across imaging, genomics, cognitive, and behavioral data, agentic AI can track disease progression, identify therapeutic targets, and support clinical decision-making. Over time, these systems may detect gaps in their own information and request targeted data, moving closer to real clinical reasoning while keeping clinicians in control. The next frontier in medical AI lies in developing autonomous, multimodal agents capable of integrating diverse data, adapting through experience, supporting decision-making, and collaborating with clinicians. Furthermore, ethical, patient-centered AI requires close technical-clinical collaboration to support clinicians and improve patient outcomes. This perspective examines AI's", "source": "PubMed"}, {"chunk_id": "41561816_1", "pmid": "41561816", "title": "AI agents in Alzheimer's disease management: challenges and future directions.", "authors": "Grammenos G, Vrahatis AG, Lazaros K et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, autonomous AI agents, clinical decision, explainable AI, large language models", "chunk": "diverse data, adapting through experience, supporting decision-making, and collaborating with clinicians. Furthermore, ethical, patient-centered AI requires close technical-clinical collaboration to support clinicians and improve patient outcomes. This perspective examines AI's current role in Alzheimer's care, identifies key challenges in integration, interpretability, and regulation, and explores pathways for safely deploying these agentic systems in clinical practice.", "source": "PubMed"}, {"chunk_id": "40197092_0", "pmid": "40197092", "title": "Comparison of Deuterium Metabolic Imaging with FDG PET in Alzheimer Disease.", "authors": "B\u00f8gh N, Aastrup M, Mortensen JK et al.", "year": "2025", "journal": "Radiology", "keywords": "None", "chunk": "Background The approval of amyloid-targeting therapies has made it increasingly important to differentiate Alzheimer disease (AD) from other causes of dementia. Dysfunctional glucose metabolism is a recognized pathophysiological element in AD that may be visualized with spectroscopic MRI of deuterated glucose and its metabolites, also known as deuterium metabolic imaging (DMI). Purpose To explore the potential of DMI as a diagnostic tool for AD. Materials and Methods In this prospective cross-sectional study, participants with newly diagnosed AD and age-matched controls were recruited from April to October 2023. DMI was performed with a 3-T system equipped with a proton/deuterium head coil following oral consumption of 75 g of deuterated glucose. Clinical fluorodeoxyglucose (FDG) PET data were acquired from patient records for comparison. The predefined primary outcome, the ratio between lactate and glutamine plus glutamate (Glx) at DMI, was analyzed using age-corrected linear mixed-effect models. Results Ten participants with AD (mean age,", "source": "PubMed"}, {"chunk_id": "40197092_1", "pmid": "40197092", "title": "Comparison of Deuterium Metabolic Imaging with FDG PET in Alzheimer Disease.", "authors": "B\u00f8gh N, Aastrup M, Mortensen JK et al.", "year": "2025", "journal": "Radiology", "keywords": "None", "chunk": "comparison. The predefined primary outcome, the ratio between lactate and glutamine plus glutamate (Glx) at DMI, was analyzed using age-corrected linear mixed-effect models. Results Ten participants with AD (mean age, 72 years \u00b1 6 [SD]; six women) and five age-matched healthy controls (mean age, 68 years \u00b1 7; four men) were included. The primary analysis revealed no evidence of a difference in the ratio of lactate to Glx between participants with AD and controls (<i>P</i> = .24 across all regions of interest). Exploratory analyses revealed that participants with AD had reduced signals for medial temporal lactate (0.7 \u00b1 0.2 vs 0.5 \u00b1 0.1, <i>P</i> = .04) and Glx (0.5 \u00b1 0.03 vs 0.48 \u00b1 0.05, <i>P</i> = .03) compared with controls. Finally, a strong correlation (<i>r</i> = 0.73) was observed between DMI and FDG PET. Conclusion This study did not find evidence to support a shift from oxidative to anaerobic", "source": "PubMed"}, {"chunk_id": "40197092_2", "pmid": "40197092", "title": "Comparison of Deuterium Metabolic Imaging with FDG PET in Alzheimer Disease.", "authors": "B\u00f8gh N, Aastrup M, Mortensen JK et al.", "year": "2025", "journal": "Radiology", "keywords": "None", "chunk": "controls. Finally, a strong correlation (<i>r</i> = 0.73) was observed between DMI and FDG PET. Conclusion This study did not find evidence to support a shift from oxidative to anaerobic metabolism in AD. Exploratory analyses revealed a decrease in glucose metabolism in the medial temporal lobe. In extension hereof, a similar distribution of low DMI metabolism and decreased FDG PET glucose uptake was observed. \u00a9 RSNA, 2025 <i>Supplemental material is available for this article.</i> See also the article by Liu et al in this issue. See also the editorial by Port in this issue.", "source": "PubMed"}, {"chunk_id": "40355750_0", "pmid": "40355750", "title": "Monoclonal antibody administration in an academic institution and private neurological practice: a tale of two clinics.", "authors": "Rosenbloom M, Schnee A, Nimma S et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Alzheimer's, Amyloid lowering, Biomarker, Monoclonal antibody, Real world, Therapeutics", "chunk": "The emergence of monoclonal antibody (MABs) drugs since the FDA approval of lecanemab has resulted in dramatic changes in the clinical approach and management of early-stage Alzheimer's disease (AD). Challenges with MAB adoption into clinical practice may vary depending on whether the institution is an academic/integrated healthcare organization versus a private neurological practice. We have combined demographic and clinical data from a high-volume East coast private neurology practice and a West coast academic memory clinic at post-MAB adoption. Combined data of N = 165 patient showed the following demographics: mean age 72, 67% female, 92% Caucasian, average MOCA 18/30 with amyloid status confirmed by CSF in 72% of patients. Overall, ARIA rates were 8% for ARIA-E and 7% for ARIA-H, and there were no mortalities over the observation period. Three patients required immediate medical attention due to ARIA radiographic findings associated with clinical symptoms. The private practice enrolled patients with", "source": "PubMed"}, {"chunk_id": "40355750_1", "pmid": "40355750", "title": "Monoclonal antibody administration in an academic institution and private neurological practice: a tale of two clinics.", "authors": "Rosenbloom M, Schnee A, Nimma S et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Alzheimer's, Amyloid lowering, Biomarker, Monoclonal antibody, Real world, Therapeutics", "chunk": "and there were no mortalities over the observation period. Three patients required immediate medical attention due to ARIA radiographic findings associated with clinical symptoms. The private practice enrolled patients with lower average cognitive screening scores than the academic practice, but was more efficient at initiation therapy (mean # of weeks between diagnosis and treatment 97 versus 149 days). The average patient out-of-pocket cost was ($654.38) significantly less than the 20% of the annual drug cost as previously estimated. The findings from two separate clinical environments support the notion that ARIA risk associated with lecanemab is no greater than what was found in the CLARITY-AD trial and that the costs to the patient were less than predicted. This study was limited by the lack of 12 month efficacy data. Additional real-world data relating to the clinical effectiveness of MAB use in clinical practice will be necessary to best determine the risk/benefit", "source": "PubMed"}, {"chunk_id": "40355750_2", "pmid": "40355750", "title": "Monoclonal antibody administration in an academic institution and private neurological practice: a tale of two clinics.", "authors": "Rosenbloom M, Schnee A, Nimma S et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Alzheimer's, Amyloid lowering, Biomarker, Monoclonal antibody, Real world, Therapeutics", "chunk": "by the lack of 12 month efficacy data. Additional real-world data relating to the clinical effectiveness of MAB use in clinical practice will be necessary to best determine the risk/benefit ratio of these drugs in community populations.", "source": "PubMed"}, {"chunk_id": "40592256_0", "pmid": "40592256", "title": "Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study.", "authors": "Wang T, Arnold M, Huynh K et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "AD biomarkers, Alzheimer's disease, Cognitively normal, Lipidomics, Mild cognitive impairment", "chunk": "Comprehensive lipidomic studies have demonstrated strong cross-sectional associations between the blood lipidome and late-onset Alzheimer's disease (AD) dementia and its risk factors, yet the longitudinal relationship between lipidome changes and AD progression remains unclear. We employed longitudinal lipidomic profiling on 4730 plasma samples from 1517 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to investigate the temporal evolution of lipidomes among diagnostic groups. At baseline (n = 1393), participants were classified as stable diagnosis status including stable AD (n = 243), stable cognitive normal (CN; n = 337), and stable mild cognitive impairment (MCI; n = 413), or converters (AD converters: n = 329; MCI converters: n = 71). We developed a dementia risk classification model to stratify the non-converting MCI group into dementia-like and non-dementia-like MCI based on their baseline lipidomic profiles, aiming to identify early metabolic signatures predictive of dementia progression. Longitudinal analysis identified significant associations between", "source": "PubMed"}, {"chunk_id": "40592256_1", "pmid": "40592256", "title": "Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study.", "authors": "Wang T, Arnold M, Huynh K et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "AD biomarkers, Alzheimer's disease, Cognitively normal, Lipidomics, Mild cognitive impairment", "chunk": "non-converting MCI group into dementia-like and non-dementia-like MCI based on their baseline lipidomic profiles, aiming to identify early metabolic signatures predictive of dementia progression. Longitudinal analysis identified significant associations between the change in ether lipid species (including alkylphosphatidylcholine, alkenylphosphatidylcholine, lysoalkylphosphatidylcholine, and lysoalkenylphosphatidylcholine) and AD dementia conversion. Specifically, AD dementia converters show a 3-4.8% reduction in these ether lipid species compared to the non-converting CN and MCI groups, suggesting metabolic dysregulation as a key feature of AD progression. Further, The Dementia Risk Model effectively distinguished MCI from AD dementia converters (AUC = 0.70; 95% CI: 0.66-0.74). Within the MCI group, the model identified a high-risk subgroup with a twofold higher likelihood of conversion to AD dementia compared to the low-risk group. External validation in the ASPREE cohort confirmed its predictive utility, with the Dementia Risk Score discriminating incident dementia from cognitively normal individuals (C-index = 0.75, 95% CI: 0.73-0.78), improving prediction", "source": "PubMed"}, {"chunk_id": "40592256_2", "pmid": "40592256", "title": "Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study.", "authors": "Wang T, Arnold M, Huynh K et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "AD biomarkers, Alzheimer's disease, Cognitively normal, Lipidomics, Mild cognitive impairment", "chunk": "External validation in the ASPREE cohort confirmed its predictive utility, with the Dementia Risk Score discriminating incident dementia from cognitively normal individuals (C-index = 0.75, 95% CI: 0.73-0.78), improving prediction by 2% over the combination of traditional risk factors and APOE genetic risk factor. Additionally, the Dementia Risk Score was significantly associated with reduced temporal lobar fludeoxyglucose uptake (\u03b2 = -0.286, p = 1.34 \u00d7 10<sup>-4</sup>), higher amyloid PET levels (\u03b2 = 0.308, p = 4.03 \u00d7 10<sup>-4</sup>), and elevated p-tau levels (\u03b2 = 0.167, p = 2.37 \u00d7 10<sup>-2</sup>), reinforcing its pathophysiological relevance in tracking neurodegeneration, amyloid burden, and tau pathology. These findings highlight lipidomic profiling as a potential blood-based biomarker for identifying individuals at high risk of AD progression, offering a scalable, non-invasive approach for early detection, risk stratification, and targeted interventions in AD. The National Health and Medical Research Council of Australia (#1101320 and #1157607); NHMRC Investigator", "source": "PubMed"}, {"chunk_id": "40592256_3", "pmid": "40592256", "title": "Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study.", "authors": "Wang T, Arnold M, Huynh K et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "AD biomarkers, Alzheimer's disease, Cognitively normal, Lipidomics, Mild cognitive impairment", "chunk": "progression, offering a scalable, non-invasive approach for early detection, risk stratification, and targeted interventions in AD. The National Health and Medical Research Council of Australia (#1101320 and #1157607); NHMRC Investigator grant (#GNT1197190); Victorian Government's Operational Infrastructure Support Program; National Heart Foundation of Australia, Future Leader Fellowship (#102604), and National Health and Medical Research Council Investigator Grant (#2026325); Investigator grant (#2009965) from the National Health and Medical Research Council of Australia; a National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095); National Institutes of Health grants: P30AG010133, P30AG072976, R01AG019771, R01AG057739, U19AG024904, R01LM013463, R01AG068193, T32AG071444, U01AG068057, U01AG072177, U19AG074879, R01AG069901, R01AG046171, RF1AG051550, RF1AG057452; National Institutes of Health/National Institute on Aging grants RF1AG058942, RF1AG059093, U01AG061359, U19AG063744, and R01AG081322, NIH/NLM R01LM012535; FNIH: DAOU16AMPA.", "source": "PubMed"}, {"chunk_id": "40592256_4", "pmid": "40592256", "title": "Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study.", "authors": "Wang T, Arnold M, Huynh K et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "AD biomarkers, Alzheimer's disease, Cognitively normal, Lipidomics, Mild cognitive impairment", "chunk": "DAOU16AMPA.", "source": "PubMed"}, {"chunk_id": "41460671_0", "pmid": "41460671", "title": "Plasma biomarkers for Alzheimer's disease in middle-aged and older Japanese men: A population-based cross-sectional study.", "authors": "Nakano M, Kondo K, Ishiki K et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, age, amyloid-\u03b2, blood-based biomarker, cognitive impairment, renal function, tau", "chunk": "BackgroundThe diagnostic value of blood-based biomarkers for Alzheimer's disease (AD) neuropathology has been demonstrated in individuals with cognitive impairment; however, evidence for reliable preclinical stage diagnostic methods remains insufficient.ObjectiveTo identify confounding variables that may obscure the interpretation of these biomarkers, we examined their associations with various physiological indices including age, renal function, and cognitive function in Japanese men from the general population.MethodsPlasma were collected from 845 randomly selected Japanese men participants (aged >40 years) to measure 40- and 42-amino acid amyloid-\u03b2 (A\u03b2<sub>40</sub> and A\u03b2<sub>42</sub>), total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and neurofilament light chain (NfL) using an automated immunoassay system. Cognitive function was assessed using the Cognitive Abilities Screening Instrument (CASI). Linear regression models were constructed to estimate association strengths with correction for possible confounding variables.ResultsPlasma A\u03b2<sub>40</sub>, A\u03b2<sub>42</sub>, T-tau, P-tau181, NfL, and P-tau181/T-tau increased with age and declining glomerular filtration rate (eGFR), whereas A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> decreased with age.", "source": "PubMed"}, {"chunk_id": "41460671_1", "pmid": "41460671", "title": "Plasma biomarkers for Alzheimer's disease in middle-aged and older Japanese men: A population-based cross-sectional study.", "authors": "Nakano M, Kondo K, Ishiki K et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, age, amyloid-\u03b2, blood-based biomarker, cognitive impairment, renal function, tau", "chunk": "estimate association strengths with correction for possible confounding variables.ResultsPlasma A\u03b2<sub>40</sub>, A\u03b2<sub>42</sub>, T-tau, P-tau181, NfL, and P-tau181/T-tau increased with age and declining glomerular filtration rate (eGFR), whereas A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> decreased with age. Higher T-tau and P-tau181 were associated with lower CASI scores after adjusting for age and eGFR. Individuals in older age groups with A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratios less than or equal to a cutoff (\"amyloid-positive\") also exhibited higher P-tau181, NfL, and P-tau181/T-tau than amyloid-negative individuals, with no significant difference in mean CASI score.ConclusionsOur results confirm that plasma AD biomarkers are significantly influenced by age and renal clearance rate. Notably, higher T-tau and P-tau181 were associated with preclinical cognitive impairment. Additionally, a lower A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> was associated with asymptomatic tau pathology and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "35159288_0", "pmid": "35159288", "title": "Can We Use <i>Ginkgo biloba</i> Extract to Treat Alzheimer's Disease? Lessons from Preclinical and Clinical Studies.", "authors": "Xie L, Zhu Q, Lu J", "year": "2022", "journal": "Cells", "keywords": "Alzheimer\u2019s disease, Ginkgo biloba extract, clinical trial, meta-analysis", "chunk": "(1) Background: <i>Ginkgo biloba</i> extract (GBE) has been widely used to treat central nervous system and cardiovascular diseases. Accumulating evidence has revealed the therapeutic potential of GBE against Alzheimer's disease (AD); however, no systematic evaluation has been performed; (2) Methods: a total of 17 preclinical studies and 20 clinical trials assessing the therapeutic effects of GBE against AD were identified from electronic databases. The data in the reports were extracted to conduct a meta-analysis of the AD-related pathological features or symptoms; (3) Results: For the preclinical reports, 45 animals treated with GBE, in six studies, were subjected to cognitive function assessments by the Morris water maze. GBE was shown to reduce the escape latencies in several studies, in both rats and mice (I<sup>2</sup> > 70%, <i>p</i> < 0.005). For the clinical trials, eight trials, including 2100 individuals, were conducted. The results show that GBE improved the SKT and ADAS-Cog scores", "source": "PubMed"}, {"chunk_id": "35159288_1", "pmid": "35159288", "title": "Can We Use <i>Ginkgo biloba</i> Extract to Treat Alzheimer's Disease? Lessons from Preclinical and Clinical Studies.", "authors": "Xie L, Zhu Q, Lu J", "year": "2022", "journal": "Cells", "keywords": "Alzheimer\u2019s disease, Ginkgo biloba extract, clinical trial, meta-analysis", "chunk": "and mice (I<sup>2</sup> > 70%, <i>p</i> < 0.005). For the clinical trials, eight trials, including 2100 individuals, were conducted. The results show that GBE improved the SKT and ADAS-Cog scores in early-stage AD patients after high doses and long-term administration; (4) Conclusions: GBE displayed generally consistent anti-AD effects in animal experiments, and it might improve AD symptoms in early-stage AD patients after high doses and long-term administration. A lack of sample size calculations and the poor quality of the methods are two obvious limitations of the studies. Nevertheless, the preclinical and clinical data suggest that further large-scale clinical trials may be needed in order to examine the effects of long-term GEB administration on early-stage AD.", "source": "PubMed"}, {"chunk_id": "36118683_0", "pmid": "36118683", "title": "Use of machine learning to identify functional connectivity changes in a clinical cohort of patients at risk for dementia.", "authors": "Shen Y, Lu Q, Zhang T et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain network, dementia, functional connectivity, graph theory", "chunk": "Progressive conditions characterized by cognitive decline, including mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are clinical conditions representing a major risk factor to develop dementia, however, the diagnosis of these pre-dementia conditions remains a challenge given the heterogeneity in clinical trajectories. Earlier diagnosis requires data-driven approaches for improved and targeted treatment modalities. Neuropsychological tests, baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 35 patients with SCD, 19 with MCI, and 36 age-matched healthy controls (HC). A recently developed machine learning technique, Hollow Tree Super (HoTS) was utilized to classify subjects into diagnostic categories based on their FC, and derive network and parcel-based FC features contributing to each model. The same approach was used to identify features associated with performance in a range of neuropsychological tests. We concluded our analysis by looking at changes in PageRank centrality (a measure", "source": "PubMed"}, {"chunk_id": "36118683_1", "pmid": "36118683", "title": "Use of machine learning to identify functional connectivity changes in a clinical cohort of patients at risk for dementia.", "authors": "Shen Y, Lu Q, Zhang T et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain network, dementia, functional connectivity, graph theory", "chunk": "The same approach was used to identify features associated with performance in a range of neuropsychological tests. We concluded our analysis by looking at changes in PageRank centrality (a measure of node hubness) between the diagnostic groups. Subjects were classified into diagnostic categories with a high area under the receiver operating characteristic curve (AUC-ROC), ranging from 0.73 to 0.84. The language networks were most notably associated with classification. Several central networks and sensory brain regions were predictors of poor performance in neuropsychological tests, suggesting maladaptive compensation. PageRank analysis highlighted that basal and limbic deep brain region, along with the frontal operculum demonstrated a reduction in centrality in both SCD and MCI patients compared to controls. Our methods highlight the potential to explore the underlying neural networks contributing to the cognitive changes and neuroplastic responses in prodromal dementia.", "source": "PubMed"}, {"chunk_id": "36118683_2", "pmid": "36118683", "title": "Use of machine learning to identify functional connectivity changes in a clinical cohort of patients at risk for dementia.", "authors": "Shen Y, Lu Q, Zhang T et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain network, dementia, functional connectivity, graph theory", "chunk": "to explore the underlying neural networks contributing to the cognitive changes and neuroplastic responses in prodromal dementia.", "source": "PubMed"}, {"chunk_id": "39954137_0", "pmid": "39954137", "title": "IRS gene polymorphisms in Turkish patients with late-onset Alzheimer's disease.", "authors": "Ozkan H, Yildiz M, Ustundag A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer, Insulin receptor substrate, Polymorphism, rs1801278, rs1805097", "chunk": "Factors that cause changes in insulin signaling in the brain are thought to affect the synaptic plasticity and accelerate the process of brain aging and neurodegeneration. Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling. The aim of the current study is to determine whether there is an association between IRS gene polymorphisms, which are critical for insulin signaling, and the late-onset Alzheimer's disease in Turkish patients. Demographic and clinical characteristics of 115 patients with late-onset Alzheimer's disease (age of onset \u2265 65 years) and 107 age-matched control subjects were obtained. DNAs were isolated from patient and control groups, IRS-1 and IRS-2 gene polymorphisms were investigated and genotyped according to the PCR-RFLP method. No statistically significant difference was observed in the genotypes for IRS-1 Gly972Arg (rs1801278) (p = 0.499) and IRS-2 Gly1057Asp (rs1805097) polymorphism between late-onset Alzheimer's disease patients and controls (p = 0.658). However, when the compliance", "source": "PubMed"}, {"chunk_id": "39954137_1", "pmid": "39954137", "title": "IRS gene polymorphisms in Turkish patients with late-onset Alzheimer's disease.", "authors": "Ozkan H, Yildiz M, Ustundag A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer, Insulin receptor substrate, Polymorphism, rs1801278, rs1805097", "chunk": "observed in the genotypes for IRS-1 Gly972Arg (rs1801278) (p = 0.499) and IRS-2 Gly1057Asp (rs1805097) polymorphism between late-onset Alzheimer's disease patients and controls (p = 0.658). However, when the compliance of IRS-2 polymorphism with Hardy- Weinberg distribution was tested, in the case-control comparison, G allele frequency of IRS-2 polymorphisms was significantly higher in the patient population than in the control group in the Turkish population of the Thrace region. Despite the potential role of insulin resistance and hyperinsulinemia in the development of Alzheimer's disease, we did not find any association between polymorphism of the IRS-1 and IRS-2 genes and late-onset Alzheimer's disease. However, compared to the healthy subjects, Gly/Gly genotypes and the G allele in the IRS-2 were significantly more frequent in patients with late-onset Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "39954137_2", "pmid": "39954137", "title": "IRS gene polymorphisms in Turkish patients with late-onset Alzheimer's disease.", "authors": "Ozkan H, Yildiz M, Ustundag A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer, Insulin receptor substrate, Polymorphism, rs1801278, rs1805097", "chunk": "frequent in patients with late-onset Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41063440_0", "pmid": "41063440", "title": "Diffusion Tractography Biomarker for Epilepsy Severity in Children With Drug-Resistant Epilepsy.", "authors": "Jeong JW, Lee MH, Uda H et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "To develop a novel deep-learning model of clinical DWI tractography that can accurately predict the general assessment of epilepsy severity (GASE) in pediatric drug-resistant epilepsy (DRE) and test if it can screen diverse neurocognitive impairments identified through neuropsychological assessments. DRE children and age-sex-matched healthy controls were enrolled to construct an epilepsy severity network (ESN), whose edges were significantly correlated with GASE scores of DRE children. An ESN-based biomarker called the predicted GASE score was obtained using dilated deep convolutional neural network with a relational network (dilated DCNN+RN) and used to quantify the risk of neurocognitive impairments using global/verbal/non-verbal neuropsychological assessments of 36/37/32 children performed on average 3.2 \u00b1 2.7 months prior to the MRI scan. To warrant the generalizability, the proposed biomarker was trained and evaluated using separate development and independent test sets, with the random score learning experiment included to assess potential overfitting. The dilated DCNN+RN outperformed other state-of-the", "source": "PubMed"}, {"chunk_id": "41063440_1", "pmid": "41063440", "title": "Diffusion Tractography Biomarker for Epilepsy Severity in Children With Drug-Resistant Epilepsy.", "authors": "Jeong JW, Lee MH, Uda H et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "proposed biomarker was trained and evaluated using separate development and independent test sets, with the random score learning experiment included to assess potential overfitting. The dilated DCNN+RN outperformed other state-of-the art methods to create the predicted GASE scores with significant correlation (r = 0.92 and 0.83 for development and test sets with clinical GASE scores) and minimal overfitting (r = -0.25 and 0.00 for development and test sets with random GASE scores). Both univariate and multivariate models demonstrated that compared with the clinical GASE scores, the predicted GASE scores provide better model fit and discriminatory ability, suggesting more adjusted and accurate estimate of epilepsy severity contributing to the overall risk. The proposed biomarker shows strong potential for early identification of DRE children at risk of neurocognitive impairments, enabling timely, personalized interventions to prevent long-term effects.", "source": "PubMed"}, {"chunk_id": "41063440_2", "pmid": "41063440", "title": "Diffusion Tractography Biomarker for Epilepsy Severity in Children With Drug-Resistant Epilepsy.", "authors": "Jeong JW, Lee MH, Uda H et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "DRE children at risk of neurocognitive impairments, enabling timely, personalized interventions to prevent long-term effects.", "source": "PubMed"}, {"chunk_id": "38145469_0", "pmid": "38145469", "title": "Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE \u03b54 homozygotes.", "authors": "Riviere ME, Langbaum JB, Turner RS et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, CAD106, active immunotherapy, amyloid, apolipoprotein E genotype, biomarkers, cognitively unimpaired, positron emission tomography, preclinical, prevention, vaccine", "chunk": "Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (A\u03b2) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. Sixty-five apolipoprotein E \u03b54 homozygotes with/without amyloid deposition received intramuscular CAD106 450 \u03bcg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up A\u03b2 positron emission tomography (PET) scans at 18 to 24 months. CAD106 induced measurable serum A\u03b2 immunoglobulin G titers in 41/42 participants, slower rates of A\u03b2 plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic). Despite early termination, these findings support the potential value of", "source": "PubMed"}, {"chunk_id": "38145469_1", "pmid": "38145469", "title": "Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE \u03b54 homozygotes.", "authors": "Riviere ME, Langbaum JB, Turner RS et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, CAD106, active immunotherapy, amyloid, apolipoprotein E genotype, biomarkers, cognitively unimpaired, positron emission tomography, preclinical, prevention, vaccine", "chunk": "Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic). Despite early termination, these findings support the potential value of conducting larger prevention trials of A\u03b2 active immunotherapies in individuals at risk for AD. This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.", "source": "PubMed"}, {"chunk_id": "39739252_0", "pmid": "39739252", "title": "Brain 18FDG-PET pattern in cognitively impaired elderly patients with bipolar disorder.", "authors": "Saleh N, Blaise C, Daoudi A et al.", "year": "2024", "journal": "International journal of bipolar disorders", "keywords": "Alzheimer\u2019s disease, Bipolar disorder, Dementia, Elderly, Neurodegenerative disorder", "chunk": "Patients with bipolar disorder (BD) are at increased risk of dementia. The underlying mechanisms are debated. FDG-PET elucidates glucose metabolic reductions due to altered neuronal activity in the cerebral cortex, allowing detection and identification of neurodegenerative processes. This study aims to investigate cerebral glucose metabolism in cognitively impaired elderly patients with BD using FDG-PET imaging, to elucidate potential underlying mechanisms and improve diagnostic accuracy. We conducted a retrospective analysis of FDG-PET scans from 32 cognitively impaired elderly patients with BD (mean age 70.4 years). These were compared with scans from 35 non-degenerative controls (NDC) and patients diagnosed with Alzheimer's disease (AD, n = 27), frontotemporal dementia (FTD, n = 26), and dementia with Lewy bodies (DLB, n = 18). Voxel-wise statistical analysis was performed using SPM software, adjusting for age and sex. No significant cortical hypometabolism was found in patients with BD compared to NDC. In contrast, typical patterns of", "source": "PubMed"}, {"chunk_id": "39739252_1", "pmid": "39739252", "title": "Brain 18FDG-PET pattern in cognitively impaired elderly patients with bipolar disorder.", "authors": "Saleh N, Blaise C, Daoudi A et al.", "year": "2024", "journal": "International journal of bipolar disorders", "keywords": "Alzheimer\u2019s disease, Bipolar disorder, Dementia, Elderly, Neurodegenerative disorder", "chunk": "statistical analysis was performed using SPM software, adjusting for age and sex. No significant cortical hypometabolism was found in patients with BD compared to NDC. In contrast, typical patterns of hypometabolism were observed in the AD, FTD, and DLB groups. The findings suggest that late-life cognitive impairment in patients with BD is not due to a single common neurodegenerative process. The absence of abnormal cortical metabolism in cognitively impaired elderly patients with BD suggests that cognitive impairment in this population may not be driven by a common neurodegenerative pathway. Further studies using other biomarkers are needed to investigate the brain processes involved, which could lead to improved understanding and management of cognitive impairment in patients with BD.", "source": "PubMed"}, {"chunk_id": "41516103_0", "pmid": "41516103", "title": "CaMKII Neurons in the Dentate Gyrus Are Involved in Regulating Cognitive Impairment in Mice Induced by Stress Caused by Violence.", "authors": "Shao G, Liu D, Liu Z et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "3D behavior atlas, post-stress cognitive impairment, stress caused by violence", "chunk": "Post-stress cognitive impairment (PSCI) is defined as a persistent neuropsychiatric condition characterized by deficits in memory consolidation, executive functioning, and environmental interaction following exposure to violent stress. Despite its high incidence, PSCI remains underdiagnosed and lacks effective therapeutic strategies, posing a substantial societal burden and highlighting a critical gap in neuropsychiatric research. A major constraint in mechanistic studies is the persistent reliance on conventional paradigms, notably the Y-maze and novel object recognition test. Their limited sensitivity and poor translational relevance to human cognitive dysfunction, compounded by slow methodological innovation, significantly impede progress. Furthermore, the specific brain regions or neuronal populations contributing to PSCI pathogenesis are insufficiently explored. To address this, we assessed post-stress cognitive impairment in mice using a triple approach: Skinner box assays, traditional behavioral paradigms, and integrated 3D ethological analysis. This multi-method framework provides novel insights for refining animal models and advancing mechanistic understanding. Using c-Fos-based whole-brain screening,", "source": "PubMed"}, {"chunk_id": "41516103_1", "pmid": "41516103", "title": "CaMKII Neurons in the Dentate Gyrus Are Involved in Regulating Cognitive Impairment in Mice Induced by Stress Caused by Violence.", "authors": "Shao G, Liu D, Liu Z et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "3D behavior atlas, post-stress cognitive impairment, stress caused by violence", "chunk": "approach: Skinner box assays, traditional behavioral paradigms, and integrated 3D ethological analysis. This multi-method framework provides novel insights for refining animal models and advancing mechanistic understanding. Using c-Fos-based whole-brain screening, we identified the dentate gyrus (DG) as a key region involved in PSCI. Stress caused by violence markedly increased activity in DG CaMKII-expressing neurons. Chemogenetic inhibition of these neurons effectively alleviated stress-induced mild cognitive impairment phenotypes. In summary, by applying novel behavioral assessment tools, this study demonstrates that DG CaMKII neurons play a critical role in regulating post-stress cognitive impairment.", "source": "PubMed"}, {"chunk_id": "39381682_0", "pmid": "39381682", "title": "Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer's disease.", "authors": "Kim BH, Seo SW, Park YH et al.", "year": "2024", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid beta (Ab), cortical thickness, genetics, single nucleotide polymorphism (SNP), sparse canonical correlation analysis", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction. We recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in A\u03b2 negative (-) and A\u03b2 positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs. We identified SNPs related to cortical thickness using SCCA in A\u03b2 negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating A\u03b2 uptake, and three SNPs (rs2271920, rs6859, rs9270580)", "source": "PubMed"}, {"chunk_id": "39381682_1", "pmid": "39381682", "title": "Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer's disease.", "authors": "Kim BH, Seo SW, Park YH et al.", "year": "2024", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid beta (Ab), cortical thickness, genetics, single nucleotide polymorphism (SNP), sparse canonical correlation analysis", "chunk": "groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating A\u03b2 uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of <i>CHRNA2</i>, <i>NECTIN2</i>, and <i>HLA</i> genes. Our findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.", "source": "PubMed"}, {"chunk_id": "33849249_0", "pmid": "33849249", "title": "Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study.", "authors": "Cho Y, Han K, Kim DH et al.", "year": "2021", "journal": "Endocrinology and metabolism (Seoul, Korea)", "keywords": "Alzheimer disease, Dementia, Metabolic syndrome", "chunk": "Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia. Adults (n=1,492,776; \u226545-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model. Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase", "source": "PubMed"}, {"chunk_id": "33849249_1", "pmid": "33849249", "title": "Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study.", "authors": "Cho Y, Han K, Kim DH et al.", "year": "2021", "journal": "Endocrinology and metabolism (Seoul, Korea)", "keywords": "Alzheimer disease, Dementia, Metabolic syndrome", "chunk": "with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer's disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer's disease. More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.", "source": "PubMed"}, {"chunk_id": "33849249_2", "pmid": "33849249", "title": "Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study.", "authors": "Cho Y, Han K, Kim DH et al.", "year": "2021", "journal": "Endocrinology and metabolism (Seoul, Korea)", "keywords": "Alzheimer disease, Dementia, Metabolic syndrome", "chunk": "of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.", "source": "PubMed"}, {"chunk_id": "41373784_0", "pmid": "41373784", "title": "From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.", "authors": "Basavarajappa BS, Subbanna S", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "alcohol, brain circuits, cannabinoid receptors, cell death, drug reinforcement, drugs of abuse, pathology", "chunk": "The endocannabinoid system (eCBS) is a versatile neuromodulatory network that orchestrates synaptic plasticity, reward processing, and neuronal homeostasis. Increasing evidence implicates eCBS dysregulation in both addiction and neurodegenerative (ND) disorders, suggesting overlapping molecular and cellular mechanisms underlying these conditions. This review synthesizes recent advances in understanding how eCBS components-cannabinoid receptors (CB1 and CB2), endogenous ligands (anandamide and 2-arachidonoylglycerol), and their metabolic enzymes-modulate dopaminergic and glutamatergic signaling within reward and reinforcement circuits. Chronic exposure to drugs of abuse, including alcohol, opioids, cocaine, and methamphetamine, perturbs eCBS homeostasis, promoting oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and protein aggregation-pathological features common to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. These overlapping mechanisms disrupt neuronal integrity and contribute to progressive neurotoxicity, highlighting shared pathogenic pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS", "source": "PubMed"}, {"chunk_id": "41373784_1", "pmid": "41373784", "title": "From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.", "authors": "Basavarajappa BS, Subbanna S", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "alcohol, brain circuits, cannabinoid receptors, cell death, drug reinforcement, drugs of abuse, pathology", "chunk": "pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS as a therapeutic target to mitigate addiction-driven neurotoxicity and age-related cognitive decline.", "source": "PubMed"}, {"chunk_id": "40453306_0", "pmid": "40453306", "title": "Hashimoto's Encephalopathy With Progressive Cognitive Decline: A Rare Autoimmune Disorder in Central America.", "authors": "Hong A, Santos AB, Moya Porras LF et al.", "year": "2025", "journal": "Cureus", "keywords": "anti-thyroglobulin antibodies, anti-thyroid peroxidase antibodies, autoimmune, encephalopathy, hashimoto", "chunk": "Hashimoto's encephalopathy (HE) is a rare autoimmune disorder, typically associated with Hashimoto's thyroiditis, and often presents with rapidly progressive cognitive impairment, psychiatric symptoms, and neurological deficits. Since the first case reported, there have been relatively few reports of HE cases, and it remains rare in Central America. A 59-year-old male patient with a past medical history of hypertension (HTN) and type 2 diabetes mellitus (DM2) was hospitalized due to a one-month history of rapidly progressive cognitive impairment associated with behavioral changes and episodes of amnesia. It was not associated with motor or sensory deficits, seizures, or movement disorders. Given this presentation, alongside normal head CT findings and mild age-related brain atrophy on MRI, the initial diagnosis posed a challenge. Further investigations, including cerebrospinal fluid (CSF) analysis, autoimmune panels, and viral encephalitis testing, helped exclude other potential causes of encephalopathy. Notably, elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies were detected,", "source": "PubMed"}, {"chunk_id": "40453306_1", "pmid": "40453306", "title": "Hashimoto's Encephalopathy With Progressive Cognitive Decline: A Rare Autoimmune Disorder in Central America.", "authors": "Hong A, Santos AB, Moya Porras LF et al.", "year": "2025", "journal": "Cureus", "keywords": "anti-thyroglobulin antibodies, anti-thyroid peroxidase antibodies, autoimmune, encephalopathy, hashimoto", "chunk": "investigations, including cerebrospinal fluid (CSF) analysis, autoimmune panels, and viral encephalitis testing, helped exclude other potential causes of encephalopathy. Notably, elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies were detected, strongly suggesting HE. The patient responded favorably to immunosuppressive treatment with intravenous methylprednisolone and subsequent oral prednisone, leading to significant cognitive improvement and recovery of function. This case highlights the importance of considering HE in the differential diagnosis of rapidly progressive cognitive decline, especially when routine standard investigations do not reveal an alternative cause.", "source": "PubMed"}, {"chunk_id": "38898183_0", "pmid": "38898183", "title": "Apolipoprotein E in Alzheimer's disease trajectories and the next-generation clinical care pathway.", "authors": "Narasimhan S, Holtzman DM, Apostolova LG et al.", "year": "2024", "journal": "Nature neuroscience", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a complex, progressive primary neurodegenerative disease. Since pivotal genetic studies in 1993, the \u03b54 allele of the apolipoprotein E gene (APOE \u03b54) has remained the strongest single genome-wide associated risk variant in AD. Scientific advances in APOE biology, AD pathophysiology and ApoE-targeted therapies have brought APOE to the forefront of research, with potential translation into routine AD clinical care. This contemporary Review will merge APOE research with the emerging AD clinical care pathway and discuss APOE genetic risk as a conduit to genomic-based precision medicine in AD, including ApoE's influence in the ATX(N) biomarker framework of AD. We summarize the evidence for APOE as an important modifier of AD clinical-biological trajectories. We then illustrate the utility of APOE testing and the future of ApoE-targeted therapies in the next-generation AD clinical-diagnostic pathway. With the emergence of new AD therapies, understanding how APOE modulates AD pathophysiology will become", "source": "PubMed"}, {"chunk_id": "38898183_1", "pmid": "38898183", "title": "Apolipoprotein E in Alzheimer's disease trajectories and the next-generation clinical care pathway.", "authors": "Narasimhan S, Holtzman DM, Apostolova LG et al.", "year": "2024", "journal": "Nature neuroscience", "keywords": "None", "chunk": "of APOE testing and the future of ApoE-targeted therapies in the next-generation AD clinical-diagnostic pathway. With the emergence of new AD therapies, understanding how APOE modulates AD pathophysiology will become critical for personalized AD patient care.", "source": "PubMed"}, {"chunk_id": "41621641_0", "pmid": "41621641", "title": "Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.", "authors": "Chen L, Yang Y, Zhang Y et al.", "year": "2026", "journal": "Cellular and molecular gastroenterology and hepatology", "keywords": "Cognitive Function, Gut Barrier, Gut Microbes, Tuft Cell", "chunk": "Tuft cells, a type of epithelial cell in the gut, play a pivotal role in regulating type 2 immunity and maintaining the gut barrier. However, their role in cognitive impairments remains unclear. We compared behavioral performance between male tuft cell-absent mice (Pou2f3<sup>-/-</sup>) and their wild-type (WT) littermates. We analyzed gut microbiota using fecal 16S rRNA, measured gut permeability via FITC-dextran assay, and detected CD4<sup>+</sup>-T cells and type 2 innate lymphoid cells by flow cytometry in both genotypes. Co-housing and fecal microbiota transplantation experiments were conducted to explore the role of gut microbiota in cognitive diseases. Single-cell RNA sequencing and fluorescence imaging were used to examine tuft cell changes in the colon of WT and Alzheimer's disease (AD) model mice. Colonic organoids were used to assess the effect of \u03b2-amyloid on tuft cell differentiation. Succinic acid, a promoter of tuft cells, was administered, and tuft cell-deficient AD mice were generated to", "source": "PubMed"}, {"chunk_id": "41621641_1", "pmid": "41621641", "title": "Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.", "authors": "Chen L, Yang Y, Zhang Y et al.", "year": "2026", "journal": "Cellular and molecular gastroenterology and hepatology", "keywords": "Cognitive Function, Gut Barrier, Gut Microbes, Tuft Cell", "chunk": "organoids were used to assess the effect of \u03b2-amyloid on tuft cell differentiation. Succinic acid, a promoter of tuft cells, was administered, and tuft cell-deficient AD mice were generated to evaluate its impact on behavior and gut homeostasis. Increased gut permeability, immune imbalance, neuroinflammation, and cognitive dysfunction occurred in 10-month-old mice lacking tuft cells. These alterations were mediated by gut microbiota, evidenced by shifts in microbiota composition and abundance, and supported by co-housing and fecal microbiota transplantation experiments. AD model mice had fewer tuft cells and impaired type 2 immunity in the gut, potentially because of \u03b2-amyloid inhibiting tuft cell differentiation. Succinic acid, a tuft cell activator, restored cognitive function and gut homeostasis in AD mice. Tuft cells may be necessary for maintaining gut homeostasis in cognitive disorders.", "source": "PubMed"}, {"chunk_id": "41621641_2", "pmid": "41621641", "title": "Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.", "authors": "Chen L, Yang Y, Zhang Y et al.", "year": "2026", "journal": "Cellular and molecular gastroenterology and hepatology", "keywords": "Cognitive Function, Gut Barrier, Gut Microbes, Tuft Cell", "chunk": "necessary for maintaining gut homeostasis in cognitive disorders.", "source": "PubMed"}, {"chunk_id": "38238285_0", "pmid": "38238285", "title": "Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.", "authors": "Cho SY, Kim EW, Park SJ et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer's disease (AD), also known as \"type 3 diabetes\". Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (\u226416 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment", "source": "PubMed"}, {"chunk_id": "38238285_1", "pmid": "38238285", "title": "Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.", "authors": "Cho SY, Kim EW, Park SJ et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "associative learning in younger NT mice (\u226416 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPK\u03b11-subunit, \u03b2-amyloid oligomers, plaques, phosphorylated tau, and GSK3\u03b2 expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP<sub>695</sub> cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.", "source": "PubMed"}, {"chunk_id": "38238285_2", "pmid": "38238285", "title": "Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.", "authors": "Cho SY, Kim EW, Park SJ et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "when this drug is used for individuals with AD.", "source": "PubMed"}, {"chunk_id": "35673950_0", "pmid": "35673950", "title": "In Alzheimer's disease, amyloid beta accumulation is a protective mechanism that ultimately fails.", "authors": "Rischel EB, Gejl M, Brock B et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, [11C]Pittsburgh compound B, [18F]fluorodeoxyglucose, amyloid beta, blood\u2013brain barrier, cerebral blood flow, cerebral glucose metabolism, positron emission tomography", "chunk": "Here, we claim that amyloid beta (A\u03b2) accumulation is a protective mechanism that ultimately fails. We predict that more A\u03b2 accumulates in regions with higher rates of glucose metabolism, reaching a maximum followed by progression of pathology. A\u03b2 accumulation is characteristic of Alzheimer's disease (AD) but the accumulation does not correlate with cognitive decline, unlike the rates of glucose metabolism. We compared averaged and individual estimates of regional binding potentials of [<sup>11</sup>C]Pittsburgh compound B to regionally averaged and individual values of metabolism of [<sup>18</sup>F]fluorodeoxyglucose in brain regions of volunteers with AD. The claim explains the cognitive decline in some patients at a significantly lower level of A\u03b2 deposition than in other patients, as well as the presence of cognitively healthy individuals with high A\u03b2 accumulation. With further support of the hypothesis, the significance of A\u03b2 accumulation in brains of patients with AD may require revision.", "source": "PubMed"}, {"chunk_id": "35673950_1", "pmid": "35673950", "title": "In Alzheimer's disease, amyloid beta accumulation is a protective mechanism that ultimately fails.", "authors": "Rischel EB, Gejl M, Brock B et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, [11C]Pittsburgh compound B, [18F]fluorodeoxyglucose, amyloid beta, blood\u2013brain barrier, cerebral blood flow, cerebral glucose metabolism, positron emission tomography", "chunk": "individuals with high A\u03b2 accumulation. With further support of the hypothesis, the significance of A\u03b2 accumulation in brains of patients with AD may require revision.", "source": "PubMed"}, {"chunk_id": "41154195_0", "pmid": "41154195", "title": "Therapeutic Advances in Targeting the Amyloid-\u03b2 Pathway for Alzheimer's Disease.", "authors": "Zhang B, Li Y, Li H et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, amyloid precursor protein (APP) processing, amyloid-\u03b2 hypothesis, anti\u2013amyloid-\u03b2 (A\u03b2) vaccines, biomarkers, gene therapy, monoclonal antibodies, small-molecule drugs, \u03b2-secretase 1 (BACE1) inhibitors, \u03b3-secretase modulators", "chunk": "Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-\u03b2 (A\u03b2) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, A\u03b2 has remained a central therapeutic target, with interventions aiming to reduce A\u03b2 production, aggregation, or downstream toxicity. This review first outlines the historical development of the A\u03b2 hypothesis and the two major APP processing pathways (\u03b1-cleavage and \u03b2-cleavage), highlighting the role of biomarkers in early diagnosis, patient stratification, and regulatory approval. We then summarize the development and clinical outcomes of anti-A\u03b2 small-molecule drugs, including \u03b2-secretase inhibitors, \u03b3-secretase modulators, A\u03b2 aggregation inhibitors, receptor/synapse modulators, and metabolic or antioxidant modalities. We further review the progression of biologic therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics,", "source": "PubMed"}, {"chunk_id": "41154195_1", "pmid": "41154195", "title": "Therapeutic Advances in Targeting the Amyloid-\u03b2 Pathway for Alzheimer's Disease.", "authors": "Zhang B, Li Y, Li H et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, amyloid precursor protein (APP) processing, amyloid-\u03b2 hypothesis, anti\u2013amyloid-\u03b2 (A\u03b2) vaccines, biomarkers, gene therapy, monoclonal antibodies, small-molecule drugs, \u03b2-secretase 1 (BACE1) inhibitors, \u03b3-secretase modulators", "chunk": "therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics, multi-target approaches, optimized delivery platforms, and early-prevention strategies. Collectively, these efforts underscore both the challenges and opportunities in translating anti-A\u03b2 therapies into meaningful clinical benefits for patients with AD.", "source": "PubMed"}, {"chunk_id": "40938598_0", "pmid": "40938598", "title": "Childhood Loneliness and Cognitive Decline and Dementia Risk in Middle-Aged and Older Adults.", "authors": "Wang J, Jiao D, Zhao X et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "Adult loneliness has been linked to cognitive decline and dementia risk, but the long-term implications of childhood loneliness remain underexplored. To investigate whether childhood loneliness is associated with cognitive decline and dementia risk and whether adult loneliness mediates or modifies these associations. This cohort study used data from the China Health and Retirement Longitudinal Study, a nationally representative cohort study conducted between June 1, 2011, and December 31, 2018, with a maximum follow-up of 7 years. Data analyses were performed from October 1, 2024, to January 15, 2025. Childhood loneliness was defined as self-reported frequent feelings of loneliness and the absence of close friendships before age 17 years. Adult loneliness was measured by a single item from the Centre for Epidemiological Studies Depression Scale. Cognitive function was assessed through measures of episodic memory and executive function. Dementia was identified as the coexistence of cognitive and functional impairments or a self-", "source": "PubMed"}, {"chunk_id": "40938598_1", "pmid": "40938598", "title": "Childhood Loneliness and Cognitive Decline and Dementia Risk in Middle-Aged and Older Adults.", "authors": "Wang J, Jiao D, Zhao X et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "Epidemiological Studies Depression Scale. Cognitive function was assessed through measures of episodic memory and executive function. Dementia was identified as the coexistence of cognitive and functional impairments or a self- or caregiver-reported physician diagnosis of dementia. Associations between childhood loneliness and cognitive decline were evaluated using linear mixed-effects models, and dementia risk was analyzed using Cox proportional hazards regression models. Among 13 592 participants (mean [SD] age, 58.34 [9.39] years; 7175 [52.8%] female), 6525 (48.0%) experienced possible childhood loneliness, and 565 (4.2%) reported childhood loneliness. Compared with no childhood loneliness, childhood loneliness was associated with significantly faster cognitive decline (\u03b2, -0.03 [95% CI, -0.05 to -0.02] SD per year), as was possible childhood loneliness (\u03b2, -0.02 [95% CI, -0.02 to -0.01] SD per year). Moreover, childhood loneliness was associated with an increased risk of dementia (hazard ratio, 1.41 [95% CI, 1.03 to 1.93]). These associations remained significant when adjusted for", "source": "PubMed"}, {"chunk_id": "40938598_2", "pmid": "40938598", "title": "Childhood Loneliness and Cognitive Decline and Dementia Risk in Middle-Aged and Older Adults.", "authors": "Wang J, Jiao D, Zhao X et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "-0.01] SD per year). Moreover, childhood loneliness was associated with an increased risk of dementia (hazard ratio, 1.41 [95% CI, 1.03 to 1.93]). These associations remained significant when adjusted for adult loneliness and restricted to participants without adult loneliness. Adult loneliness mediated 8.5% (95% CI, 2.9% to 14.1%) of the association of childhood loneliness with cognitive decline and 17.2% (95% CI, 4.9%-29.5%) of the association with dementia risk but did not significantly modify these associations. In this cohort study, childhood loneliness was associated with cognitive decline and dementia risk in middle and later adulthood, even in the absence of adult loneliness. Early interventions aimed at reducing childhood loneliness may help promote lifelong cognitive health and reducing dementia risk.", "source": "PubMed"}, {"chunk_id": "40417692_0", "pmid": "40417692", "title": "Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus.", "authors": "Li J, An Y, Qin J et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "abnormal bone metabolism, bone mineral density, cognitive impairment, osteocalcin, type 2 diabetes mellitus", "chunk": "Type 2 diabetes mellitus (T2DM) is often accompanied by bone metabolic disorders and cognitive impairment, forming an interactive network through metabolic derangements, oxidative stress, and inflammatory responses. Hyperglycemia and insulin resistance disrupt bone remodeling leading to osteoporosis while simultaneously impairing cognition via blood-brain barrier damage and neuroinflammation. Osteogenic factors like osteocalcin may bidirectionally regulate glucose metabolism and brain function, suggesting that \"bone-brain axis\" dysregulation could be a potential mechanism underlying cognitive impairment in T2DM. This study aims to characterize cognitive function patterns in T2DM patients with bone metabolic abnormalities and their clinical correlations, providing a basis for multisystemic interventions. The general clinical data, osteocalcin (OC), glycosylated hemoglobin (HbA1c), bone mineral density (BMD), and the Montreal Cognitive Assessment (MoCA) scores of 50 patients with T2DM were collected. According to whether cognitive impairment occurred or not, one-way ANOVA was performed to analyze the correlation between cognitive and clinical indicators, BMD and OC.", "source": "PubMed"}, {"chunk_id": "40417692_1", "pmid": "40417692", "title": "Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus.", "authors": "Li J, An Y, Qin J et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "abnormal bone metabolism, bone mineral density, cognitive impairment, osteocalcin, type 2 diabetes mellitus", "chunk": "50 patients with T2DM were collected. According to whether cognitive impairment occurred or not, one-way ANOVA was performed to analyze the correlation between cognitive and clinical indicators, BMD and OC. Multiple linear regression analysis was performed with cognition and bone density as dependent variables and other factors as independent variables. T2DM subjects were grouped according to bone mass. The osteoporosis group had the lowest MoCA score and bone density, followed by the osteopenia group. There were 16 cases (16/17 94.12%) of cognitive impairment in the osteoporosis group, 13 cases (13/17 76.47%) of cognitive impairment in the osteopenia group, and 3 cases (3/16 18.75%) of cognitive impairment in the normal bone mass group. Compared with the normal cognitive group, the MoCA score, OC measurement and BMD of the patients in the cognitive impairment group were lower (<i>P</i> < 0.05). BMD (<i>r</i> = 0.686, <i>P</i> = 0.000), OC (<i>r</i> = 0.756, <i>P</i>", "source": "PubMed"}, {"chunk_id": "40417692_2", "pmid": "40417692", "title": "Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus.", "authors": "Li J, An Y, Qin J et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "abnormal bone metabolism, bone mineral density, cognitive impairment, osteocalcin, type 2 diabetes mellitus", "chunk": "score, OC measurement and BMD of the patients in the cognitive impairment group were lower (<i>P</i> < 0.05). BMD (<i>r</i> = 0.686, <i>P</i> = 0.000), OC (<i>r</i> = 0.756, <i>P</i> = 0.000) are positively correlated with MoCA score. OC (<i>r</i> = 0.690, <i>P</i> = 0.000) and Age (<i>r</i> = -0.032, <i>P</i> = 0.045) are positively correlated with BMD. Multivariate linear regression analysis found that with cognition as the dependent variable, the decrease in BMD (<i>P</i> = 0.028) and OC (<i>P</i> = 0.000) aggravated the occurrence of cognitive impairment; with BMD as the dependent variable, the decline in cognition (<i>P</i> = 0.028) and OC (<i>P</i> = 0.029) aggravated the decrease in BMD. T2DM, osteoporosis, and cognitive impairment form pathological connections through metabolic disorders, chronic inflammation, and bidirectional regulatory networks of the \"bone-brain axis,\" with osteocalcin serving as a key mediator that maintains bone remodeling balance while also exerting cross-domain regulation over", "source": "PubMed"}, {"chunk_id": "40417692_3", "pmid": "40417692", "title": "Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus.", "authors": "Li J, An Y, Qin J et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "abnormal bone metabolism, bone mineral density, cognitive impairment, osteocalcin, type 2 diabetes mellitus", "chunk": "metabolic disorders, chronic inflammation, and bidirectional regulatory networks of the \"bone-brain axis,\" with osteocalcin serving as a key mediator that maintains bone remodeling balance while also exerting cross-domain regulation over central insulin signaling and synaptic plasticity. Understanding these interactive mechanisms provides a basis for developing combined screening models integrating bone density and cognitive assessments, and promotes multidisciplinary collaborative interventions across endocrinology, orthopedics, and neurology to improve overall outcomes for T2DM patients.", "source": "PubMed"}, {"chunk_id": "39880333_0", "pmid": "39880333", "title": "Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.", "authors": "Izrael M, Chebath J, Molakandov K et al.", "year": "2025", "journal": "Advanced drug delivery reviews", "keywords": "Astrocytes, Dopaminergic neurons, Embryonic stem cells, Induced pluripotent stem cells, Pluripotent stem cells, Retina pigmented epithelial cell", "chunk": "Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in", "source": "PubMed"}, {"chunk_id": "39880333_1", "pmid": "39880333", "title": "Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.", "authors": "Izrael M, Chebath J, Molakandov K et al.", "year": "2025", "journal": "Advanced drug delivery reviews", "keywords": "Astrocytes, Dopaminergic neurons, Embryonic stem cells, Induced pluripotent stem cells, Pluripotent stem cells, Retina pigmented epithelial cell", "chunk": "highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer's disease and epilepsy.", "source": "PubMed"}, {"chunk_id": "38570813_0", "pmid": "38570813", "title": "Addition of inflammation-related biomarkers to the CAIDE model for risk prediction of all-cause dementia, Alzheimer's disease and vascular dementia in a prospective study.", "authors": "Trares K, Wiesenfarth M, Stocker H et al.", "year": "2024", "journal": "Immunity & ageing : I & A", "keywords": "Alzheimer\u2019s disease, Cohort study, Dementia, Inflammation, Risk prediction, Vascular dementia", "chunk": "It is of interest whether inflammatory biomarkers can improve dementia prediction models, such as the widely used Cardiovascular Risk Factors, Aging and Dementia (CAIDE) model. The Olink Target 96 Inflammation panel was assessed in a nested case-cohort design within a large, population-based German cohort study (n = 9940; age-range: 50-75 years). All study participants who developed dementia over 20 years of follow-up and had complete CAIDE variable data (n = 562, including 173 Alzheimer's disease (AD) and 199 vascular dementia (VD) cases) as well as n = 1,356 controls were selected for measurements. 69 inflammation-related biomarkers were eligible for use. LASSO logistic regression and bootstrapping were utilized to select relevant biomarkers and determine areas under the curve (AUCs). The CAIDE model 2 (including Apolipoprotein E (APOE) \u03b54 carrier status) predicted all-cause dementia, AD, and VD better than CAIDE model 1 (without APOE \u03b54) with AUCs of 0.725, 0.752 and 0.707,", "source": "PubMed"}, {"chunk_id": "38570813_1", "pmid": "38570813", "title": "Addition of inflammation-related biomarkers to the CAIDE model for risk prediction of all-cause dementia, Alzheimer's disease and vascular dementia in a prospective study.", "authors": "Trares K, Wiesenfarth M, Stocker H et al.", "year": "2024", "journal": "Immunity & ageing : I & A", "keywords": "Alzheimer\u2019s disease, Cohort study, Dementia, Inflammation, Risk prediction, Vascular dementia", "chunk": "model 2 (including Apolipoprotein E (APOE) \u03b54 carrier status) predicted all-cause dementia, AD, and VD better than CAIDE model 1 (without APOE \u03b54) with AUCs of 0.725, 0.752 and 0.707, respectively. Although 20, 7, and 4 inflammation-related biomarkers were selected by LASSO regression to improve CAIDE model 2, the AUCs did not increase markedly. CAIDE models 1 and 2 generally performed better in mid-life (50-64 years) than in late-life (65-75 years) sub-samples of our cohort, but again, inflammation-related biomarkers did not improve their predictive abilities. Despite a lack of improvement in dementia risk prediction, the selected inflammation-related biomarkers were significantly associated with dementia outcomes and may serve as a starting point to further elucidate the pathogenesis of dementia.", "source": "PubMed"}, {"chunk_id": "41451854_0", "pmid": "41451854", "title": "APOE \u025b4 carriership determines a faster plasma p-tau217 progression in A\u03b2-positive individuals.", "authors": "Woo MS, Macedo AC, Hosseini SA et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, apolipoprotein E, biomarker, disease progression, phosphorylated tau217", "chunk": "It is unclear whether the different Alzheimer's disease (AD) progression trajectories of apolipoprotein E (APOE) \u025b4 carriers is reflected by blood phosphorylated tau (p-tau) analytes. We assessed longitudinal trajectories in plasma p-tau181, 217, and 231, in amyloid beta-positive (A+) and negative (A-) APOE \u025b4 carriers (E+) or non-carriers (E-). We included 2039 participants from the observational Translational Biomarkers in Aging and Dementia (TRIAD) and Alzheimer's Disease Neuroimaging Initiative cohorts, categorized into 840 A-E-, 251 A-E+, 386 A+E4-, and 616 A+E4+. Longitudinal data were available for 1045 participants. In TRIAD, ALZpath p-tau217 (\u03b2 = 0.45, p = 0.02) and p-tau217+<sup>Janssen</sup> (\u03b2 = 0.67, p = 0.002), and in ADNI p-tau217 (\u03b2 = 0.90, p = 0.002) increased faster in A+E4+. This was not the case in E- or A- individuals or for p-tau181 and p-tau231. These findings suggest p-tau217 as a marker of faster progression in APOE \u025b4 carriers, highlighting its", "source": "PubMed"}, {"chunk_id": "41451854_1", "pmid": "41451854", "title": "APOE \u025b4 carriership determines a faster plasma p-tau217 progression in A\u03b2-positive individuals.", "authors": "Woo MS, Macedo AC, Hosseini SA et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, apolipoprotein E, biomarker, disease progression, phosphorylated tau217", "chunk": "was not the case in E- or A- individuals or for p-tau181 and p-tau231. These findings suggest p-tau217 as a marker of faster progression in APOE \u025b4 carriers, highlighting its potential in disease stratification. Blood phosphorylated tau (p-tau)217 increases faster in apolipoprotein E (APOE) \u025b4 carriers with amyloid pathology. p-tau181 and p-tau231 do not increase faster in APOE \u025b4 carriers. APOE \u025b4 carriership does not change p-tau in individuals without amyloid pathology.", "source": "PubMed"}, {"chunk_id": "37357292_0", "pmid": "37357292", "title": "Association of Circulating Caprylic Acid with Risk of Mild Cognitive Impairment and Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort.", "authors": "Fan L, Zhu X, Borenstein AR et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "ADAS-Cog 13, APOE \u03b54 allele, Alzheimer\u2019s Disease, Medium-chain fatty acids, caprylic acid, cardiometabolic diseases, mild cognitive impairment", "chunk": "Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1) whether plasma caprylic acid (C8:0) is associated with risk of incident mild cognitive impairment (MCI) among baseline cognitively normal (CN) participants, and incident Alzheimer's Disease (AD) among baseline MCI participants; and 2) whether these associations differ by sex, comorbidity of cardiometabolic diseases, apolipoprotein E (APOE) \u03b54 alleles, and ADAS-Cog 13. Within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, plasma C8:0 was measured at baseline in 618 AD-free participants aged 55 to 91. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs with incident MCI and AD as dependent variables, separately. The inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among", "source": "PubMed"}, {"chunk_id": "37357292_1", "pmid": "37357292", "title": "Association of Circulating Caprylic Acid with Risk of Mild Cognitive Impairment and Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort.", "authors": "Fan L, Zhu X, Borenstein AR et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "ADAS-Cog 13, APOE \u03b54 allele, Alzheimer\u2019s Disease, Medium-chain fatty acids, caprylic acid, cardiometabolic diseases, mild cognitive impairment", "chunk": "inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among CN participants with \u22651 cardiometabolic diseases [OR (95% CI): 0.75 (0.58-0.98) (P=0.03)], those with one copy of APOE \u03b54 alleles [OR (95% CI): 0.43 (0.21-0.89) (P=0.02)], female [OR (95% CI): 0.60 (0.38-0.94) (P=0.02)], and ADAS-Cog 13 above the median [OR (95%CI): 0.69 (0.50-0.97)(P=0.03)] after adjusting for all covariates. The inverse associations were present only among subgroups of CN participants, including female individuals, those with one or more cardiometabolic diseases, or one APOE \u03b54 allele, or higher ADAS-Cog 13 scores. If confirmed, this finding will facilitate precision prevention of MCI, in turn, AD among CN older adults.", "source": "PubMed"}, {"chunk_id": "37357292_2", "pmid": "37357292", "title": "Association of Circulating Caprylic Acid with Risk of Mild Cognitive Impairment and Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort.", "authors": "Fan L, Zhu X, Borenstein AR et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "ADAS-Cog 13, APOE \u03b54 allele, Alzheimer\u2019s Disease, Medium-chain fatty acids, caprylic acid, cardiometabolic diseases, mild cognitive impairment", "chunk": "turn, AD among CN older adults.", "source": "PubMed"}, {"chunk_id": "40128515_0", "pmid": "40128515", "title": "GALM Alleviates A\u03b2 Pathology and Cognitive Deficit Through Increasing ADAM10 Maturation in a Mouse Model of Alzheimer's Disease.", "authors": "Tian N, Li J, Shi X et al.", "year": "2025", "journal": "Neuroscience bulletin", "keywords": "ADAM10, Alzheimer\u2019s disease, GALM, Learning and memory, Long-term potentiation, \u03b1-D-galactose", "chunk": "Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of \u03b2-D-galactose into \u03b1-D-galactose (\u03b1-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), \u03b2-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and A\u03b2 deposition by increasing", "source": "PubMed"}, {"chunk_id": "40128515_1", "pmid": "40128515", "title": "GALM Alleviates A\u03b2 Pathology and Cognitive Deficit Through Increasing ADAM10 Maturation in a Mouse Model of Alzheimer's Disease.", "authors": "Tian N, Li J, Shi X et al.", "year": "2025", "journal": "Neuroscience bulletin", "keywords": "ADAM10, Alzheimer\u2019s disease, GALM, Learning and memory, Long-term potentiation, \u03b1-D-galactose", "chunk": "and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), \u03b2-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and A\u03b2 deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct \u03b1-D-G (20 mg/kg, i.p.) also inhibited A\u03b2 deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards \u03b1-cleavage, preventing A\u03b2 generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and \u03b1-D-G has the potential to be used as a dietary supplement", "source": "PubMed"}, {"chunk_id": "40128515_2", "pmid": "40128515", "title": "GALM Alleviates A\u03b2 Pathology and Cognitive Deficit Through Increasing ADAM10 Maturation in a Mouse Model of Alzheimer's Disease.", "authors": "Tian N, Li J, Shi X et al.", "year": "2025", "journal": "Neuroscience bulletin", "keywords": "ADAM10, Alzheimer\u2019s disease, GALM, Learning and memory, Long-term potentiation, \u03b1-D-galactose", "chunk": "the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and \u03b1-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.", "source": "PubMed"}, {"chunk_id": "41455993_0", "pmid": "41455993", "title": "Microglial interferon signaling and A\u03b2 plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.", "authors": "Calcines-Rodr\u00edguez L, Noyes-Martel N, Becker JL et al.", "year": "2025", "journal": "Journal of neuroinflammation", "keywords": "5xFAD, Alzheimer\u2019s, Amyloid, Estrous, IRM, Interferon, Microglia, Plaques, Sex, Transcriptome", "chunk": "Alzheimer\u2019s disease (AD) presents with a sex bias in which women are at higher risk and exhibit more rapid cognitive decline and brain atrophy compared to men. Microglia play a significant role in the pathogenesis and progression of AD and have been shown to be sexually differentiated in health and disease. Whether and how microglia contribute to the sex differences in AD remains to be elucidated. Herein, we characterized the sex differences in amyloid-beta (A\u03b2) plaque pathology and microglia-plaque interaction using the 5xFAD mouse model and revealed microglial transcriptomic changes that occur in females and males. Despite women with symptomatic late-onset AD being in the post-menopausal stage, metabolic and pathological changes are seen prior to menopause. For this reason, and because A\u03b2 pathology develops decades prior to clinical presentation, we focused on two hormonally distinct stages of the female rodent estrous cycle (proestrus and diestrus). Our results showed that A\u03b2", "source": "PubMed"}, {"chunk_id": "41455993_1", "pmid": "41455993", "title": "Microglial interferon signaling and A\u03b2 plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.", "authors": "Calcines-Rodr\u00edguez L, Noyes-Martel N, Becker JL et al.", "year": "2025", "journal": "Journal of neuroinflammation", "keywords": "5xFAD, Alzheimer\u2019s, Amyloid, Estrous, IRM, Interferon, Microglia, Plaques, Sex, Transcriptome", "chunk": "because A\u03b2 pathology develops decades prior to clinical presentation, we focused on two hormonally distinct stages of the female rodent estrous cycle (proestrus and diestrus). Our results showed that A\u03b2 plaque morphology is sexually distinct, with females having greater plaque volume and lower plaque compaction compared to males of the same age. Neuritic dystrophy was also increased in female 5xFAD mice, independent of estrous cycle stage. While microglia transcriptomes were not overtly different at the proestrus or diestrus stages, female 5xFAD microglia upregulated genes involved in glycolytic metabolism, antigen presentation, disease-associated microglia, and microglia neurodegenerative phenotype compared to males, some of which have been previously reported. In addition, we found a novel female-specific enhancement of IFN signaling in microglia, as <b>evidenced</b> by a striking proportion of differentially expressed type 1 interferon genes characteristic of interferon-responsive microglia (IRM). Finally, we validated our transcriptomic results at the protein level and observed that", "source": "PubMed"}, {"chunk_id": "41455993_2", "pmid": "41455993", "title": "Microglial interferon signaling and A\u03b2 plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.", "authors": "Calcines-Rodr\u00edguez L, Noyes-Martel N, Becker JL et al.", "year": "2025", "journal": "Journal of neuroinflammation", "keywords": "5xFAD, Alzheimer\u2019s, Amyloid, Estrous, IRM, Interferon, Microglia, Plaques, Sex, Transcriptome", "chunk": "<b>evidenced</b> by a striking proportion of differentially expressed type 1 interferon genes characteristic of interferon-responsive microglia (IRM). Finally, we validated our transcriptomic results at the protein level and observed that female 5xFAD mice had an enrichment in A\u03b2<sup>+</sup> IRMs compared to males. Collectively, we show that there are sex-specific alterations in A\u03b2 plaque morphology and that endogenous hormonal fluctuations across the estrous cycle do not overtly affect A\u03b2 pathology or microglial transcriptomic profiles. Furthermore, our study identifies a novel sex-specific enhancement of interferon signaling in female microglia responding to A\u03b2, which may constitute a new therapeutic target for personalized medicine in AD. The online version contains supplementary material available at 10.1186/s12974-025-03659-1.", "source": "PubMed"}, {"chunk_id": "40727659_0", "pmid": "40727659", "title": "Integrating chemical artificial intelligence and cognitive computing for predictive analysis of biological pathways: a case for intrinsically disordered proteins.", "authors": "Coskuner-Weber O, Gentili PL, Uversky VN", "year": "2025", "journal": "Biophysical reviews", "keywords": "Artificial intelligence, Cognitive computing, Intrinsically disordered proteins", "chunk": "Incorporating biological molecular interactions into cognitive computing through chemical artificial intelligence (AI) presents a transformative approach with far-reaching implications for various fields, such as protein engineering, drug discovery, bioinformatics, synthetic biology, and unconventional computing. Cognitive computing, designed to emulate human thought processes and enhance decision-making, utilizes technologies, such as machine learning, natural language processing, and speech recognition for better human-system interactions. Despite advancements, the integration of biological processes with cognitive computing remains fraught with challenges, particularly due to the complexity and scale of biological data. Here, we explore the possible benefits of connecting cognitive computing with biological knowledge, including more precise models of protein interactions, gene regulation, and metabolic pathways, which could lead to personalized treatments and early disease detection. Furthermore, we discuss the intersection of cognitive computing and biophysical research techniques, examining how analogies from neuroscience-like synaptic communication and neural plasticity-can inform the development of neuromorphic chips and enhance", "source": "PubMed"}, {"chunk_id": "40727659_1", "pmid": "40727659", "title": "Integrating chemical artificial intelligence and cognitive computing for predictive analysis of biological pathways: a case for intrinsically disordered proteins.", "authors": "Coskuner-Weber O, Gentili PL, Uversky VN", "year": "2025", "journal": "Biophysical reviews", "keywords": "Artificial intelligence, Cognitive computing, Intrinsically disordered proteins", "chunk": "Furthermore, we discuss the intersection of cognitive computing and biophysical research techniques, examining how analogies from neuroscience-like synaptic communication and neural plasticity-can inform the development of neuromorphic chips and enhance predictive models. Additionally, the study delves into intrinsically disordered proteins (IDPs) and their crucial roles in brain function and information processing. These insights are pivotal for advancing neuroinformatics and creating more adaptive, context-aware cognitive computing algorithms. By leveraging biophysical investigations and the unique properties of IDPs, the research aims to bridge the gap between the biological processes and their computational analogs, proposing novel methods, such as chemical AI implemented in liquid solutions as promising avenues for future advancements.", "source": "PubMed"}, {"chunk_id": "39587372_0", "pmid": "39587372", "title": "Neuronal viability/astrocyte activity ratio in the dorsolateral prefrontal cortex as a biomarker of Alzheimer's dementia: a proton magnetic resonance spectroscopy study.", "authors": "Jha S, Torres-Carmona E, Iwata Y et al.", "year": "2024", "journal": "Cerebral cortex (New York, N.Y. : 1991)", "keywords": "Myo-inositol, N-acetyl aspartate, cognition, diagnostic tests, metabolites", "chunk": "N-acetyl-aspartate (NAA) and myo-inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These are quantified using proton magnetic resonance spectroscopy (1H-MRS) and may be biomarkers for Alzheimer's disease dementia (AD). Our objectives were: 1) Compare dorsolateral prefrontal cortex (DLPFC) NAA and mI levels between AD and cognitively healthy control participants (HC) 2) assess if NAA/mI ratio can distinguish groups, and 3) explore the relationship between metabolites and cognition. The study included 64 participants over 55, 41 with AD. Bilateral DLPFC NAA and mI levels were quantified using 3 T 1H-MRS and normalized to H2O. NAA and NAA/mI ratio were lower in AD vs. HC. mI was unchanged. The NAA/mI ratio at a cut-off value of 1.69 showed 59% sensitivity and 87% specificity at distinguishing AD from HC. NAA was associated positively with cognition. In conclusion, DLPFC metabolite changes suggest altered mitochondrial function in AD. NAA/mI ratio shows good", "source": "PubMed"}, {"chunk_id": "39587372_1", "pmid": "39587372", "title": "Neuronal viability/astrocyte activity ratio in the dorsolateral prefrontal cortex as a biomarker of Alzheimer's dementia: a proton magnetic resonance spectroscopy study.", "authors": "Jha S, Torres-Carmona E, Iwata Y et al.", "year": "2024", "journal": "Cerebral cortex (New York, N.Y. : 1991)", "keywords": "Myo-inositol, N-acetyl aspartate, cognition, diagnostic tests, metabolites", "chunk": "sensitivity and 87% specificity at distinguishing AD from HC. NAA was associated positively with cognition. In conclusion, DLPFC metabolite changes suggest altered mitochondrial function in AD. NAA/mI ratio shows good specificity in distinguishing AD from HC, suggesting its role in complementing other biomarkers. Future studies should evaluate NAA/mI ratio with other disease specific biomarkers.", "source": "PubMed"}, {"chunk_id": "30569084_0", "pmid": "30569084", "title": "Plasma A\u03b242/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study.", "authors": "P\u00e9rez-Grijalba V, Romero J, Pesini P et al.", "year": "2019", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, A\u03b2 ratio, biomarker, plasma, \u03b2-amyloid (A\u03b2)", "chunk": "Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. This study evaluated the potential of plasma \u03b2-amyloid (A\u03b2) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. Total plasma A\u03b242/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). TP42/40 demonstrated value in the identification of individuals suffering a-MCI,", "source": "PubMed"}, {"chunk_id": "30569084_1", "pmid": "30569084", "title": "Plasma A\u03b242/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study.", "authors": "P\u00e9rez-Grijalba V, Romero J, Pesini P et al.", "year": "2019", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, A\u03b2 ratio, biomarker, plasma, \u03b2-amyloid (A\u03b2)", "chunk": "associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.", "source": "PubMed"}, {"chunk_id": "40034356_0", "pmid": "40034356", "title": "MRI-based mild cognitive impairment and Alzheimer's disease classification using an algorithm of combination of variational autoencoder and other machine learning classifiers.", "authors": "Bit S, Dey P, Maji A et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer\u2019s disease, XGB classifier, extra tree, light gradient boosting model, machine learning, magnetic resonance imaging, mild cognitive impairment, random forest, support vector machine linear kernel, variational autoencoder", "chunk": "Correctly diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD) is important for patient selection in drug discovery. Research outcomes on stage diagnosis using neuroimages combined with cerebrospinal fluid and genetic biomarkers are expensive and time-consuming. Only structural magnetic resonance imaging (sMRI) scans from two internationally recognized datasets are employed as input as well as test and independent validation to determine the classification of dementia by the machine learning algorithm. We extract the reduced dimensional latent feature vector from the sMRI scans using a variational autoencoder (VAE). The objective is to classify AD, MCI, and control (CN) using MRI and without any other information. The extracted feature vectors from MRI scans by VAE are used as input conditions for different advanced machine-learning classifiers. Classification of AD/CN/MCI are conducted using the output of VAE from MRI images and different artificial intelligence/machine learning classifier models in two cohorts. Using only MRI scans,", "source": "PubMed"}, {"chunk_id": "40034356_1", "pmid": "40034356", "title": "MRI-based mild cognitive impairment and Alzheimer's disease classification using an algorithm of combination of variational autoencoder and other machine learning classifiers.", "authors": "Bit S, Dey P, Maji A et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer\u2019s disease, XGB classifier, extra tree, light gradient boosting model, machine learning, magnetic resonance imaging, mild cognitive impairment, random forest, support vector machine linear kernel, variational autoencoder", "chunk": "advanced machine-learning classifiers. Classification of AD/CN/MCI are conducted using the output of VAE from MRI images and different artificial intelligence/machine learning classifier models in two cohorts. Using only MRI scans, the primary goal of the study is to test the ability to classify AD from CN and MCI cases. The current study achieved classification accuracies of AD versus CN 75.45% (F1-score = 79.52%), AD versus MCI 81.41% (F1-Score = 87.06%), and autopsy-confirmed AD versus MCI 92.75% (F1-Score = 95.52%) in test sets and AD versus CN 86.16% (F1-score = 92.03%) and AD versus MCI 70.03% (F1-Score = 82.1%) in validation data set. By overcoming the data leakage problem, the autopsy-confirmed machine learning classification model is tested in two independent cohorts. External validation by an independent cohort improved the quality and novelty of the classification algorithm.", "source": "PubMed"}, {"chunk_id": "40034356_2", "pmid": "40034356", "title": "MRI-based mild cognitive impairment and Alzheimer's disease classification using an algorithm of combination of variational autoencoder and other machine learning classifiers.", "authors": "Bit S, Dey P, Maji A et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer\u2019s disease, XGB classifier, extra tree, light gradient boosting model, machine learning, magnetic resonance imaging, mild cognitive impairment, random forest, support vector machine linear kernel, variational autoencoder", "chunk": "External validation by an independent cohort improved the quality and novelty of the classification algorithm.", "source": "PubMed"}, {"chunk_id": "34920062_0", "pmid": "34920062", "title": "Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences.", "authors": "Kawatra A, Dhankhar R, Gulati P", "year": "2022", "journal": "International journal of biological macromolecules", "keywords": "Antiviral, Applications, Arginine deiminase (ADI), Biomedical sciences, Cancer, Improvement strategies", "chunk": "Arginine deiminase is a well-recognized guanidino-modifying hydrolase that catalyzes the conversion of L-arginine to citrulline and ammonia. Their biopotential to regress tumors via amino acid deprivation therapy (AADT) has been well established. PEGylated formulation of recombinant Mycoplasma ADI is in the last-phase clinical trials against various arginine-auxotrophic cancers like hepatocellular carcinoma, melanoma, and mesothelioma. Recently, ADIs have attained immense importance in several other biomedical applications, namely treatment of Alzheimer's, as an antiviral drug, bioproduction of nutraceutical L-citrulline and bio-analytics involving L-arginine detection. Considering the wide applications of this biodrug, the demand for ADI is expected to escalate several-fold in the coming years. However, the sustainable production aspects of the enzyme with improved pharmacokinetics is still limited, creating bottlenecks for effective biopharmaceutical development. To circumvent the lacunae in enzyme production with appropriate paradigms of 'quality-by-design' an explicit overview of its properties with 'biobetter' formulations strategies are required. Present review provides an", "source": "PubMed"}, {"chunk_id": "34920062_1", "pmid": "34920062", "title": "Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences.", "authors": "Kawatra A, Dhankhar R, Gulati P", "year": "2022", "journal": "International journal of biological macromolecules", "keywords": "Antiviral, Applications, Arginine deiminase (ADI), Biomedical sciences, Cancer, Improvement strategies", "chunk": "biopharmaceutical development. To circumvent the lacunae in enzyme production with appropriate paradigms of 'quality-by-design' an explicit overview of its properties with 'biobetter' formulations strategies are required. Present review provides an insight into all the potential biomedical applications of ADI along with the improvements required for its reach to clinics. Recent research advances with special emphasis on the development of ADI as a 'biobetter' enzyme have also been comprehensively elaborated.", "source": "PubMed"}, {"chunk_id": "38315899_0", "pmid": "38315899", "title": "Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.", "authors": "Yang HS, Yau WW, Carlyle BC et al.", "year": "2024", "journal": "Brain : a journal of neurology", "keywords": "VCID, angiogenesis, biomarker, dementia", "chunk": "Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated. We included 317 older adults from the Harvard Aging Brain Study, a cohort of individuals who were cognitively unimpaired at baseline and followed longitudinally for up to 12 years. Baseline VEGF family protein levels (VEGFA, VEGFC, VEGFD, PGF and FLT1) were measured in fasting plasma using high-sensitivity immunoassays. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET burden (Pittsburgh Compound-B) on longitudinal cognition (Preclinical Alzheimer Cognitive Composite-5). We further investigated if effects on cognition were mediated by early neocortical tau accumulation (flortaucipir", "source": "PubMed"}, {"chunk_id": "38315899_1", "pmid": "38315899", "title": "Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.", "authors": "Yang HS, Yau WW, Carlyle BC et al.", "year": "2024", "journal": "Brain : a journal of neurology", "keywords": "VCID, angiogenesis, biomarker, dementia", "chunk": "VEGF proteins and amyloid PET burden (Pittsburgh Compound-B) on longitudinal cognition (Preclinical Alzheimer Cognitive Composite-5). We further investigated if effects on cognition were mediated by early neocortical tau accumulation (flortaucipir PET burden in the inferior temporal cortex) or hippocampal atrophy. Lastly, we examined the impact of adjusting for baseline cardiovascular risk score or white matter hyperintensity volume. Baseline plasma VEGFA and PGF each showed a significant interaction with amyloid burden on prospective cognitive decline. Specifically, low VEGFA and high PGF were associated with greater cognitive decline in individuals with elevated amyloid, i.e. those on the Alzheimer's disease continuum. Concordantly, low VEGFA and high PGF were associated with accelerated longitudinal tau accumulation in those with elevated amyloid. Moderated mediation analyses confirmed that accelerated tau accumulation fully mediated the effects of low VEGFA and partially mediated (31%) the effects of high PGF on faster amyloid-related cognitive decline. The effects of VEGFA and", "source": "PubMed"}, {"chunk_id": "38315899_2", "pmid": "38315899", "title": "Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.", "authors": "Yang HS, Yau WW, Carlyle BC et al.", "year": "2024", "journal": "Brain : a journal of neurology", "keywords": "VCID, angiogenesis, biomarker, dementia", "chunk": "that accelerated tau accumulation fully mediated the effects of low VEGFA and partially mediated (31%) the effects of high PGF on faster amyloid-related cognitive decline. The effects of VEGFA and PGF on tau and cognition remained significant after adjusting for cardiovascular risk score or white matter hyperintensity volume. There were concordant but non-significant associations with longitudinal hippocampal atrophy. Together, our findings implicate low VEGFA and high PGF in accelerating early neocortical tau pathology and cognitive decline in preclinical Alzheimer's disease. Additionally, our results underscore the potential of these minimally-invasive plasma biomarkers to inform the risk of Alzheimer's disease progression in the preclinical population. Importantly, VEGFA and PGF appear to capture distinct effects from vascular risks and cerebrovascular injury. This highlights their potential as new therapeutic targets, in combination with anti-amyloid and traditional vascular risk reduction therapies, to slow the trajectory of preclinical Alzheimer's disease and delay or prevent the onset", "source": "PubMed"}, {"chunk_id": "38315899_3", "pmid": "38315899", "title": "Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.", "authors": "Yang HS, Yau WW, Carlyle BC et al.", "year": "2024", "journal": "Brain : a journal of neurology", "keywords": "VCID, angiogenesis, biomarker, dementia", "chunk": "their potential as new therapeutic targets, in combination with anti-amyloid and traditional vascular risk reduction therapies, to slow the trajectory of preclinical Alzheimer's disease and delay or prevent the onset of cognitive decline.", "source": "PubMed"}, {"chunk_id": "25200290_0", "pmid": "25200290", "title": "IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity.", "authors": "White MF", "year": "2014", "journal": "Diabetes, obesity & metabolism", "keywords": "ageing, central nervous system, energy balance, glucose homeostasis, insulin/IGF signalling, leptin, life span, metabolism, neurodegeneration", "chunk": "Understanding how metabolism and nutrient homeostasis integrates with life span and neurodegeneration is a complicated undertaking. Important inconsistencies have emerged recently regarding the role of insulin-like signalling and the progression of neurodegenerative disease. Insulin resistance and type 2 diabetes are associated with clinical Alzheimer's disease, whereas study in lower organisms shows that reduced insulin-like signalling slows the progressive neurodegeneration and increases life span. From a clinical perspective, compensatory hyperinsulinaemia to overcome systemic insulin resistance is thought to be a healthy goal, because it circumvents immediate catastrophic consequences of hyperglycaemia; however, study in flies, nematodes and mice indicate that excess insulin signalling can damage cellular function and accelerate ageing. Maintenance of the central nervous system (CNS) has particular importance for life span and metabolism. A conflict arises because reduced insulin/IGF1 signalling in the CNS is associated with longevity, but can dysregulate glucose and energy homeostasis, and promote overweight. Here, we explore", "source": "PubMed"}, {"chunk_id": "25200290_1", "pmid": "25200290", "title": "IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity.", "authors": "White MF", "year": "2014", "journal": "Diabetes, obesity & metabolism", "keywords": "ageing, central nervous system, energy balance, glucose homeostasis, insulin/IGF signalling, leptin, life span, metabolism, neurodegeneration", "chunk": "span and metabolism. A conflict arises because reduced insulin/IGF1 signalling in the CNS is associated with longevity, but can dysregulate glucose and energy homeostasis, and promote overweight. Here, we explore how the genetic manipulation of insulin/IGF1 signalling system can influence systemic metabolism, life span and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "39305703_0", "pmid": "39305703", "title": "Resting-state functional connectivity abnormalities in subjective cognitive decline: A 7T MRI study.", "authors": "Pievani M, Ribaldi F, Toussas K et al.", "year": "2024", "journal": "Neurobiology of aging", "keywords": "7T MRI, Human brain networks, Intrinsic functional connectivity, Subjective cognitive decline", "chunk": "Resting-state functional connectivity (FC) MRI is sensitive to brain changes in Alzheimer's disease in preclinical stages, however studies in persons with subjective cognitive decline (SCD) have reported conflicting findings, and no study is available at 7T MRI. In this study, we investigated FC alterations in sixty-six participants recruited at the Geneva Memory Center (24 controls, 14 SCD, 28 cognitively impaired [CI]). Participants were classified as SCD if they reported cognitive complaints without objective cognitive deficits, and underwent 7T fMRI to assess FC in canonical brain networks and their association with cognitive/clinical features. SCD showed normal cognition, a trend for higher depressive symptoms, and normal AD biomarkers. Compared to the other two groups, SCD showed higher FC in frontal default mode network (DMN) and insular and superior temporal nodes of ventral attention network (VAN). Higher FC in the DMN and VAN was associated with worse cognition but not depression, suggesting that", "source": "PubMed"}, {"chunk_id": "39305703_1", "pmid": "39305703", "title": "Resting-state functional connectivity abnormalities in subjective cognitive decline: A 7T MRI study.", "authors": "Pievani M, Ribaldi F, Toussas K et al.", "year": "2024", "journal": "Neurobiology of aging", "keywords": "7T MRI, Human brain networks, Intrinsic functional connectivity, Subjective cognitive decline", "chunk": "network (DMN) and insular and superior temporal nodes of ventral attention network (VAN). Higher FC in the DMN and VAN was associated with worse cognition but not depression, suggesting that hyper-connectivity in these networks may be a signature of age-related cognitive decline in SCD at low risk of developing AD.", "source": "PubMed"}, {"chunk_id": "41221779_0", "pmid": "41221779", "title": "Depression in Premanifest Huntington's Disease: Aberrant Effective Connectivity of Striatum and Default Mode Network.", "authors": "Barta T, Novelli L, Georgiou-Karistianis N et al.", "year": "2026", "journal": "Movement disorders : official journal of the Movement Disorder Society", "keywords": "TrackOn\u2010HD, connectivity, dynamic causal modeling, rs\u2010fMRI", "chunk": "Depression frequently precedes motor symptoms in Huntington's disease gene expansion carriers (HDGECs), yet the neural mechanisms remain poorly characterized. We investigated effective connectivity between the default mode network (DMN) and striatal regions in HDGECs. We analyzed 3-T resting-state functional magnetic resonance imaging data from 98 HDGECs (48.98% females; mean age, 42.82 years). Spectral dynamic causal modeling estimated subject-level connectivity, whereas parametric empirical Bayes determined group-level effective connectivity differences between participants with a diagnosed depression history and those without, across current, remitted, and never-depressed states. Brain-behavior associations with clinical depression measures were examined. Model estimation was excellent (89.82% variance-explained). HDGECs with depression history showed decreased inhibitory posterior cingulate cortex-to-hippocampal connectivity, increased hippocampus-to-posterior cingulate cortex inhibition, and increased inhibitory influence of striatum on DMN. HDGECs with a depression history showed increased inhibitory striatal influence on DMN, including left putamen, a propensity for right hippocampal involvement, and disinhibitory posterior cingulate-hippocampal connectivity. Current versus", "source": "PubMed"}, {"chunk_id": "41221779_1", "pmid": "41221779", "title": "Depression in Premanifest Huntington's Disease: Aberrant Effective Connectivity of Striatum and Default Mode Network.", "authors": "Barta T, Novelli L, Georgiou-Karistianis N et al.", "year": "2026", "journal": "Movement disorders : official journal of the Movement Disorder Society", "keywords": "TrackOn\u2010HD, connectivity, dynamic causal modeling, rs\u2010fMRI", "chunk": "on DMN. HDGECs with a depression history showed increased inhibitory striatal influence on DMN, including left putamen, a propensity for right hippocampal involvement, and disinhibitory posterior cingulate-hippocampal connectivity. Current versus never-depressed comparisons showed more pronounced dysconnectivity, with stronger striatum-to-network connections. Current versus remitted depression exhibited distinct patterns with increased medial prefrontal cortex-to-posterior cingulate cortex connectivity, increased medial prefrontal cortex self-connectivity, and decreased posterior cingulate cortex-to-medial prefrontal cortex connectivity. These findings establish distinct striatal-network interaction patterns in depression for HDGECs that differ from non-neurological depression. Our findings suggested the posterior DMN-posterior cingulate and hippocampus-as drivers of depression for HDGECs and potential involvement of right DMN in keeping with compensatory patterns broadly in HD. These connectivity patterns could serve as functional biomarkers for depression in HDGECs. \u00a9 2025 International Parkinson and Movement Disorder Society.", "source": "PubMed"}, {"chunk_id": "41221779_2", "pmid": "41221779", "title": "Depression in Premanifest Huntington's Disease: Aberrant Effective Connectivity of Striatum and Default Mode Network.", "authors": "Barta T, Novelli L, Georgiou-Karistianis N et al.", "year": "2026", "journal": "Movement disorders : official journal of the Movement Disorder Society", "keywords": "TrackOn\u2010HD, connectivity, dynamic causal modeling, rs\u2010fMRI", "chunk": "for depression in HDGECs. \u00a9 2025 International Parkinson and Movement Disorder Society.", "source": "PubMed"}, {"chunk_id": "41393811_0", "pmid": "41393811", "title": "The Rapid Naming Test: Neuroanatomical validity and clinical utility.", "authors": "Atkins KJ, Katteri S, Weigand AJ et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "dementia, digital assessment, language, neuroimaging, neuropsychology", "chunk": "The Rapid Naming Test (RNT) is a tablet-administered confrontation naming task. We evaluated its concurrent validity, neuroanatomical correlates, sensitivity to cognitive impairment, and discriminant validity across neurodegenerative syndromes. We compared RNT performance of 263 healthy adults (mean [SD] age = 73.6 [9.3]; 60.5% female) and 185 people with neurodegenerative syndromes (mean [SD] age = 68.3 [9.0]; 38.9% female), including primary progressive aphasias (PPA). RNT performance were correlated with traditional cognitive test performance and with regional gray matter volumes using voxel-based morphometry. RNT performance was associated with language, memory, executive function, and processing speed (<i>p</i> < 0.05), as well as with gray matter volume in the left insula, temporal pole, fusiform gyrus, and the inferior and middle temporal gyri. The RNT was sensitive to cognitive impairment (AUC = 0.90, 95% CI 0.87-0.93), with the greatest impairments in people with logopenic and semantic variant PPA. The RNT is sensitive to cognitive impairment", "source": "PubMed"}, {"chunk_id": "41393811_1", "pmid": "41393811", "title": "The Rapid Naming Test: Neuroanatomical validity and clinical utility.", "authors": "Atkins KJ, Katteri S, Weigand AJ et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "dementia, digital assessment, language, neuroimaging, neuropsychology", "chunk": "was sensitive to cognitive impairment (AUC = 0.90, 95% CI 0.87-0.93), with the greatest impairments in people with logopenic and semantic variant PPA. The RNT is sensitive to cognitive impairment and associated with brain regions involved in language and cognitive control, with left hemisphere predominance. The Rapid Naming Test (RNT) is a 1-min tablet-based confrontation naming task.The pattern of performance across clinical cohorts supports the construct validity of the RNT.RNT performance was associated with gray matter volumes in regions important for object recognition and semantic knowledge.Age adjusted norms of the RNT were sensitive to mild cognitive impairment.", "source": "PubMed"}, {"chunk_id": "39853853_0", "pmid": "39853853", "title": "Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.", "authors": "McKeever A, Swann P, Malpetti M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Lewy body dementia, plasma biomarkers, plasma phosphorylated tau, polygenic risk score", "chunk": "Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification. We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRS<sub>no</sub> <sub>APOE</sub>), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (A\u03b2)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls. Together AD-PRS<sub>no</sub> <sub>APOE</sub> and APOE-RS performed similarly to p-tau181 in discriminating MCI+/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, A\u03b2 positivity was significantly associated with APOE-RS, but not with AD-PRS<sub>no</sub> <sub>APOE</sub>, or p-tau181. Combining AD-PRS<sub>no</sub> <sub>APOE</sub>, APOE-RS, and p-tau181 improved the discrimination of MCI+/AD from controls (81%) and LBD (75%), and the detection of A\u03b2 in LBD (82%). A\u03b2 deposition in LBD was associated with APOE, while", "source": "PubMed"}, {"chunk_id": "39853853_1", "pmid": "39853853", "title": "Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.", "authors": "McKeever A, Swann P, Malpetti M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Lewy body dementia, plasma biomarkers, plasma phosphorylated tau, polygenic risk score", "chunk": "and p-tau181 improved the discrimination of MCI+/AD from controls (81%) and LBD (75%), and the detection of A\u03b2 in LBD (82%). A\u03b2 deposition in LBD was associated with APOE, while MCI+/AD was also associated with AD-PRS beyond APOE. AD-PRS explains phenotypic variance not captured by APOE or p-tau181. We investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (APOE), and plasma phosphorylated tau 181 (p-tau181) to classify AD and Lewy body dementia (LBD). AD-PRS with APOE achieved similar classification accuracy to p-tau181. AD-PRS without APOE significantly contributed to discriminating AD from LBD. Amyloid beta positivity in LBD was associated with APOE but not AD-PRS without APOE or p-tau181. Combining AD-PRS, APOE, and p-tau181 improved diagnostic classification accuracy.", "source": "PubMed"}, {"chunk_id": "41125573_0", "pmid": "41125573", "title": "Status dystonicus is a distinct state characterized by pallidal beta-band activity.", "authors": "Balachandar A, Vogt LM, Mithani K et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "Status dystonicus (SD) is a poorly known neurological emergency requiring urgent interventions, including deep brain stimulation (DBS) targeting the globus pallidus interna (GPi). The sensing capabilities of DBS electrodes provide an opportunity to study the pathophysiology of SD. Here, we study local field potentials (LFPs) from GPi-DBS electrodes implanted in a cohort of 10 children longitudinally during SD, recovery and relapse (recording range 11-1155 days). During SD, we report an increase in the periodic component of the power spectrum within the beta-band along with increases in burst amplitude compared to recordings in non-SD states. Furthermore, relapsed SD is characterized by a return of excessive beta signatures. Beta-specific LFP power is also significantly associated with worse quality-of-life scores (PedsQL, R<sup>2</sup> = 0.695). We identify circadian pallidal beta-band periodicity in one participant with chronic narrowband beta-power recordings over months, with significant increase in power during SD. These rare recordings in children with", "source": "PubMed"}, {"chunk_id": "41125573_1", "pmid": "41125573", "title": "Status dystonicus is a distinct state characterized by pallidal beta-band activity.", "authors": "Balachandar A, Vogt LM, Mithani K et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "0.695). We identify circadian pallidal beta-band periodicity in one participant with chronic narrowband beta-power recordings over months, with significant increase in power during SD. These rare recordings in children with SD point to excessive pallidal beta-band activity as a biomarker of SD. Our findings further suggest that SD is a distinct state with important implications for understanding dystonia pathophysiology, tracking dystonia states from intracranial activity and potential adaptive DBS treatments.", "source": "PubMed"}, {"chunk_id": "41512495_0", "pmid": "41512495", "title": "Leveraging hemispheric asymmetry in structural MRI with an attention-guided 3D CNN for early prediction of Alzheimer's conversion.", "authors": "Liu Y, Yao L, Liu J et al.", "year": "2026", "journal": "Neural networks : the official journal of the International Neural Network Society", "keywords": "3D CNN, Alzheimer\u2019s disease, Attention mechanism, Progress prediction, Structural MRI", "chunk": "Early identification of mild cognitive impairment (MCI) progressing to Alzheimer's disease (AD) is of paramount importance. Despite the notable advances in deep learning in this domain, current approaches are largely based on global brain analysis and often overlook the hemispheric asymmetry, which is a critical biomarker for AD progression. Although longitudinal studies can capture temporal dynamics, their clinical feasibility is constrained by the need for multiple follow-up visits. To address this issue, we propose HemiNet, a lightweight 3D convolutional neural network based on hemispheric difference analysis, enabling accurate prediction of MCI progression from structural MRI at a single time point. HemiNet is designed with three key modules. First, the asymmetry discrepancy mining strategy is employed to quantify interhemispheric structural differences, derive disease-specific biomarkers, and effectively capture multi-level asymmetry features. Second, the contralateral hemispheric fusion mechanism is designed to adaptively unify bilateral features through discrepancy-aware gating combined with depthwise separable convolution,", "source": "PubMed"}, {"chunk_id": "41512495_1", "pmid": "41512495", "title": "Leveraging hemispheric asymmetry in structural MRI with an attention-guided 3D CNN for early prediction of Alzheimer's conversion.", "authors": "Liu Y, Yao L, Liu J et al.", "year": "2026", "journal": "Neural networks : the official journal of the International Neural Network Society", "keywords": "3D CNN, Alzheimer\u2019s disease, Attention mechanism, Progress prediction, Structural MRI", "chunk": "derive disease-specific biomarkers, and effectively capture multi-level asymmetry features. Second, the contralateral hemispheric fusion mechanism is designed to adaptively unify bilateral features through discrepancy-aware gating combined with depthwise separable convolution, thus strengthening asymmetry patterns indicative of AD. Finally, the pathology focal attention mechanism is applied with sequential channel-spatial attention to highlight pivotal pathological regions, such as the hippocampus and temporal lobe, thereby enhancing the discriminative capacity of the learned features. Extensive experiments and cross-validation on the ADNI dataset demonstrate that HemiNet achieves an AUC of 84.01% and an accuracy of 78.19% for MCI prediction. This study validates the value of hemispheric asymmetry analysis for early AD detection and presents an efficient, lightweight, and interpretable method for MCI progression prediction from a single scan.", "source": "PubMed"}, {"chunk_id": "41512495_2", "pmid": "41512495", "title": "Leveraging hemispheric asymmetry in structural MRI with an attention-guided 3D CNN for early prediction of Alzheimer's conversion.", "authors": "Liu Y, Yao L, Liu J et al.", "year": "2026", "journal": "Neural networks : the official journal of the International Neural Network Society", "keywords": "3D CNN, Alzheimer\u2019s disease, Attention mechanism, Progress prediction, Structural MRI", "chunk": "a single scan.", "source": "PubMed"}, {"chunk_id": "30784077_0", "pmid": "30784077", "title": "Metformin protects PC12 cells and hippocampal neurons from H<sub>2</sub> O <sub>2</sub> -induced oxidative damage through activation of AMPK pathway.", "authors": "Zhao X, Zeng Z, Gaur U et al.", "year": "2019", "journal": "Journal of cellular physiology", "keywords": "AMP-activated protein kinase, PC12 cells, aging, hydrogen peroxide, metformin", "chunk": "Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H<sub>2</sub> O<sub>2</sub> -induced cell death. Metformin signi\ufb01cantly ameliorated cell death due to H<sub>2</sub> O<sub>2</sub> insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H<sub>2</sub> O<sub>2</sub> . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H<sub>2</sub> O<sub>2</sub> . Western blot analysis further demonstrated", "source": "PubMed"}, {"chunk_id": "30784077_1", "pmid": "30784077", "title": "Metformin protects PC12 cells and hippocampal neurons from H<sub>2</sub> O <sub>2</sub> -induced oxidative damage through activation of AMPK pathway.", "authors": "Zhao X, Zeng Z, Gaur U et al.", "year": "2019", "journal": "Journal of cellular physiology", "keywords": "AMP-activated protein kinase, PC12 cells, aging, hydrogen peroxide, metformin", "chunk": "H<sub>2</sub> O<sub>2</sub> . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H<sub>2</sub> O<sub>2</sub> . Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.", "source": "PubMed"}, {"chunk_id": "30784077_2", "pmid": "30784077", "title": "Metformin protects PC12 cells and hippocampal neurons from H<sub>2</sub> O <sub>2</sub> -induced oxidative damage through activation of AMPK pathway.", "authors": "Zhao X, Zeng Z, Gaur U et al.", "year": "2019", "journal": "Journal of cellular physiology", "keywords": "AMP-activated protein kinase, PC12 cells, aging, hydrogen peroxide, metformin", "chunk": "our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.", "source": "PubMed"}, {"chunk_id": "40111590_0", "pmid": "40111590", "title": "Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-\u03b2 Accumulation, with a Shift to Reduced Amyloid-\u03b2 Accumulation in Alzheimer's Disease.", "authors": "Azargoonjahromi A, Eivazi M, Nasiri H et al.", "year": "2025", "journal": "Journal of molecular neuroscience : MN", "keywords": "Amyloid-\u03b2, A\u03b2 Accumulation, Cognitive Function, Growth-Associated Protein 43, Neurodegeneration, Synaptic Dysfunction", "chunk": "Growth-associated protein 43 (GAP-43), a key regulator of synaptic plasticity, neuronal growth, and memory, has recently been identified as a crucial biomarker for synaptic dysfunction in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. This study aimed to explore the mechanisms underlying GAP-43's role in cognitive impairment by examining the relationship between CSF GAP-43 levels and amyloid-\u03b2 (A\u03b2) accumulation in brain regions like the frontal, temporal, and parietal lobes. This study included 332 participants sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI), categorized into three groups: 93 cognitively normal (CN), 218 with MCI, and 21 with AD dementia. Cognitive status was assessed with ADAS-Cog 13, CSF GAP-43 levels via ELISA, and A\u03b2 accumulation using florbetapir PET imaging and Syngo.PET for SUVr values in key brain regions. The results revealed that CSF GAP-43 levels were highest in the AD dementia group, followed by the MCI group, and lowest in the", "source": "PubMed"}, {"chunk_id": "40111590_1", "pmid": "40111590", "title": "Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-\u03b2 Accumulation, with a Shift to Reduced Amyloid-\u03b2 Accumulation in Alzheimer's Disease.", "authors": "Azargoonjahromi A, Eivazi M, Nasiri H et al.", "year": "2025", "journal": "Journal of molecular neuroscience : MN", "keywords": "Amyloid-\u03b2, A\u03b2 Accumulation, Cognitive Function, Growth-Associated Protein 43, Neurodegeneration, Synaptic Dysfunction", "chunk": "for SUVr values in key brain regions. The results revealed that CSF GAP-43 levels were highest in the AD dementia group, followed by the MCI group, and lowest in the CN group, with a significant difference (p < 0.001), indicating a link between elevated CSF GAP-43 and cognitive impairment. In MCI group, CSF GAP-43 positively correlated with A\u03b2 accumulation in all regions: Globally (\u03b2 = 0.362, p < 0.001), frontal (\u03b2 = 0.388, p < 0.001), temporal (\u03b2 = 0.382, p < 0.001), and parietal lobes (\u03b2 = 0.344, p < 0.001). In contrast, the AD dementia group exhibited negative correlations between CSF GAP-43 levels and A\u03b2 accumulation, significantly in the frontal (\u03b2 = - 0.513, p = 0.035) and parietal lobes (\u03b2 = - 0.513, p = 0.035), suggesting a shift in the CSF GAP-43-A\u03b2 relationship in AD dementia. Mediation analysis, adjusted for age, gender, education, and ApoE \u025b4", "source": "PubMed"}, {"chunk_id": "40111590_2", "pmid": "40111590", "title": "Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-\u03b2 Accumulation, with a Shift to Reduced Amyloid-\u03b2 Accumulation in Alzheimer's Disease.", "authors": "Azargoonjahromi A, Eivazi M, Nasiri H et al.", "year": "2025", "journal": "Journal of molecular neuroscience : MN", "keywords": "Amyloid-\u03b2, A\u03b2 Accumulation, Cognitive Function, Growth-Associated Protein 43, Neurodegeneration, Synaptic Dysfunction", "chunk": "parietal lobes (\u03b2 = - 0.513, p = 0.035), suggesting a shift in the CSF GAP-43-A\u03b2 relationship in AD dementia. Mediation analysis, adjusted for age, gender, education, and ApoE \u025b4 status, revealed that elevated CSF GAP-43 is linked to increased cognitive impairment via increasing A\u03b2 accumulation solely in MCI, with significant effects in global (\u03b2 = 0.0894, CI: [0.0427, 0.1457]), frontal (\u03b2 = 0.0895, CI: [0.0422, 0.1443]), temporal (\u03b2 = 0.0941, CI: [0.0466, 0.1522]), and parietal (\u03b2 = 0.0499, CI: [0.0100, 0.0945]) regions. Thus, elevated CSF GAP-43 may contribute to cognitive impairment by promoting A\u03b2 accumulation in individuals with MCI, while in AD dementia, it may be associated with reduced A\u03b2 accumulation, potentially reflecting a compensatory or disease-stage-dependent effect. This dynamic relationship suggests that GAP-43 could play a dual role in neurodegeneration, influencing A\u03b2 pathology differently across disease stages.", "source": "PubMed"}, {"chunk_id": "40111590_3", "pmid": "40111590", "title": "Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-\u03b2 Accumulation, with a Shift to Reduced Amyloid-\u03b2 Accumulation in Alzheimer's Disease.", "authors": "Azargoonjahromi A, Eivazi M, Nasiri H et al.", "year": "2025", "journal": "Journal of molecular neuroscience : MN", "keywords": "Amyloid-\u03b2, A\u03b2 Accumulation, Cognitive Function, Growth-Associated Protein 43, Neurodegeneration, Synaptic Dysfunction", "chunk": "dynamic relationship suggests that GAP-43 could play a dual role in neurodegeneration, influencing A\u03b2 pathology differently across disease stages.", "source": "PubMed"}, {"chunk_id": "41836919_0", "pmid": "41836919", "title": "Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.", "authors": "Aguzin Parrilli LJ, Belzunce MA", "year": "2026", "journal": "Imaging neuroscience (Cambridge, Mass.)", "keywords": "aging, brain age gap (BAG), brain age prediction, deep learning, interpretability, neuroimaging", "chunk": "Brain age prediction from T1-weighted MRI and its associated brain age gap (BAG) has emerged as a promising neuroimaging biomarker for assessing deviations from normative aging. However, the robustness, bias, and interpretability of existing models across external datasets remain poorly understood, limiting clinical translation. In this study, we evaluated four publicly available brain age models (ENIGMA, DeepBrainNet, Pyment, and BrainAgeNeXt) across four independent MRI datasets (ADNI, UNSAM Long COVID, and two OpenNeuro cohorts), comprising 1,634 subjects with diverse demographic and clinical profiles. Models were tested using their original preprocessing pipelines, and performance was assessed using mean absolute error (MAE), mean error (ME), and BAG variability metrics, with additional analyses of biases related to age, dataset, ethnicity, and education. Interpretability was evaluated using Layer-wise Relevance Propagation, and anatomical correlates were explored using BrainChart-derived centile scores. Group-level comparisons were performed between cognitively normal (CN) individuals and patients with Mild Cognitive Impairment (MCI),", "source": "PubMed"}, {"chunk_id": "41836919_1", "pmid": "41836919", "title": "Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.", "authors": "Aguzin Parrilli LJ, Belzunce MA", "year": "2026", "journal": "Imaging neuroscience (Cambridge, Mass.)", "keywords": "aging, brain age gap (BAG), brain age prediction, deep learning, interpretability, neuroimaging", "chunk": "evaluated using Layer-wise Relevance Propagation, and anatomical correlates were explored using BrainChart-derived centile scores. Group-level comparisons were performed between cognitively normal (CN) individuals and patients with Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), or Long COVID (LC). Models based on 3D convolutional neural networks (Pyment and BrainAgeNeXt) outperformed the DeepBrainNet 2D CNN and the ENIGMA ridge regression model in both accuracy (MAE: 3.9-3.7 vs. 6.2-12.4 years respectively) and stability (ASTD: 3.2-2.9 vs. 4.6-8.3 years). Dataset-specific BAG differences were largely explained by age distributions, whereas ethnicity showed a statistically significant but small effect on BAG in some models. Relevance maps highlighted the lateral ventricles as the most consistently relevant anatomical region, with additional cerebellar contributions emerging in older adults for BrainAgeNeXt. Group-level analyses confirmed elevated BAG in MCI and AD patients compared to CN, while no significant differences were observed in Long COVID participants. These findings suggest that, while BAG is", "source": "PubMed"}, {"chunk_id": "41836919_2", "pmid": "41836919", "title": "Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.", "authors": "Aguzin Parrilli LJ, Belzunce MA", "year": "2026", "journal": "Imaging neuroscience (Cambridge, Mass.)", "keywords": "aging, brain age gap (BAG), brain age prediction, deep learning, interpretability, neuroimaging", "chunk": "Group-level analyses confirmed elevated BAG in MCI and AD patients compared to CN, while no significant differences were observed in Long COVID participants. These findings suggest that, while BAG is a promising biomarker for group-level analyses, current models are required to address age and demographic biases to enable individual-level clinical application.", "source": "PubMed"}, {"chunk_id": "35482908_0", "pmid": "35482908", "title": "Clinical advances of RNA therapeutics for treatment of neurological and neuromuscular diseases.", "authors": "Holm A, Hansen SN, Klitgaard H et al.", "year": "2022", "journal": "RNA biology", "keywords": "CNS, RNA-based therapeutics, Small interfering RNA, antisense oligonucleotide, clinical trial, gene silencing, neurological disease, neuromuscular disorder", "chunk": "RNA therapeutics comprise a diverse group of oligonucleotide-based drugs such as antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and short hairpin RNAs (shRNAs) that can be designed to selectively interact with drug targets currently undruggable with small molecule-based drugs or monoclonal antibodies. Furthermore, RNA-based therapeutics have the potential to modulate entire disease pathways, and thereby represent a new modality with unprecedented potential for generating disease-modifying drugs for a wide variety of human diseases, including central nervous system (CNS) disorders. Here, we describe different strategies for delivering RNA drugs to the CNS and review recent advances in clinical development of ASO drugs and siRNA-based therapeutics for the treatment of neurological diseases and neuromuscular disorders.<b>Abbreviations</b> 2'-MOE: 2'-<i>O</i>-(2-methoxyethyl); 2'-<i>O</i>-Me: 2'-<i>O</i>-methyl; 2'-F: 2'-fluoro; AD: Alzheimer's disease; ALS: Amyotrophic lateral sclerosis; ALSFRS-R: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale; ARC: Antibody siRNA Conjugate; AS: Angelman Syndrome; ASGRP: Asialoglycoprotein receptor; ASO: Antisense oligonucleotide; AxD: Alexander Disease;", "source": "PubMed"}, {"chunk_id": "35482908_1", "pmid": "35482908", "title": "Clinical advances of RNA therapeutics for treatment of neurological and neuromuscular diseases.", "authors": "Holm A, Hansen SN, Klitgaard H et al.", "year": "2022", "journal": "RNA biology", "keywords": "CNS, RNA-based therapeutics, Small interfering RNA, antisense oligonucleotide, clinical trial, gene silencing, neurological disease, neuromuscular disorder", "chunk": "Alzheimer's disease; ALS: Amyotrophic lateral sclerosis; ALSFRS-R: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale; ARC: Antibody siRNA Conjugate; AS: Angelman Syndrome; ASGRP: Asialoglycoprotein receptor; ASO: Antisense oligonucleotide; AxD: Alexander Disease; BBB: Blood brain barrier; Bp: Basepair; CNM: Centronuclear myopathies; CNS: Central Nervous System; CPP: Cell-penetrating Peptide; CSF: Cerebrospinal fluid; DMD: Duchenne muscular dystrophy; DNA: Deoxyribonucleic acid; FAP: Familial amyloid polyneuropathy; FALS: Familial amyotrophic lateral sclerosis; FDA: The United States Food and Drug Administration; GalNAc: N-acetylgalactosamine; GoF: Gain of function; hATTR: Hereditary transthyretin amyloidosis; HD: Huntington's disease; HRQOL: health-related quality of life; ICV: Intracerebroventricular; IT: Intrathecal; LNA: Locked nucleic acid; LoF: Loss of function; mRNA: Messenger RNA; MS: Multiple Sclerosis; MSA: Multiple System Atrophy; NBE: New Biological Entity; NCE: New Chemical Entity; NHP: Nonhuman primate; nt: Nucleotide; PD: Parkinson's disease; PNP: Polyneuropathy; PNS: Peripheral nervous system; PS: Phosphorothioate; RISC: RNA-Induced Silencing Complex; RNA: Ribonucleic acid; RNAi: RNA interference; s.c.: Subcutaneous; siRNA:", "source": "PubMed"}, {"chunk_id": "35482908_2", "pmid": "35482908", "title": "Clinical advances of RNA therapeutics for treatment of neurological and neuromuscular diseases.", "authors": "Holm A, Hansen SN, Klitgaard H et al.", "year": "2022", "journal": "RNA biology", "keywords": "CNS, RNA-based therapeutics, Small interfering RNA, antisense oligonucleotide, clinical trial, gene silencing, neurological disease, neuromuscular disorder", "chunk": "Entity; NHP: Nonhuman primate; nt: Nucleotide; PD: Parkinson's disease; PNP: Polyneuropathy; PNS: Peripheral nervous system; PS: Phosphorothioate; RISC: RNA-Induced Silencing Complex; RNA: Ribonucleic acid; RNAi: RNA interference; s.c.: Subcutaneous; siRNA: Small interfering RNA; SMA: Spinal muscular atrophy; SMN: Survival motor neuron; TTR: Transthyretin.", "source": "PubMed"}, {"chunk_id": "41239318_0", "pmid": "41239318", "title": "The relationship between oral frailty and cognitive function in elderly patients with chronic diseases: the chain-mediated effect of nutrition status and the inflammatory marker CRP.", "authors": "Sun Y, Zhang Z, Wang S et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Chain mediation, Cognitive function, Inflammatory marker CRP, Nutritional status, Oral frailty", "chunk": "This study aims to investigate the mediating role of nutritional status and the inflammatory marker C-reactive protein (CRP) in the relationship between oral frailty and cognitive function in elderly patients with chronic diseases. A cross-sectional design was employed, and From June to December 2024, patients aged \u2265 60 years with chronic diseases from three tertiary hospitals in Henan Province were selected using convenience sampling. Data were collected using questionnaires, including the general information questionnaire, the Oral Frailty Screening Index-8 (OFI-8), the Mini Nutritional Assessment Short Form, the Montreal Cognitive Assessment, and laboratory tests for CRP. Descriptive demographic analysis and Pearson correlation analysis were conducted using SPSS 26.0, and the model 6 in macro program Process 4.1 was employed to test the chain mediation effect. (1) Regression analysis showed that oral frailty had a significant direct impact on cognitive function (\u03b2 = -0.154, P < 0.01), and nutritional status (\u03b2 =", "source": "PubMed"}, {"chunk_id": "41239318_1", "pmid": "41239318", "title": "The relationship between oral frailty and cognitive function in elderly patients with chronic diseases: the chain-mediated effect of nutrition status and the inflammatory marker CRP.", "authors": "Sun Y, Zhang Z, Wang S et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Chain mediation, Cognitive function, Inflammatory marker CRP, Nutritional status, Oral frailty", "chunk": "the chain mediation effect. (1) Regression analysis showed that oral frailty had a significant direct impact on cognitive function (\u03b2 = -0.154, P < 0.01), and nutritional status (\u03b2 = 0.228, P < 0.001) and CRP (\u03b2 = -0.200, P < 0.001) also had significant effects on cognitive function. (2) The results of the mediating effect analysis showed that the simple mediating effects of nutritional status and CRP between oral frailty and cognitive function were -0.088 (95% CI: -0.138 to -0.048) and -0.056(95% CI: -0.097 to -0.029), respectively, and the chain mediating effect was - 0.022 (95% CI: -0.040 to -0.010). This study found direct and chain-mediated effects of nutritional status and CRP between oral frailty and cognitive function. It suggests that cognitive function can be improved by early identification of oral frailty, improving nutritional status and reducing chronic inflammation levels to delay or even reverse the onset and progression", "source": "PubMed"}, {"chunk_id": "41239318_2", "pmid": "41239318", "title": "The relationship between oral frailty and cognitive function in elderly patients with chronic diseases: the chain-mediated effect of nutrition status and the inflammatory marker CRP.", "authors": "Sun Y, Zhang Z, Wang S et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Chain mediation, Cognitive function, Inflammatory marker CRP, Nutritional status, Oral frailty", "chunk": "suggests that cognitive function can be improved by early identification of oral frailty, improving nutritional status and reducing chronic inflammation levels to delay or even reverse the onset and progression of cognitive dysfunction in elderly patients with chronic diseases.", "source": "PubMed"}, {"chunk_id": "37102472_0", "pmid": "37102472", "title": "Remote Digital Technologies for the Early Detection and Monitoring of Cognitive Decline in Patients With Type 2 Diabetes: Insights From Studies of Neurodegenerative Diseases.", "authors": "DuBord AY, Paolillo EW, Staffaroni AM", "year": "2024", "journal": "Journal of diabetes science and technology", "keywords": "Alzheimer\u2019s disease, cognitive decline, digital biomarkers, health technology, mild cognitive impairment, type 2 diabetes", "chunk": "Type 2 diabetes (T2D) is a risk factor for cognitive decline. In neurodegenerative disease research, remote digital cognitive assessments and unobtrusive sensors are gaining traction for their potential to improve early detection and monitoring of cognitive impairment. Given the high prevalence of cognitive impairments in T2D, these digital tools are highly relevant. Further research incorporating remote digital biomarkers of cognition, behavior, and motor functioning may enable comprehensive characterizations of patients with T2D and may ultimately improve clinical care and equitable access to research participation. The aim of this commentary article is to review the feasibility, validity, and limitations of using remote digital cognitive tests and unobtrusive detection methods to identify and monitor cognitive decline in neurodegenerative conditions and apply these insights to patients with T2D.", "source": "PubMed"}, {"chunk_id": "37102472_1", "pmid": "37102472", "title": "Remote Digital Technologies for the Early Detection and Monitoring of Cognitive Decline in Patients With Type 2 Diabetes: Insights From Studies of Neurodegenerative Diseases.", "authors": "DuBord AY, Paolillo EW, Staffaroni AM", "year": "2024", "journal": "Journal of diabetes science and technology", "keywords": "Alzheimer\u2019s disease, cognitive decline, digital biomarkers, health technology, mild cognitive impairment, type 2 diabetes", "chunk": "insights to patients with T2D.", "source": "PubMed"}, {"chunk_id": "41334588_0", "pmid": "41334588", "title": "Movement Disorders Associated with 22q11.2 Microdeletion: A Scoping Review.", "authors": "Reyes NGD, Di Luca DG, Marras C et al.", "year": "2025", "journal": "Movement disorders clinical practice", "keywords": "22q11.2 deletion syndrome, 22q11.2 microdeletion, motor dysfunction, movement disorder", "chunk": "Movement disorders have recently emerged as important neurologic manifestations of the 22q11.2 microdeletion that affects nearly one in every 2000 live births. We aimed to map the existing evidence regarding the spectrum, diagnosis and treatment, and etiopathogenesis of movement disorders associated with 22q11.2 microdeletion, highlight key gaps, and provide recommendations for future research. We conducted a comprehensive search of MEDLINE, Embase, CENTRAL, and reference lists to identify relevant clinical and preclinical studies, and summarize data on clinico-pathologic features, risk factors, and pathophysiology of movement disorders associated with molecularly defined 22q11.2 microdeletions. Forty-three (clinical: n = 41/43, 95%; preclinical: n = 2/43, 5%) studies met eligibility criteria. Most clinical studies (35/41, 85%) involved adults, of which 51% (21/41) were case series/reports, and the remainder observational studies. Key findings included: (1) emphasis on parkinsonism but emerging evidence for multiple other motor phenotypes, (2) non-specific findings on routine neuroimaging, albeit with promising early", "source": "PubMed"}, {"chunk_id": "41334588_1", "pmid": "41334588", "title": "Movement Disorders Associated with 22q11.2 Microdeletion: A Scoping Review.", "authors": "Reyes NGD, Di Luca DG, Marras C et al.", "year": "2025", "journal": "Movement disorders clinical practice", "keywords": "22q11.2 deletion syndrome, 22q11.2 microdeletion, motor dysfunction, movement disorder", "chunk": "and the remainder observational studies. Key findings included: (1) emphasis on parkinsonism but emerging evidence for multiple other motor phenotypes, (2) non-specific findings on routine neuroimaging, albeit with promising early results of certain modalities (eg, volumetric analyses, molecular imaging) and fluid-based biomarkers, particularly for parkinsonism, and (3) multifaceted etiologic and pathophysiologic processes beyond those attributable to medication side effects. Prevailing gaps include research design limitations, heterogeneity of diagnostic methods, and limited systematic data on etiopathogenesis and treatments. Current evidence supports an expanding spectrum of motor phenotypes associated with 22q11.2 microdeletion, with emerging data reporting potentially useful clinical markers and non-drug-related risk modifiers and underlying mechanisms. Addressing prevailing gaps will require enhanced research designs with up-to-date diagnostic and genetic methodologies, robust preclinical models, and cross-disciplinary collaborations.", "source": "PubMed"}, {"chunk_id": "41334588_2", "pmid": "41334588", "title": "Movement Disorders Associated with 22q11.2 Microdeletion: A Scoping Review.", "authors": "Reyes NGD, Di Luca DG, Marras C et al.", "year": "2025", "journal": "Movement disorders clinical practice", "keywords": "22q11.2 deletion syndrome, 22q11.2 microdeletion, motor dysfunction, movement disorder", "chunk": "preclinical models, and cross-disciplinary collaborations.", "source": "PubMed"}, {"chunk_id": "39376966_0", "pmid": "39376966", "title": "Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.", "authors": "Yao L, Li MY, Wang KC et al.", "year": "2024", "journal": "Frontiers in psychiatry", "keywords": "cognitive decline, hippocampus, resting-state functional connectivity, subregion; peripheral inflammation, type 2 diabetes mellitus", "chunk": "Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-\u03b1 in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to", "source": "PubMed"}, {"chunk_id": "39376966_1", "pmid": "39376966", "title": "Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.", "authors": "Yao L, Li MY, Wang KC et al.", "year": "2024", "journal": "Frontiers in psychiatry", "keywords": "cognitive decline, hippocampus, resting-state functional connectivity, subregion; peripheral inflammation, type 2 diabetes mellitus", "chunk": "performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response", "source": "PubMed"}, {"chunk_id": "39376966_2", "pmid": "39376966", "title": "Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.", "authors": "Yao L, Li MY, Wang KC et al.", "year": "2024", "journal": "Frontiers in psychiatry", "keywords": "cognitive decline, hippocampus, resting-state functional connectivity, subregion; peripheral inflammation, type 2 diabetes mellitus", "chunk": "left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, <i>P</i>=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.", "source": "PubMed"}, {"chunk_id": "39376966_3", "pmid": "39376966", "title": "Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.", "authors": "Yao L, Li MY, Wang KC et al.", "year": "2024", "journal": "Frontiers in psychiatry", "keywords": "cognitive decline, hippocampus, resting-state functional connectivity, subregion; peripheral inflammation, type 2 diabetes mellitus", "chunk": "of this study may provide a basis for the preliminary diagnosis of T2DACD.", "source": "PubMed"}, {"chunk_id": "41480929_0", "pmid": "41480929", "title": "Innate Immune Tolerance Regulates Microglia Response to A\u03b2 Oligomers.", "authors": "Valerio RR, Santos \u00c1R, N\u00f3brega AHL et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, cytokines, immune tolerance, innate immune memory, microglia, neuroinflammation", "chunk": "Microglia are the main innate immune cells residing in the brain parenchyma. Their activation and resulting neuroinflammation have emerged as major pathogenic mechanisms in neurodegenerative disorders, particularly in Alzheimer's disease (AD). The accumulation of amyloid-\u03b2 oligomers (A\u03b2Os) and microglia activation play crucial roles in the pathogenesis of AD. In a second vein, the development of innate immune memory in response to different stimuli is a vital mechanism that enables microglia to adjust their response to subsequent inflammatory challenges. While there is increasing evidence that repeated bouts of peripheral inflammation lead to training or tolerance in microglia, the impact of tolerance on the inflammatory response induced by A\u03b2Os remains to be determined. In this study, we investigated whether lipopolysaccharide (LPS)-induced tolerance affects microglial responses to A\u03b2Os. For that, organotypic hippocampal cultures were repeatedly challenged with LPS before being exposed to A\u03b2Os. We measured cytokine levels and evaluated changes in microglial activation", "source": "PubMed"}, {"chunk_id": "41480929_1", "pmid": "41480929", "title": "Innate Immune Tolerance Regulates Microglia Response to A\u03b2 Oligomers.", "authors": "Valerio RR, Santos \u00c1R, N\u00f3brega AHL et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, cytokines, immune tolerance, innate immune memory, microglia, neuroinflammation", "chunk": "affects microglial responses to A\u03b2Os. For that, organotypic hippocampal cultures were repeatedly challenged with LPS before being exposed to A\u03b2Os. We measured cytokine levels and evaluated changes in microglial activation and morphology following exposure of cultures to A\u03b2Os. A significant decrease in cytokine production was observed when hippocampal slice cultures were repeatedly challenged with LPS. Interestingly, microglial activation and the resulting inflammatory response induced by A\u03b2Os were prevented when these cultures had been previously challenged with LPS. Moreover, the changes in microglial morphology and cytokine production resulting from repeated LPS stimulation were associated with reduced activation of nuclear factor kappa B (NF-\u03baB). These results indicate that preconditioning microglia with LPS induces a physiological immune tolerance response rather than pathological inflammation, which may have implications for developing therapeutic strategies for AD aimed at modulating innate immune memory.", "source": "PubMed"}, {"chunk_id": "41480929_2", "pmid": "41480929", "title": "Innate Immune Tolerance Regulates Microglia Response to A\u03b2 Oligomers.", "authors": "Valerio RR, Santos \u00c1R, N\u00f3brega AHL et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, cytokines, immune tolerance, innate immune memory, microglia, neuroinflammation", "chunk": "which may have implications for developing therapeutic strategies for AD aimed at modulating innate immune memory.", "source": "PubMed"}, {"chunk_id": "41092455_0", "pmid": "41092455", "title": "DUNE: a versatile neuroimaging encoder captures brain complexity across 3 major diseases: cancer, dementia, and schizophrenia.", "authors": "Barba T, Bagley BA, Steyaert S et al.", "year": "2025", "journal": "GigaScience", "keywords": "autoencoders, deep learning, feature extraction, neuroimaging", "chunk": "Magnetic resonance imaging (MRI) of the brain contains complex data that pose significant challenges for computational analysis. While models proposed for brain MRI analyses yield encouraging results, the high complexity of neuroimaging data hinders generalizability and clinical application. We introduce DUNE, a neuroimaging-oriented workflow that transforms raw brain MRI scans into standardized compact patient-level embeddings through integrated preprocessing and deep feature extraction, thereby enabling their processing by basic machine learning algorithms. A UNet-based autoencoder was trained using 3,814 selected scans of morphologically normal (healthy volunteers) or abnormal (glioma patients) brains, to generate comprehensive compact representations of the full-sized images. To evaluate their quality, these embeddings were utilized to train machine learning models to predict a wide range of clinical variables. Embeddings were extracted for cohorts used for the model development (21,102 individuals), along with 3 additional independent cohorts (Alzheimer's disease, schizophrenia, and glioma cohorts, 1,322 individuals), to evaluate the model's", "source": "PubMed"}, {"chunk_id": "41092455_1", "pmid": "41092455", "title": "DUNE: a versatile neuroimaging encoder captures brain complexity across 3 major diseases: cancer, dementia, and schizophrenia.", "authors": "Barba T, Bagley BA, Steyaert S et al.", "year": "2025", "journal": "GigaScience", "keywords": "autoencoders, deep learning, feature extraction, neuroimaging", "chunk": "Embeddings were extracted for cohorts used for the model development (21,102 individuals), along with 3 additional independent cohorts (Alzheimer's disease, schizophrenia, and glioma cohorts, 1,322 individuals), to evaluate the model's generalization capabilities. The embeddings extracted from healthy volunteers' scans could predict a broad spectrum of clinical parameters, including volumetry metrics, cardiovascular disease (area under the receiver operating characteristic curve [AUROC] = 0.80) and alcohol consumption (AUROC = 0.99), and more nuanced parameters such as the Alzheimer's predisposing APOE4 allele (AUROC = 0.67). Embeddings derived from the validation cohorts successfully predicted the diagnoses of Alzheimer's dementia (AUROC = 0.92) and schizophrenia (AUROC = 0.64). Embeddings extracted from glioma scans successfully predicted survival (C-index = 0.608) and IDH molecular status (AUROC = 0.92), matching the performances of previous task-oriented models. DUNE efficiently represents clinically relevant patterns from full-size brain MRI scans across several disease areas, opening ways for innovative clinical applications in", "source": "PubMed"}, {"chunk_id": "41092455_2", "pmid": "41092455", "title": "DUNE: a versatile neuroimaging encoder captures brain complexity across 3 major diseases: cancer, dementia, and schizophrenia.", "authors": "Barba T, Bagley BA, Steyaert S et al.", "year": "2025", "journal": "GigaScience", "keywords": "autoencoders, deep learning, feature extraction, neuroimaging", "chunk": "0.92), matching the performances of previous task-oriented models. DUNE efficiently represents clinically relevant patterns from full-size brain MRI scans across several disease areas, opening ways for innovative clinical applications in neurology.", "source": "PubMed"}, {"chunk_id": "34311421_0", "pmid": "34311421", "title": "Learning to synthesise the ageing brain without longitudinal data.", "authors": "Xia T, Chartsias A, Wang C et al.", "year": "2021", "journal": "Medical image analysis", "keywords": "Brain ageing, Generative adversarial network, Magnetic resonance imaging (MRI), Neurodegenerative disease", "chunk": "How will my face look when I get older? Or, for a more challenging question: How will my brain look when I get older? To answer this question one must devise (and learn from data) a multivariate auto-regressive function which given an image and a desired target age generates an output image. While collecting data for faces may be easier, collecting longitudinal brain data is not trivial. We propose a deep learning-based method that learns to simulate subject-specific brain ageing trajectories without relying on longitudinal data. Our method synthesises images conditioned on two factors: age (a continuous variable), and status of Alzheimer's Disease (AD, an ordinal variable). With an adversarial formulation we learn the joint distribution of brain appearance, age and AD status, and define reconstruction losses to address the challenging problem of preserving subject identity. We compare with several benchmarks using two widely used datasets. We evaluate the quality", "source": "PubMed"}, {"chunk_id": "34311421_1", "pmid": "34311421", "title": "Learning to synthesise the ageing brain without longitudinal data.", "authors": "Xia T, Chartsias A, Wang C et al.", "year": "2021", "journal": "Medical image analysis", "keywords": "Brain ageing, Generative adversarial network, Magnetic resonance imaging (MRI), Neurodegenerative disease", "chunk": "and AD status, and define reconstruction losses to address the challenging problem of preserving subject identity. We compare with several benchmarks using two widely used datasets. We evaluate the quality and realism of synthesised images using ground-truth longitudinal data and a pre-trained age predictor. We show that, despite the use of cross-sectional data, our model learns patterns of gray matter atrophy in the middle temporal gyrus in patients with AD. To demonstrate generalisation ability, we train on one dataset and evaluate predictions on the other. In conclusion, our model shows an ability to separate age, disease influence and anatomy using only 2D cross-sectional data that should be useful in large studies into neurodegenerative disease, that aim to combine several data sources. To facilitate such future studies by the community at large our code is made available at https://github.com/xiat0616/BrainAgeing.", "source": "PubMed"}, {"chunk_id": "34311421_2", "pmid": "34311421", "title": "Learning to synthesise the ageing brain without longitudinal data.", "authors": "Xia T, Chartsias A, Wang C et al.", "year": "2021", "journal": "Medical image analysis", "keywords": "Brain ageing, Generative adversarial network, Magnetic resonance imaging (MRI), Neurodegenerative disease", "chunk": "sources. To facilitate such future studies by the community at large our code is made available at https://github.com/xiat0616/BrainAgeing.", "source": "PubMed"}, {"chunk_id": "41766754_0", "pmid": "41766754", "title": "Epilepsy and Alzheimer Disease: Epidemiologic, Clinical, Molecular, and Neuropathologic Convergences and Divergences.", "authors": "Devinsky O, Leitner DF, Kamondi A et al.", "year": "2026", "journal": "Neurology. Clinical practice", "keywords": "None", "chunk": "Alzheimer disease (AD) and epilepsy are major causes of neurologic disability and are reciprocally related: epileptiform discharges, subclinical seizures, and epilepsy are more prevalent in patients with AD compared with controls; progressive cognitive impairment commonly afflicts epilepsy patients; and late-onset epilepsy patients have higher rates of new-onset dementia. Epidemiologic studies support shared risk factors (e.g., genetic variants, vascular disease, sleep disorders, microbiome) with notable divergences. AD and epilepsy have some overlapping anatomic (e.g., hippocampus, entorhinal, and association cortex), clinical (e.g., memory, attentional, and executive) impairments, and neuropathologic (e.g., amyloid, tau, neurofibrillary tangles) features. Shared clinical and translational challenges include underlying mechanisms (e.g., genetic variants, neuroinflammation, metabolic and mitochondrial dysfunction, excitatory/inhibitory imbalance, microbiome, and sociodemographic factors) and identifying valid and reliable biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, A\u03b242/A\u03b240 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. Identifying convergences and divergences between epilepsy and", "source": "PubMed"}, {"chunk_id": "41766754_1", "pmid": "41766754", "title": "Epilepsy and Alzheimer Disease: Epidemiologic, Clinical, Molecular, and Neuropathologic Convergences and Divergences.", "authors": "Devinsky O, Leitner DF, Kamondi A et al.", "year": "2026", "journal": "Neurology. Clinical practice", "keywords": "None", "chunk": "biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, A\u03b242/A\u03b240 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. Identifying convergences and divergences between epilepsy and AD may inform our understanding. The clinical, neurophysiologic, neuropathologic, and molecular pathologic changes in AD and epilepsy may reveal pathophysiologic insights and therapeutic opportunities.", "source": "PubMed"}, {"chunk_id": "39335651_0", "pmid": "39335651", "title": "Analysis of Brain Age Gap across Subject Cohorts and Prediction Model Architectures.", "authors": "Dular L, \u0160piclin \u017d, For The Alzheimer's Disease Neuroimaging Initiative  et al.", "year": "2024", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s dementia, Parkinson\u2019s disease, UK Biobank, brain age, brain age gap, deep regression models, diabetes, multiple sclerosis, sleep apnea", "chunk": "<b>Background:</b> Brain age prediction from brain MRI scans and the resulting brain age gap (BAG)-the difference between predicted brain age and chronological age-is a general biomarker for a variety of neurological, psychiatric, and other diseases or disorders. <b>Methods:</b> This study examined the differences in BAG values derived from T1-weighted scans using five state-of-the-art deep learning model architectures previously used in the brain age literature: 2D/3D VGG, RelationNet, ResNet, and SFCN. The models were evaluated on healthy controls and cohorts with sleep apnea, diabetes, multiple sclerosis, Parkinson's disease, mild cognitive impairment, and Alzheimer's disease, employing rigorous statistical analysis, including repeated model training and linear mixed-effects models. <b>Results:</b> All five models consistently identified a statistically significant positive BAG for diabetes (ranging from 0.79 years with RelationNet to 2.13 years with SFCN), multiple sclerosis (2.67 years with 3D VGG to 4.24 years with 2D VGG), mild cognitive impairment (2.13 years with 2D VGG", "source": "PubMed"}, {"chunk_id": "39335651_1", "pmid": "39335651", "title": "Analysis of Brain Age Gap across Subject Cohorts and Prediction Model Architectures.", "authors": "Dular L, \u0160piclin \u017d, For The Alzheimer's Disease Neuroimaging Initiative  et al.", "year": "2024", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s dementia, Parkinson\u2019s disease, UK Biobank, brain age, brain age gap, deep regression models, diabetes, multiple sclerosis, sleep apnea", "chunk": "0.79 years with RelationNet to 2.13 years with SFCN), multiple sclerosis (2.67 years with 3D VGG to 4.24 years with 2D VGG), mild cognitive impairment (2.13 years with 2D VGG to 2.59 years with 3D VGG), and Alzheimer's dementia (5.54 years with ResNet to 6.48 years with SFCN). For Parkinson's disease, a statistically significant BAG increase was observed in all models except ResNet (1.30 years with 2D VGG to 2.59 years with 3D VGG). For sleep apnea, a statistically significant BAG increase was only detected with the SFCN model (1.59 years). Additionally, we observed a trend of decreasing BAG with increasing chronological age, which was more pronounced in diseased cohorts, particularly those with the largest BAG, such as multiple sclerosis (-0.34 to -0.2), mild cognitive impairment (-0.37 to -0.26), and Alzheimer's dementia (-0.66 to -0.47), compared to healthy controls (-0.18 to -0.1). <b>Conclusions:</b> Consistent with previous research, Alzheimer's dementia and", "source": "PubMed"}, {"chunk_id": "39335651_2", "pmid": "39335651", "title": "Analysis of Brain Age Gap across Subject Cohorts and Prediction Model Architectures.", "authors": "Dular L, \u0160piclin \u017d, For The Alzheimer's Disease Neuroimaging Initiative  et al.", "year": "2024", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s dementia, Parkinson\u2019s disease, UK Biobank, brain age, brain age gap, deep regression models, diabetes, multiple sclerosis, sleep apnea", "chunk": "(-0.34 to -0.2), mild cognitive impairment (-0.37 to -0.26), and Alzheimer's dementia (-0.66 to -0.47), compared to healthy controls (-0.18 to -0.1). <b>Conclusions:</b> Consistent with previous research, Alzheimer's dementia and multiple sclerosis exhibited the largest BAG across all models, with SFCN predicting the highest BAG overall. The negative BAG trend suggests a complex interplay of survival bias, disease progression, adaptation, and therapy that influences brain age prediction across the age spectrum.", "source": "PubMed"}, {"chunk_id": "37885919_0", "pmid": "37885919", "title": "Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease.", "authors": "Ally M, Sugarman MA, Zetterberg H et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, glial fibrillary acidic protein, neurofilament light chain, neuropsychology, phosphorylated tau, plasma biomarkers", "chunk": "This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)<sub>181+231</sub>. Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes. Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia. Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel", "source": "PubMed"}, {"chunk_id": "37885919_1", "pmid": "37885919", "title": "Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease.", "authors": "Ally M, Sugarman MA, Zetterberg H et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, glial fibrillary acidic protein, neurofilament light chain, neuropsychology, phosphorylated tau, plasma biomarkers", "chunk": "not predict conversion to mild cognitive impairment or dementia. Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.", "source": "PubMed"}, {"chunk_id": "36280690_0", "pmid": "36280690", "title": "Genetic polymorphism in BIN1 rather than APOE is associated with poor recognition memory among men without dementia.", "authors": "Mehta K, Mohebbi M, Pasco JA et al.", "year": "2022", "journal": "Scientific reports", "keywords": "None", "chunk": "Although several genetic polymorphisms have been linked with the risk of Alzheimer's disease, less is known about their impact on cognitive performance among cognitively healthy individuals. Our aim was to investigate the association of the genetic variant, rs744373 in the bridging integrator 1 gene (BIN1), the strongest genetic risk factor for Alzheimer's disease after the APOE \u03b54 allele, with different cognitive domains among non-demented older men. Cognitive function was measured using the CogState Brief Battery, which assessed cognitive performance across four domains: psychomotor function, visual attention, recognition memory and working memory. Linear regression analysis revealed that individuals with the BIN1 risk allele performed poorly on the recognition memory task as compared to those without the risk allele. However, this was in contrast with the individuals who harboured the APOE \u03b54 risk allele as they displayed better performance on the recognition task in comparison to those without the \u03b54 risk allele.", "source": "PubMed"}, {"chunk_id": "36280690_1", "pmid": "36280690", "title": "Genetic polymorphism in BIN1 rather than APOE is associated with poor recognition memory among men without dementia.", "authors": "Mehta K, Mohebbi M, Pasco JA et al.", "year": "2022", "journal": "Scientific reports", "keywords": "None", "chunk": "in contrast with the individuals who harboured the APOE \u03b54 risk allele as they displayed better performance on the recognition task in comparison to those without the \u03b54 risk allele. To the best of our knowledge, this is the first study that demonstrates genetic variation in BIN1 to be a better predictor of recognition memory than APOE, which remains the biggest genetic risk factor for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41482165_0", "pmid": "41482165", "title": "USP53 promotes NOTCH2-induced neuroinflammation in Alzheimer's disease.", "authors": "He D, Zhao H, Zhu Y et al.", "year": "2026", "journal": "Neurochemistry international", "keywords": "Alzheimer's disease, NOTCH2, Neuroinflammation, USP53", "chunk": "This study aimed to investigate the role of USP53 and its associated signaling pathway associated with USP53 in Alzheimer's disease (AD). In vivo experiments were conducted in C57BL/6, 5XFAD, and USP53-knockout 5XFAD (USP53<sup>-/-</sup>) mice. In vitro experiments were performed using primary human microglia cells. mRNA expression was examined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Protein expression was measured using western blotting and immunofluorescence (IF). Immunoprecipitation (Co-IP) was used to detect protein-protein interactions. Morris Water Maze (MWM) was used to evaluate the learning ability and memory of mice. USP53 was overexpressed in patients with AD. Knockout of USP53 downregulated the expression of CD68, glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (Iba1) and neuronal nuclear protein (NeuN), as well as the inflammatory mediators, interleukin-1 beta (IL-1\u03b2) and tumor necrosis factor alpha (TNF-\u03b1). The accumulation of Tau protein was reduced, and the learning ability and memory", "source": "PubMed"}, {"chunk_id": "41482165_1", "pmid": "41482165", "title": "USP53 promotes NOTCH2-induced neuroinflammation in Alzheimer's disease.", "authors": "He D, Zhao H, Zhu Y et al.", "year": "2026", "journal": "Neurochemistry international", "keywords": "Alzheimer's disease, NOTCH2, Neuroinflammation, USP53", "chunk": "protein (NeuN), as well as the inflammatory mediators, interleukin-1 beta (IL-1\u03b2) and tumor necrosis factor alpha (TNF-\u03b1). The accumulation of Tau protein was reduced, and the learning ability and memory was improved in USP53<sup>-/-</sup> mice compared to 5XFAD mice. In vitro experiments demonstrated that protein-protein interaction existed between USP53 and NOTCH2 and that the inhibition of USP53 prevented amyloid-beta (A\u03b2)-induced deubiquitination of NOTCH2. Knockdown of USP53 reduced A\u03b2-induced elevation of inflammatory mediators and repressed A\u03b2-induced activation of IKK\u03b2/NF\u03baB signaling pathway in microglia. USP53 promotes the activation of neuroinflammation and worsens learning ability and memory in AD mice, mediated by NOTCH2.", "source": "PubMed"}, {"chunk_id": "37759689_0", "pmid": "37759689", "title": "Metformin Prevents NDEA-Induced Memory Impairments Associated with Attenuating Beta-Amyloid, Tumor Necrosis Factor-Alpha, and Interleukin-6 Levels in the Hippocampus of Rats.", "authors": "Ponce-Lopez T, Gonz\u00e1lez \u00c1lvarez Tostado JA, Dias F et al.", "year": "2023", "journal": "Biomolecules", "keywords": "N-nitrosodiethylamine, TNF-\u03b1, interleukin-6, memory impairment, metformin, \u03b2-amyloid", "chunk": "N-nitrosodiethylamine (NDEA) is a potential carcinogen known to cause liver tumors and chronic inflammation, diabetes, cognitive problems, and signs like Alzheimer's disease (AD) in animals. This compound is classified as probably carcinogenic to humans. Usual sources of exposure include food, beer, tobacco, personal care products, water, and medications. AD is characterized by cognitive decline, amyloid-\u03b2 (A\u03b2) deposit, tau hyperphosphorylation, and cell loss. This is accompanied by neuroinflammation, which involves release of microglial cytokines, such as tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and interleukin 1\u03b2 (IL-1\u03b2), by nuclear factor kappa B (NF-\u03baB) upregulation; each are linked to AD progression. Weak PI3K/Akt insulin-signaling inhibits IRS-1 phosphorylation, activates GSK3\u03b2 and promotes tau hyperphosphorylation. Metformin, an antihyperglycemic agent, has potent anti-inflammatory efficacy. It reduces proinflammatory cytokines such as IL-6, IL-1\u03b2, and TNF-\u03b1 via NF-\u03baB inhibition. Metformin also reduces reactive oxidative species (ROS) and modulates cognitive disorders reported due to brain insulin resistance links. Our", "source": "PubMed"}, {"chunk_id": "37759689_1", "pmid": "37759689", "title": "Metformin Prevents NDEA-Induced Memory Impairments Associated with Attenuating Beta-Amyloid, Tumor Necrosis Factor-Alpha, and Interleukin-6 Levels in the Hippocampus of Rats.", "authors": "Ponce-Lopez T, Gonz\u00e1lez \u00c1lvarez Tostado JA, Dias F et al.", "year": "2023", "journal": "Biomolecules", "keywords": "N-nitrosodiethylamine, TNF-\u03b1, interleukin-6, memory impairment, metformin, \u03b2-amyloid", "chunk": "proinflammatory cytokines such as IL-6, IL-1\u03b2, and TNF-\u03b1 via NF-\u03baB inhibition. Metformin also reduces reactive oxidative species (ROS) and modulates cognitive disorders reported due to brain insulin resistance links. Our study examined how NDEA affects spatial memory in Wistar rats. We found that all NDEA doses tested impaired memory. The 80 \u00b5g/kg dose of NDEA increased levels of A\u03b21-42, TNF-\u03b1, and IL-6 in the hippocampus, which correlated with memory loss. Nonetheless, treatment with 100 mg/kg of metformin attenuated the levels of pro-inflammatory cytokines and A\u03b21-42, and enhanced memory. It suggests that metformin may protect against NDEA-triggered memory issues and brain inflammation.", "source": "PubMed"}, {"chunk_id": "38982272_0", "pmid": "38982272", "title": "Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer's disease.", "authors": "Medegan Fagla B, York J, Christensen A et al.", "year": "2024", "journal": "Scientific reports", "keywords": "None", "chunk": "Apolipoprotein E (APOE) is a major cholesterol carrier responsible for lipid transport and injury repair in the brain. The human APOE gene (h-APOE) has 3 naturally occurring alleles: \u03b53, the common allele; \u03b54, which increases Alzheimer's disease (AD) risk up to 15-fold; and \u03b52, the rare allele which protects against AD. Although APOE4 has negative effects on neurocognition in old age, its persistence in the population suggests a survival advantage. We investigated the relationship between APOE genotypes and fertility in EFAD mice, a transgenic mouse model expressing h-APOE. We show that APOE4 transgenic mice had the highest level of reproductive performance, followed by APOE3 and APOE2. Intriguingly, APOE3 pregnancies had more fetal resorptions and reduced fetal weights relative to APOE4 pregnancies. In conclusion, APOE genotypes impact fertility and pregnancy outcomes in female mice, in concordance with findings in human populations. These mouse models may help elucidate how h-APOE4 promotes reproductive", "source": "PubMed"}, {"chunk_id": "38982272_1", "pmid": "38982272", "title": "Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer's disease.", "authors": "Medegan Fagla B, York J, Christensen A et al.", "year": "2024", "journal": "Scientific reports", "keywords": "None", "chunk": "pregnancies. In conclusion, APOE genotypes impact fertility and pregnancy outcomes in female mice, in concordance with findings in human populations. These mouse models may help elucidate how h-APOE4 promotes reproductive fitness at the cost of AD in later life.", "source": "PubMed"}, {"chunk_id": "37172880_0", "pmid": "37172880", "title": "Association of Deja vu With Cardiovascular Diseases.", "authors": "Rashid S, Khenhrani RR, Devi S et al.", "year": "2023", "journal": "Current problems in cardiology", "keywords": "None", "chunk": "Recent studies have suggested a link between d\u00e9j\u00e0 vu and cardiovascular diseases (CVDs). While the mechanism for this association is not fully understood, 1 theory suggests that d\u00e9j\u00e0 vu may be a result of a disruption in the temporal lobe, which is also responsible for regulating blood pressure and heart rate. Another theory suggests that there may be a shared genetic factor between the 2 conditions, with certain individuals being predisposed to experiencing both. The Apolipoprotein E (APOE) gene, in particular, has been associated with memory processing, Alzheimer's disease, and an increased risk of CVD. The protein encoded by this gene is involved in the metabolism of lipoproteins, including cholesterol and triglycerides, and is also involved in the development of atherosclerosis, which is a key risk factor for CVD. Several hypotheses have been proposed to explain how the APOE4 isoform contributes to CVD, including impairing the clearance of lipoproteins, promoting", "source": "PubMed"}, {"chunk_id": "37172880_1", "pmid": "37172880", "title": "Association of Deja vu With Cardiovascular Diseases.", "authors": "Rashid S, Khenhrani RR, Devi S et al.", "year": "2023", "journal": "Current problems in cardiology", "keywords": "None", "chunk": "atherosclerosis, which is a key risk factor for CVD. Several hypotheses have been proposed to explain how the APOE4 isoform contributes to CVD, including impairing the clearance of lipoproteins, promoting inflammation, and causing endothelial dysfunction. Psychological factors such as stress may also contribute to the development of CVD, and d\u00e9j\u00e0 vu may be associated with emotional arousal and stress. Further research is needed to fully understand the link between d\u00e9j\u00e0 vu and CVDs and to explore potential treatment options for individuals who experience both conditions.", "source": "PubMed"}, {"chunk_id": "27068280_0", "pmid": "27068280", "title": "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Olsson B, Lautner R, Andreasson U et al.", "year": "2016", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (A\u03b242, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (A\u03b242, A\u03b240, A\u03b238, sAPP\u03b1, and sAPP\u03b2), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from", "source": "PubMed"}, {"chunk_id": "27068280_1", "pmid": "27068280", "title": "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Olsson B, Lautner R, Andreasson U et al.", "year": "2016", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "A\u03b240, A\u03b238, sAPP\u03b1, and sAPP\u03b2), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and", "source": "PubMed"}, {"chunk_id": "27068280_2", "pmid": "27068280", "title": "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Olsson B, Lautner R, Andreasson U et al.", "year": "2016", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline. Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2\u00b754, 95% CI 2\u00b744-2\u00b764, p<0\u00b70001), P-tau (1\u00b788, 1\u00b779-1\u00b797, p<0\u00b70001), and A\u03b242 (0\u00b756, 0\u00b755-0\u00b758, p<0\u00b70001). Differentiation between cohorts with mild cognitive impairment due to Alzheimer's disease and those with stable mild cognitive impairment was also strong (average ratio 0\u00b767 for CSF A\u03b242, 1\u00b772 for P-tau, and 1\u00b776 for T-tau). Furthermore, CSF NFL (2\u00b735, 1\u00b790-2\u00b791, p<0\u00b70001) and plasma T-tau (1\u00b795, 1\u00b712-3\u00b738, p=0\u00b702) had large effect sizes when differentiating between controls and patients with", "source": "PubMed"}, {"chunk_id": "27068280_3", "pmid": "27068280", "title": "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Olsson B, Lautner R, Andreasson U et al.", "year": "2016", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "1\u00b772 for P-tau, and 1\u00b776 for T-tau). Furthermore, CSF NFL (2\u00b735, 1\u00b790-2\u00b791, p<0\u00b70001) and plasma T-tau (1\u00b795, 1\u00b712-3\u00b738, p=0\u00b702) had large effect sizes when differentiating between controls and patients with Alzheimer's disease, whereas those of CSF NSE, VLP-1, HFABP, and YKL-40 were moderate (average ratios 1\u00b728-1\u00b747). Other assessed biomarkers had only marginal effect sizes or did not differentiate between control and patient samples. The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and A\u03b242), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma A\u03b242 and A\u03b240 were not. Due to their consistency, T-tau, P-tau, A\u03b242, and NFL in CSF should be used in clinical practice and clinical research. Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's", "source": "PubMed"}, {"chunk_id": "27068280_4", "pmid": "27068280", "title": "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Olsson B, Lautner R, Andreasson U et al.", "year": "2016", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "Due to their consistency, T-tau, P-tau, A\u03b242, and NFL in CSF should be used in clinical practice and clinical research. Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten S\u00f6derberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.", "source": "PubMed"}, {"chunk_id": "34838263_0", "pmid": "34838263", "title": "Deep learning based pipelines for Alzheimer's disease diagnosis: A comparative study and a novel deep-ensemble method.", "authors": "Loddo A, Buttau S, Di Ruberto C", "year": "2022", "journal": "Computers in biology and medicine", "keywords": "Alzheimer's disease, Computer-aided diagnosis, Convolutional neural networks, Deep learning, Image classification, MRI image Analysis", "chunk": "Alzheimer's disease is a chronic neurodegenerative disease that destroys brain cells, causing irreversible degeneration of cognitive functions and dementia. Its causes are not yet fully understood, and there is no curative treatment. However, neuroimaging tools currently offer help in clinical diagnosis, and, recently, deep learning methods have rapidly become a key methodology applied to these tools. The reason is that they require little or no image preprocessing and can automatically infer an optimal representation of the data from raw images without requiring prior feature selection, resulting in a more objective and less biased process. However, training a reliable model is challenging due to the significant differences in brain image types. We aim to contribute to the research and study of Alzheimer's disease through computer-aided diagnosis (CAD) by comparing different deep learning models. In this work, there are three main objectives: i) to present a fully automated deep-ensemble approach for dementia-level", "source": "PubMed"}, {"chunk_id": "34838263_1", "pmid": "34838263", "title": "Deep learning based pipelines for Alzheimer's disease diagnosis: A comparative study and a novel deep-ensemble method.", "authors": "Loddo A, Buttau S, Di Ruberto C", "year": "2022", "journal": "Computers in biology and medicine", "keywords": "Alzheimer's disease, Computer-aided diagnosis, Convolutional neural networks, Deep learning, Image classification, MRI image Analysis", "chunk": "Alzheimer's disease through computer-aided diagnosis (CAD) by comparing different deep learning models. In this work, there are three main objectives: i) to present a fully automated deep-ensemble approach for dementia-level classification from brain images, ii) to compare different deep learning architectures to obtain the most suitable one for the task, and (iii) evaluate the robustness of the proposed strategy in a deep learning framework to detect Alzheimer's disease and recognise different levels of dementia. The proposed approach is specifically designed to be potential support for clinical care based on patients' brain images. Our strategy was developed and tested on three MRI and one fMRI public datasets with heterogeneous characteristics. By performing a comprehensive analysis of binary classification (Alzheimer's disease status or not) and multiclass classification (recognising different levels of dementia), the proposed approach can exceed state of the art in both tasks, reaching an accuracy of 98.51% in the binary", "source": "PubMed"}, {"chunk_id": "34838263_2", "pmid": "34838263", "title": "Deep learning based pipelines for Alzheimer's disease diagnosis: A comparative study and a novel deep-ensemble method.", "authors": "Loddo A, Buttau S, Di Ruberto C", "year": "2022", "journal": "Computers in biology and medicine", "keywords": "Alzheimer's disease, Computer-aided diagnosis, Convolutional neural networks, Deep learning, Image classification, MRI image Analysis", "chunk": "or not) and multiclass classification (recognising different levels of dementia), the proposed approach can exceed state of the art in both tasks, reaching an accuracy of 98.51% in the binary case, and 98.67% in the multiclass case averaged over the four different data sets. We strongly believe that integrating the proposed deep-ensemble approach will result in robust and reliable CAD systems, considering the numerous cross-dataset experiments performed. Being tested on MRIs and fMRIs, our strategy can be easily extended to other imaging techniques. In conclusion, we found that our deep-ensemble strategy could be efficiently applied for this task with a considerable potential benefit for patient management.", "source": "PubMed"}, {"chunk_id": "41828511_0", "pmid": "41828511", "title": "Can IVIG Intervene in AD? Insights from Animal Experiments and Clinical Trials-A Systematic Review and Synthesis Without Meta-Analysis.", "authors": "Zhao H, Zhang Z, Wang C et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, cognition, encephalatrophy, intravenous immunoglobulin, \u03b2-amyloid protein", "chunk": "The clinical safety of intravenous immunoglobulin (IVIG) is well-established, offering potential as a \"one-drug, multi-target\" intervention for Alzheimer's disease (AD). However, its efficacy remains inconclusive and appears closely related to specific functional properties. Therefore, we conducted a systematic review based on the analysis of prior animal and clinical trials to provide insights for future IVIG-based therapeutic development. A systematic search was conducted across PubMed, Embase, the Cochrane Library, Web of Science, PsycInfo, ClinicalTrials.gov, SinoMed, and Wanfang databases for the relevant literature published up to 30 October 2025, using terms related to Alzheimer's, IVIG, and \u03b2-amyloid protein. Consequently, IVIG demonstrated clinical safety, though methodologies-including dosages, models, and manufacturers-varied significantly across studies. In most cases, IVIG treatment delayed cognitive degradation in both AD mice and patients. Biologically, A\u03b2 and tau levels increased in plasma while decreasing in the brain or cerebrospinal fluid (CSF), suggesting a peripheral clearance mechanism distinct from that of", "source": "PubMed"}, {"chunk_id": "41828511_1", "pmid": "41828511", "title": "Can IVIG Intervene in AD? Insights from Animal Experiments and Clinical Trials-A Systematic Review and Synthesis Without Meta-Analysis.", "authors": "Zhao H, Zhang Z, Wang C et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, cognition, encephalatrophy, intravenous immunoglobulin, \u03b2-amyloid protein", "chunk": "AD mice and patients. Biologically, A\u03b2 and tau levels increased in plasma while decreasing in the brain or cerebrospinal fluid (CSF), suggesting a peripheral clearance mechanism distinct from that of monoclonal antibody interventions. Additionally, brain atrophy was alleviated, and pathological plaques were reduced. In the context of plasma exchange (PE) combination therapy, the administration of IVIG further contributed to improvements in language, memory, and praxis. IVIG possesses a favorable safety profile and can ameliorate AD symptoms, yet efficacy varies considerably between trials. To advance treatment, future research should investigate the reasons for these variances and establish a standardized system for evaluating preclinical IVIG interventions, thereby facilitating the development of specific IVIG products for AD.", "source": "PubMed"}, {"chunk_id": "35454316_0", "pmid": "35454316", "title": "Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review.", "authors": "Altuna M, Ruiz I, Zelaya MV et al.", "year": "2022", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "biomarkers, dementia, diagnosis, neurodegeneration, prion disease", "chunk": "Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5-2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on", "source": "PubMed"}, {"chunk_id": "35454316_1", "pmid": "35454316", "title": "Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review.", "authors": "Altuna M, Ruiz I, Zelaya MV et al.", "year": "2022", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "biomarkers, dementia, diagnosis, neurodegeneration, prion disease", "chunk": "such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases.", "source": "PubMed"}, {"chunk_id": "41428317_0", "pmid": "41428317", "title": "Skull-stripping induces shortcut learning in MRI-based Alzheimer's disease classification.", "authors": "Tinauer C, Sackl M, Stollberger R et al.", "year": "2025", "journal": "Insights into imaging", "keywords": "Alzheimer\u2019s disease, Explainable deep learning, Preprocessing bias, Shortcut learning", "chunk": "High classification accuracy of Alzheimer's disease (AD) from structural MRI has been achieved using deep neural networks, yet the specific image features contributing to these decisions remain unclear. In this study, the contributions of T1-weighted (T1w) gray-white matter texture, volumetric information, and preprocessing-particularly skull-stripping-were systematically assessed. A dataset of 990 matched T1w MRIs from AD patients and cognitively normal controls from the ADNI database was used. Preprocessing was varied through skull-stripping and intensity binarization to isolate texture and shape contributions. A 3D convolutional neural network was trained on each configuration, and classification performance was compared using exact McNemar tests with discrete Bonferroni-Holm correction. Feature relevance was analyzed using Layer-wise Relevance Propagation, image similarity metrics, and spectral clustering of relevance maps. Despite substantial differences in image content, classification accuracy, sensitivity, and specificity remained stable across preprocessing conditions. Models trained on binarized images preserved performance, indicating minimal reliance on gray-white matter texture.", "source": "PubMed"}, {"chunk_id": "41428317_1", "pmid": "41428317", "title": "Skull-stripping induces shortcut learning in MRI-based Alzheimer's disease classification.", "authors": "Tinauer C, Sackl M, Stollberger R et al.", "year": "2025", "journal": "Insights into imaging", "keywords": "Alzheimer\u2019s disease, Explainable deep learning, Preprocessing bias, Shortcut learning", "chunk": "Despite substantial differences in image content, classification accuracy, sensitivity, and specificity remained stable across preprocessing conditions. Models trained on binarized images preserved performance, indicating minimal reliance on gray-white matter texture. Instead, volumetric features-particularly brain contours introduced through skull-stripping-were consistently used by the models. This behavior reflects a shortcut learning phenomenon, where preprocessing artifacts act as potentially unintended cues. The resulting Clever Hans effect emphasizes the critical importance of interpretability tools to reveal hidden biases and to ensure robust and trustworthy deep learning in medical imaging. We investigated the mechanisms underlying deep learning-based disease classification using a widely utilized Alzheimer's disease dataset, and our findings reveal a reliance on features induced through skull-stripping, highlighting the need for careful preprocessing to ensure clinically relevant and interpretable models. Shortcut learning is induced by skull-stripping applied to T1-weighted MRIs. Explainable deep learning and spectral clustering estimate the bias. Highlights the importance of understanding the", "source": "PubMed"}, {"chunk_id": "41428317_2", "pmid": "41428317", "title": "Skull-stripping induces shortcut learning in MRI-based Alzheimer's disease classification.", "authors": "Tinauer C, Sackl M, Stollberger R et al.", "year": "2025", "journal": "Insights into imaging", "keywords": "Alzheimer\u2019s disease, Explainable deep learning, Preprocessing bias, Shortcut learning", "chunk": "clinically relevant and interpretable models. Shortcut learning is induced by skull-stripping applied to T1-weighted MRIs. Explainable deep learning and spectral clustering estimate the bias. Highlights the importance of understanding the dataset, image preprocessing and deep learning model, for interpretation and validation.", "source": "PubMed"}, {"chunk_id": "41607299_0", "pmid": "41607299", "title": "Alpha-Synuclein Dynamics in Cerebral Ischemia.", "authors": "Bordbar S, Molavizade S, Dehghani F et al.", "year": "2026", "journal": "ASN neuro", "keywords": "Alpha-synuclein, cerebral ischemia, ischemia, neuroinflammation, regulators, stroke", "chunk": "Cerebral ischemia is defined by insufficient blood supply to the brain and is a leading cause of mortality and neurological disability worldwide. Alpha-synuclein (\u03b1-Syn) is a protein associated with several neurodegenerative disorders, including Parkinson's disease, and has also been linked to the pathophysiology of cerebral ischemia. This narrative review provides a detailed overview of the current understanding of \u03b1-Syn in cerebral ischemia. We examine its impact on neuroinflammation, synaptic dysfunction, oxidative stress, and neuronal cell death, as well as its potential protective roles. Additionally, we explore therapeutic strategies targeting \u03b1-Syn, including pharmacological agents, gene knockdown models, and RNA-based therapies. We also discuss \u03b1-Syn expression changes in animal and human studies and its potential as a diagnostic biomarker. By clarifying the complex interplay between \u03b1-Syn and cerebral ischemia, this review aims to deepen our understanding of ischemic brain injury mechanisms and support the development of novel treatment approaches.", "source": "PubMed"}, {"chunk_id": "41607299_1", "pmid": "41607299", "title": "Alpha-Synuclein Dynamics in Cerebral Ischemia.", "authors": "Bordbar S, Molavizade S, Dehghani F et al.", "year": "2026", "journal": "ASN neuro", "keywords": "Alpha-synuclein, cerebral ischemia, ischemia, neuroinflammation, regulators, stroke", "chunk": "complex interplay between \u03b1-Syn and cerebral ischemia, this review aims to deepen our understanding of ischemic brain injury mechanisms and support the development of novel treatment approaches.", "source": "PubMed"}, {"chunk_id": "41762531_0", "pmid": "41762531", "title": "Amyloid fibrils in Alzheimer's disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid.", "authors": "Sanagi T, Okumura M, Lin Y et al.", "year": "2026", "journal": "Biophysical chemistry", "keywords": "Amyloid fibrils, A\u03b240, A\u03b242, Cortical oscillation, REM sleep", "chunk": "Alzheimer's disease (AD) is characterized by aggregation and deposition of the amyloid-beta (A\u03b2) protein in patients' brains, with aging contributing through oxidative stress and neuroinflammation. Sleep disturbances are common in patients with AD and exacerbate cognitive impairment. However, it remains unclear how aggregation of specific A\u03b2 species in distinct brain regions contributes to sleep dysfunction. To address this, we characterized amyloid fibrils formed by A\u03b21-40 (A\u03b240) and A\u03b21-42 (A\u03b242) by assessing their structural and surface properties using fluorescence, CD, and NMR spectroscopy. Their morphology was also visualized using TEM and AFM. These analyses revealed that A\u03b242 aggregates faster than A\u03b240 and forms amyloid fibrils with distinct structural, surface, and morphological properties. To investigate their effects in vivo, we bilaterally injected A\u03b240 and A\u03b242 fibrils into the hippocampus of wild-type mice and recorded the electroencephalogram and electromyogram under freely moving conditions. A\u03b242 amyloid fibrils significantly disrupted sleep architecture, particularly REM sleep,", "source": "PubMed"}, {"chunk_id": "41762531_1", "pmid": "41762531", "title": "Amyloid fibrils in Alzheimer's disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid.", "authors": "Sanagi T, Okumura M, Lin Y et al.", "year": "2026", "journal": "Biophysical chemistry", "keywords": "Amyloid fibrils, A\u03b240, A\u03b242, Cortical oscillation, REM sleep", "chunk": "A\u03b240 and A\u03b242 fibrils into the hippocampus of wild-type mice and recorded the electroencephalogram and electromyogram under freely moving conditions. A\u03b242 amyloid fibrils significantly disrupted sleep architecture, particularly REM sleep, and altered oscillations, accompanied by neuronal loss. In contrast, A\u03b240 amyloid fibrils mainly affected cortical activity with minimal neuronal loss and caused comparatively modest changes in sleep. These findings demonstrate that a single administration of A\u03b2 amyloid fibril is sufficient to alter sleep/wakefulness state and cortical oscillations. The observed effects differ depending on the type of A\u03b2 administered, suggesting that the physicochemical properties of the fibrils are closely linked to their capacity to induce sleep impairment. These findings shed light on AD-associated sleep disorders, which are differentially affected by the distinct properties of A\u03b240 and A\u03b242 aggregates.", "source": "PubMed"}, {"chunk_id": "41762531_2", "pmid": "41762531", "title": "Amyloid fibrils in Alzheimer's disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid.", "authors": "Sanagi T, Okumura M, Lin Y et al.", "year": "2026", "journal": "Biophysical chemistry", "keywords": "Amyloid fibrils, A\u03b240, A\u03b242, Cortical oscillation, REM sleep", "chunk": "distinct properties of A\u03b240 and A\u03b242 aggregates.", "source": "PubMed"}, {"chunk_id": "41295414_0", "pmid": "41295414", "title": "Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease.", "authors": "Favari E, Parolini C", "year": "2025", "journal": "Marine drugs", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, astaxanthin, immune system, marine bioactive components, multiple sclerosis, neurodegenerative diseases, neuroinflammation", "chunk": "Advances in neuroscience, immunology, and neuroimmunology have revealed that the nervous and immune systems form a bidirectional integrated network, ranging from regulating inflammation to directing stress responses, pivotal for the maintenance of the brain-body physiology. Like peripheral inflammation, neuroinflammation is a conserved process aimed at activating innate/adaptive immune and non-immune cells to effectively deal with bacteria, viruses, toxins, and injuries, and eventually at removing the microbial pathogens and supporting tissue repair and recovery. A failure of this process or the permanent release of pro-inflammatory mediators causes a condition called \"chronic low-grade neuroinflammation\" resulting in tissue damage and an increased risk of developing neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement", "source": "PubMed"}, {"chunk_id": "41295414_1", "pmid": "41295414", "title": "Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease.", "authors": "Favari E, Parolini C", "year": "2025", "journal": "Marine drugs", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, astaxanthin, immune system, marine bioactive components, multiple sclerosis, neurodegenerative diseases, neuroinflammation", "chunk": "(ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement in the pathogenesis and progression of AD, PD, MS, and ALS. Then, we discuss the potential therapeutic efficacy of select marine-derived bioactive components.", "source": "PubMed"}, {"chunk_id": "41720088_0", "pmid": "41720088", "title": "Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer's disease.", "authors": "Luo S, Liu H, Xiao T et al.", "year": "2026", "journal": "Cell reports. Medicine", "keywords": "Alzheimer\u2019s disease, PPP2R5C, Tau, autophagy, biomarker", "chunk": "Early intervention is the most effective strategy to impede the progression of Alzheimer's disease (AD), depending on the identification of early diagnostic biomarkers. Here, we isolate neuron-derived exosomes (NDEs) from plasma of familial AD (FAD), presymptomatic FAD (pre-FAD), and healthy controls (cognitively normal [CN]), followed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A specific peptide from protein phosphatase 2 regulatory subunit B'\u03b2 (PPP2R5C) shows a progressive decrease from CN to pre-FAD and FAD patients. This decline is further validated in plasma NDEs and brain tissue from amnestic mild cognitive impairment (aMCI) and sporadic AD (SAD) patients. Two independent cohorts confirm the early and differential diagnostic value of plasma PPP2R5C. Immunohistochemistry of Tau Braak-staged brains reveals PPP2R5C reduction preceding Tau hyperphosphorylation. Mechanistically, PPP2R5C interacts with Tau, reducing Tau levels and phosphorylation via unc-51-like kinase 1 (ULK1)-dependent autophagolysosomal activation and PP2A regulation. Our findings suggest that plasma PPP2R5C has the potential", "source": "PubMed"}, {"chunk_id": "41720088_1", "pmid": "41720088", "title": "Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer's disease.", "authors": "Luo S, Liu H, Xiao T et al.", "year": "2026", "journal": "Cell reports. Medicine", "keywords": "Alzheimer\u2019s disease, PPP2R5C, Tau, autophagy, biomarker", "chunk": "hyperphosphorylation. Mechanistically, PPP2R5C interacts with Tau, reducing Tau levels and phosphorylation via unc-51-like kinase 1 (ULK1)-dependent autophagolysosomal activation and PP2A regulation. Our findings suggest that plasma PPP2R5C has the potential to serve as an ideal biomarker for the early diagnosis of AD.", "source": "PubMed"}, {"chunk_id": "41298940_0", "pmid": "41298940", "title": "Neuropathologic correlates of cognitive impairment in Alzheimer's disease with discordant CSF biomarker profiles: co-pathologies in focus.", "authors": "Ioannou K, Perrin RJ, Abdullaieva K et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "ADNC, AT biomarker system, Alzheimer, CSF, Co-pathologies, p-tau, \u03b2-amyloid", "chunk": "CSF A\u03b2 reflects Alzheimer's disease neuropathologic change (ADNC), while CSF p-tau offers an indirect indication of tangle pathology. However, interpretation can be challenging when cognitive impairment is present alongside A\u03b2 positivity (\u0391 +) but p-tau negativity (T -). We examined neuropathologic differences between CSF A + T - and A + T + profiles, defined by CSF A\u03b242 and p-tau181 levels, hypothesizing that cognitively impaired older adults with a CSF A + T - profile would exhibit a greater co-pathology burden, suggesting alternative contributing disease processes. We identified 77 ADNI participants with available CSF biomarkers and neuropathologic assessments (median age = 79.8 years; IQR = 74.7-84.5). Depending on the presence-alone or in combination-of ADNC intermediate/high and non-ADNC pathologies (e.g., Lewy bodies (LB), argyrophilic grain disease (AGD), limbic-predominant age-related TDP-43 encephalopathy-neuropathologic change (LATE-NC)), individuals were classified as ADNC dominant, mixed ADNC, or non-ADNC dominant. The two CSF A + profiles were", "source": "PubMed"}, {"chunk_id": "41298940_1", "pmid": "41298940", "title": "Neuropathologic correlates of cognitive impairment in Alzheimer's disease with discordant CSF biomarker profiles: co-pathologies in focus.", "authors": "Ioannou K, Perrin RJ, Abdullaieva K et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "ADNC, AT biomarker system, Alzheimer, CSF, Co-pathologies, p-tau, \u03b2-amyloid", "chunk": "bodies (LB), argyrophilic grain disease (AGD), limbic-predominant age-related TDP-43 encephalopathy-neuropathologic change (LATE-NC)), individuals were classified as ADNC dominant, mixed ADNC, or non-ADNC dominant. The two CSF A + profiles were similar in demographics, frequency of cognitive impairment, longitudinal cognitive performance, clinical comorbidities, CSF A\u03b242 levels, CSF \u03b1-synuclein positivity rates, and A\u03b2 PET burden. ADNC intermediate/high was significantly more frequent in the CSF A + T + profile than in the CSF A + T - profile (100% vs. 78%, p value = 0.008). The most common co-pathologies contributing to cognitive impairment in the CSF A + T - profile were LATE-NC (stages 2-3) (47%), LB limbic/neocortical (44%), and AGD (stages II-III) (33%), while in the CSF A + T + profile, LB limbic/neocortical (28%) and LATE-NC (stages 2-3) (22%) predominated. The CSF A + T - profile showed 17% ADNC dominant, 61% mixed ADNC, and 22% non-ADNC dominant pathology, whereas", "source": "PubMed"}, {"chunk_id": "41298940_2", "pmid": "41298940", "title": "Neuropathologic correlates of cognitive impairment in Alzheimer's disease with discordant CSF biomarker profiles: co-pathologies in focus.", "authors": "Ioannou K, Perrin RJ, Abdullaieva K et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "ADNC, AT biomarker system, Alzheimer, CSF, Co-pathologies, p-tau, \u03b2-amyloid", "chunk": "profile, LB limbic/neocortical (28%) and LATE-NC (stages 2-3) (22%) predominated. The CSF A + T - profile showed 17% ADNC dominant, 61% mixed ADNC, and 22% non-ADNC dominant pathology, whereas the CSF A + T + profile showed 51% ADNC dominant and 49% mixed ADNC pathology (p = 0.001). Within the mixed ADNC subgroup, individuals with a CSF A + T - profile more often exhibited two or more non-ADNC co-pathologies compared to those with a CSF A + T + profile (73% vs. 21%, p = 0.009). Despite clinical similarities among cognitively impaired individuals with CSF A + T - and A + T + profiles, the CSF A + T - profile may reflect a greater burden of non-ADNC pathology. Extending biomarker profiling beyond A\u03b2 and tau may facilitate more personalized care.", "source": "PubMed"}, {"chunk_id": "41298940_3", "pmid": "41298940", "title": "Neuropathologic correlates of cognitive impairment in Alzheimer's disease with discordant CSF biomarker profiles: co-pathologies in focus.", "authors": "Ioannou K, Perrin RJ, Abdullaieva K et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "ADNC, AT biomarker system, Alzheimer, CSF, Co-pathologies, p-tau, \u03b2-amyloid", "chunk": "non-ADNC pathology. Extending biomarker profiling beyond A\u03b2 and tau may facilitate more personalized care.", "source": "PubMed"}, {"chunk_id": "39122449_0", "pmid": "39122449", "title": "COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.", "authors": "Shyam S, G\u00f3mez-Mart\u00ednez C, Ni J et al.", "year": "2024", "journal": "Aging and disease", "keywords": "None", "chunk": "Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m<sup>2</sup>, harboring \u2265 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear", "source": "PubMed"}, {"chunk_id": "39122449_1", "pmid": "39122449", "title": "COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.", "authors": "Shyam S, G\u00f3mez-Mart\u00ednez C, Ni J et al.", "year": "2024", "journal": "Aging and disease", "keywords": "None", "chunk": "General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (\u03b2adj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However,", "source": "PubMed"}, {"chunk_id": "39122449_2", "pmid": "39122449", "title": "COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.", "authors": "Shyam S, G\u00f3mez-Mart\u00ednez C, Ni J et al.", "year": "2024", "journal": "Aging and disease", "keywords": "None", "chunk": "and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.", "source": "PubMed"}, {"chunk_id": "40968567_0", "pmid": "40968567", "title": "Bidirectional impact of dementia and aspiration pneumonia on cognitive decline in older adults: A retrospective cohort analysis.", "authors": "Xu J, Meng R, Yan J et al.", "year": "2025", "journal": "Geriatrics & gerontology international", "keywords": "aspiration pneumonia, cognitive decline, dementia, swallowing dysfunction", "chunk": "Dementia and aspiration pneumonia are common and debilitating conditions in older adults. While both are significant contributors to morbidity and mortality, the interaction between these conditions remains inadequately understood. This study aimed to explore the bidirectional relationship between dementia and aspiration pneumonia and to assess its impact on cognitive decline in older patients. A retrospective cohort analysis of 500 elderly dementia patients at a tertiary care center (2018--2022) was conducted, and participants were classified by aspiration pneumonia occurrence. Cognitive function was assessed via the Mini-Mental State Examination (MMSE) at baseline and follow-up, with Kaplan-Meier analysis evaluating time-to-pneumonia and Cox regression modeling of bidirectional relationships while adjusting for confounders. Among 500 dementia patients (mean age 78.3 \u00b1 7.2 years), Kaplan-Meier analysis revealed significantly earlier pneumonia onset in severe dementia patients (log-rank P < 0.001), with Cox regression showing that severe dementia conferred triple the pneumonia risk (hazard ratio [HR] = 3.01,", "source": "PubMed"}, {"chunk_id": "40968567_1", "pmid": "40968567", "title": "Bidirectional impact of dementia and aspiration pneumonia on cognitive decline in older adults: A retrospective cohort analysis.", "authors": "Xu J, Meng R, Yan J et al.", "year": "2025", "journal": "Geriatrics & gerontology international", "keywords": "aspiration pneumonia, cognitive decline, dementia, swallowing dysfunction", "chunk": "revealed significantly earlier pneumonia onset in severe dementia patients (log-rank P < 0.001), with Cox regression showing that severe dementia conferred triple the pneumonia risk (hazard ratio [HR] = 3.01, 95% confidence interval [CI]: 2.15-4.21) and that swallowing dysfunction independently increased the hazard ratio 3.45-fold (95% CI: 2.61-4.55); aspiration pneumonia accelerated cognitive decline (\u03b2 = -2.35, 95% CI: -3.12 to -1.58). This study revealed that dementia severity substantially increases time-dependent pneumonia hazard (severe dementia HR = 3.01), while pneumonia accelerates cognitive deterioration, forming a bidirectional cycle amplified by swallowing dysfunction. Early dysphagia management and pneumonia prevention strategies are crucial for disrupting this progression in older adults. Geriatr Gerontol Int 2025; 25: 1481-1487.", "source": "PubMed"}, {"chunk_id": "41530426_0", "pmid": "41530426", "title": "Real-world evidence from 50,000 online participants using MoCA-XpressO for cognitive prescreening.", "authors": "Huijbers W, Wischmann HA, Gruber J et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive prescreening, Digital cognitive test", "chunk": "XpressO is a digital cognitive prescreening tool developed by Montreal Cognition (MoCA Test Inc.). In this study, we evaluated real-world online data collected through XpressO in 2024 and early 2025, based on over 50,000 self-enrolled online participants. In line with expectations, we found that the XpressO score-which predicts screening positive for (mild) cognitive impairment-is associated with sex, age, and education. The results indicated that women have a 5.8% [5.3%, 6.3%] lower relative risk of prescreening positive for cognitive impairment, each additional year of age increases the relative risk by 0.59% [0.57%, 0.60%], whereas each year of education decreases the relative risk by 0.99% [0.94%, 1.06%]. We also visualized and quantified interaction effects among these demographic variables as predictors of the XpressO score. While the interaction effect between sex and age was not statistically significant, all other interaction terms, including the three-way interaction between sex, age, and education, were significantly associated", "source": "PubMed"}, {"chunk_id": "41530426_1", "pmid": "41530426", "title": "Real-world evidence from 50,000 online participants using MoCA-XpressO for cognitive prescreening.", "authors": "Huijbers W, Wischmann HA, Gruber J et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive prescreening, Digital cognitive test", "chunk": "XpressO score. While the interaction effect between sex and age was not statistically significant, all other interaction terms, including the three-way interaction between sex, age, and education, were significantly associated with the XpressO score. Additionally, adjusting for demographic factors reduced the observed effect of potential confounders, the language and the platform used. However, when we evaluated a score adjusted for demographics in a clinical cohort of 101 participants, we found that this adjustment slightly but significantly reduced the discriminatory power of the XpressO tool in identifying individuals with cognitive impairment from 0.86 to 0.81. These findings from a real-world online cohort offer novel insights into the complex influence of demographic factors on digital cognitive prescreening. Moreover, they demonstrate that XpressO is a viable tool for online prescreening and can help streamline the diagnostic pathway for individuals who may be eligible for disease-modifying treatments for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41530426_2", "pmid": "41530426", "title": "Real-world evidence from 50,000 online participants using MoCA-XpressO for cognitive prescreening.", "authors": "Huijbers W, Wischmann HA, Gruber J et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive prescreening, Digital cognitive test", "chunk": "is a viable tool for online prescreening and can help streamline the diagnostic pathway for individuals who may be eligible for disease-modifying treatments for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "40598606_0", "pmid": "40598606", "title": "Safety, tolerability, pharmacokinetic and pharmacodynamic effects of the muscarinic M<sub>1</sub> positive allosteric modulator VU0467319 for Alzheimer's disease: a single ascending-dose study in healthy participants.", "authors": "Conley AC, Key AP, Blackford JU et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Metabolism, Muscarinic acetylcholine receptor subtype 1 (M1), Pharmacodynamics, Pharmacokinetics, Positive allosteric modulator (PAM)", "chunk": "The development of cholinergic neurotransmitter based cognitive enhancers for Alzheimer's disease and other neuropsychiatric disorders have focused recently on allosteric modulation of specific muscarinic acetylcholine receptor (mAChR) subtypes to reduce dose-limiting side-effects that have been the hallmark of earlier orthosteric mAChR agonists. VU0467319 (VU319) is an investigational positive allosteric modulator of the M<sub>1</sub> mAChR. A Phase 1 first-in-human study was conducted assessing safety and brain activity utilizing cognitive tasks and event-related potentials (ERPs) in single-ascending dose and food effect studies. VU319 was given orally to 52 healthy volunteers aged 18-55 years. The single ascending dose study tested 40 participants in five dose escalating cohorts (60, 120, 240, 400, 600 mg; 6 VU319/2 placebo per dose). The food effect study involved 12 participants, 10 VU319 (120 mg)/2 placebo. Exploratory cognitive and electrophysiological tasks were examined pre-dosing and at 5 h post-dose. Tolerability was good with no observed dose limiting side effects", "source": "PubMed"}, {"chunk_id": "40598606_1", "pmid": "40598606", "title": "Safety, tolerability, pharmacokinetic and pharmacodynamic effects of the muscarinic M<sub>1</sub> positive allosteric modulator VU0467319 for Alzheimer's disease: a single ascending-dose study in healthy participants.", "authors": "Conley AC, Key AP, Blackford JU et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Metabolism, Muscarinic acetylcholine receptor subtype 1 (M1), Pharmacodynamics, Pharmacokinetics, Positive allosteric modulator (PAM)", "chunk": "12 participants, 10 VU319 (120 mg)/2 placebo. Exploratory cognitive and electrophysiological tasks were examined pre-dosing and at 5 h post-dose. Tolerability was good with no observed dose limiting side effects throughout the full dose range tested. In the single ascending dose study, there were 47 TEAEs reported across the 5 cohorts, 14 in the placebo group and 33 across the 5 active dose cohorts. In the food effect study, there were 20 TEAEs reported, 6 in the placebo group and 14 in the fed and fasted conditions. Drug exposure increased with dose in a less than dose-proportional manner with a half-life ranging from 30 to 55 h. Peak concentration was observed between 5 and 9.5 h across the dosage groups. Absorption was increased with food. Exploratory cognitive/ERP testing showed evidence for drug-induced CNS activity on higher doses of VU319 compared to placebo. Single dose VU319 across five ascending cohorts appeared", "source": "PubMed"}, {"chunk_id": "40598606_2", "pmid": "40598606", "title": "Safety, tolerability, pharmacokinetic and pharmacodynamic effects of the muscarinic M<sub>1</sub> positive allosteric modulator VU0467319 for Alzheimer's disease: a single ascending-dose study in healthy participants.", "authors": "Conley AC, Key AP, Blackford JU et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Metabolism, Muscarinic acetylcholine receptor subtype 1 (M1), Pharmacodynamics, Pharmacokinetics, Positive allosteric modulator (PAM)", "chunk": "Absorption was increased with food. Exploratory cognitive/ERP testing showed evidence for drug-induced CNS activity on higher doses of VU319 compared to placebo. Single dose VU319 across five ascending cohorts appeared to have a favorable safety profile and a PK profile consistent with once daily dosing. Target engagement results suggest stimulation of the cholinergic system functioning in healthy adults following a single dose of VU319. These results provide a strong foundation for further studies of positive allosteric modulators of muscarinic M<sub>1</sub> receptors for potential cognitive or behavioral benefits.", "source": "PubMed"}, {"chunk_id": "33383712_0", "pmid": "33383712", "title": "Alzheimer's Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology.", "authors": "Agarwal M, Alam MR, Haider MK et al.", "year": "2020", "journal": "Nanomaterials (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, blood\u2013brain barrier, drug delivery, nanotechnological approaches, neurodegeneration", "chunk": "Alzheimer's disease (AD), a progressively fatal neurodegenerative disorder, is the most prominent form of dementia found today. Patients suffering from Alzheimer's begin to show the signs and symptoms, like decline in memory and cognition, long after the cellular damage has been initiated in their brain. There are several hypothesis for the neurodegeneration process; however, the lack of availability of in vivo models makes the recapitulation of AD in humans impossible. Moreover, the drugs currently available in the market serve to alleviate the symptoms and there is no cure for the disease. There have been two major hurdles in the process of finding the same-the inefficiency in cracking the complexity of the disease pathogenesis and the inefficiency in delivery of drugs targeted for AD. This review discusses the different drugs that have been designed over the recent years and the drug delivery options in the field of nanotechnology that have been", "source": "PubMed"}, {"chunk_id": "33383712_1", "pmid": "33383712", "title": "Alzheimer's Disease: An Overview of Major Hypotheses and Therapeutic Options in Nanotechnology.", "authors": "Agarwal M, Alam MR, Haider MK et al.", "year": "2020", "journal": "Nanomaterials (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, blood\u2013brain barrier, drug delivery, nanotechnological approaches, neurodegeneration", "chunk": "targeted for AD. This review discusses the different drugs that have been designed over the recent years and the drug delivery options in the field of nanotechnology that have been found most feasible in surpassing the blood-brain barrier (BBB) and reaching the brain.", "source": "PubMed"}, {"chunk_id": "41440520_0", "pmid": "41440520", "title": "Neurocognitive Impairment in Idiopathic Pulmonary Fibrosis: A Systematic Review of Current Evidence.", "authors": "Mihart D, Crisan AF, Carunta V et al.", "year": "2025", "journal": "Medical sciences (Basel, Switzerland)", "keywords": "cognitive impairment, executive function, idiopathic pulmonary fibrosis, neuropsychological assessment, working memory", "chunk": "Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a major impact on respiratory function, but also with possible underestimated effects on cognitive function. Although interest in cognitive impairment in chronic respiratory diseases, such as COPD, has increased, data on IPF remain limited and heterogeneous. This systematic review aimed to synthesize current evidence on cognitive impairment in IPF, identify the most affected domains, and evaluate the certainty of evidence using standardized methodological tools. A systematic review was conducted according to PRISMA 2020, with a registered PROSPERO protocol (CRD420251041866). Four databases (PubMed, Scopus, Web of Science, Cochrane Library) were searched for studies from 2014 to 2025. Methodological quality and certainty of evidence were appraised with the Joanna Briggs Institute (JBI) and GRADE frameworks. Four studies met the inclusion criteria (two cross-sectional, one descriptive, one case-control). Across investigations, working and verbal memory emerged as the most consistently impaired domains, followed by processing", "source": "PubMed"}, {"chunk_id": "41440520_1", "pmid": "41440520", "title": "Neurocognitive Impairment in Idiopathic Pulmonary Fibrosis: A Systematic Review of Current Evidence.", "authors": "Mihart D, Crisan AF, Carunta V et al.", "year": "2025", "journal": "Medical sciences (Basel, Switzerland)", "keywords": "cognitive impairment, executive function, idiopathic pulmonary fibrosis, neuropsychological assessment, working memory", "chunk": "GRADE frameworks. Four studies met the inclusion criteria (two cross-sectional, one descriptive, one case-control). Across investigations, working and verbal memory emerged as the most consistently impaired domains, followed by processing speed and executive function, whereas visuospatial and language abilities were less frequently affected. Cognitive impairment was present even in mild IPF and became more pronounced with lower DLCO, shorter 6 min walk distance, greater desaturation, and obstructive sleep apnea. Certainty of evidence ranged from low to moderate due to small samples and heterogeneous testing. Cognitive dysfunction, particularly in memory, attention, and executive domains, is a frequent but under-recognized feature of IPF. Routine screening with brief, validated tools such as the MoCA may facilitate early detection and guide individualized rehabilitation.", "source": "PubMed"}, {"chunk_id": "41718203_0", "pmid": "41718203", "title": "Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.", "authors": "Grzybowska-Ganszczyk D, Myler A, Nowak-Lis A et al.", "year": "2026", "journal": "Journal of functional morphology and kinesiology", "keywords": "Parkinson\u2019s disease, biomarkers, cognitive functions, hypoxia, juggling, visuomotor coordination", "chunk": "Parkinson's disease (PD) is a heterogeneous clinical syndrome representing the final stage of a complex and long-lasting neurodegenerative process that involves not only dysfunction of the dopaminergic system but also impairments in other neurotransmitter systems. The diversity of the clinical presentation of PD, together with the existence of Parkinsonian syndromes and atypical Parkinsonism-such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB)-has important implications for rehabilitation outcomes and underscores the need for individualized, stage-dependent therapeutic approaches. Juggling is a complex motor activity that integrates cognitive, visuomotor, and balance processes, requiring a high level of concentration, precision, and motor adaptation. In recent years, there has been growing interest in this form of activity as a potential tool for supporting neuroplasticity, cognitive functions, and neurological rehabilitation. The aim of this review was to summarize current scientific evidence on the effects of juggling training on cognitive functions,", "source": "PubMed"}, {"chunk_id": "41718203_1", "pmid": "41718203", "title": "Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.", "authors": "Grzybowska-Ganszczyk D, Myler A, Nowak-Lis A et al.", "year": "2026", "journal": "Journal of functional morphology and kinesiology", "keywords": "Parkinson\u2019s disease, biomarkers, cognitive functions, hypoxia, juggling, visuomotor coordination", "chunk": "potential tool for supporting neuroplasticity, cognitive functions, and neurological rehabilitation. The aim of this review was to summarize current scientific evidence on the effects of juggling training on cognitive functions, visuomotor coordination, and balance, as well as to discuss the potential benefits of combining it with controlled hypoxia in patients with Parkinson's disease (PD). This narrative review additionally considers how disease heterogeneity and stage of progression may influence the effectiveness of such multimodal interventions. This paper reviews the literature concerning the neurophysiological basis of learning to juggle and the mechanisms of brain plasticity, including increases in gray matter volume, improvements in white matter integrity, and reorganization of neuronal networks in motor and associative regions. Attention is drawn to the synergistic potential of combining juggling training with exposure to moderate, controlled hypoxia, which may induce an adaptive response involving the transcription factor HIF-1\u03b1, enhance the expression of brain-derived neurotrophic factor (BDNF),", "source": "PubMed"}, {"chunk_id": "41718203_2", "pmid": "41718203", "title": "Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.", "authors": "Grzybowska-Ganszczyk D, Myler A, Nowak-Lis A et al.", "year": "2026", "journal": "Journal of functional morphology and kinesiology", "keywords": "Parkinson\u2019s disease, biomarkers, cognitive functions, hypoxia, juggling, visuomotor coordination", "chunk": "potential of combining juggling training with exposure to moderate, controlled hypoxia, which may induce an adaptive response involving the transcription factor HIF-1\u03b1, enhance the expression of brain-derived neurotrophic factor (BDNF), and promote angiogenesis and mitochondrial biogenesis. Although juggling and hypoxia are not directly related to training stimuli, both interventions activate overlapping and complementary neuroplastic pathways, providing a conceptual rationale for their parallel consideration and potential integration within future rehabilitation protocols. Juggling delivers task-specific motor-cognitive learning, whereas hypoxia may amplify molecular plasticity signaling, potentially enhancing responsiveness to motor interventions, particularly in patients at early stages of PD when compensatory mechanisms and neuroplastic capacity are relatively preserved. Findings from existing studies suggest that juggling under controlled hypoxic conditions may represent an innovative, safe, and multimodal form of training that supports both cognitive and motor components. Such effects may be particularly relevant in patients at early stages of PD, when compensatory mechanisms and", "source": "PubMed"}, {"chunk_id": "41718203_3", "pmid": "41718203", "title": "Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.", "authors": "Grzybowska-Ganszczyk D, Myler A, Nowak-Lis A et al.", "year": "2026", "journal": "Journal of functional morphology and kinesiology", "keywords": "Parkinson\u2019s disease, biomarkers, cognitive functions, hypoxia, juggling, visuomotor coordination", "chunk": "safe, and multimodal form of training that supports both cognitive and motor components. Such effects may be particularly relevant in patients at early stages of PD, when compensatory mechanisms and neuroplastic potential are relatively preserved. Such an intervention may contribute to improvements in balance, attention, executive functions, and cognitive flexibility, which is particularly relevant in the context of rehabilitation for patients with neurodegenerative diseases. Importantly, to date, no randomized clinical trials have directly examined juggling performed under controlled hypoxic conditions in PD. Therefore, the present concept should be regarded as translational and exploratory, integrating evidence from juggling-induced neuroplasticity and hypoxia-related physiological adaptations. In this context, the proposed approach represents a proof-of-concept framework for future multimodal interventions rather than an established therapeutic strategy. Available evidence suggests that combining complex sensorimotor skill training with physiological modulation of the internal environment may constitute a novel direction in PD rehabilitation, extending beyond conventional exercise-based", "source": "PubMed"}, {"chunk_id": "41718203_4", "pmid": "41718203", "title": "Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.", "authors": "Grzybowska-Ganszczyk D, Myler A, Nowak-Lis A et al.", "year": "2026", "journal": "Journal of functional morphology and kinesiology", "keywords": "Parkinson\u2019s disease, biomarkers, cognitive functions, hypoxia, juggling, visuomotor coordination", "chunk": "therapeutic strategy. Available evidence suggests that combining complex sensorimotor skill training with physiological modulation of the internal environment may constitute a novel direction in PD rehabilitation, extending beyond conventional exercise-based models. Despite promising reports, further well-designed clinical studies are needed to determine the optimal training parameters (frequency, intensity, duration, and degree of hypoxia), to evaluate the long-term sustainability of therapeutic effects, and to account for the heterogeneity of PD and related Parkinsonian disorders.", "source": "PubMed"}, {"chunk_id": "39512702_0", "pmid": "39512702", "title": "Lecanemab: Appropriate Use Recommendations by Korean Dementia Association.", "authors": "Park KH, Kim GH, Kim CH et al.", "year": "2024", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer's Disease, Amyloid, Lecanemab, Magnetic Resonance Imaging, Monoclonal Antibody", "chunk": "Lecanemab (product name Leqembi\u00ae) is an anti-amyloid monoclonal antibody treatment approved for use in Korea for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. The Korean Dementia Association has created recommendations for the appropriate use of lecanemab to assist clinicians. These recommendations include selecting patients for administration, necessary pre-administration tests and preparations, administration methods, monitoring for amyloid related imaging abnormalities (ARIA), and communication with patients and caregivers. Lecanemab is recommended for patients with MCI or mild dementia who confirmed positive amyloid biomarkers, and should not be administered to patients with severe hypersensitivity to lecanemab or those unable to undergo magnetic resonance imaging (MRI) evaluation. To predict the risk of ARIA before administration, apolipoprotein E genotyping is conducted, and regular brain MRI evaluations are recommended to monitor for ARIA during treatment. The most common adverse reactions are infusion-related reactions, which require appropriate management upon occurrence. Additional", "source": "PubMed"}, {"chunk_id": "39512702_1", "pmid": "39512702", "title": "Lecanemab: Appropriate Use Recommendations by Korean Dementia Association.", "authors": "Park KH, Kim GH, Kim CH et al.", "year": "2024", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer's Disease, Amyloid, Lecanemab, Magnetic Resonance Imaging, Monoclonal Antibody", "chunk": "is conducted, and regular brain MRI evaluations are recommended to monitor for ARIA during treatment. The most common adverse reactions are infusion-related reactions, which require appropriate management upon occurrence. Additional caution is needed when co-administering with anticoagulants or tissue plasminogen activator due to the risk of macrohemorrhage. Clinicians should consider the efficacy and necessary conditions for administration, as well as the safety of lecanemab, to make a comprehensive decision regarding its use.", "source": "PubMed"}, {"chunk_id": "40947752_0", "pmid": "40947752", "title": "Association of Early Life Risk Factors and APOE \u03b54 With Incident Dementia: Evidence From 14\u2009Years of U.S. Data.", "authors": "Choi EY, Cho G, Chang VW", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "APOE \u03b54, childhood exposure, dementia, gene\u2013environment interaction", "chunk": "Early life is a critical period for brain development, laying the foundation for cognitive reserve. However, it remains unclear how various aspects of early life independently contribute to dementia risk, and whether these associations are modified by APOE \u03b54 genotype. We used data from the U.S. Health and Retirement Study (HRS), a nationally representative cohort of older adults, followed from 2006 to 2020. Our sample included 8678 community-dwelling, dementia-free participants aged \u2265 60 and < 90 at baseline with data on APOE genotype and retrospective early life conditions. Dementia incidence was classified using the validated Langa-Weir algorithm. Early life risk domains included financial capital, social capital, human capital, adversity, and health conditions. Cause-specific Cox proportional hazards models assessed the associations between these domains and incident dementia, adjusting for demographics and adulthood risk factors. To examine effect modification by genetic risk, we created 4-category group variables combining APOE \u03b54 status and", "source": "PubMed"}, {"chunk_id": "40947752_1", "pmid": "40947752", "title": "Association of Early Life Risk Factors and APOE \u03b54 With Incident Dementia: Evidence From 14\u2009Years of U.S. Data.", "authors": "Choi EY, Cho G, Chang VW", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "APOE \u03b54, childhood exposure, dementia, gene\u2013environment interaction", "chunk": "between these domains and incident dementia, adjusting for demographics and adulthood risk factors. To examine effect modification by genetic risk, we created 4-category group variables combining APOE \u03b54 status and early life risk. Deficits in financial, social, and human capital, as well as poor childhood health, were each associated with a 12%-46% increased dementia risk, independently of APOE \u03b54 status. After further adjusting for adulthood risk factors, low social and human capital remained significant predictors (16% and 21% increased risk, respectively). APOE \u03b54 was associated with an 83%-86% increased risk across all models. In effect modification analyses, early life disadvantage was associated with dementia only among non-carriers of APOE \u03b54, whereas \u03b54 carriers had elevated dementia risk regardless of early life conditions. Inadequate childhood resources may have enduring impacts on dementia risk among individuals without the APOE \u03b54 allele. Genetic predisposition via APOE \u03b54 overwhelms the influence of early life", "source": "PubMed"}, {"chunk_id": "40947752_2", "pmid": "40947752", "title": "Association of Early Life Risk Factors and APOE \u03b54 With Incident Dementia: Evidence From 14\u2009Years of U.S. Data.", "authors": "Choi EY, Cho G, Chang VW", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "APOE \u03b54, childhood exposure, dementia, gene\u2013environment interaction", "chunk": "life conditions. Inadequate childhood resources may have enduring impacts on dementia risk among individuals without the APOE \u03b54 allele. Genetic predisposition via APOE \u03b54 overwhelms the influence of early life disadvantage. These findings underscore the need for dementia prevention strategies that jointly consider genetic vulnerability and early life conditions.", "source": "PubMed"}, {"chunk_id": "33739235_0", "pmid": "33739235", "title": "Potential value and impact of data mining and machine learning in clinical diagnostics.", "authors": "Saberi-Karimian M, Khorasanchi Z, Ghazizadeh H et al.", "year": "2021", "journal": "Critical reviews in clinical laboratory sciences", "keywords": "Data mining, decision tree, machine learning", "chunk": "Data mining involves the use of mathematical sciences, statistics, artificial intelligence, and machine learning to determine the relationships between variables from a large sample of data. It has previously been shown that data mining can improve the prediction and diagnostic precision of type 2 diabetes mellitus. A few studies have applied machine learning to assess hypertension and metabolic syndrome-related biomarkers, as well as refine the assessment of cardiovascular disease risk. Machine learning methods have also been applied to assess new biomarkers and survival outcomes in patients with renal diseases to predict the development of chronic kidney disease, disease progression, and renal graft survival. In the latter, random forest methods were found to be the best for the prediction of chronic kidney disease. Some studies have investigated the prognosis of nonalcoholic fatty liver disease and acute liver failure, as well as therapy response prediction in patients with viral disorders, using decision", "source": "PubMed"}, {"chunk_id": "33739235_1", "pmid": "33739235", "title": "Potential value and impact of data mining and machine learning in clinical diagnostics.", "authors": "Saberi-Karimian M, Khorasanchi Z, Ghazizadeh H et al.", "year": "2021", "journal": "Critical reviews in clinical laboratory sciences", "keywords": "Data mining, decision tree, machine learning", "chunk": "kidney disease. Some studies have investigated the prognosis of nonalcoholic fatty liver disease and acute liver failure, as well as therapy response prediction in patients with viral disorders, using decision tree models. Machine learning techniques, such as Sparse High-Order Interaction Model with Rejection Option, have been used for diagnosing Alzheimer's disease. Data mining techniques have also been applied to identify the risk factors for serious mental illness, such as depression and dementia, and help to diagnose and predict the quality of life of such patients. In relation to child health, some studies have determined the best algorithms for predicting obesity and malnutrition. Machine learning has determined the important risk factors for preterm birth and low birth weight. Published studies of patients with cancer and bacterial diseases are limited and should perhaps be addressed more comprehensively in future studies. Herein, we provide an in-depth review of studies in which biochemical biomarker", "source": "PubMed"}, {"chunk_id": "33739235_2", "pmid": "33739235", "title": "Potential value and impact of data mining and machine learning in clinical diagnostics.", "authors": "Saberi-Karimian M, Khorasanchi Z, Ghazizadeh H et al.", "year": "2021", "journal": "Critical reviews in clinical laboratory sciences", "keywords": "Data mining, decision tree, machine learning", "chunk": "patients with cancer and bacterial diseases are limited and should perhaps be addressed more comprehensively in future studies. Herein, we provide an in-depth review of studies in which biochemical biomarker data were analyzed using machine learning methods to assess the risk of several common diseases, in order to summarize the potential applications of data mining methods in clinical diagnosis. Data mining techniques have now been increasingly applied to clinical diagnostics, and they have the potential to support this field.", "source": "PubMed"}, {"chunk_id": "41047654_0", "pmid": "41047654", "title": "[Precautions for Neurosurgeons in Administering Anti-Amyloid \u03b2 Antibody Therapy].", "authors": "Shichijo F", "year": "2025", "journal": "No shinkei geka. Neurological surgery", "keywords": "None", "chunk": "In Japan, anti-amyloid \u03b2 (A\u03b2) monoclonal antibodies, including lecanemab and donanemab, have recently been approved as disease-modifying therapies for early-stage Alzheimer's disease (AD). These drugs, developed based on the amyloid cascade hypothesis, target toxic A\u03b2 aggregates: lecanemab selectively binds to soluble protofibrils, while donanemab targets A\u03b2 plaques. The Ministry of Health, Labour and Welfare (MHLW) has issued Optimal Use Guidelines that specify criteria for administration: informed consent from both patients and caregivers; cognitive assessments (MMSE and CDR); confirmation of A\u03b2 pathology via amyloid PET or cerebrospinal fluid (CSF) testing; and MRI screening to assess the risk of amyloid-related imaging abnormalities (ARIA). ARIA is a significant adverse event and requires regular MRI monitoring. Initial administration is limited to certified facilities staffed by experienced specialists and equipped with the necessary diagnostic infrastructure. After six months, treatment may be continued at collaborating institutions. The APOE\u03b54 genotype is a known risk factor for ARIA", "source": "PubMed"}, {"chunk_id": "41047654_1", "pmid": "41047654", "title": "[Precautions for Neurosurgeons in Administering Anti-Amyloid \u03b2 Antibody Therapy].", "authors": "Shichijo F", "year": "2025", "journal": "No shinkei geka. Neurological surgery", "keywords": "None", "chunk": "by experienced specialists and equipped with the necessary diagnostic infrastructure. After six months, treatment may be continued at collaborating institutions. The APOE\u03b54 genotype is a known risk factor for ARIA but is not covered by insurance. Caution is advised when co-administering anticoagulants or antiplatelet agents. The guidelines also require the use of official treatment cards to inform healthcare providers. This article summarizes the clinical precautions, diagnostic requirements, and facility standards necessary for implementing anti-A\u03b2 antibody therapy in accordance with current MHLW Guidelines in Japan.", "source": "PubMed"}, {"chunk_id": "40221237_0", "pmid": "40221237", "title": "Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing.", "authors": "Rajendra A, Bondonno NP, Murray K et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer's disease, Apoe, Brain atrophy, Cerebral beta-amyloid, Dementia, Diet, Neuroimaging brain biomarkers, Nitrate", "chunk": "Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia. Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD). Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had \u03b2-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline. Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates of cerebral \u03b2-amyloid (A\u03b2) deposition, measured using PET, and rates of brain atrophy, measured using MRI, were assessed between baseline and 126-months follow-up, at intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral A\u03b2 deposition and (ii) brain atrophy,", "source": "PubMed"}, {"chunk_id": "40221237_1", "pmid": "40221237", "title": "Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing.", "authors": "Rajendra A, Bondonno NP, Murray K et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer's disease, Apoe, Brain atrophy, Cerebral beta-amyloid, Dementia, Diet, Neuroimaging brain biomarkers, Nitrate", "chunk": "intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral A\u03b2 deposition and (ii) brain atrophy, over the 126 months of follow-up. Analyses were carried out following stratification of the sample by established dementia Alzheimer's disease (AD) risk factors including sex and presence or absence of the apolipoprotein E (APOE) \u03b54 allele. In women carriers of the APOE \u03b54 allele, higher plant sourced nitrate intake (median intake 121 mg/day), was associated with a slower rate of cerebral A\u03b2 deposition [\u03b2: 4.47 versus 8.99 Centiloid (CL) /18 months, p < 0.05] and right hippocampal atrophy [-0.01 versus -0.03 mm3 /18 months, p < 0.01], after multivariable adjustments. Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE \u03b54. Associations were observed between plant-derived nitrate intake and cerebral A\u03b2 deposition, particularly", "source": "PubMed"}, {"chunk_id": "40221237_2", "pmid": "40221237", "title": "Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing.", "authors": "Rajendra A, Bondonno NP, Murray K et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer's disease, Apoe, Brain atrophy, Cerebral beta-amyloid, Dementia, Diet, Neuroimaging brain biomarkers, Nitrate", "chunk": "Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE \u03b54. Associations were observed between plant-derived nitrate intake and cerebral A\u03b2 deposition, particularly in high-risk populations (women and APOE \u03b54 carriers). Associations were also observed for brain volume atrophy, however these exhibited subgroup variability without clear patterns relative to sex and APOE \u03b54 allele carriage. These findings suggest a potential link between plant-sourced nitrate and AD related neuroimaging markers of brain health improved brain health, but further validation in larger studies is required.", "source": "PubMed"}, {"chunk_id": "41503482_0", "pmid": "41503482", "title": "Explainable Machine Learning for Early Detection of Mild Cognitive Impairment, Fall Risk, and Frailty Using Sensor-Based Motor Function Data.", "authors": "Akter S, Guess TM, Sarker S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "This study aimed to design and evaluate an explainable machine learning (ML) framework that integrates sensor-based motor assessments with demographic and clinical data to identify early indicators of mild cognitive impairment (MCI), fall risk, and frailty in older adults. Eighty-three community-dwelling older adults (60 years or older) completed multimodal motor assessments using the Mizzou Point-of-Care Assessment System (MPASS) to capture synchronized gait, balance, and sit-to-stand performance. Sensor-derived motor features were combined with demographic and clinical variables to develop predictive models for MCI, frailty, and fall risk using XGBoost and Decision Tree algorithms. A unified multilabel framework was also developed using XGBoost, Decision Tree, and AdaBoost to predict all three outcomes. Model interpretability was evaluated using SHapley Additive exPlanations (SHAP). The ML model for MCI achieved the highest performance (94% accuracy, AUC = 0.88, F1 = 0.94), followed by fall risk (94% accuracy, AUC = 0.90) and frailty (82% accuracy, AUC", "source": "PubMed"}, {"chunk_id": "41503482_1", "pmid": "41503482", "title": "Explainable Machine Learning for Early Detection of Mild Cognitive Impairment, Fall Risk, and Frailty Using Sensor-Based Motor Function Data.", "authors": "Akter S, Guess TM, Sarker S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "ML model for MCI achieved the highest performance (94% accuracy, AUC = 0.88, F1 = 0.94), followed by fall risk (94% accuracy, AUC = 0.90) and frailty (82% accuracy, AUC = 0.77). Unified multilabel models showed moderate performance (67-73% accuracy), with XGBoost achieving the highest accuracy (73%), sensitivity, and F1 score, while the Decision Tree showed higher discrimination (AUC = 0.72). SHAP analyses identified stride length and time, center-of-pressure-based balance measures, and knee angular velocity during sit-to-stand as dominant predictors. This work introduces a novel ML framework using multimodal sensor-based motor assessments to predict MCI, fall risk, and frailty individually and within a unified model. By combining explainable ML with motor-function data, the framework supports transparent early screening of multidomain cognitive and physical decline in aging.", "source": "PubMed"}, {"chunk_id": "41503482_2", "pmid": "41503482", "title": "Explainable Machine Learning for Early Detection of Mild Cognitive Impairment, Fall Risk, and Frailty Using Sensor-Based Motor Function Data.", "authors": "Akter S, Guess TM, Sarker S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "cognitive and physical decline in aging.", "source": "PubMed"}, {"chunk_id": "19387108_0", "pmid": "19387108", "title": "Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis.", "authors": "Lyn-Cook LE, Lawton M, Tong M et al.", "year": "2009", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can be complicated by cognitive impairment and neurodegeneration. Experimentally, high fat diet (HFD)-induced obesity with T2DM causes mild neurodegeneration with brain insulin resistance. Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated the potential role of ceramides as mediators of neurodegeneration in the HFD obesity/T2DM model. We pair-fed C57BL/6 mice with a HFD or control diet for 4-20 weeks and examined pro-ceramide gene expression in liver and brain and neurodegeneration in the temporal lobe. HFD feeding gradually increased body weight, but after 16 weeks, liver weight surged (P<0.001) due to lipid (triglyceride) accumulation (P<0.001), and brain weight declined (P<0.0001-Trend analysis). HFD feeding increased ceramide synthase, serine palmitoyl transferase, and sphingomyelinase expression in liver (P<0.05-P<0.001), but not brain. In HFD fed mice, temporal lobe levels of ubiquitin (P<0.001) and 4-hydroxynonenal (P<0.05 or P<0.01) increased, and tau,", "source": "PubMed"}, {"chunk_id": "19387108_1", "pmid": "19387108", "title": "Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis.", "authors": "Lyn-Cook LE, Lawton M, Tong M et al.", "year": "2009", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "serine palmitoyl transferase, and sphingomyelinase expression in liver (P<0.05-P<0.001), but not brain. In HFD fed mice, temporal lobe levels of ubiquitin (P<0.001) and 4-hydroxynonenal (P<0.05 or P<0.01) increased, and tau, beta-actin, and choline acetyltransferase levels decreased (P<0.05-P<0.001) with development of NASH. In obesity, T2DM, or NASH, neurodegeneration with brain insulin resistance may be mediated by excess hepatic production of neurotoxic ceramides that readily cross the blood-brain barrier.", "source": "PubMed"}, {"chunk_id": "39778970_0", "pmid": "39778970", "title": "Updated Appropriate Use Criteria for Amyloid and Tau PET: A Report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup.", "authors": "Rabinovici GD, Knopman DS, Arbizu J et al.", "year": "2025", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "Alzheimer disease, PET, PET imaging, amyloid PET, appropriate use criteria, biomarkers, brain pathology, clinical care, cognitive impairment, dementia, diagnosis, early detection, memory disorders, molecular imaging, neuroimaging, neurology, tau PET, therapeutic strategies, treatment", "chunk": "The Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened a multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET. <b>Methods:</b> The workgroup identified key research questions that guided a systematic literature review on clinical amyloid/tau PET. Building on this review, the workgroup developed 17 clinical scenarios in which amyloid or tau PET may be considered. A modified Delphi approach was used to rate each scenario by consensus as \"rarely appropriate,\" \"uncertain,\" or \"appropriate.\" Ratings were performed separately for amyloid and tau PET as stand-alone modalities. <b>Results:</b> For amyloid PET, 7 scenarios were rated as appropriate, 2 as uncertain, and 8 as rarely appropriate. For tau PET, 5 scenarios were rated as appropriate, 6 as uncertain, and 6 as rarely appropriate. <b>Conclusion:</b> AUC for amyloid and tau PET provide expert recommendations for clinical use of", "source": "PubMed"}, {"chunk_id": "39778970_1", "pmid": "39778970", "title": "Updated Appropriate Use Criteria for Amyloid and Tau PET: A Report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup.", "authors": "Rabinovici GD, Knopman DS, Arbizu J et al.", "year": "2025", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "Alzheimer disease, PET, PET imaging, amyloid PET, appropriate use criteria, biomarkers, brain pathology, clinical care, cognitive impairment, dementia, diagnosis, early detection, memory disorders, molecular imaging, neuroimaging, neurology, tau PET, therapeutic strategies, treatment", "chunk": "tau PET, 5 scenarios were rated as appropriate, 6 as uncertain, and 6 as rarely appropriate. <b>Conclusion:</b> AUC for amyloid and tau PET provide expert recommendations for clinical use of these technologies in the evolving landscape of diagnostics and therapeutics for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "39366841_0", "pmid": "39366841", "title": "Alzheimer's disease biomarkers and the tyranny of treatment.", "authors": "Karlawish J, Grill JD", "year": "2024", "journal": "EBioMedicine", "keywords": "Alzheimer, Biomarker", "chunk": "Advances in treatment are changing not only the therapeutic options for patients with Alzheimer's disease; they're also changing their diagnostic options. Technologies to detect amyloid such as PET imaging and blood or CSF testing now have a central role in Alzheimer's disease care. Notably, this role has been made possible by regulatory approval and coverage by payers of therapies. Access to treatments and the diagnostic tests needed to prescribe them is encourageing but it reveals a problem. These tests are tailored to the needs of the therapies, not to the needs of patients. Patients and families need to understand the causes of their impairments and their prognosis. This requires access to the best available diagnostic tests and this access should not depend on the availability of treatments. These tests should be used to their fullest capacity to inform patients of the causes of their cognitive impairments and their prognosis. Unfortunately,", "source": "PubMed"}, {"chunk_id": "39366841_1", "pmid": "39366841", "title": "Alzheimer's disease biomarkers and the tyranny of treatment.", "authors": "Karlawish J, Grill JD", "year": "2024", "journal": "EBioMedicine", "keywords": "Alzheimer, Biomarker", "chunk": "not depend on the availability of treatments. These tests should be used to their fullest capacity to inform patients of the causes of their cognitive impairments and their prognosis. Unfortunately, compared to diagnostic testing, treatment options are overvalued. We call this problem the tyranny of treatment.", "source": "PubMed"}, {"chunk_id": "41054340_0", "pmid": "41054340", "title": "Prognostic Value of Parkinson's Disease Subtypes in the LABS-PD Cohort: Functional Ability, Quality of Life and Mortality.", "authors": "Dash D, Eberly S, Oakes D et al.", "year": "2026", "journal": "Movement disorders clinical practice", "keywords": "Parkinson's disease, clinical, data\u2010driven, mortality, prognosis, subtypes", "chunk": "Research on Parkinson's disease (PD) heterogeneity may inform clinical prognosis. There is currently no fully validated PD subtype classification system. We aimed at assessing the prognostic relevance of a data-driven PD subtype classification system. To identify PD subtypes, we conducted cluster analyses in the Longitudinal and Biomarker Studies in Parkinson's Disease study (LABS-PD) cohort including 461 PD patients enrolled within 2 years of diagnosis and followed for at least 5 years. We determined the association of each PD subtype with the mean changes in the Schwab & England Activities of Daily Living (SE-ADL) and Parkinson's Disease Questionnaire-39 (PDQ-39). We evaluated the association of each PD subtype with the death rate and time to death, after mortality ascertainment using the National Death Index database and review of records at study sites. We identified three subtypes: Tremor Predominant, Motor Complications, and Rapid Progression. Over 2 years, the change of SE-ADL score for", "source": "PubMed"}, {"chunk_id": "41054340_1", "pmid": "41054340", "title": "Prognostic Value of Parkinson's Disease Subtypes in the LABS-PD Cohort: Functional Ability, Quality of Life and Mortality.", "authors": "Dash D, Eberly S, Oakes D et al.", "year": "2026", "journal": "Movement disorders clinical practice", "keywords": "Parkinson's disease, clinical, data\u2010driven, mortality, prognosis, subtypes", "chunk": "Death Index database and review of records at study sites. We identified three subtypes: Tremor Predominant, Motor Complications, and Rapid Progression. Over 2 years, the change of SE-ADL score for the \"Motor Complications\" subtype (-4.26, 95% CI: -6.60, -1.91) was worse compared to the \"Tremor Predominant\" subtype (0.43, 95% CI: -1.35, 2.22). The adjusted death rate was lower for the \"Tremor Predominant\" subtype compared to the \"Motor Complications\" subtype (HR [time to death]: 0.27, 95% CI: 0.14, 0.52). PD subtypes generated in LABS-PD cohort have prognostic value, for short-term functional ability and long-term survival. Membership in the \"Tremor Predominant\" subtype 5 years after PD diagnosis was associated with preserved functional ability and longer survival compared to the \"Motor Complications\" subtype.", "source": "PubMed"}, {"chunk_id": "41480709_0", "pmid": "41480709", "title": "Role and mechanisms of ferroptosis in cognitive impairment: From molecular pathways to therapeutic targets (Review).", "authors": "Ge S, Kong D, Fan S et al.", "year": "2026", "journal": "International journal of molecular medicine", "keywords": "cognitive impairment, ferroptosis, molecular mechanisms, neurodegenerative diseases, therapeutic strategies", "chunk": "Cognitive impairment remains an important global health concern, with the molecular mechanisms regulating its progression being a primary research focus. Ferroptosis, a unique form of programmed cell death characterized by iron\u2011dependent lipid peroxidation, has been increasingly recognized for its essential role in the progression of various neurodegenerative diseases and diabetes\u2011associated cognitive impairment. The present review summarizes current evidence on how ferroptosis contributes to cognitive decline and outlines its regulation through lipid, iron and glutathione metabolism; it further discusses how diverse upstream pathologies converge on ferroptosis as a shared mechanism underlying cognitive dysfunction. In addition, recent advances in ferroptosis\u2011related biomarkers and therapeutic strategies are highlighted, with the aim of providing a clearer framework for understanding its pathogenic roles and guiding future clinical translation.", "source": "PubMed"}, {"chunk_id": "41480709_1", "pmid": "41480709", "title": "Role and mechanisms of ferroptosis in cognitive impairment: From molecular pathways to therapeutic targets (Review).", "authors": "Ge S, Kong D, Fan S et al.", "year": "2026", "journal": "International journal of molecular medicine", "keywords": "cognitive impairment, ferroptosis, molecular mechanisms, neurodegenerative diseases, therapeutic strategies", "chunk": "clinical translation.", "source": "PubMed"}, {"chunk_id": "38224658_0", "pmid": "38224658", "title": "Entropy-driven catalysis-based lateral flow assay for sensitive detection of Alzheimer 's-associated MicroRNA.", "authors": "Wang J, Shi L, Zhu X et al.", "year": "2024", "journal": "Talanta", "keywords": "Alzheimer's disease, Entropy-driven catalysis, Lateral flow assay, MiRNA-16", "chunk": "Alzheimer's disease (AD) is a degenerative disease of the brain worldwide. Currently, there is no effective cure. But accurate and early diagnosis of AD is critical to the development of patient care and future treatments. MiRNA-16 has been considered as an effective diagnostic biomarker for AD because of its regulatory effect on key proteins of AD. Herein, a colorimetric lateral flow assay (LFA) was developed for sensitive detection of miRNA-16 based on entropy-driven catalysis (EDC) amplification strategy. MiRNA-16 triggered EDC and released more linker DNAs (LDNA) of sandwich structure. Thus, AuNPs were enriched at the T-line to enhance the colorimetric signal and improve the sensitivity of visual assay. It showed good specificity and sensitivity for detecting miRNA-16 with a detection limit of 1.01 pM. The practical detection of miRNA-16 in human serum obtained satisfactory result. Significantly, EDC achieved signal amplification in homogeneous solution without enzyme and DNA labeling, leading to", "source": "PubMed"}, {"chunk_id": "38224658_1", "pmid": "38224658", "title": "Entropy-driven catalysis-based lateral flow assay for sensitive detection of Alzheimer 's-associated MicroRNA.", "authors": "Wang J, Shi L, Zhu X et al.", "year": "2024", "journal": "Talanta", "keywords": "Alzheimer's disease, Entropy-driven catalysis, Lateral flow assay, MiRNA-16", "chunk": "limit of 1.01 pM. The practical detection of miRNA-16 in human serum obtained satisfactory result. Significantly, EDC achieved signal amplification in homogeneous solution without enzyme and DNA labeling, leading to a cheap and easy detection of miRNA-16. Therefore, it provided a portable and rapid assay for AD-related nucleic acid, which holds a potential for point-of-care testing (POCT) of AD.", "source": "PubMed"}, {"chunk_id": "41039812_0", "pmid": "41039812", "title": "Quantitative Assessment of Upper Limb Ataxia Using a Virtual Reality-Based Evaluation System.", "authors": "Sato M, Abe T, Aoki S et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "digital biomarker, finger\u2010to\u2010nose test, quantitative assessment, upper limb ataxia, virtual reality", "chunk": "Cerebellar ataxia impairs coordination and balance, reducing quality of life. Conventional clinical scales, including the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), are widely used to assess ataxia but are limited by subjectivity and inter-rater variability. Therefore, we aimed to develop a virtual reality-based system to objectively and quantitatively assess upper limb ataxia. A \"virtual nose-finger test\" was implemented using a head-mounted display, in which participants performed repetitive reaching tasks. Six parameters were measured: four spatial (subtracted length, trajectory ratio, terminal trajectory length, and maximum overshoot distance) and two temporal (required time and movement speed). These parameters were compared across groups, correlated with clinical scales, and analyzed for diagnostic accuracy using receiver operating characteristic curves. Motor adaptation was assessed using parameter changes across trials. Ninety-five participants were recruited: 39 with cerebellar ataxia, 30 controls, and 26 with Parkinsonian disorders. Participants", "source": "PubMed"}, {"chunk_id": "41039812_1", "pmid": "41039812", "title": "Quantitative Assessment of Upper Limb Ataxia Using a Virtual Reality-Based Evaluation System.", "authors": "Sato M, Abe T, Aoki S et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "digital biomarker, finger\u2010to\u2010nose test, quantitative assessment, upper limb ataxia, virtual reality", "chunk": "using receiver operating characteristic curves. Motor adaptation was assessed using parameter changes across trials. Ninety-five participants were recruited: 39 with cerebellar ataxia, 30 controls, and 26 with Parkinsonian disorders. Participants with ataxia exhibited significantly greater spatial deviations and temporal variability than other groups did. Trajectory ratio, required time, and movement speed variability coefficient significantly correlated with clinical ataxia scores. The system demonstrated high diagnostic accuracy from the receiver operating characteristic analyses, and participants with ataxia showed different motor adaptations by compensating for spatial errors through reduced movement speed. This virtual reality-based system enables objective, quantitative, portable, and ambulatory-independent evaluation of upper limb ataxia, enhancing its feasibility in clinical and research settings and its potential as a biomarker for cerebellar ataxia.", "source": "PubMed"}, {"chunk_id": "35395381_0", "pmid": "35395381", "title": "Pharmacological activities and pharmacokinetics of liquiritin: A review.", "authors": "Qin J, Chen J, Peng F et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "Liquiritin, Mechanism, Pharmacokinetics, Pharmacological activities", "chunk": "Liquiritin is a flavonoid derived from Radix et Rhizoma Glycyrrhizae, which is a widely used traditional Chinese medicine with the effects of invigorating spleen qi, clearing heat, resolving toxins, and dispelling phlegm to stop coughs. In this review,the pharmacokinetics and pharmacological activities of liquiritin have been summarized. The information on liquiritin up to 2021 was collected from PubMed, Web of Science, Springer Link, and China National Knowledge Infrastructure databases. The key words were \"liquiritin\", \"nerve\", \"tumor\", \"cardiac\", etc. RESULTS: The absorption mechanism of liquiritin conforms to the passive diffusion and first-order kinetics while with low bioavailability. Liquiritin can penetrate the blood-brain-barrier. Besides, liquiritin displays numerous pharmacological effects including anti-Alzheimer's disease, antidepressant, antitumor, anti-inflammatory, cardiovascular protection, antitussive, hepatoprotection, and skin protective effects. In addition, the novel preparations, new pharmacological effects,and cdusafty of liquiritin are also discussed in this review. This review provides a comprehensive state of knowledge on the pharmacokinetics and", "source": "PubMed"}, {"chunk_id": "35395381_1", "pmid": "35395381", "title": "Pharmacological activities and pharmacokinetics of liquiritin: A review.", "authors": "Qin J, Chen J, Peng F et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "Liquiritin, Mechanism, Pharmacokinetics, Pharmacological activities", "chunk": "effects. In addition, the novel preparations, new pharmacological effects,and cdusafty of liquiritin are also discussed in this review. This review provides a comprehensive state of knowledge on the pharmacokinetics and pharmacological activities of liquiritin, and makes a forecast for its research directions and applications in clinic.", "source": "PubMed"}, {"chunk_id": "41516046_0", "pmid": "41516046", "title": "Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.", "authors": "Abbasi Kasbi N, Stopschinski BE, Polyak AG et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, immune regulation, leptin, leptin resistance, multiple sclerosis, neurodegenerative diseases, neuroinflammatory diseases", "chunk": "The neuroendocrine and immune systems interact bidirectionally through shared ligands and receptors during inflammation, thereby regulating immune responses. Leptin, primarily known for its role in energy metabolism and appetite regulation, also modulates neuroinflammatory pathways. Its receptors are widely expressed on immune cells and contribute to immune mechanisms implicated in the pathogenesis of neuroinflammatory disorders such as multiple sclerosis (MS) and Alzheimer's disease (AD). This review highlights recent advances in understanding leptin's role in immune regulation, with a focus on its impact on MS and AD. A comprehensive literature review was conducted until October 2025, using PubMed, Google Scholar, and Scopus to identify studies investigating leptin in neuroinflammatory conditions, particularly MS and AD. Leptin exerts broad immunomodulatory effects by activating T cells, dendritic cells, and microglia, and promoting their proliferation and phagocytosis. Its elevation enhances Th1 and Th17 responses, drives pro-inflammatory macrophage phenotype polarization, and suppresses regulatory T cell and Th2", "source": "PubMed"}, {"chunk_id": "41516046_1", "pmid": "41516046", "title": "Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.", "authors": "Abbasi Kasbi N, Stopschinski BE, Polyak AG et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, immune regulation, leptin, leptin resistance, multiple sclerosis, neurodegenerative diseases, neuroinflammatory diseases", "chunk": "cells, dendritic cells, and microglia, and promoting their proliferation and phagocytosis. Its elevation enhances Th1 and Th17 responses, drives pro-inflammatory macrophage phenotype polarization, and suppresses regulatory T cell and Th2 responses, immune pathways involved in MS. Peripheral leptin levels are increased in MS, especially during disease exacerbations. In contrast, in AD, they are typically reduced, particularly in patients with normal body mass index (BMI), where their decline contributes to amyloid-\u03b2 and tau pathology. These divergent patterns position leptin as a bidirectional regulator at the intersection of immunity and neurodegeneration. Additionally, its protective or detrimental effects likely depend on whether it acts under physiological conditions or in the context of obesity-induced leptin resistance. Elevated leptin levels in obesity exacerbate inflammation and diminish its neuroprotective effects. In conclusion, leptin is elevated in MS patients but downregulated in AD, reflecting its bidirectional effects. In leptin resistance, peripheral proinflammatory signaling is maintained while central", "source": "PubMed"}, {"chunk_id": "41516046_2", "pmid": "41516046", "title": "Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.", "authors": "Abbasi Kasbi N, Stopschinski BE, Polyak AG et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, immune regulation, leptin, leptin resistance, multiple sclerosis, neurodegenerative diseases, neuroinflammatory diseases", "chunk": "diminish its neuroprotective effects. In conclusion, leptin is elevated in MS patients but downregulated in AD, reflecting its bidirectional effects. In leptin resistance, peripheral proinflammatory signaling is maintained while central leptin signaling is restricted, thereby potentially promoting autoimmunity in MS and limiting neuroprotection in AD. Further mechanistic and longitudinal studies are needed to clarify the relationship between leptin dysregulation, leptin resistance, neuroinflammatory and neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "31730144_0", "pmid": "31730144", "title": "Nontoxic amphiphilic carbon dots as promising drug nanocarriers across the blood-brain barrier and inhibitors of \u03b2-amyloid.", "authors": "Zhou Y, Liyanage PY, Devadoss D et al.", "year": "2019", "journal": "Nanoscale", "keywords": "None", "chunk": "The blood-brain barrier (BBB) is a main obstacle for drug delivery targeting the central nervous system (CNS) and treating Alzheimer's disease (AD). In order to enhance the efficiency of drug delivery without harming the BBB integrity, nanoparticle-mediated drug delivery has become a popular therapeutic strategy. Carbon dots (CDs) are one of the most promising and novel nanocarriers. In this study, amphiphilic yellow-emissive CDs (Y-CDs) were synthesized with an ultrasonication-mediated methodology using citric acid and o-phenylenediamine with a size of 3 nm that emit an excitation-independent yellow photoluminescence (PL). The content of primary amine and carboxyl groups on CDs was measured as 6.12 \u00d7 10-5 and 8.13 \u00d7 10-3 mmol mg-1, respectively, indicating the potential for small-molecule drug loading through bioconjugation. Confocal image analyses revealed that Y-CDs crossed the BBB of 5-day old wild-type zebrafish, most probably by passive diffusion due to the amphiphilicity of Y-CDs. And the amphiphilicity and BBB", "source": "PubMed"}, {"chunk_id": "31730144_1", "pmid": "31730144", "title": "Nontoxic amphiphilic carbon dots as promising drug nanocarriers across the blood-brain barrier and inhibitors of \u03b2-amyloid.", "authors": "Zhou Y, Liyanage PY, Devadoss D et al.", "year": "2019", "journal": "Nanoscale", "keywords": "None", "chunk": "Confocal image analyses revealed that Y-CDs crossed the BBB of 5-day old wild-type zebrafish, most probably by passive diffusion due to the amphiphilicity of Y-CDs. And the amphiphilicity and BBB penetration ability didn't change when Y-CDs were coated with different hydrophilic molecules. Furthermore, Y-CDs were observed to enter cells to inhibit the overexpression of human amyloid precursor protein (APP) and \u03b2-amyloid (A\u03b2) which is a major factor responsible for AD pathology. Therefore, data suggest that Y-CDs have a great potential as nontoxic nanocarriers for drug delivery towards the CNS as well as a promising inhibiting agent of A\u03b2-related pathology of the AD.", "source": "PubMed"}, {"chunk_id": "41689888_0", "pmid": "41689888", "title": "Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes.", "authors": "Perry R, Kipps C, Soto Mart\u00edn ME et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes, Lecanemab", "chunk": "Lecanemab, an antibody directed at A\u03b2-protofibrils and plaque, showed meaningful delay in disease progression and biological effects consistent with disease modification in the phase 3 Clarity AD trial. The objective of this paper is to present efficacy and safety results in ApoE \u03b54 non-carriers or heterozygotes population of Clarity AD. Clarity AD is an 18-month, randomized study (core) in participants with early AD, with an open-label extension phase (OLE) phase. Academic and clinical centers. All eligible ApoE \u03b54 participants were randomized 1:1 across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly); the results presented herein are for the ApoE4 heterozygote or non-carrier participants. Endpoints included change from baseline at 18 months in the global cognitive and functional scale, CDR-SB, amyloid positron emission tomography (PET), Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), and health-related quality-of-life (HRQoL) assessments.", "source": "PubMed"}, {"chunk_id": "41689888_1", "pmid": "41689888", "title": "Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes.", "authors": "Perry R, Kipps C, Soto Mart\u00edn ME et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes, Lecanemab", "chunk": "amyloid positron emission tomography (PET), Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), and health-related quality-of-life (HRQoL) assessments. Amyloid imaging related abnormalities (ARIA) occurrence was monitored throughout the study by central reading of magnetic resonance imaging. Following 18 months treatment in the Core, eligible participants transitioned to the OLE where they received open-label lecanemab. Clinical outcomes (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL) were evaluated by examining 'delayed start' (core:placebo followed by OLE:lecanemab) and 'early start' (core:lecanemab followed by OLE:lecanemab) cohorts as well as natural history cohorts. Time to progression to next stage of AD was also evaluated through 36 months. 1795 participants with early AD were enrolled in Clarity AD, of which 1521 were ApoE \u03b54 heterozygotes or non-carriers (85 %). Lecanemab significantly reduced clinical decline on CDR-SB at 18 months compared to placebo in the ApoE\u03b54 heterozygotes or non-carriers", "source": "PubMed"}, {"chunk_id": "41689888_2", "pmid": "41689888", "title": "Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes.", "authors": "Perry R, Kipps C, Soto Mart\u00edn ME et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes, Lecanemab", "chunk": "of which 1521 were ApoE \u03b54 heterozygotes or non-carriers (85 %). Lecanemab significantly reduced clinical decline on CDR-SB at 18 months compared to placebo in the ApoE\u03b54 heterozygotes or non-carriers subgroup. Amyloid PET, ADAS-Cog14, ADCS-MCI-ADL, and HRQoL results were consistent with the CDR-SB findings. In the analysis subgroup, the most common adverse reactions for lecanemab were infusion-related reactions (26 %), ARIA-H (13 %), fall (11 %), headache (11 %), and ARIA-E (9 %). In the OLE, lecanemab-treated participants continued to accrue benefit in CDR-SB through 36 months, with continued separation through 36 months relative to the ADNI natural history cohort. Delayed start results follow a parallel trajectory relative to early start results, but do not catch up, confirming a disease modifying effect and reflecting importance of early treatment initiation. Results were similar for ADAS-Cog14 and ADCS-MCI-ADL. Lecanemab reduced the risk of progression to next stage of AD by 28 %", "source": "PubMed"}, {"chunk_id": "41689888_3", "pmid": "41689888", "title": "Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes.", "authors": "Perry R, Kipps C, Soto Mart\u00edn ME et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E \u03b54 (ApoE \u03b54) non-carriers or heterozygotes, Lecanemab", "chunk": "modifying effect and reflecting importance of early treatment initiation. Results were similar for ADAS-Cog14 and ADCS-MCI-ADL. Lecanemab reduced the risk of progression to next stage of AD by 28 % on lecanemab as compared to the ADNI natural history cohort. In the ApoE \u03b54 heterozygotes or non-carrier subgroup of Clarity AD, lecanemab slowed decline in disease progression and reduced markers of amyloid, with expanding benefit over time. Clarity AD NCT03887455.", "source": "PubMed"}, {"chunk_id": "41603947_0", "pmid": "41603947", "title": "Stage-specific temporal associations between body mass index trajectories and Alzheimer's disease pathologies.", "authors": "Dang M, Chen K, Wang D et al.", "year": "2026", "journal": "European radiology", "keywords": "Alzheimer\u2019s disease, Body mass index, Magnetic resonance imaging, Mild cognitive impairment, Positron emission tomography", "chunk": "Preclinical declines in body mass index (BMI) are linked to accelerated Alzheimer's disease (AD) neurodegeneration and mortality, yet the temporal relationship between premorbid BMI trajectories and AD neuropathology remains unclear. This study aims to characterize stage-specific BMI dynamics preceding mild cognitive impairment (MCI)/AD diagnosis and evaluate their bidirectional associations with core AD pathologies. This longitudinal cohort study analyzed 1570 participants (mean age 73.2 \u00b1 6.9 years; 53% male) from the Alzheimer's Disease Neuroimaging Initiative, applied linear mixed-effect models to construct BMI trajectories, and used partial correlation analysis and cross-lagged panel model to assess bidirectional associations between BMI changes and pathological progression, including \u03b2-amyloid (A\u03b2), tau, and neurodegeneration. Frontotemporal A\u03b2 deposition preceded and predicted preclinical BMI decline (\u03b2 = -5.74, p = 0.003), which subsequently correlated with accelerated neurodegeneration during MCI transition, including hypometabolism (r = 0.42, p < 0.001) and gray matter atrophy (r = 0.24, p = 0.01). Post-MCI", "source": "PubMed"}, {"chunk_id": "41603947_1", "pmid": "41603947", "title": "Stage-specific temporal associations between body mass index trajectories and Alzheimer's disease pathologies.", "authors": "Dang M, Chen K, Wang D et al.", "year": "2026", "journal": "European radiology", "keywords": "Alzheimer\u2019s disease, Body mass index, Magnetic resonance imaging, Mild cognitive impairment, Positron emission tomography", "chunk": "= 0.003), which subsequently correlated with accelerated neurodegeneration during MCI transition, including hypometabolism (r = 0.42, p < 0.001) and gray matter atrophy (r = 0.24, p = 0.01). Post-MCI diagnosis, BMI trajectories stabilized, yet lower BMI was associated with elevated cerebrospinal fluid tau levels, regardless of AD conversion. Importantly, lower premorbid BMI at MCI diagnosis was linked to faster temporo-occipital tau accumulation (r = -0.53, p = 0.01) and temporal hypometabolism (r = 0.23, p = 0.002) during MCI-to-AD progression. This study suggests a temporal relationship between BMI trajectories and AD pathology: early A\u03b2 deposition predicts preclinical BMI decline, which exacerbates tauopathy and neurodegeneration. These findings reveal a self-reinforcing cycle wherein BMI decline reflects incipient pathology and amplifies disease progression through stage-specific mechanisms. Question What is the association between changes in body mass index (BMI) and the pathological progression of Alzheimer's disease? Findings Early frontotemporal \u03b2-amyloid deposition predicts preclinical", "source": "PubMed"}, {"chunk_id": "41603947_2", "pmid": "41603947", "title": "Stage-specific temporal associations between body mass index trajectories and Alzheimer's disease pathologies.", "authors": "Dang M, Chen K, Wang D et al.", "year": "2026", "journal": "European radiology", "keywords": "Alzheimer\u2019s disease, Body mass index, Magnetic resonance imaging, Mild cognitive impairment, Positron emission tomography", "chunk": "progression through stage-specific mechanisms. Question What is the association between changes in body mass index (BMI) and the pathological progression of Alzheimer's disease? Findings Early frontotemporal \u03b2-amyloid deposition predicts preclinical BMI decline, which in turn is associated with accelerated tau accumulation and neurodegeneration during symptomatic progression. Clinical relevance Monitoring BMI trajectories provides a low-cost approach to identifying individuals at high risk for Alzheimer's disease and tracking its pathological progression, highlighting the potential value of metabolic interventions during preclinical stages.", "source": "PubMed"}, {"chunk_id": "37874083_0", "pmid": "37874083", "title": "Geroscience and Alzheimer's Disease Drug Development.", "authors": "Cummings J, Leisgang Osse AM, Kinney J", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Geroscience, Alzheimer\u2019s disease, aging, drug development, pipeline, senolytics", "chunk": "Age is the most important risk factor for Alzheimer's disease (AD). The acceptable age range for participation in AD clinical trials is 50 to 90, and this 40-year span incorporates enormous age-related change. Clinical trial participants tend to be younger and healthier than the general population. They are also younger than the general population of AD patients. Drug development from a geroscience perspective would take greater account of effects of aging on clinical trial outcomes. The AD clinical trial pipeline has diversified beyond the canonical targets of amyloid beta protein and tau. Many of these interventions apply to age-related disorders. Anti-inflammatory agents and bioenergetic and metabolic therapies are among the well represented classes in the pipeline and are applicable to AD and non-AD age-related conditions. Drug development strategies can be adjusted to better inform outcomes of trials regarding aged individuals. Inclusion of older individuals in the multiple ascending dose trials", "source": "PubMed"}, {"chunk_id": "37874083_1", "pmid": "37874083", "title": "Geroscience and Alzheimer's Disease Drug Development.", "authors": "Cummings J, Leisgang Osse AM, Kinney J", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Geroscience, Alzheimer\u2019s disease, aging, drug development, pipeline, senolytics", "chunk": "AD and non-AD age-related conditions. Drug development strategies can be adjusted to better inform outcomes of trials regarding aged individuals. Inclusion of older individuals in the multiple ascending dose trials of Phase 1, use of geriatric-related clinical outcomes and biomarkers in Phase 2, and extension of these Phase 2 learnings to Phase 3 will result in a more comprehensive understanding of AD therapies and their relationship to aging. Clinical trials can employ a more comprehensive geriatric assessment approach and biomarkers more relevant to aging at baseline and as exploratory outcomes. Greater attention to the role of aging and its influence in AD clinical trials can result in better understanding of the generalizability of clinical trial findings to the older AD population.", "source": "PubMed"}, {"chunk_id": "37874083_2", "pmid": "37874083", "title": "Geroscience and Alzheimer's Disease Drug Development.", "authors": "Cummings J, Leisgang Osse AM, Kinney J", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Geroscience, Alzheimer\u2019s disease, aging, drug development, pipeline, senolytics", "chunk": "population.", "source": "PubMed"}, {"chunk_id": "39435635_0", "pmid": "39435635", "title": "Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases.", "authors": "Yang X, Gao X, Jiang X et al.", "year": "2025", "journal": "Neural regeneration research", "keywords": "None", "chunk": "Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases. Owing to their therapeutic properties and ability to cross the blood-brain barrier, extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions, including ischemic stroke, traumatic brain injury, neurodegenerative diseases, glioma, and psychosis. However, the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body. To address these limitations, multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles, thereby enabling the delivery of therapeutic contents to specific tissues or cells. Therefore, this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles, exploring their applications in treating traumatic brain injury, ischemic stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, glioma, and psychosis. Additionally, we summarized recent clinical trials involving extracellular vesicles and", "source": "PubMed"}, {"chunk_id": "39435635_1", "pmid": "39435635", "title": "Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases.", "authors": "Yang X, Gao X, Jiang X et al.", "year": "2025", "journal": "Neural regeneration research", "keywords": "None", "chunk": "exploring their applications in treating traumatic brain injury, ischemic stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, glioma, and psychosis. Additionally, we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases. This review offers new insights for developing highly targeted therapies in this field.", "source": "PubMed"}, {"chunk_id": "38463796_0", "pmid": "38463796", "title": "Interaction between A\u03b2 and tau on reversion and conversion in mild cognitive impairment patients: After 2-year follow-up.", "authors": "Tang J, Chen Q, Fu Z et al.", "year": "2024", "journal": "Heliyon", "keywords": "Amyloid-\u03b2, Conversion, Mild cognitive impairment, Reversion, Tau", "chunk": "The role of amyloid-\u03b2 (A\u03b2) and tau in reversion and conversion in patients with mild cognitive impairment (MCI) remains unclear. This study aimed to investigate the influence of cerebrospinal fluid (CSF) A\u03b2 and tau on reversion and conversion and the temporal sequence of their pathogenicity in MCI patients. 179 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database and classified into two groups based on cognitive changes after follow-up: reversal group (MCI to cognitively normal) and conversion group (MCI to Alzheimer's disease). CSF biomarkers and cognitive function were measured at baseline and 2-year follow-up. Partial correlation was used to analyze the association between CSF biomarkers and cognitive function, and multivariable logistic regression to identify independent risk factors for cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes. The differences in cognitive", "source": "PubMed"}, {"chunk_id": "38463796_1", "pmid": "38463796", "title": "Interaction between A\u03b2 and tau on reversion and conversion in mild cognitive impairment patients: After 2-year follow-up.", "authors": "Tang J, Chen Q, Fu Z et al.", "year": "2024", "journal": "Heliyon", "keywords": "Amyloid-\u03b2, Conversion, Mild cognitive impairment, Reversion, Tau", "chunk": "cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes. The differences in cognitive function and CSF biomarkers between the two groups remained consistent with baseline after 2-year follow-up. After controlling for confounding variables, there was still a correlation between CSF biomarkers and cognitive function at baseline and 2-year follow-up. Multivariable regression analysis found that at baseline, only A\u03b2 level was independently associated with cognitive changes, while A\u03b2 and tau were both predictive factors after 2-year follow-up. ROC curve analysis revealed that the combination of A\u03b2 and tau [area under the curve (AUC) 0.91, sensitivity 84%, specificity 86%] in predicting cognitive changes after 2-year follow-up had better efficacy than baseline A\u03b2 alone (AUC 0.81). A\u03b2 may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This", "source": "PubMed"}, {"chunk_id": "38463796_2", "pmid": "38463796", "title": "Interaction between A\u03b2 and tau on reversion and conversion in mild cognitive impairment patients: After 2-year follow-up.", "authors": "Tang J, Chen Q, Fu Z et al.", "year": "2024", "journal": "Heliyon", "keywords": "Amyloid-\u03b2, Conversion, Mild cognitive impairment, Reversion, Tau", "chunk": "follow-up had better efficacy than baseline A\u03b2 alone (AUC 0.81). A\u03b2 may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This study provides new clinical evidence to support the view that A\u03b2 pathology precedes tau pathology, which together contribute to the changes in cognitive function.", "source": "PubMed"}, {"chunk_id": "37867511_0", "pmid": "37867511", "title": "Sphingolipid metabolism in brain insulin resistance and neurological diseases.", "authors": "Mei M, Liu M, Mei Y et al.", "year": "2023", "journal": "Frontiers in endocrinology", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, brain insulin resistance, ceramide, sphingolipid metabolism, sphingosine-1-phosphate", "chunk": "Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.", "source": "PubMed"}, {"chunk_id": "37867511_1", "pmid": "37867511", "title": "Sphingolipid metabolism in brain insulin resistance and neurological diseases.", "authors": "Mei M, Liu M, Mei Y et al.", "year": "2023", "journal": "Frontiers in endocrinology", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, brain insulin resistance, ceramide, sphingolipid metabolism, sphingosine-1-phosphate", "chunk": "in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.", "source": "PubMed"}, {"chunk_id": "40939527_0", "pmid": "40939527", "title": "Safety, tolerability and potential biomarkers of vodobatinib in patients with dementia with Lewy bodies.", "authors": "Pagan FL, Torres-Yaghi Y, Hebron ML et al.", "year": "2025", "journal": "Parkinsonism & related disorders", "keywords": "Alzheimer's disease, Dementia with Lewy bodies, Dopamine, Falls, Hyper-phosphorylated tau", "chunk": "Activation of the tyrosine kinase Abelson (Abl) was suggested in the pathogenesis of neurodegenerative diseases. We investigated the effects of a potent and highly specific Abl kinase inhibitor vodobatinib (K0706) in patients diagnosed with dementia with Lewy bodies (DLB). We determined safety, tolerability and potential biomarkers following oral administration of vodobatinib versus placebo in DLB patients. Participants were randomized 1:1:1 into vodobatinib 192 mg, or 384 mg or matching placebo in a single-center, double-blind study. Study drug was taken orally once daily for 3 months followed by one-month wash-out. Twenty-nine individuals were enrolled, 3 were women (10.3 %), age 76.3 \u00b1 6 years (mean \u00b1 SD). Vodobatinib was safe and well-tolerated and more adverse events were noted in the placebo (56) vs vodobatinib 192 mg (19) or 384 mg (6) groups. The number of falls were reduced in the vodobatinib 192 mg (6) and 384 mg (0) compared to placebo", "source": "PubMed"}, {"chunk_id": "40939527_1", "pmid": "40939527", "title": "Safety, tolerability and potential biomarkers of vodobatinib in patients with dementia with Lewy bodies.", "authors": "Pagan FL, Torres-Yaghi Y, Hebron ML et al.", "year": "2025", "journal": "Parkinsonism & related disorders", "keywords": "Alzheimer's disease, Dementia with Lewy bodies, Dopamine, Falls, Hyper-phosphorylated tau", "chunk": "(56) vs vodobatinib 192 mg (19) or 384 mg (6) groups. The number of falls were reduced in the vodobatinib 192 mg (6) and 384 mg (0) compared to placebo (28) groups. The only potential significant change in cerebrospinal fluid (CSF) biomarkers was A\u03b242/A\u03b240 in 192 mg vodobatinib (p = 0.0002) and 384 mg (0.0121) compared to placebo. There was no change in homovanillic acid, a biomarker of dopamine level, or other potential CSF and plasma biomarkers of DLB. Exploratory clinical outcomes were not different between baseline and 3 months in vodobatinib compared to placebo. Vodobatinib appears to be safe and tolerated, but larger trials and longer treatment periods are needed to determine its effects on biomarkers and clinical outcomes.", "source": "PubMed"}, {"chunk_id": "40107604_0", "pmid": "40107604", "title": "Structural innovation for hypoglycemia prevention in high-risk patients with type 2 diabetes: Design and implementation of a pragmatic, randomized, quality improvement trial.", "authors": "Chen MW, Parker MM, Karter AJ et al.", "year": "2025", "journal": "Contemporary clinical trials", "keywords": "Diabetes, Hypoglycemia, Quality improvement, Trial", "chunk": "Severe hypoglycemia is a potentially life-threatening complication of diabetes treatment, associated with increased risks of falls, cardiovascular events, cognitive decline, and mortality. This critical public health concern remains inadequately recognized and addressed in many clinical settings. Here we describe the development of a clinical guideline and associated protocol for a quality improvement randomized trial for hypoglycemia prevention, embedded within an integrated healthcare system. First, we engaged expert clinical stakeholders and experienced guideline developers to create an evidence-based hypoglycemia prevention algorithm, \"Hypoglycemia on a Page\" (HOAP), which was published internally as a healthcare system guideline. After system-wide, passive dissemination of HOAP, a pragmatic, quality improvement, randomized trial was implemented to study the benefit of a proactive, HOAP protocol-driven outreach by a clinical pharmacist targeting hypoglycemia-prone patients with T2D (Intervention Arm) compared to usual care (Usual Care Arm). As the primary outcome, we will assess whether patients in the Intervention Arm are", "source": "PubMed"}, {"chunk_id": "40107604_1", "pmid": "40107604", "title": "Structural innovation for hypoglycemia prevention in high-risk patients with type 2 diabetes: Design and implementation of a pragmatic, randomized, quality improvement trial.", "authors": "Chen MW, Parker MM, Karter AJ et al.", "year": "2025", "journal": "Contemporary clinical trials", "keywords": "Diabetes, Hypoglycemia, Quality improvement, Trial", "chunk": "clinical pharmacist targeting hypoglycemia-prone patients with T2D (Intervention Arm) compared to usual care (Usual Care Arm). As the primary outcome, we will assess whether patients in the Intervention Arm are prescribed safer (less hypoglycemia-prone) diabetes regimens compared to the Usual Care Arm. We hypothesize that the proactive, protocol-driven outreach will result in safer diabetes regimens compared to HOAP dissemination alone. Secondary outcomes of interest include prescribing of glucagon (for rapid treatment of severe hypoglycemia episodes), prescribing and dispensing of continuous glucose monitoring (CGM), documenting hypoglycemia on the problem list, glycemic control (HbA1c <8 %), and ED visit or hospital admission for hypoglycemia. This pragmatic clinical trial will evaluate a structural innovation that included care strategies designed to reduce harm, improve patient outcomes and reduce healthcare resource utilization and cost.", "source": "PubMed"}, {"chunk_id": "40107604_2", "pmid": "40107604", "title": "Structural innovation for hypoglycemia prevention in high-risk patients with type 2 diabetes: Design and implementation of a pragmatic, randomized, quality improvement trial.", "authors": "Chen MW, Parker MM, Karter AJ et al.", "year": "2025", "journal": "Contemporary clinical trials", "keywords": "Diabetes, Hypoglycemia, Quality improvement, Trial", "chunk": "patient outcomes and reduce healthcare resource utilization and cost.", "source": "PubMed"}, {"chunk_id": "41487867_0", "pmid": "41487867", "title": "Acute Traumatic Intracerebral Hematoma: To Operate or Not to Operate?", "authors": "Grabarczyk L, Grosz A, Waska G et al.", "year": "2025", "journal": "Cureus", "keywords": "conservative medical management, intracranial hemorrhage, medical intensive care unit (micu), severe combined traumatic brain injury, traumatic intracerebral hematoma", "chunk": "Acute traumatic intracerebral hematoma (TICH) is a severe complication of head injury, often associated with high morbidity and mortality. We report the case of a 44-year-old man admitted to the ED after a craniocerebral trauma caused by a fall from a tractor. On admission, he presented with impaired consciousness, scoring 8 on the Glasgow Coma Scale, with eye opening to pain (E2), incomprehensible verbal responses (V2), and withdrawal to painful stimuli (M4). Seizures and hemodynamic instability were also noted. CT revealed a large left frontal lobe hematoma with intraventricular and subarachnoid hemorrhage. In cooperation with the neurosurgical team, a decision was made to initiate conservative treatment in the ICU, focusing on airway protection, intracranial pressure control, hemodynamic stabilization, seizure prophylaxis, and infection prevention. During the following days, gradual clinical improvement was observed, with restoration of consciousness and regression of neurological deficits. Serial imaging demonstrated progressive resorption of the hematoma. The", "source": "PubMed"}, {"chunk_id": "41487867_1", "pmid": "41487867", "title": "Acute Traumatic Intracerebral Hematoma: To Operate or Not to Operate?", "authors": "Grabarczyk L, Grosz A, Waska G et al.", "year": "2025", "journal": "Cureus", "keywords": "conservative medical management, intracranial hemorrhage, medical intensive care unit (micu), severe combined traumatic brain injury, traumatic intracerebral hematoma", "chunk": "and infection prevention. During the following days, gradual clinical improvement was observed, with restoration of consciousness and regression of neurological deficits. Serial imaging demonstrated progressive resorption of the hematoma. The patient was discharged after 17 days in good general condition and transferred for rehabilitation, with only mild residual right lower limb weakness and minor cognitive impairment. This case highlights that, in selected patients, conservative management of TICH may lead to a favorable outcome despite extensive hemorrhage.", "source": "PubMed"}, {"chunk_id": "39989429_0", "pmid": "39989429", "title": "Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.", "authors": "Zeng X, Sehrawat A, Lafferty TK et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "NULISA with next\u2010generation sequencing readout (NULISAseq), NUcleic acid\u2010Linked Immuno\u2010Sandwich Assay (NULISA), amyloid pathology, neurodegeneration, plasma biomarkers, preclinical Alzheimer's disease, proteomics", "chunk": "Proteomic evaluation of plasma samples could accelerate the identification of novel Alzheimer's disease (AD) biomarkers. We evaluated the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort. Plasma biomarkers were measured with NULISA in the Human Connectome Project, a predominantly preclinical biracial community cohort in southwestern Pennsylvania. Selected biomarkers were additionally measured using Simoa and Quest immunoassays and compared. On NULISA, phosphorylated tau (p-tau217, p-tau231, and p-tau181), glial fibrillary acidic protein (GFAP), and microtubule-associated protein tau (MAPT-tau) showed the top significant association with amyloid beta (A\u03b2) positron emission tomography (PET) status, followed by the neuroinflammation markers C-C motif ligand 2 (CCL2), chitotriosidase 1 (CHIT1) and interleukin-8 (CXCL8), and the synaptic marker neurogranin (NRGN). Biomarkers associated with cortical thickness included astrocytic protein chitinase-3-like protein 1 (CHI3L1), cytokine CD40 ligand (CD40LG), brain-derived neurotrophic factor (BDNF), the A\u03b2-associated metalloprotein TIMP3 (tissue inhibitor of metalloprotein 3), and ficolin 2", "source": "PubMed"}, {"chunk_id": "39989429_1", "pmid": "39989429", "title": "Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.", "authors": "Zeng X, Sehrawat A, Lafferty TK et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "NULISA with next\u2010generation sequencing readout (NULISAseq), NUcleic acid\u2010Linked Immuno\u2010Sandwich Assay (NULISA), amyloid pathology, neurodegeneration, plasma biomarkers, preclinical Alzheimer's disease, proteomics", "chunk": "with cortical thickness included astrocytic protein chitinase-3-like protein 1 (CHI3L1), cytokine CD40 ligand (CD40LG), brain-derived neurotrophic factor (BDNF), the A\u03b2-associated metalloprotein TIMP3 (tissue inhibitor of metalloprotein 3), and ficolin 2 (FCN2). Furthermore, moderate to strong between-platform correlations were observed for various assays. NULISA multiplexing advantage allowed concurrent assessment of established and novel plasma biomarkers of A\u03b2 pathology and neurodegeneration. Classical Alzheimer's disease (AD) biomarkers measured using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) with next-generation sequencing readout (NULISAseq) CNS panel showed strong concordance with those measured using established immunoassay methods from Quanterix and Quest, with glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) exhibiting the strongest correlation. NULISAseq proteomic analysis identified several plasma biomarkers strongly associated with AD pathology in a biracial community cohort of older adults. Notably, phosphorylated tau-217 (p-tau217), GFAP, and p-tau231 displayed the strongest association with amyloid beta (A\u03b2) pathology, whereas brain-derived neurotrophic factor (BDNF) was", "source": "PubMed"}, {"chunk_id": "39989429_2", "pmid": "39989429", "title": "Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.", "authors": "Zeng X, Sehrawat A, Lafferty TK et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "NULISA with next\u2010generation sequencing readout (NULISAseq), NUcleic acid\u2010Linked Immuno\u2010Sandwich Assay (NULISA), amyloid pathology, neurodegeneration, plasma biomarkers, preclinical Alzheimer's disease, proteomics", "chunk": "in a biracial community cohort of older adults. Notably, phosphorylated tau-217 (p-tau217), GFAP, and p-tau231 displayed the strongest association with amyloid beta (A\u03b2) pathology, whereas brain-derived neurotrophic factor (BDNF) was strongly associated with neurodegeneration. We demonstrate that plasma biomarker levels could be influenced by age, sex, apolipoprotein E (APOE) genotype, and self-identified race. Specifically, GFAP, NfL, and surfactant protein D (SFTPD) showed a strong association with age; CD63 and S100 calcium-binding protein B (S100B) with self-identified race; synaptosomal-associated protein 25 (SNAP25) with APOE genotype; and serum amyloid A1 (SAA1) and superoxide dismutase 1 (SOD1) with significant sex differences.", "source": "PubMed"}, {"chunk_id": "34951376_0", "pmid": "34951376", "title": "Recent Advancements in Nanodiamond Mediated Brain Targeted Drug Delivery and Bioimaging of Brain Ailments: A Holistic Review.", "authors": "Singh M, Mazumder B", "year": "2022", "journal": "Pharmaceutical nanotechnology", "keywords": "Blood brain barrier, alzheimer\u2019s, bioimaging, brain targeting, glioblastomas, nanodiamonds, nanothernostics, neuro- degenerative diseases", "chunk": "The brain is a vital and composite organ. By nature, the innate make-up of the brain is such that in anatomical parlance, it is highly protected by the \"Blood-Brain Barrier\", which is a nexus of capillary endothelial cells, basement membrane, neuroglial membrane and glialpodocytes. The same barrier, which protects and isolates the interstitial fluid of the brain from capillary circulation, also restricts the therapeutic intervention. Many standing pharmaceutical formulations are ineffective in the treatment of inimical brain ailments because of the inability of the API to surpass and subsist inside the Blood Brain Barrier. This is an integrated review that emphasizes on the recent advancements in brain-targeted drug delivery utilizing nanodiamonds (NDs) as a carrier of therapeutic agents. NDs are a novel nanoparticulate drug delivery system, having carbon moieties as their building blocks and their surface tenability is remarkable. These neoteric carbon-based carriers have exceptional, mechanical, electrical, chemical, optical, and", "source": "PubMed"}, {"chunk_id": "34951376_1", "pmid": "34951376", "title": "Recent Advancements in Nanodiamond Mediated Brain Targeted Drug Delivery and Bioimaging of Brain Ailments: A Holistic Review.", "authors": "Singh M, Mazumder B", "year": "2022", "journal": "Pharmaceutical nanotechnology", "keywords": "Blood brain barrier, alzheimer\u2019s, bioimaging, brain targeting, glioblastomas, nanodiamonds, nanothernostics, neuro- degenerative diseases", "chunk": "a novel nanoparticulate drug delivery system, having carbon moieties as their building blocks and their surface tenability is remarkable. These neoteric carbon-based carriers have exceptional, mechanical, electrical, chemical, optical, and biological properties, which can be further rationally modified and augmented. NDs could be the next\"revolution \"in the field of nanoscience for the treatment of neurodegenerative disorders, brain tumors, and other pernicious brain ailments. What sets them apart from other nanocarriers is their versatile properties like diverse size range and surface modification potential, which makes them efficient enough to move across certain biological barriers and offer a plethora of brain targeting and bioimaging abilities. The blood-brain barrier (BBB) poses a major hurdle in the way of treating many serious brain ailments. A range of nanoparticle based drug delivering systems have been formulated, including solid lipid nanoparticles, liposomes, dendrimers, nanogels, polymeric NPs, metallic NPs (gold, platinum, andironoxide) and diamondoids (carbonnanotubes). Despite this", "source": "PubMed"}, {"chunk_id": "34951376_2", "pmid": "34951376", "title": "Recent Advancements in Nanodiamond Mediated Brain Targeted Drug Delivery and Bioimaging of Brain Ailments: A Holistic Review.", "authors": "Singh M, Mazumder B", "year": "2022", "journal": "Pharmaceutical nanotechnology", "keywords": "Blood brain barrier, alzheimer\u2019s, bioimaging, brain targeting, glioblastomas, nanodiamonds, nanothernostics, neuro- degenerative diseases", "chunk": "A range of nanoparticle based drug delivering systems have been formulated, including solid lipid nanoparticles, liposomes, dendrimers, nanogels, polymeric NPs, metallic NPs (gold, platinum, andironoxide) and diamondoids (carbonnanotubes). Despite this development, only a few of these formulations have shown the ability to cross the BBB. Nanodiamonds, because of their small size, shape, and surface characteristics, have a potential in moving beyond the diverse and intricate BBB, and offer a plethora of brain targeting capabilities.", "source": "PubMed"}, {"chunk_id": "32668504_0", "pmid": "32668504", "title": "Brain-targeted co-delivery of \u03b2-amyloid converting enzyme 1 shRNA and epigallocatechin-3-gallate by multifunctional nanocarriers for Alzheimer's disease treatment.", "authors": "Lv L, Yang F, Li H et al.", "year": "2020", "journal": "IUBMB life", "keywords": "Alzheimer's disease, BACE1, blood brain barrier, brain-targeted therapy, polymer nanoparticles", "chunk": "Progressive memory loss and cognitive dysfunction are hallmark clinical features of Alzheimer's disease (AD). As a possible treatment for AD, we developed an epigallocatechin-3-gallate (EGCG) and \u03b2-site amyloid precursor protein (APP) cleaving enzyme 1 antisense (BACE1-AS) shRNA-encoded plasmid. The plasmid was loaded on to RVG29 peptide-targeted multifunctional nanoparticles (NPs) (REGS-PN). The polymeric NPs were characterized by flow cytometry, biocompatibility assay, pharmacokinetic analysis, Western blot analysis, and the Morris water maze (MWM) test. The differences in plasma and brain NP accumulation following intravenous administration showed a significantly longer circulation time for EGS-PN and REGS-PN in the blood stream. In contrast, free EGCG was rapidly eliminated from the circulation. REGS-PM successfully travelled through the blood-brain barrier and was present at a higher concentration in the brain compared with both non-targeted NPs and free EGCG. REGS-PN administration to APPswe/PS1dE9 double transgenic mice (APP/PS1 mice) resulted in downregulation of the key enzyme in amyloid-\u03b2", "source": "PubMed"}, {"chunk_id": "32668504_1", "pmid": "32668504", "title": "Brain-targeted co-delivery of \u03b2-amyloid converting enzyme 1 shRNA and epigallocatechin-3-gallate by multifunctional nanocarriers for Alzheimer's disease treatment.", "authors": "Lv L, Yang F, Li H et al.", "year": "2020", "journal": "IUBMB life", "keywords": "Alzheimer's disease, BACE1, blood brain barrier, brain-targeted therapy, polymer nanoparticles", "chunk": "concentration in the brain compared with both non-targeted NPs and free EGCG. REGS-PN administration to APPswe/PS1dE9 double transgenic mice (APP/PS1 mice) resulted in downregulation of the key enzyme in amyloid-\u03b2 formation (BACE1) and amyloid beta, indicating synergistic therapeutic activity. The MWM test revealed that simultaneous delivery of a therapeutic gene and EGCG (REGS-PN) remarkably improved the spatial learning and memory capabilities of APP/PS1 mice as well as wild type mice compared with the free EGCG-treated group. With these results, we propose that co-delivery of a therapeutic gene (shRNA) and EGCG in a multifunctional nanocarrier could achieve higher therapeutic concentrations in the brain and could be an excellent strategy for AD treatment.", "source": "PubMed"}, {"chunk_id": "40171859_0", "pmid": "40171859", "title": "Characterization of brain morphology associated with metabolic dysfunction-associated steatotic liver disease in the UK Biobank.", "authors": "Fan W, Yang S, Wei Y et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "Alzheimer's disease\u2010signature cortical thickness, grey matter volume, metabolic dysfunction\u2010associated steatotic liver disease, population\u2010based study, white matter hyperintensity", "chunk": "Emerging evidence has linked metabolic dysfunction-associated steatotic liver disease (MASLD) with accelerated cognitive decline and dementia. We aimed to investigate the associations of MASLD with volumes of total brain tissue and subcortical grey matter, and white matter microstructures in the UK Biobank. This cross-sectional study included 29,195 individuals (aged 45-82 years) from the UK Biobank who undertook a magnetic resonance imaging (MRI) sub-study between 2014 and 2022. The brain MRI covers three modalities (T1, T2 FLAIR, and diffusion). Volumes of grey matter, subcortical grey matter structures, and regional cortex were derived from T1-weighted images. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI) to assess global and tract-specific microstructure. MASLD was defined as the MRI-derived proton density fat fraction (MRI-PDFF) \u22655% and the presence of at least one cardiometabolic criterion. Data were analysed using multiple linear regression models. MASLD was significantly associated with smaller volumes", "source": "PubMed"}, {"chunk_id": "40171859_1", "pmid": "40171859", "title": "Characterization of brain morphology associated with metabolic dysfunction-associated steatotic liver disease in the UK Biobank.", "authors": "Fan W, Yang S, Wei Y et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "Alzheimer's disease\u2010signature cortical thickness, grey matter volume, metabolic dysfunction\u2010associated steatotic liver disease, population\u2010based study, white matter hyperintensity", "chunk": "proton density fat fraction (MRI-PDFF) \u22655% and the presence of at least one cardiometabolic criterion. Data were analysed using multiple linear regression models. MASLD was significantly associated with smaller volumes of total grey matter and subcortical grey matter (p < 0.05) and reduced Alzheimer's disease (AD)-signature cortical thickness (multivariable-adjusted \u03b2 = -0.04; 95% confidence interval [CI]: -0.07, -0.01). Having MASLD was associated with higher total white matter hyperintensity (WMH) volume (multivariable-adjusted \u03b2 = 0.12; 95% CI: 0.10, 0.15). For white matter microstructure, MASLD was associated with increased global FA (multivariable-adjusted \u03b2 = 0.05; 95% CI: 0.03, 0.08) and reduced global MD (multivariable-adjusted \u03b2 = -0.04; 95% CI: -0.07, -0.01). Brain morphology associated with MASLD is characterized by smaller subcortical grey matter volume and higher coherence but lower magnitudes of white matter microstructure.", "source": "PubMed"}, {"chunk_id": "40171859_2", "pmid": "40171859", "title": "Characterization of brain morphology associated with metabolic dysfunction-associated steatotic liver disease in the UK Biobank.", "authors": "Fan W, Yang S, Wei Y et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "Alzheimer's disease\u2010signature cortical thickness, grey matter volume, metabolic dysfunction\u2010associated steatotic liver disease, population\u2010based study, white matter hyperintensity", "chunk": "matter volume and higher coherence but lower magnitudes of white matter microstructure.", "source": "PubMed"}, {"chunk_id": "34367470_0", "pmid": "34367470", "title": "Integrated Analysis of Weighted Gene Coexpression Network Analysis Identifying Six Genes as Novel Biomarkers for Alzheimer's Disease.", "authors": "Zhang T, Liu N, Wei W et al.", "year": "2021", "journal": "Oxidative medicine and cellular longevity", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease; however, there are no comprehensive therapeutic interventions. Therefore, this study is aimed at identifying novel molecular targets that may improve the diagnosis and treatment of patients with AD. In our study, GSE5281 microarray dataset from the GEO database was collected and screened for differential expression analysis. Genes with a <i>P</i> value of <0.05 and \u2223log2FoldChange | >0.5 were considered differentially expressed genes (DEGs). We further profiled and identified AD-related coexpression genes using weighted gene coexpression network analysis (WGCNA). Functional enrichment analysis was performed to determine the characteristics and pathways of the key modules. We constructed an AD-related model based on hub genes by logistic regression and least absolute shrinkage and selection operator (LASSO) analyses, which was also verified by the receiver operating characteristic (ROC) curve. In total, 4674 DEGs were identified. Nine distinct coexpression modules were identified via WGCNA; among these", "source": "PubMed"}, {"chunk_id": "34367470_1", "pmid": "34367470", "title": "Integrated Analysis of Weighted Gene Coexpression Network Analysis Identifying Six Genes as Novel Biomarkers for Alzheimer's Disease.", "authors": "Zhang T, Liu N, Wei W et al.", "year": "2021", "journal": "Oxidative medicine and cellular longevity", "keywords": "None", "chunk": "operator (LASSO) analyses, which was also verified by the receiver operating characteristic (ROC) curve. In total, 4674 DEGs were identified. Nine distinct coexpression modules were identified via WGCNA; among these modules, the blue module showed the highest positive correlation with AD (<i>r</i> = 0.64, <i>P</i> = 3<i>e</i> - 20), and it was visualized by establishing a protein-protein interaction network. Moreover, this module was particularly enriched in \"pathways of neurodegeneration-multiple diseases,\" \"Alzheimer disease,\" \"oxidative phosphorylation,\" and \"proteasome.\" Sixteen genes were identified as hub genes and further submitted to a LASSO regression model, and six genes (<i>EIF3H</i>, <i>RAD51C</i>, <i>FAM162A</i>, <i>BLVRA</i>, <i>ATP6V1H</i>, and <i>BRAF</i>) were identified based on the model index. Additionally, we assessed the accuracy of the LASSO model by plotting an ROC curve (AUC = 0.940). Using the WGCNA and LASSO models, our findings provide a better understanding of the role of biomarkers <i>EIF3H</i>, <i>RAD51C</i>, <i>FAM162A</i>, <i>BLVRA</i>, <i>ATP6V1H</i>, and <i>BRAF</i> and", "source": "PubMed"}, {"chunk_id": "34367470_2", "pmid": "34367470", "title": "Integrated Analysis of Weighted Gene Coexpression Network Analysis Identifying Six Genes as Novel Biomarkers for Alzheimer's Disease.", "authors": "Zhang T, Liu N, Wei W et al.", "year": "2021", "journal": "Oxidative medicine and cellular longevity", "keywords": "None", "chunk": "ROC curve (AUC = 0.940). Using the WGCNA and LASSO models, our findings provide a better understanding of the role of biomarkers <i>EIF3H</i>, <i>RAD51C</i>, <i>FAM162A</i>, <i>BLVRA</i>, <i>ATP6V1H</i>, and <i>BRAF</i> and provide a basis for further studies on AD progression.", "source": "PubMed"}, {"chunk_id": "38165328_0", "pmid": "38165328", "title": "C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis.", "authors": "McCabe JJ, Walsh C, Gorey S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after log<sub>e</sub> transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. IPD was obtained", "source": "PubMed"}, {"chunk_id": "38165328_1", "pmid": "38165328", "title": "C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis.", "authors": "McCabe JJ, Walsh C, Gorey S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "after log<sub>e</sub> transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, <i>p</i> = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, <i>p</i> = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, <i>p</i> = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per log<sub>e</sub> unit increase for MACE (LAA, RR 1.26 [1.06-1.50], <i>p</i> = 0.009; SVO, RR 1.22 [1.01-1.47], <i>p</i> = 0.04; UND, RR 1.18 [1.04-1.34], <i>p</i> = 0.01). High-sensitivity CRP was", "source": "PubMed"}, {"chunk_id": "38165328_2", "pmid": "38165328", "title": "C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis.", "authors": "McCabe JJ, Walsh C, Gorey S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "per log<sub>e</sub> unit increase for MACE (LAA, RR 1.26 [1.06-1.50], <i>p</i> = 0.009; SVO, RR 1.22 [1.01-1.47], <i>p</i> = 0.04; UND, RR 1.18 [1.04-1.34], <i>p</i> = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], <i>p</i> = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.", "source": "PubMed"}, {"chunk_id": "39201303_0", "pmid": "39201303", "title": "Interconnections between the Gut Microbiome and Alzheimer's Disease: Mechanisms and Therapeutic Potential.", "authors": "Sait AM, Day PJR", "year": "2024", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease (AD), gut microbiome, lipopolysaccharide (LPS), short-chain fatty acids (SCFAs)", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-\u03b2 (A\u03b2) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The A\u03b2 monoclonal antibody lecanemab reduces A\u03b2 plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood-brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.", "source": "PubMed"}, {"chunk_id": "39201303_1", "pmid": "39201303", "title": "Interconnections between the Gut Microbiome and Alzheimer's Disease: Mechanisms and Therapeutic Potential.", "authors": "Sait AM, Day PJR", "year": "2024", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease (AD), gut microbiome, lipopolysaccharide (LPS), short-chain fatty acids (SCFAs)", "chunk": "summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.", "source": "PubMed"}, {"chunk_id": "26400113_0", "pmid": "26400113", "title": "Down syndrome--genetic and nutritional aspects of accompanying disorders.", "authors": "Mazurek D, Wyka J", "year": "2015", "journal": "Roczniki Panstwowego Zakladu Higieny", "keywords": "None", "chunk": "Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases. It is caused by having a third copy of chromosome 21, and there exist 3 forms; Simple Trisomy 21, Translocation Trisomy and Mosaic Trisomy. Symptoms include intellectual disability/mental retardation, early onset of Alzheimer's disease and the appearance of various phenotypic features such as narrow slanted eyes, flat nose and short stature. In addition, there are other health problems throughout the body, consisting in part of cardiac defects and thyroid function abnormalities along with nutritional disorders (ie. overweight, obesity, hypercholesterolemia and deficiencies of vitamins and minerals). Those suffering DS have widespread body frame abnormalities and impaired brain development and function; the latter leading to impaired intellectual development. Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (eg. celiac disease) or malabsorption. DS persons with", "source": "PubMed"}, {"chunk_id": "26400113_1", "pmid": "26400113", "title": "Down syndrome--genetic and nutritional aspects of accompanying disorders.", "authors": "Mazurek D, Wyka J", "year": "2015", "journal": "Roczniki Panstwowego Zakladu Higieny", "keywords": "None", "chunk": "latter leading to impaired intellectual development. Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (eg. celiac disease) or malabsorption. DS persons with overweight or obesity are linked with a slow metabolic rate, abnormal blood leptin concentrations and exhibit low levels of physical activity. Vitamin B group deficiencies and abnormal blood homocysteine levels decrease the rate of intellectual development in DS cases. Zinc deficiencies result in short stature, thyroid function disorders and an increased appetite caused by excessive supplementation. Scientific advances in the research and diagnosis of DS, as well as preventing any associated conditions, have significantly increased life expectancies of those with this genetic disorder. Early dietary interventions by parents or guardians of DS children afford an opportunity for decreasing the risk or delaying some of the DS associated conditions from appearing, thus beneficially impacting on their quality of life.", "source": "PubMed"}, {"chunk_id": "26400113_2", "pmid": "26400113", "title": "Down syndrome--genetic and nutritional aspects of accompanying disorders.", "authors": "Mazurek D, Wyka J", "year": "2015", "journal": "Roczniki Panstwowego Zakladu Higieny", "keywords": "None", "chunk": "of DS children afford an opportunity for decreasing the risk or delaying some of the DS associated conditions from appearing, thus beneficially impacting on their quality of life.", "source": "PubMed"}, {"chunk_id": "41314150_0", "pmid": "41314150", "title": "Quantitative susceptibility mapping at 7T as a biomarker of post- and interictal extravascular iron in patients with focal epilepsy.", "authors": "Held NR, Bauer T, Stirnberg R et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Blood\u2013brain-barrier dysfunction, Neuroinflammation, Postictal imaging, Ultra-high-field MRI", "chunk": "Iron deposition in the brain has been associated with epilepsy, but its anatomical distribution and its temporal association to seizures remain unclear. Here, we investigate brain iron in individuals with focal epilepsy using interictal and postictal quantitative susceptibility mapping (QSM) at 7 T MRI and explore its functional relevance. 80 consecutive participants with focal epilepsy undergoing presurgical evaluation and 50 healthy controls were included. 8/80 participants with focal epilepsy had interictal and postictal scans. High-resolution T1- and susceptibility-weighted images were acquired and processed using custom pipelines for QSM. Seizure onset zones were determined by expert consensus, and neuropsychological assessments included memory and mood. Parcel-wise analyses examined group differences and correlations with cognitive scores, controlling for age and sex. Participants with focal epilepsy showed significantly higher interictal susceptibility, which colocalised with the presumed seizure onset zone. Impaired memory performance and more severe depressive symptoms were correlated with higher interictal susceptibility. Postictal", "source": "PubMed"}, {"chunk_id": "41314150_1", "pmid": "41314150", "title": "Quantitative susceptibility mapping at 7T as a biomarker of post- and interictal extravascular iron in patients with focal epilepsy.", "authors": "Held NR, Bauer T, Stirnberg R et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Blood\u2013brain-barrier dysfunction, Neuroinflammation, Postictal imaging, Ultra-high-field MRI", "chunk": "focal epilepsy showed significantly higher interictal susceptibility, which colocalised with the presumed seizure onset zone. Impaired memory performance and more severe depressive symptoms were correlated with higher interictal susceptibility. Postictal susceptibility was significantly higher than interictal susceptibility and associated to the number of preceding seizures. QSM reflects both ictal iron extravasation and interictal iron accumulation. If further validated, it may help to non-invasively delineate the epileptogenic zone and become a long-term biomarker for seizure-burden. N.R.H. and T.Bauer were supported by the BONFOR research commission of the Medical Faculty of the University of Bonn. T.Bauer was funded by the Deutsche Forschungsgemeinschaft. T.Bauer., L.W., A.L. and T.R. are funded by the German Ministry for Research, Technology and Space.", "source": "PubMed"}, {"chunk_id": "39371344_0", "pmid": "39371344", "title": "Enhancing healthcare recommendation: transfer learning in deep convolutional neural networks for Alzheimer disease detection.", "authors": "Pandey PK, Pruthi J, Alzahrani S et al.", "year": "2024", "journal": "Frontiers in medicine", "keywords": "Densenet, EfficientNet-B0, Resnet, clustering, decision making, deep learning, healthcare, skull stripping", "chunk": "Neurodegenerative disorders such as Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) significantly impact brain function and cognition. Advanced neuroimaging techniques, particularly Magnetic Resonance Imaging (MRI), play a crucial role in diagnosing these conditions by detecting structural abnormalities. This study leverages the ADNI and OASIS datasets, renowned for their extensive MRI data, to develop effective models for detecting AD and MCI. The research conducted three sets of tests, comparing multiple groups: multi-class classification (AD vs. Cognitively Normal (CN) vs. MCI), binary classification (AD vs. CN, and MCI vs. CN), to evaluate the performance of models trained on ADNI and OASIS datasets. Key preprocessing techniques such as Gaussian filtering, contrast enhancement, and resizing were applied to both datasets. Additionally, skull stripping using U-Net was utilized to extract features by removing the skull. Several prominent deep learning architectures including DenseNet-201, EfficientNet-B0, ResNet-50, ResNet-101, and ResNet-152 were investigated to identify subtle patterns associated", "source": "PubMed"}, {"chunk_id": "39371344_1", "pmid": "39371344", "title": "Enhancing healthcare recommendation: transfer learning in deep convolutional neural networks for Alzheimer disease detection.", "authors": "Pandey PK, Pruthi J, Alzahrani S et al.", "year": "2024", "journal": "Frontiers in medicine", "keywords": "Densenet, EfficientNet-B0, Resnet, clustering, decision making, deep learning, healthcare, skull stripping", "chunk": "using U-Net was utilized to extract features by removing the skull. Several prominent deep learning architectures including DenseNet-201, EfficientNet-B0, ResNet-50, ResNet-101, and ResNet-152 were investigated to identify subtle patterns associated with AD and MCI. Transfer learning techniques were employed to enhance model performance, leveraging pre-trained datasets for improved Alzheimer's MCI detection. ResNet-101 exhibited superior performance compared to other models, achieving 98.21% accuracy on the ADNI dataset and 97.45% accuracy on the OASIS dataset in multi-class classification tasks encompassing AD, CN, and MCI. It also performed well in binary classification tasks distinguishing AD from CN. ResNet-152 excelled particularly in binary classification between MCI and CN on the OASIS dataset. These findings underscore the utility of deep learning models in accurately identifying and distinguishing neurodegenerative diseases, showcasing their potential for enhancing clinical diagnosis and treatment monitoring.", "source": "PubMed"}, {"chunk_id": "39371344_2", "pmid": "39371344", "title": "Enhancing healthcare recommendation: transfer learning in deep convolutional neural networks for Alzheimer disease detection.", "authors": "Pandey PK, Pruthi J, Alzahrani S et al.", "year": "2024", "journal": "Frontiers in medicine", "keywords": "Densenet, EfficientNet-B0, Resnet, clustering, decision making, deep learning, healthcare, skull stripping", "chunk": "and distinguishing neurodegenerative diseases, showcasing their potential for enhancing clinical diagnosis and treatment monitoring.", "source": "PubMed"}, {"chunk_id": "39832138_0", "pmid": "39832138", "title": "Cortical Gyrification and Cognitive Decline in the Human Brain With Type 2 Diabetes Mellitus.", "authors": "Lu W, Chen Y, Cao Z et al.", "year": "2025", "journal": "Brain and behavior", "keywords": "cognition, local gyrification index, type 2 diabetes mellitus", "chunk": "Type 2 diabetes mellitus (T2DM) is linked to abnormal brain structure and cognitive dysfunction. However, there is a lack of studies conducted to assess the impact of diabetes on cortical gyrification and cognition. The aim of this cross-sectional study was to assess the potential negative effects of glucose metabolism levels on cognition and cortical gyrification in T2DM. The current study comprised 83 patients with T2DM and 60 individuals with normal glucose metabolism (NGM). The calculation of the local gyrification index (LGI) was performed utilizing the FreeSurfer software. Subsequently, between-group differences were examined through the utilization of analysis of covariance. Multivariable linear regression and mediation models were employed to investigate the relationships among LGI, glucose metabolism and cognition. Our study found that the mean LGI of the entire brain in individuals with T2DM was lower than that of NGM, and these significant hypogyria were mainly located in the bilateral temporal lobes,", "source": "PubMed"}, {"chunk_id": "39832138_1", "pmid": "39832138", "title": "Cortical Gyrification and Cognitive Decline in the Human Brain With Type 2 Diabetes Mellitus.", "authors": "Lu W, Chen Y, Cao Z et al.", "year": "2025", "journal": "Brain and behavior", "keywords": "cognition, local gyrification index, type 2 diabetes mellitus", "chunk": "that the mean LGI of the entire brain in individuals with T2DM was lower than that of NGM, and these significant hypogyria were mainly located in the bilateral temporal lobes, including the left superior temporal cortex, left transverse temporal cortex, and bilateral temporal pole, with the greatest effect size in the left temporal pole (p = 5.7\u00d710<sup>-7</sup>, Cohen's f<sup>2</sup> = 0.169). In addition, the relationship between fasting blood glucose and working memory was mediated by the LGI in the right temporal pole. Our experiment suggests that the decreased LGI in the right temporal pole explains poorer working memory performance in patients with T2DM.", "source": "PubMed"}, {"chunk_id": "40757742_0", "pmid": "40757742", "title": "Multifunctional Amyloid-Like Porous Nanofilm-Decorated Transistor-Based Biosensor for Accurate Detection of Alzheimer's Disease Biomarker.", "authors": "Wang X, Zou Q, Chen W et al.", "year": "2025", "journal": "Analytical chemistry", "keywords": "None", "chunk": "The high sensitivity of field-effect transistor (FET) biosensors has made them a valuable tool for detecting low abundance biomarkers in AD diagnosis, but it faces ongoing challenges, particularly in their susceptibility to interference from complex sample matrices. Here, an amyloid-like nanofilm was introduced as an intermediate layer to enhance the antifouling ability and sensitivity of FET biosensors in complex systems. This nanofilm serves a dual purpose: due to the size-selective mechanism of the amyloid-like nanofilm, which prevents interference from nonspecific proteins, the proposed biosensor exhibited enhanced stability and antifouling capability in complex samples (nonspecific response of less than 5%). Weakening Debye shielding through its undulating porous structure enabled the highly sensitive detection of biomarkers even in solutions with high ionic strength. The biosensor successfully detected Alzheimer's disease (AD) biomarker P-tau181 with a low limit of detection down to 0.1 fg/mL and achieved a remarkable 100% diagnostic accuracy across 25 serum", "source": "PubMed"}, {"chunk_id": "40757742_1", "pmid": "40757742", "title": "Multifunctional Amyloid-Like Porous Nanofilm-Decorated Transistor-Based Biosensor for Accurate Detection of Alzheimer's Disease Biomarker.", "authors": "Wang X, Zou Q, Chen W et al.", "year": "2025", "journal": "Analytical chemistry", "keywords": "None", "chunk": "strength. The biosensor successfully detected Alzheimer's disease (AD) biomarker P-tau181 with a low limit of detection down to 0.1 fg/mL and achieved a remarkable 100% diagnostic accuracy across 25 serum samples. This study provides a highly stable and sensitive FET biosensor that is expected to be used for early screening of AD.", "source": "PubMed"}, {"chunk_id": "30108983_0", "pmid": "30108983", "title": "Live-cell fluorescence imaging: assessment of thioflavin T uptake in human epidermal carcinoma cells.", "authors": "Sundaram GSM, Binz K, Sharma V et al.", "year": "2018", "journal": "MedChemComm", "keywords": "None", "chunk": "Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely used fluorescent marker of amyloid pathophysiology to confirm the cause of death in <i>post mortem</i> brain tissue of Alzheimer's disease (AD) patients. Literature precedents indicate that current positron emission tomography (PET) agents, such as <sup>11</sup>C-PIB and <sup>18</sup>F-flutemetamol, share significant structural similarity with ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to enable the detection of A\u03b2 plaques <i>in vivo</i>. While vital for maintaining normal physiology and healthy brain function, the BBB comprises brain endothelial cells sealed <i>via</i> paracellular protein complexes, bound by an extracellular matrix forming tight junctions thus controlling the delivery of molecules into the brain. The human P-glycoprotein (Pgp/ABCB1, 170 kD plasma membrane protein), belonging to the ABC family of efflux transporter proteins, also lines the luminal surface of brain endothelial cells thus poised to secrete its recognized substrates into the blood.", "source": "PubMed"}, {"chunk_id": "30108983_1", "pmid": "30108983", "title": "Live-cell fluorescence imaging: assessment of thioflavin T uptake in human epidermal carcinoma cells.", "authors": "Sundaram GSM, Binz K, Sharma V et al.", "year": "2018", "journal": "MedChemComm", "keywords": "None", "chunk": "membrane protein), belonging to the ABC family of efflux transporter proteins, also lines the luminal surface of brain endothelial cells thus poised to secrete its recognized substrates into the blood. Herein, we postulate that thioflavin T (ThT), due to its physico-chemical attributes, such as moderate lipophilicity and protonated nitrogen, could very well be recognized as a transport substrate of Pgp (P-glycoprotein, ABCB1) thus restricting its permeation into the brain. To evaluate whether or not ThT is indeed recognized by Pgp as its transport substrate thus limiting its BBB permeability, herein, we evaluate cellular accumulation profiles of ThT and PiB (a similar structural uncharged mimetic) in human epidermal carcinoma KB-3-1 (Pgp-) and MDR KB-8-5 (Pgp+) cells, using live-cell fluorescence imaging. While ThT penetrates KB-3-1 cells, it gets excluded from KB-8-5 cells, and also indicates LY335979-induced uptake in Pgp-expressing cells. Furthermore, the cellular uptake profiles of PiB are not impacted by the", "source": "PubMed"}, {"chunk_id": "30108983_2", "pmid": "30108983", "title": "Live-cell fluorescence imaging: assessment of thioflavin T uptake in human epidermal carcinoma cells.", "authors": "Sundaram GSM, Binz K, Sharma V et al.", "year": "2018", "journal": "MedChemComm", "keywords": "None", "chunk": "ThT penetrates KB-3-1 cells, it gets excluded from KB-8-5 cells, and also indicates LY335979-induced uptake in Pgp-expressing cells. Furthermore, the cellular uptake profiles of PiB are not impacted by the expression of Pgp under identical conditions. These data show that uptake profiles of ThT have been modified by the expression of Pgp in these cells, and are inversely proportional to the expression of the transporter protein located on the plasma membrane of these cells. Combined data demonstrate that ThT is efficiently recognized by Pgp as its transport substrate.", "source": "PubMed"}, {"chunk_id": "36566957_0", "pmid": "36566957", "title": "Insulin resistance in Alzheimer's disease: The genetics and metabolomics links.", "authors": "Amin AM, Mostafa H, Khojah HMJ", "year": "2023", "journal": "Clinica chimica acta; international journal of clinical chemistry", "keywords": "Alzheimer\u2019s disease, Diabetes, Genetic, Insulin resistance, Metabolomics, Obesity, Therapeutics", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disease with significant socioeconomic burden worldwide. Although genetics and environmental factors play a role, AD is highly associated with insulin resistance (IR) disorders such as metabolic syndrome (MS), obesity, and type two diabetes mellitus (T2DM). These findings highlight a shared pathogenesis. The use of metabolomics as a downstream systems' biology (omics) approach can help to identify these shared metabolic traits and assist in the early identification of at-risk groups and potentially guide therapy. Targeting the shared AD-IR metabolic trait with lifestyle interventions and pharmacological treatments may offer promising AD therapeutic approach. In this narrative review, we reviewed the literature on the AD-IR pathogenic link, the shared genetics and metabolomics biomarkers between AD and IR disorders, as well as the lifestyle interventions and pharmacological treatments which target this pathogenic link.", "source": "PubMed"}, {"chunk_id": "36566957_1", "pmid": "36566957", "title": "Insulin resistance in Alzheimer's disease: The genetics and metabolomics links.", "authors": "Amin AM, Mostafa H, Khojah HMJ", "year": "2023", "journal": "Clinica chimica acta; international journal of clinical chemistry", "keywords": "Alzheimer\u2019s disease, Diabetes, Genetic, Insulin resistance, Metabolomics, Obesity, Therapeutics", "chunk": "disorders, as well as the lifestyle interventions and pharmacological treatments which target this pathogenic link.", "source": "PubMed"}, {"chunk_id": "38509675_0", "pmid": "38509675", "title": "Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions.", "authors": "Haskologlu IC, Erdag E, Sehirli AO et al.", "year": "2024", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease., Bmal1, FDA-approved drugs, chronotherapy, melatonin, molecular docking", "chunk": "Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal in regulating the body's intrinsic circadian rhythm, also acts as a catalyst in the breakdown of beta-amyloid deposits, offering a promising therapeutic approach for AD. The upregulation of Brain and Muscle ARNT-Like 1 (Bmal1) gene expression, stimulated by melatonin, emerges as a potential contributor to AD intervention. Current pharmacological interventions, such as FDA-approved cholinesterase inhibitors and the recently authorized monoclonal antibody, Lecanemab, are utilized in AD management. However, the connection between these medications and Bmal1 remains insufficiently explored. This study aims to investigate the molecular effects of FDA-endorsed drugs on the CLOCK: Bmal1 dimer. Furthermore, considering the interactions between melatonin and Bmal1, this research explores the potential synergistic efficacy of combining these pharmaceutical agents with melatonin for AD treatment. Using molecular docking and MM/PBSA methodologies, this research", "source": "PubMed"}, {"chunk_id": "38509675_1", "pmid": "38509675", "title": "Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions.", "authors": "Haskologlu IC, Erdag E, Sehirli AO et al.", "year": "2024", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease., Bmal1, FDA-approved drugs, chronotherapy, melatonin, molecular docking", "chunk": "interactions between melatonin and Bmal1, this research explores the potential synergistic efficacy of combining these pharmaceutical agents with melatonin for AD treatment. Using molecular docking and MM/PBSA methodologies, this research determines the binding affinities of drugs within the Bmal1 binding site, constructing interaction profiles. The findings reveal that, among FDA-approved drugs, galanthamine and donepezil demonstrate notably similar binding energy values to melatonin, interacting within the Bmal1 binding site through analogous amino acid residues and functional groups. A novel therapeutic approach emerges, suggesting the combination of melatonin with Lecanemab as a monoclonal antibody therapy. Importantly, prior research has not explored the effects of FDA-approved drugs on Bmal1 expression or their potential for synergistic effects.", "source": "PubMed"}, {"chunk_id": "36457825_0", "pmid": "36457825", "title": "Conserved YKL-40 changes in mice and humans after postoperative delirium.", "authors": "David-Bercholz J, Acker L, Caceres AI et al.", "year": "2022", "journal": "Brain, behavior, & immunity - health", "keywords": "4-OHT, 4-hydroxytamoxifen, 5-CSRTT, 5-Choice Serial Reaction Time Test, AD, Alzheimer\u2019s disease, Aging, Attention, BBB, blood-brain barrier, Biomarkers, CAM, Confusion AssessmentMethod, CNS, central nervous system, CSF, cerebrospinal fluid, Delirium, ELISA, enzyme-linked immunosorbent assay, GFAP, glial fibrillary acidic protein, IHC, immunohistochemistry, IL-6, interleukin-6, MMSE, mini-mental status exam, NfL, neurofilament light chain, PBS, phosphate-buffered saline, PFA, paraformaldehyde, PLC, prelimbic cortex, ROI, regions of interest, SIMOA, single molecule array, Surgery, TRAP, Targeted Recombination in Active Populations, YKL-40, YKL-40, chitinase-3-like protein 1", "chunk": "Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the \"Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults\" (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased.", "source": "PubMed"}, {"chunk_id": "36457825_1", "pmid": "36457825", "title": "Conserved YKL-40 changes in mice and humans after postoperative delirium.", "authors": "David-Bercholz J, Acker L, Caceres AI et al.", "year": "2022", "journal": "Brain, behavior, & immunity - health", "keywords": "4-OHT, 4-hydroxytamoxifen, 5-CSRTT, 5-Choice Serial Reaction Time Test, AD, Alzheimer\u2019s disease, Aging, Attention, BBB, blood-brain barrier, Biomarkers, CAM, Confusion AssessmentMethod, CNS, central nervous system, CSF, cerebrospinal fluid, Delirium, ELISA, enzyme-linked immunosorbent assay, GFAP, glial fibrillary acidic protein, IHC, immunohistochemistry, IL-6, interleukin-6, MMSE, mini-mental status exam, NfL, neurofilament light chain, PBS, phosphate-buffered saline, PFA, paraformaldehyde, PLC, prelimbic cortex, ROI, regions of interest, SIMOA, single molecule array, Surgery, TRAP, Targeted Recombination in Active Populations, YKL-40, YKL-40, chitinase-3-like protein 1", "chunk": "not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.", "source": "PubMed"}, {"chunk_id": "36457825_2", "pmid": "36457825", "title": "Conserved YKL-40 changes in mice and humans after postoperative delirium.", "authors": "David-Bercholz J, Acker L, Caceres AI et al.", "year": "2022", "journal": "Brain, behavior, & immunity - health", "keywords": "4-OHT, 4-hydroxytamoxifen, 5-CSRTT, 5-Choice Serial Reaction Time Test, AD, Alzheimer\u2019s disease, Aging, Attention, BBB, blood-brain barrier, Biomarkers, CAM, Confusion AssessmentMethod, CNS, central nervous system, CSF, cerebrospinal fluid, Delirium, ELISA, enzyme-linked immunosorbent assay, GFAP, glial fibrillary acidic protein, IHC, immunohistochemistry, IL-6, interleukin-6, MMSE, mini-mental status exam, NfL, neurofilament light chain, PBS, phosphate-buffered saline, PFA, paraformaldehyde, PLC, prelimbic cortex, ROI, regions of interest, SIMOA, single molecule array, Surgery, TRAP, Targeted Recombination in Active Populations, YKL-40, YKL-40, chitinase-3-like protein 1", "chunk": "humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.", "source": "PubMed"}, {"chunk_id": "40583796_0", "pmid": "40583796", "title": "Blood biomarkers of Alzheimer's disease in Australians habitually consuming various plant-based diets.", "authors": "Eslick S, Austin G, Ferguson JJ et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarkers, diet, plant-based, prevention", "chunk": "BackgroundEvidence suggests that plant-based diets (PBDs) may be protective against neurodegenerative diseases such as Alzheimer's disease (AD).ObjectiveThis study examined associations between blood-based AD biomarkers in individuals 30-75 years without current or diagnosed cardiovascular disease following different PBDs versus regular meat-eating diets (RMEs).MethodsThis secondary analysis of the Plant-based Diets study measured A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub>, p-tau181, NFL, and GFAP in 237 plasma samples using SIMOA from individuals following vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or RME diets. Multivariable regression adjusted for age and sex.ResultsFollowing adjustments for age and sex, plasma A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub> ratio was significantly higher in PVs 0.011 (CI: 0.006, 0.016, p < 0.01), LOVs 0.011 (CI: 0.007, 0.016, p < 0.01) and SVs 0.015 (0.009-0.020, p < 0.01) groups compared to RMEs. Plasma p-tau181 was significantly higher in PVs 3.4 (CI: 0.4-6.4, p < 0.05) and LOVs 7.1 (CI: 2.5, 11.8, p < 0.01), NFL higher in PVs 5.2 (CI: 1.6,", "source": "PubMed"}, {"chunk_id": "40583796_1", "pmid": "40583796", "title": "Blood biomarkers of Alzheimer's disease in Australians habitually consuming various plant-based diets.", "authors": "Eslick S, Austin G, Ferguson JJ et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarkers, diet, plant-based, prevention", "chunk": "RMEs. Plasma p-tau181 was significantly higher in PVs 3.4 (CI: 0.4-6.4, p < 0.05) and LOVs 7.1 (CI: 2.5, 11.8, p < 0.01), NFL higher in PVs 5.2 (CI: 1.6, 8.7, p < 0.01) and LOVs 4.0 (CI: 1.6, 6.5, p = 0.01), and GFAP higher in PVs 26 (CI: 6, 47, p < 0.05) and LOVs 21 (5, 367, p = 0.01), all compared to RMEs.ConclusionsThis analysis suggests that PBDs may be associated with blood-based AD biomarkers. Higher A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub> levels in PV, LOV and SV dietary patterns compared to RMEs could indicate lesser amyloid burden, but elevated levels of other AD biomarkers in some PBDs warrant further investigation into nutrient-specific roles in AD pathology.", "source": "PubMed"}, {"chunk_id": "40067299_0", "pmid": "40067299", "title": "Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults.", "authors": "Dhana A, DeCarli CS, Dhana K et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "Cardiovascular health (CVH), defined by the American Heart Association as Life's Simple 7 to promote a healthy lifestyle and manage vascular risk factors, has been associated with a low risk of Alzheimer disease and less vascular dementia. However, the association between CVH and biomarkers of neurodegeneration remains less understood. To investigate the association of CVH with serum biomarkers of neurodegeneration, including neurofilament light chain (NfL) and total tau (t-tau). This cohort study was conducted within the biracial, population-based Chicago Health and Aging Project (CHAP) of adults aged 65 years or older between 1993 and 2012. Participants who had measured serum NfL and t-tau levels and data on all components of the CVH score were included. The statistical analysis was conducted from April 10 to September 26, 2024. The CVH score includes 7 components: a healthy diet; regular exercise; normal body mass index; nonsmoking status; and the absence of dyslipidemia, diabetes,", "source": "PubMed"}, {"chunk_id": "40067299_1", "pmid": "40067299", "title": "Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults.", "authors": "Dhana A, DeCarli CS, Dhana K et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "from April 10 to September 26, 2024. The CVH score includes 7 components: a healthy diet; regular exercise; normal body mass index; nonsmoking status; and the absence of dyslipidemia, diabetes, and hypertension. The scores were divided into 3 groups from lowest to highest CVH (0-6 points, 7-9 points, and 10-14 points). The main outcome was the association of CVH score with serum biomarkers of NfL and t-tau as measured using linear regression and mixed-effects models. A total of 1018 CHAP participants were included in the analysis (mean [SD] age, 73.1 [6.1] years; 625 female [61.4%]; 610 Black or African American [59.9%] and 408 White [40.1%]). Participants with a high CVH score (ie, 10-14 points) were predominantly White (151 [64.3%]) and had a higher education (mean [SD], 13.6 [3.7] years). Compared with participants with low CVH scores (ie, 0-6 points), those with CVH scores of 10 to 14 points had significantly", "source": "PubMed"}, {"chunk_id": "40067299_2", "pmid": "40067299", "title": "Cardiovascular Health and Biomarkers of Neurodegenerative Disease in Older Adults.", "authors": "Dhana A, DeCarli CS, Dhana K et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "had a higher education (mean [SD], 13.6 [3.7] years). Compared with participants with low CVH scores (ie, 0-6 points), those with CVH scores of 10 to 14 points had significantly lower serum levels of NfL (relative difference, -18.9%; \u03b2 = -0.091; SE, 0.025). A higher CVH score was associated with a slower annual increase in NfL levels as participants aged (relative difference in rate, -1.7%; \u03b2 = -0.008; SE, 0.004). Cardiovascular health was not associated with serum levels of t-tau. These findings suggest that promoting CVH in older adults may help alleviate the burden of neurodegenerative diseases, particularly among Black adults, who are known to experience a higher prevalence of cardiovascular disease.", "source": "PubMed"}, {"chunk_id": "38674233_0", "pmid": "38674233", "title": "Brodmann Areas, V1 Atlas and Cognitive Impairment: Assessing Cortical Thickness for Cognitive Impairment Diagnostics.", "authors": "Tri\u0161ins M, Zdanovskis N, Platk\u0101jis A et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "Alzheimer\u2019s disease, Brodmann areas, atlas-based segmentation, cognition, cortical thickness, dementia, mild cognitive impairment, neuroimaging, structural MRI", "chunk": "<i>Background and Objectives</i>: Magnetic resonance imaging is vital for diagnosing cognitive decline. Brodmann areas (BA), distinct regions of the cerebral cortex categorized by cytoarchitectural variances, provide insights into cognitive function. This study aims to compare cortical thickness measurements across brain areas identified by BA mapping. We assessed these measurements among patients with and without cognitive impairment, and across groups categorized by cognitive performance levels using the Montreal Cognitive Assessment (MoCA) test. <i>Materials and Methods</i>: In this cross-sectional study, we included 64 patients who were divided in two ways: in two groups with (CI) or without (NCI) impaired cognitive function and in three groups with normal (NC), moderate (MPG) and low (LPG) cognitive performance according to MoCA scores. Scans with a 3T MRI scanner were carried out, and cortical thickness data was acquired using Freesurfer 7.2.0 software. <i>Results</i>: By analyzing differences between the NCI and CI groups cortical thickness of BA3a", "source": "PubMed"}, {"chunk_id": "38674233_1", "pmid": "38674233", "title": "Brodmann Areas, V1 Atlas and Cognitive Impairment: Assessing Cortical Thickness for Cognitive Impairment Diagnostics.", "authors": "Tri\u0161ins M, Zdanovskis N, Platk\u0101jis A et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "Alzheimer\u2019s disease, Brodmann areas, atlas-based segmentation, cognition, cortical thickness, dementia, mild cognitive impairment, neuroimaging, structural MRI", "chunk": "3T MRI scanner were carried out, and cortical thickness data was acquired using Freesurfer 7.2.0 software. <i>Results</i>: By analyzing differences between the NCI and CI groups cortical thickness of BA3a in left hemisphere (U = 241.000, <i>p</i> = 0.016), BA4a in right hemisphere (U = 269.000, <i>p</i> = 0.048) and BA28 in left hemisphere (U = 584.000, <i>p</i> = 0.005) showed significant differences. In the LPG, MPG and NC cortical thickness in BA3a in left hemisphere (H (2) = 6.268, <i>p</i> = 0.044), in V2 in right hemisphere (H (2) = 6.339, <i>p</i> = 0.042), in BA28 in left hemisphere (H (2) = 23.195, <i>p</i> < 0.001) and in BA28 in right hemisphere (H (2) = 10.015, <i>p</i> = 0.007) showed significant differences. <i>Conclusions</i>: Our study found that cortical thickness in specific Brodmann Areas-BA3a and BA28 in the left hemisphere, and BA4a in the right-differ significantly between NCI and CI", "source": "PubMed"}, {"chunk_id": "38674233_2", "pmid": "38674233", "title": "Brodmann Areas, V1 Atlas and Cognitive Impairment: Assessing Cortical Thickness for Cognitive Impairment Diagnostics.", "authors": "Tri\u0161ins M, Zdanovskis N, Platk\u0101jis A et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "Alzheimer\u2019s disease, Brodmann areas, atlas-based segmentation, cognition, cortical thickness, dementia, mild cognitive impairment, neuroimaging, structural MRI", "chunk": "showed significant differences. <i>Conclusions</i>: Our study found that cortical thickness in specific Brodmann Areas-BA3a and BA28 in the left hemisphere, and BA4a in the right-differ significantly between NCI and CI groups. Significant differences were also observed in BA3a (left), V2 (right), and BA28 (both hemispheres) across LPG, MPG, NC groups. Despite a small sample size, these findings suggest cortical thickness measurements can serve as effective biomarkers for cognitive impairment diagnosis, warranting further validation with a larger cohort.", "source": "PubMed"}, {"chunk_id": "36858305_0", "pmid": "36858305", "title": "Association of plasma phosphor-tau181 with A\u03b2 levels may vary by APOE \u03b54 status and sex among non-demented old adults.", "authors": "Cai Y, Fu P, Zhang X et al.", "year": "2023", "journal": "Neuroscience letters", "keywords": "Apolipoprotein E \u03b54, Blood biomarker, Plasma phosphorylated tau181, Sex differences, \u03b2-Amyloid", "chunk": "To evaluate the relationship between blood tau phosphorylated at threonine 181 (p-tau181) levels and \u03b2-amyloid (A\u03b2) levels, this study took the potential role of sex differences and apolipoprotein E (APOE)-\u03b54 status into account. We examined 620 participants with normal cognition (n = 178) and mild cognitive impairment (n = 442). Three-way interactions between sex, APOE \u03b54 status, and the levels of plasma p-tau181 were examined with linear regression models for A\u03b2 levels adjusting for age, education, and diagnosis. The correlation analysis was performed to detect the association of the levels of plasma p-tau181 with brain A\u03b2 stratified for APOE status and sex. Blood p-tau181 levels were higher in APOE \u03b54+ participants as compared to APOE \u03b54 - participants (p < 0.001). A comparison of APOE \u03b54 status within each gender showed that APOE \u03b54 carriers had higher levels of plasma p-tau181 and amyloid-\u03b2 than APOE \u03b54 noncarriers in both men", "source": "PubMed"}, {"chunk_id": "36858305_1", "pmid": "36858305", "title": "Association of plasma phosphor-tau181 with A\u03b2 levels may vary by APOE \u03b54 status and sex among non-demented old adults.", "authors": "Cai Y, Fu P, Zhang X et al.", "year": "2023", "journal": "Neuroscience letters", "keywords": "Apolipoprotein E \u03b54, Blood biomarker, Plasma phosphorylated tau181, Sex differences, \u03b2-Amyloid", "chunk": "0.001). A comparison of APOE \u03b54 status within each gender showed that APOE \u03b54 carriers had higher levels of plasma p-tau181 and amyloid-\u03b2 than APOE \u03b54 noncarriers in both men and women (p < 0.001). In sex/APOE-stratified analyses, individuals with the APOE \u03b54 allele showed stronger correlations between plasma p-tau181 and brain A\u03b2 levels in both females (r = 0.49, p < 0.001 for APOE \u03b54 carriers vs r = 0.28, p < 0.001 for APOE \u03b54 noncarrier.) and males (r = 0.34, p < 0.001 for APOE \u03b54 carriers vs r = 0.21, p = 0.04 for APOE \u03b54 noncarriers.). In interactive analysis, the association of plasma p-tau181 and A\u03b2 levels was significant in the female APOE \u03b54 carriers (p < 0.003). APOE \u03b54 status and female sex interact to impact the correlation between plasma p-tau181 and A\u03b2 levels. Although the APOE \u03b54 genotype is one of the most", "source": "PubMed"}, {"chunk_id": "36858305_2", "pmid": "36858305", "title": "Association of plasma phosphor-tau181 with A\u03b2 levels may vary by APOE \u03b54 status and sex among non-demented old adults.", "authors": "Cai Y, Fu P, Zhang X et al.", "year": "2023", "journal": "Neuroscience letters", "keywords": "Apolipoprotein E \u03b54, Blood biomarker, Plasma phosphorylated tau181, Sex differences, \u03b2-Amyloid", "chunk": "(p < 0.003). APOE \u03b54 status and female sex interact to impact the correlation between plasma p-tau181 and A\u03b2 levels. Although the APOE \u03b54 genotype is one of the most important risky genes for AD, sex differences may also modify the degree of risk at critical times among non-demented older adults.", "source": "PubMed"}, {"chunk_id": "40290782_0", "pmid": "40290782", "title": "The relationship of <sup>18</sup>F-FDG-PET to other common biomarkers of dementia in a clinical cohort with memory deficits.", "authors": "Woyk K, Hansen N, Wiltfang J et al.", "year": "2025", "journal": "Journal of Alzheimer's disease reports", "keywords": "18F-FDG-PET, 18F-Florbetaben, Alzheimer\u2019s disease, biomarkers, cerebrospinal fluid, positron emission tomography", "chunk": "Early biomarker-based diagnosis of Alzheimer's disease (AD) is essential, particularly with the increasing availability of new therapeutic options. However, the relationship between imaging and cerebrospinal fluid (CSF) biomarkers, especially in the context of <sup>18</sup>Fluorine-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG-PET), remains insufficiently understood. The aim of this study was the evaluation of the relationship between <sup>18</sup>F-FDG-PET and other common fluid and imaging AD-biomarkers in a clinical cohort of patients with cognitive decline and suspected AD. We included n = 90 patients with cognitive decline and clinically suspected AD that underwent <sup>18</sup>F-FDG-PET imagining at our facility. Clinical and imaging data including patient characteristics, CSF biomarkers, Mini-Mental State Examination (MMSE), <sup>18</sup>F-FDG-PET and <sup>18</sup>F-Florbetaben-PET were retrospectively analyzed. PET images were quantified in several brain regions. <sup>18</sup>F-FDG uptake correlated with CSF amyloid-\u03b2 (A\u03b2)<sub>40</sub>, A\u03b2<sub>42</sub>, and the A\u03b2<sub>42/40</sub> ratio in several brain regions, but not with regional <sup>18</sup>F-Florbetaben uptake. <sup>18</sup>F-FDG uptake inversely correlated with t-tau and p-tau", "source": "PubMed"}, {"chunk_id": "40290782_1", "pmid": "40290782", "title": "The relationship of <sup>18</sup>F-FDG-PET to other common biomarkers of dementia in a clinical cohort with memory deficits.", "authors": "Woyk K, Hansen N, Wiltfang J et al.", "year": "2025", "journal": "Journal of Alzheimer's disease reports", "keywords": "18F-FDG-PET, 18F-Florbetaben, Alzheimer\u2019s disease, biomarkers, cerebrospinal fluid, positron emission tomography", "chunk": "<sup>18</sup>F-FDG uptake correlated with CSF amyloid-\u03b2 (A\u03b2)<sub>40</sub>, A\u03b2<sub>42</sub>, and the A\u03b2<sub>42/40</sub> ratio in several brain regions, but not with regional <sup>18</sup>F-Florbetaben uptake. <sup>18</sup>F-FDG uptake inversely correlated with t-tau and p-tau in CSF. Furthermore, a correlation between MMSE and <sup>18</sup>F-FDG uptake was also detected in several brain regions. <sup>18</sup>F-FDG-PET and its combination with CSF markers showed the highest predictive power for disease severity. The study highlights the potential of integrating <sup>18</sup>F-FDG-PET with CSF biomarkers to improve the diagnosis, prognosis, and monitoring of AD, emphasizing the complexity and regional specificity of biomarker interactions in neurodegeneration.", "source": "PubMed"}, {"chunk_id": "39135618_0", "pmid": "39135618", "title": "Traffic-related air pollution and <i>APOE4</i> can synergistically affect hippocampal volume in older women: new findings from UK Biobank.", "authors": "Popov VA, Ukraintseva SV, Duan H et al.", "year": "2024", "journal": "Frontiers in dementia", "keywords": "APOE, Alzheimer's disease, TRAP, aging, air pollution, hippocampal volume, major road, neurodegeneration", "chunk": "A growing research body supports the connection between neurodegenerative disorders, including Alzheimer's disease (AD), and traffic-related air pollution (TRAP). However, the underlying mechanisms are not well understood. A deeper investigation of TRAP effects on hippocampal volume (HV), a major biomarker of neurodegeneration, may help clarify these mechanisms. Here, we explored TRAP associations with the HV in older participants of the UK Biobank (UKB), taking into account the presence of <i>APOE</i> e4 allele (<i>APOE4</i>), the strongest genetic risk factor for AD. Exposure to TRAP was approximated by the distance of the participant's main residence to the nearest major road (DNMR). The left/right HV was measured by magnetic resonance imaging (MRI) in cubic millimeters (mm<sup>3</sup>). Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found significant interactions between DNMR and <i>APOE4</i> that influenced HV. Specifically, DNMR <50m (equivalent of a chronically high exposure to TRAP), and", "source": "PubMed"}, {"chunk_id": "39135618_1", "pmid": "39135618", "title": "Traffic-related air pollution and <i>APOE4</i> can synergistically affect hippocampal volume in older women: new findings from UK Biobank.", "authors": "Popov VA, Ukraintseva SV, Duan H et al.", "year": "2024", "journal": "Frontiers in dementia", "keywords": "APOE, Alzheimer's disease, TRAP, aging, air pollution, hippocampal volume, major road, neurodegeneration", "chunk": "regression were used to examine statistical significance. We found significant interactions between DNMR and <i>APOE4</i> that influenced HV. Specifically, DNMR <50m (equivalent of a chronically high exposure to TRAP), and carrying <i>APOE4</i> were synergistically associated with a significant (<i>P</i> = 0.01) reduction in the right HV by about 2.5% in women aged 60-75 years (results for men didn't reach a statistical significance). Results of our study suggest that TRAP and <i>APOE4</i> jointly promote neurodegeneration in women. Living farther from major roads may help reduce the risks of neurodegenerative disorders, including AD, in female <i>APOE4</i> carriers.", "source": "PubMed"}, {"chunk_id": "39216535_0", "pmid": "39216535", "title": "The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.", "authors": "Forny Germano L, Koehler JA, Baggio LL et al.", "year": "2024", "journal": "Molecular metabolism", "keywords": "Alzheimer's, Diabetes, GLP-1, Glucagon-like peptides, Inflammation, Neurodegeneration, Obesity", "chunk": "The development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has been accompanied by evidence for anti-inflammatory and cytoprotective actions in the heart, blood vessels, kidney, and brain. Whether GLP-1R agonists might be useful clinically for attenuating deterioration of cognitive dysfunction and reducing the progression of Alzheimer's disease remains uncertain. Here we evaluated the actions of semaglutide and tirzepatide, clinically distinct GLP-1 medicines, in two mouse models of neurodegeneration. Semaglutide reduced body weight and improved glucose tolerance in 12-month-old male and female 5XFAD and APP/PS1 mice, consistent with pharmacological engagement of the GLP-1R. Nevertheless, amyloid plaque density was not different in the cerebral cortex, hippocampus, or subiculum of semaglutide-treated 12-month-old 5XFAD and APP/PS1 mice. IBA1 and GFAP expression were increased in the hippocampus of 5XFAD and APP/PS1 mice but were not reduced by semaglutide. Moreover, parameters of neurobehavioral and cognitive function evaluated using", "source": "PubMed"}, {"chunk_id": "39216535_1", "pmid": "39216535", "title": "The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.", "authors": "Forny Germano L, Koehler JA, Baggio LL et al.", "year": "2024", "journal": "Molecular metabolism", "keywords": "Alzheimer's, Diabetes, GLP-1, Glucagon-like peptides, Inflammation, Neurodegeneration, Obesity", "chunk": "mice. IBA1 and GFAP expression were increased in the hippocampus of 5XFAD and APP/PS1 mice but were not reduced by semaglutide. Moreover, parameters of neurobehavioral and cognitive function evaluated using Open Field testing or the Morris water maze were not improved following treatment with semaglutide. To explore whether incretin therapies might be more effective in younger mice, we studied semaglutide and tirzepatide action in 6-month-old male and female 5XFAD mice. Neither semaglutide nor tirzepatide modified the extent of plaque accumulation, hippocampal IBA1+ or GFAP+ cells, or parameters of neurobehavioral testing, despite improving glucose tolerance and reducing body weight. mRNA biomarkers of inflammation and neurodegeneration were increased in the hippocampus of male and female 5XFAD mice but were not reduced after treatment with semaglutide or tirzepatide. Collectively, these findings reveal preservation of the metabolic actions of two GLP-1 medicines, semaglutide and tirzepatide, yet inability to detect improvement in structural and functional", "source": "PubMed"}, {"chunk_id": "39216535_2", "pmid": "39216535", "title": "The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.", "authors": "Forny Germano L, Koehler JA, Baggio LL et al.", "year": "2024", "journal": "Molecular metabolism", "keywords": "Alzheimer's, Diabetes, GLP-1, Glucagon-like peptides, Inflammation, Neurodegeneration, Obesity", "chunk": "treatment with semaglutide or tirzepatide. Collectively, these findings reveal preservation of the metabolic actions of two GLP-1 medicines, semaglutide and tirzepatide, yet inability to detect improvement in structural and functional parameters of neurodegeneration in two mouse models of Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "38376028_0", "pmid": "38376028", "title": "Predicting the apolipoprotein E \u03b54 allele carrier status based on gray matter volumes and cognitive function.", "authors": "Kim HG, Tian Y, Jung SM et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "aging, apolipoprotein E \u03b54 status, brain atrophy, cognitive decline, machine learning, prediction", "chunk": "Apolipoprotein E (ApoE) \u03b54 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis. To predict ApoE \u03b54 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods. We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE \u03b54 carriers and 52 noncarriers) and scanned them with three-dimensional (3D) T1-weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini-mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE \u03b54 carrier with different ML models. The best model of ML analyses was", "source": "PubMed"}, {"chunk_id": "38376028_1", "pmid": "38376028", "title": "Predicting the apolipoprotein E \u03b54 allele carrier status based on gray matter volumes and cognitive function.", "authors": "Kim HG, Tian Y, Jung SM et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "aging, apolipoprotein E \u03b54 status, brain atrophy, cognitive decline, machine learning, prediction", "chunk": "ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE \u03b54 carrier with different ML models. The best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone. Our results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE \u03b54 status and identifying individuals at risk of AD progression.", "source": "PubMed"}, {"chunk_id": "40181683_0", "pmid": "40181683", "title": "Cognitive Phenotyping and Interpretation of Alzheimer Blood Biomarkers.", "authors": "Bouteloup V, Villain N, Vidal JS et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "Blood phosphorylated tau 217 (p-tau217) showed good performance in predicting brain amyloidosis. However, the importance of detailed cognitive phenotyping in patients without dementia when interpreting p-tau217 results remains unclear. To assess whether accuracy, negative predictive value (NPV), and positive predictive value (PPV) in predicting brain amyloidosis using p-tau217 varies across clinical presentations in patients without dementia. The study design included 2 observational, prospective cohort studies: The Cohort of Outpatients From French Research Memory Centers in Order to Improve Knowledge on Alzheimer's Disease and Related Disorders (MEMENTO), with enrollment from 2011 to 2014 and 5 years of follow-up, and the Biomarker of Amyloid Peptide and Alzheimer's Disease Risk (BALTAZAR) cohort study, with enrollment from 2010 to 2015 and 3 years of follow-up. Both are multicenter cohorts conducted in French memory clinics. Participants without dementia were included for analysis if they had baseline blood p-tau217 measurement and a known amyloid status through", "source": "PubMed"}, {"chunk_id": "40181683_1", "pmid": "40181683", "title": "Cognitive Phenotyping and Interpretation of Alzheimer Blood Biomarkers.", "authors": "Bouteloup V, Villain N, Vidal JS et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "follow-up. Both are multicenter cohorts conducted in French memory clinics. Participants without dementia were included for analysis if they had baseline blood p-tau217 measurement and a known amyloid status through cerebrospinal fluid amyloid \u03b2 (A\u03b2)-42/A\u03b2-40 ratio or positron emission tomography. They presented with either subjective cognitive impairment (SCI), mild cognitive impairment (MCI) with a common Alzheimer disease (AD) phenotype (cAD-MCI: amnestic syndrome of hippocampal type, posterior cortical atrophy, or logopenic primary progressive aphasia), or MCI with uncommon AD or other phenotypes (uAD-MCI). Data were analyzed from May to September 2024. Blood p-tau217 concentrations. Brain amyloidosis probabilities were derived from p-tau217 logistic regressions including age, gender, and APOE genotype. Published and internally developed cut points with 90% sensitivity and specificity were used. A total of 776 participants from the MEMENTO cohort (N = 2323 participants) and 193 participants from the BALTAZAR cohort (N = 1040) were included in this analysis. In", "source": "PubMed"}, {"chunk_id": "40181683_2", "pmid": "40181683", "title": "Cognitive Phenotyping and Interpretation of Alzheimer Blood Biomarkers.", "authors": "Bouteloup V, Villain N, Vidal JS et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "used. A total of 776 participants from the MEMENTO cohort (N = 2323 participants) and 193 participants from the BALTAZAR cohort (N = 1040) were included in this analysis. In the MEMENTO cohort (median [IQR] age, 71 [65-76] years; 444 female [57%]), brain amyloidosis prevalence was 16.5% (20 of 121) in SCI, 45.9% (78 of 170) in cAD-MCI, and 24.5% (119 of 485) in uAD-MCI. Area under the receiver operating characteristic curve for predicting brain amyloidosis with p-tau217 models was 0.78 (95% CI, 0.66-0.89), 0.91 (95% CI, 0.86-0.95), and 0.87 (95% CI, 0.84-0.91) in the SCI, cAD-MCI, and uAD-MCI subgroups, respectively. External cut points resulted in a PPV of 60.0%, 90.0%, and 74.5% in the SCI, cAD-MCI, and uAD-MCI subgroups, respectively. NPV ranged from 84.2% to 90.2%. With internally developed cut points, PPVs were 52.6%, 84.0%, and 72.3% in the SCI, cAD-MCI, and uAD-MCI subgroups, respectively. NPVs were high (91.7%-94.6%)", "source": "PubMed"}, {"chunk_id": "40181683_3", "pmid": "40181683", "title": "Cognitive Phenotyping and Interpretation of Alzheimer Blood Biomarkers.", "authors": "Bouteloup V, Villain N, Vidal JS et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "respectively. NPV ranged from 84.2% to 90.2%. With internally developed cut points, PPVs were 52.6%, 84.0%, and 72.3% in the SCI, cAD-MCI, and uAD-MCI subgroups, respectively. NPVs were high (91.7%-94.6%) in all subgroups. Rates of incident dementia strongly increased with the probability of brain amyloidosis in the cAD-MCI subgroup. Replicated analyses in the BALTAZAR cohort provided similar results. Results from 2 clinical cohorts suggest that amyloid prevalence varied across cognitive phenotypes and was associated with the diagnostic performance of blood p-tau217 models to determine brain amyloidosis. Comprehensive cognitive phenotyping beyond the basic characterization of SCI, MCI, or dementia should accompany the use of blood biomarkers in clinical practice to avoid misdiagnosis due to false positives.", "source": "PubMed"}, {"chunk_id": "33494369_0", "pmid": "33494369", "title": "Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies.", "authors": "Robinson M, Lou J, Mehrazma B et al.", "year": "2021", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, HT22 cells, aggregation inhibitors, amyloid-\u03b2, atomic force microscope, molecular dynamics, neuroprotection", "chunk": "Neurodegeneration in Alzheimer's disease (AD) is defined by pathology featuring amyloid-\u03b2 (A\u03b2) deposition in the brain. A\u03b2 monomers themselves are generally considered to be nontoxic, but misfold into \u03b2-sheets and aggregate to form neurotoxic oligomers. One suggested strategy to treat AD is to prevent the formation of toxic oligomers. The SG inhibitors are a class of pseudopeptides designed and optimized using molecular dynamics (MD) simulations for affinity to A\u03b2 and experimentally validated for their ability to inhibit amyloid-amyloid binding using single molecule force spectroscopy (SMFS). In this work, we provide a review of our previous MD and SMFS studies of these inhibitors and present new cell viability studies that demonstrate their neuroprotective effects against A\u03b2(1-42) oligomers using mouse hippocampal-derived HT22 cells. Two of the tested SG inhibitors, predicted to bind A\u03b2 in anti-parallel orientation, demonstrated neuroprotection against A\u03b2(1-42). A third inhibitor, predicted to bind parallel to A\u03b2, was not neuroprotective.", "source": "PubMed"}, {"chunk_id": "33494369_1", "pmid": "33494369", "title": "Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies.", "authors": "Robinson M, Lou J, Mehrazma B et al.", "year": "2021", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, HT22 cells, aggregation inhibitors, amyloid-\u03b2, atomic force microscope, molecular dynamics, neuroprotection", "chunk": "cells. Two of the tested SG inhibitors, predicted to bind A\u03b2 in anti-parallel orientation, demonstrated neuroprotection against A\u03b2(1-42). A third inhibitor, predicted to bind parallel to A\u03b2, was not neuroprotective. Myristoylation of SG inhibitors, intended to enhance delivery across the blood-brain barrier (BBB), resulted in cytotoxicity. This is the first use of HT22 cells for the study of peptide aggregation inhibitors. Overall, this work will inform the future development of peptide aggregation inhibitors against A\u03b2 toxicity.", "source": "PubMed"}, {"chunk_id": "32995678_0", "pmid": "32995678", "title": "Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice.", "authors": "Han Y, Gao C, Wang H et al.", "year": "2021", "journal": "Bioactive materials", "keywords": "Alzheimer's disease, Biomimetic nanosystems, Blood-brain barrier, Genistein, Macrophage-membrane coating, Neuronal mitochondria targeting", "chunk": "Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species (ROS) is an early event of sporadic Alzheimer's disease (AD), and considered to be a key pathologic factor in the progression of AD. The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD. A safe and effective drug delivery system (DDS) which is able to cross the blood-brain barrier (BBB) and target neuronal mitochondria is necessary. Recently, bioactive materials-based DDS has been widely investigated for the treatment of AD. Herein, we developed macrophage (MA) membrane-coated solid lipid nanoparticles (SLNs) by attaching rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules to the surface of MA membrane (RVG/TPP-MASLNs) for functional antioxidant delivery to neuronal mitochondria. According to the results, MA membranes camouflaged the SLNs from being eliminated by RES-rich organs by inheriting the immunological characteristics of macrophages. The unique properties of the", "source": "PubMed"}, {"chunk_id": "32995678_1", "pmid": "32995678", "title": "Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice.", "authors": "Han Y, Gao C, Wang H et al.", "year": "2021", "journal": "Bioactive materials", "keywords": "Alzheimer's disease, Biomimetic nanosystems, Blood-brain barrier, Genistein, Macrophage-membrane coating, Neuronal mitochondria targeting", "chunk": "to neuronal mitochondria. According to the results, MA membranes camouflaged the SLNs from being eliminated by RES-rich organs by inheriting the immunological characteristics of macrophages. The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons. After entering the neurons in CNS, TPP further lead the DDS to mitochondria driven by electric charge. The Genistein (GS)- encapsulated DDS (RVG/TPP-MASLNs-GS) exhibited the most favorable effects on reliveing AD symptoms <i>in vitro</i> and <i>in vivo</i> by the synergies gained from the combination of MA membranes, RVG29 and TPP. These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems.", "source": "PubMed"}, {"chunk_id": "32995678_2", "pmid": "32995678", "title": "Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice.", "authors": "Han Y, Gao C, Wang H et al.", "year": "2021", "journal": "Bioactive materials", "keywords": "Alzheimer's disease, Biomimetic nanosystems, Blood-brain barrier, Genistein, Macrophage-membrane coating, Neuronal mitochondria targeting", "chunk": "by the designed biomimetic nanosystems.", "source": "PubMed"}, {"chunk_id": "41509234_0", "pmid": "41509234", "title": "NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer's disease.", "authors": "Fan F, Joshi P, Liu X et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "Synapse degeneration is a hallmark of neurodegenerative diseases <sup>1-3</sup> , including Parkinson's and Alzheimer's disease (AD). Synapse loss has been known for decades as the strongest correlate with cognition and disease progression in AD patients <sup>4-8</sup> , but the molecular mechanisms that drive synapse degeneration remain elusive. Here, we identify Sarm1, a new class of NAD+ hydrolase required for Wallerian degeneration of periphery nerves after injuries <sup>9-12</sup> , as the key mediator of synaptic degeneration in AD brains. Sarm1 knockout largely reversed synapse loss, amyloid-\u03b2 (A\u03b2) burden, and cognitive decline in 5XFAD mice. We found that Sarm1 is enriched in synaptic terminals and becomes activated in synaptic dystrophies adjacent to A\u03b2 plaques, leading to synapse degeneration and subsequent neuroinflammation. Sarm1 deletion in the AD mice prevented synaptic dystrophies and rescued short-term and long-term synaptic plasticity. Further, Sarm1 deletion protected synapses from C1q tagging and phagocytosis, and C1q-MERTK signaling in complement", "source": "PubMed"}, {"chunk_id": "41509234_1", "pmid": "41509234", "title": "NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer's disease.", "authors": "Fan F, Joshi P, Liu X et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "deletion in the AD mice prevented synaptic dystrophies and rescued short-term and long-term synaptic plasticity. Further, Sarm1 deletion protected synapses from C1q tagging and phagocytosis, and C1q-MERTK signaling in complement cascades <sup>7,13-15</sup> was significantly reduced. The reduced synapse degeneration, in turn, broke the feed-forward loop of \"glia activation-neuroinflammation-A\u03b2 deposition\". These data suggest that Sarm1 plays a key role in driving synapse degeneration in AD before C1q-tagging and phagocytic clearance, and targeting Sarm1 may offer a novel intervention to attenuate synapse degeneration and memory loss in AD. Sarm1 is enriched at presynaptic dystrophies and correlated with A\u03b2.Genetic deletion of Sarm1 prevents synapse degeneration in AD.Sarm1 depletion is sufficient to reverse synaptic dysfunction and memory loss.Sarm1 depletion reduces A\u03b2 burden and neuroinflammationC1q--MERTK axis acts downstream of synaptic Sarm1 activation.", "source": "PubMed"}, {"chunk_id": "41509234_2", "pmid": "41509234", "title": "NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer's disease.", "authors": "Fan F, Joshi P, Liu X et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "axis acts downstream of synaptic Sarm1 activation.", "source": "PubMed"}, {"chunk_id": "40851076_0", "pmid": "40851076", "title": "Alterations in MRI-visible perivascular spaces precede dementia diagnosis by 18 years in autosomal dominant Alzheimer's disease.", "authors": "Leone R, Kobeleva X, Rowe B et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, autosomal dominant Alzheimer's disease, cerebral small vessel disease, dominantly inherited Alzheimer's disease, magnetic resonance imaging, perivascular spaces", "chunk": "Perivascular space (PVS) alterations are traditionally linked to cardiovascular risk factors and aging, but may also play a direct role in Alzheimer's disease (AD). To reduce confounding from age-related comorbidities, we examined PVSs in autosomal dominant AD (ADAD). In this cross-sectional study of 96 non-demented individuals (62 mutation carriers), we quantified PVS count fraction and mean diameter in white matter and basal ganglia using automated magnetic resonance imaging analysis. Linear mixed models assessed group differences along the disease course, adjusting for cardiovascular risk factors. Compared to non-carriers, mutation carriers showed lower PVS count fraction in white matter and basal ganglia, and larger PVS diameter in basal ganglia and the temporal lobe. Changes were evident up to 18 years before expected dementia onset and followed trajectories similar to amyloid beta 42 and tau biomarkers. ADAD is associated with early PVS alterations, suggesting perivascular changes may be integral to primary AD pathology.", "source": "PubMed"}, {"chunk_id": "40851076_1", "pmid": "40851076", "title": "Alterations in MRI-visible perivascular spaces precede dementia diagnosis by 18 years in autosomal dominant Alzheimer's disease.", "authors": "Leone R, Kobeleva X, Rowe B et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, autosomal dominant Alzheimer's disease, cerebral small vessel disease, dominantly inherited Alzheimer's disease, magnetic resonance imaging, perivascular spaces", "chunk": "dementia onset and followed trajectories similar to amyloid beta 42 and tau biomarkers. ADAD is associated with early PVS alterations, suggesting perivascular changes may be integral to primary AD pathology. Autosomal dominant Alzheimer's disease (ADAD) mutation carriers have reduced magnetic resonance imaging-visible perivascular space (PVS) count fraction in the white matter and basal ganglia. ADAD mutation carriers show enlarged PVS in the basal ganglia and temporal white matter. PVS alterations start 18 years before the estimated time of dementia diagnosis. The spatial localization of PVS changes overlaps with regions of amyloid beta (A\u03b2) accumulation. The temporal evolution of PVS alterations aligns with A\u03b2 and tau changes in the cerebrospinal fluid.", "source": "PubMed"}, {"chunk_id": "41329450_0", "pmid": "41329450", "title": "Mesenchymal cell-derived extracellular vesicles ameliorate age-related deficits in working memory and in vivo MRI measures of white matter structure and function in rhesus monkeys.", "authors": "Mackie EC, Cheng CH, Alibrio MN et al.", "year": "2025", "journal": "GeroScience", "keywords": "Cognition, Diffusion MRI, Mesenchymal stromal cell-derived extracellular vesicles, Normal aging, Resting-state functional MRI, Rhesus monkey", "chunk": "Aging humans and non-human primates both exhibit a similar pattern of cognitive decline beginning in middle age that is characterized by progressive impairments in rule learning, executive function, and working and recognition memory-functions often associated with dysfunction of prefrontal and medial temporal lobe regions. The heterogeneity and inter-subject variability in aging and age-related cognitive impairments present challenges for developing effective therapeutics and can be attributed to differing degrees of cortical white matter (WM) damage and alterations to local and long-range prefrontal and temporal networks. A promising therapeutic that has been shown to be efficacious in mitigating WM damage and improving cognitive function in rodent models is mesenchymal cell-derived extracellular vesicles (MSC-EVs). In the present study, late middle-aged rhesus monkeys were systemically administered monkey-derived MSC-EVs every 2 weeks for 18 months. We demonstrate that MSC-EV treatment improves spatial working memory and decreases the frequency of perseverative responses with largely no effects", "source": "PubMed"}, {"chunk_id": "41329450_1", "pmid": "41329450", "title": "Mesenchymal cell-derived extracellular vesicles ameliorate age-related deficits in working memory and in vivo MRI measures of white matter structure and function in rhesus monkeys.", "authors": "Mackie EC, Cheng CH, Alibrio MN et al.", "year": "2025", "journal": "GeroScience", "keywords": "Cognition, Diffusion MRI, Mesenchymal stromal cell-derived extracellular vesicles, Normal aging, Resting-state functional MRI, Rhesus monkey", "chunk": "systemically administered monkey-derived MSC-EVs every 2 weeks for 18 months. We demonstrate that MSC-EV treatment improves spatial working memory and decreases the frequency of perseverative responses with largely no effects on recognition memory. These cognitive improvements were associated with increases in MRI diffusion measures of WM structural integrity over time as well as preservation of inter-network functional connectivity as measured by resting-state functional MRI. These findings suggest that MSC-EV treatment can slow or reverse age-related cognitive decline while strengthening WM integrity and improving functional connectivity in late middle-aged rhesus monkeys.", "source": "PubMed"}, {"chunk_id": "40609062_0", "pmid": "40609062", "title": "Association of Cardiac Biomarkers With Structural Brain Changes and Cognitive Impairment: Results From the Hamburg City Health Study.", "authors": "Jensen M, Vettorazzi E, Weber P et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "Cardiovascular disease is linked to an increased risk of dementia. The aim of this study was to evaluate whether blood-based cardiac biomarkers are associated with structural brain changes and cognitive impairment and to explore whether structural brain changes mediate alterations in cognitive function. We included participants from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. High-sensitivity cardiac troponin I (hs-cTnI), midregional pro-atrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured. From brain MRI, we quantified markers of neurodegeneration (total brain volume, cortical thickness), markers of vascular brain damage (white matter hyperintensity volume, peak width of skeletonized mean diffusivity [PSMD]), and measures of structural brain network organization. Cognitive function was assessed using subtests of the CERAD-Plus battery. We applied multivariable-adjusted linear regression analyses and structural equation modeling to investigate the association of cardiac biomarkers with structural brain changes and cognitive function.", "source": "PubMed"}, {"chunk_id": "40609062_1", "pmid": "40609062", "title": "Association of Cardiac Biomarkers With Structural Brain Changes and Cognitive Impairment: Results From the Hamburg City Health Study.", "authors": "Jensen M, Vettorazzi E, Weber P et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "using subtests of the CERAD-Plus battery. We applied multivariable-adjusted linear regression analyses and structural equation modeling to investigate the association of cardiac biomarkers with structural brain changes and cognitive function. The analysis included 2,553 participants with a median age of 64 years, and 44% were women. Higher levels of natriuretic peptides were associated with imaging markers of neurodegeneration and vascular brain damage, for example, higher levels of NT-proBNP with lower cortical thickness (\u03b2 = -0.081; 95% CI [-0.127 to -0.034]) and higher PSMD (\u03b2 = 0.112; 95% CI [0.069-0.155]). Higher levels of hs-cTnI were associated with markers of vascular brain damage only, for example, with higher PSMD (\u03b2 = 0.103; 95% CI [0.060-0.146]). All cardiac biomarkers studied were associated with alterations of structural brain connectivity reflecting changes in brain network organization toward less integration and more segregation. Elevated NT-proBNP was associated with lower scores in tests of verbal memory (\u03b2", "source": "PubMed"}, {"chunk_id": "40609062_2", "pmid": "40609062", "title": "Association of Cardiac Biomarkers With Structural Brain Changes and Cognitive Impairment: Results From the Hamburg City Health Study.", "authors": "Jensen M, Vettorazzi E, Weber P et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "alterations of structural brain connectivity reflecting changes in brain network organization toward less integration and more segregation. Elevated NT-proBNP was associated with lower scores in tests of verbal memory (\u03b2 = -0.054; 95% CI [-0.100 to -0.008]) and verbal fluency (\u03b2 = -0.054; 95% CI [-0.101 to -0.008]). In structural equation modeling, there was a significant effect of NT-proBNP on cognitive function mediated by structural brain changes. Monitoring cardiac biomarkers, especially NT-proBNP, may provide a low-invasive and widely available method to assess cognitive risk and potentially guide early preventive interventions. Longitudinal studies are needed to establish causality and explore the observed associations over time. ClinicalTrials.gov number, NCT03934957.", "source": "PubMed"}, {"chunk_id": "40392273_0", "pmid": "40392273", "title": "Fluid biomarkers in atypical Parkinsonism: current state and future perspectives.", "authors": "Bougea A, Colosimo C, Falup-Pecurariu C et al.", "year": "2025", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "Atypical Parkinsonian Syndromes (APS), Biomarkers, Corticobasal degeneration (CBD), Dementia with Lewy bodies (DLB), Multiple system atrophy (MSA), Progressive supranuclear palsy (PSP)", "chunk": "Diagnosing Atypical Parkinsonian Syndromes (APS) may be challenging due to overlapping clinical features of Parkinson's disease (PD), and the lack of pathognomonic diagnostic tests. Fluid biomarkers can be useful tools that make it easier to identify and track different APS. Objectives: this narrative review aim to update the current state of fluid biomarker research in APS and their potential implications in clinical practice. A comprehensive literature search was conducted in PubMed and Scopus using the following terms: \"A\u03b242 amyloid beta with 42 amino acids'', \" alpha-synuclein'', \"Atypical Parkinsonian Syndromes'', \"corticobasaldegeneration'', \"C reactive protein'', \"cerebrospinal fluid'', \"dementia with Lewy bodies'', \"multiple system atrophy'', \"neurofilament light, oligomeric\u03b1syn, phosphorylated \u03b1 -syn'', \"tau phosphorylated at threonine 181'', \"progressive supranuclear palsy'', \"Seeding Amplification Assay'', \"t-tau; total tau\". The lack of high-affinity \u03b1-syn antibodies and ligands may contribute to \u03b1-syn's low efficacy as a diagnostic biomarker of APS. Cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer pathology, axonal", "source": "PubMed"}, {"chunk_id": "40392273_1", "pmid": "40392273", "title": "Fluid biomarkers in atypical Parkinsonism: current state and future perspectives.", "authors": "Bougea A, Colosimo C, Falup-Pecurariu C et al.", "year": "2025", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "Atypical Parkinsonian Syndromes (APS), Biomarkers, Corticobasal degeneration (CBD), Dementia with Lewy bodies (DLB), Multiple system atrophy (MSA), Progressive supranuclear palsy (PSP)", "chunk": "total tau\". The lack of high-affinity \u03b1-syn antibodies and ligands may contribute to \u03b1-syn's low efficacy as a diagnostic biomarker of APS. Cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer pathology, axonal damage (neurofilament light chain) add valuable diagnostic and prognostic information in the neurochemical characterization of APS. Inflammatoryand microRNAs markers need to be further validated before their clinical use. Seeding Amplification Assays (SAA), despite their high sensitivity and specificity, are at this point used only as a research tool, and they are not quantitative or reflective of disease severity. Biomarker research for early identification and prognosis of APS patients requires multicenter collaboration, validation, and AI-based diagnostics, despite immature biological classification systems.", "source": "PubMed"}, {"chunk_id": "29885453_0", "pmid": "29885453", "title": "Monosodium glutamate exposure during the neonatal period leads to cognitive deficits in adult Sprague-Dawley rats.", "authors": "Jin L, Lin L, Li GY et al.", "year": "2018", "journal": "Neuroscience letters", "keywords": "Alzheimer\u2019s disease, Cognitive deficits, Monosodium glutamate, Plasticity-related proteins, Tau hyperphosphorylation", "chunk": "Epidemiological surveys show that 70-80% of patients with Alzheimer's disease (AD) have type 2 diabetes mellitus (T2DM) or show an abnormality of blood glucose levels. Therefore, an increasing number of evidence has suggested that diabetic hyperglycemia is tightly linked with the pathogenesis and progression of AD. In the present study, we replicated T2DM animal model via subcutaneous injection of newborn Sprague-Dawley (SD) rats with monosodium glutamate (MSG) during the neonatal period to investigate the effects and underlying mechanisms of hyperglycemia on cognitive ability. We found that neonatal MSG exposure induced hyperglycemia as well as Alzheimer-like learning and memory deficits with decreased dendritic spine density and hippocampal synaptic-related protein expression and increased phosphorylated tau levels in \u223c3-month-old SD rats. Our results suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD.", "source": "PubMed"}, {"chunk_id": "29885453_1", "pmid": "29885453", "title": "Monosodium glutamate exposure during the neonatal period leads to cognitive deficits in adult Sprague-Dawley rats.", "authors": "Jin L, Lin L, Li GY et al.", "year": "2018", "journal": "Neuroscience letters", "keywords": "Alzheimer\u2019s disease, Cognitive deficits, Monosodium glutamate, Plasticity-related proteins, Tau hyperphosphorylation", "chunk": "suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD.", "source": "PubMed"}, {"chunk_id": "40884977_0", "pmid": "40884977", "title": "An integrative and efficient microbiosensor for \u03b2-amyloid<sub>42</sub> based on a molecularly imprinted layer coordinating built-in hemin on the acupuncture needle.", "authors": "Kong X, Yu Z, Sun Q et al.", "year": "2026", "journal": "Bioelectrochemistry (Amsterdam, Netherlands)", "keywords": "Acupuncture needle, Built-in probe, Electrochemical microbiosensor, Surface imprinted layer, \u0392-amyloid(42)", "chunk": "Monitoring beta-amyloid<sub>1</sub><sub>-</sub><sub>42</sub> (A\u03b2<sub>42</sub>) is vital and challenging, which is a typical biomarker of Alzheimer's disease. Here, a novel electrochemical microbiosensor is developed to detect A\u03b2<sub>42</sub> on an acupuncture needle. Hemin is well known for its characteristics, including its ability to self-assemble on single-walled carbon nanotube (SWCNT), the molecular interaction with A\u03b2<sub>42</sub>, and the intrinsic electroactive signal. These properties are exploited to anchor and respond to A\u03b2<sub>42</sub> after integrating a molecularly imprinted surface polymer (SMIP). The SMIP layer of polydopamine/poly (ionic liquid) can be prepared by electropolymerization on an acupuncture needle microelectrode (ANME), which undergoes growth and formation of a polymeric structure around the anchored A\u03b2<sub>42</sub>. Interestingly, the imprinted cavities express a fluent signal of built-in hemin after eluting the templates, and show a highly selective and sensitive hindrance response for the recombined A\u03b2<sub>42</sub>. Under optimized conditions, the microbiosensor displays a linear range of 100 to 1 \u00d7 10<sup>10</sup> fM with", "source": "PubMed"}, {"chunk_id": "40884977_1", "pmid": "40884977", "title": "An integrative and efficient microbiosensor for \u03b2-amyloid<sub>42</sub> based on a molecularly imprinted layer coordinating built-in hemin on the acupuncture needle.", "authors": "Kong X, Yu Z, Sun Q et al.", "year": "2026", "journal": "Bioelectrochemistry (Amsterdam, Netherlands)", "keywords": "Acupuncture needle, Built-in probe, Electrochemical microbiosensor, Surface imprinted layer, \u0392-amyloid(42)", "chunk": "and show a highly selective and sensitive hindrance response for the recombined A\u03b2<sub>42</sub>. Under optimized conditions, the microbiosensor displays a linear range of 100 to 1 \u00d7 10<sup>10</sup> fM with a limit of detection of 0.05 fM. There are development and advances for the discipline of electroanalysis after comparing the technique and important indicators with the electrochemical biosensors reported of A\u03b2<sub>42</sub>. The microbiosensor also exhibited excellent selectivity, good stability, and reproducibility, which was effectively used to detect A\u03b2<sub>42</sub> in real spiked samples. The improved behavior of the developed microbiosensor can be attributed to its superficial highly matched imprinted cavities, built-in hemin label, and electronic barrier without signal of the nonimprinted surface to outside molecules. This microbiosensor has a scientific and reference value for directly sensing non-electroactive biomarkers, functionalizing microelectrodes, and electron transport cavities. It would also be amazing if this new microbiosensor could combine with the unclear and magical property", "source": "PubMed"}, {"chunk_id": "40884977_2", "pmid": "40884977", "title": "An integrative and efficient microbiosensor for \u03b2-amyloid<sub>42</sub> based on a molecularly imprinted layer coordinating built-in hemin on the acupuncture needle.", "authors": "Kong X, Yu Z, Sun Q et al.", "year": "2026", "journal": "Bioelectrochemistry (Amsterdam, Netherlands)", "keywords": "Acupuncture needle, Built-in probe, Electrochemical microbiosensor, Surface imprinted layer, \u0392-amyloid(42)", "chunk": "reference value for directly sensing non-electroactive biomarkers, functionalizing microelectrodes, and electron transport cavities. It would also be amazing if this new microbiosensor could combine with the unclear and magical property of acupuncture in the treatment of neurological disorders.", "source": "PubMed"}, {"chunk_id": "37009451_0", "pmid": "37009451", "title": "Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis.", "authors": "Verde F, Milone I, Colombo E et al.", "year": "2023", "journal": "Frontiers in aging neuroscience", "keywords": "amyotrophic lateral sclerosis (ALS), axon, biomarker, motor neuron disease (MND), neurofilament light chain (NFL)", "chunk": "To investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS. Serum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs). sNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King's stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn", "source": "PubMed"}, {"chunk_id": "37009451_1", "pmid": "37009451", "title": "Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis.", "authors": "Verde F, Milone I, Colombo E et al.", "year": "2023", "journal": "Frontiers in aging neuroscience", "keywords": "amyotrophic lateral sclerosis (ALS), axon, biomarker, motor neuron disease (MND), neurofilament light chain (NFL)", "chunk": "and ALSFRS-R score, positively with disease progression rate, differed among King's stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR). We confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.", "source": "PubMed"}, {"chunk_id": "37009451_2", "pmid": "37009451", "title": "Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis.", "authors": "Verde F, Milone I, Colombo E et al.", "year": "2023", "journal": "Frontiers in aging neuroscience", "keywords": "amyotrophic lateral sclerosis (ALS), axon, biomarker, motor neuron disease (MND), neurofilament light chain (NFL)", "chunk": "investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.", "source": "PubMed"}, {"chunk_id": "36217177_0", "pmid": "36217177", "title": "Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients.", "authors": "Traub J, Otto M, Sell R et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Age, Alzheimer\u2019s dementia, Cognitive impairment, Heart failure, Neurofilament light chain, Phosphorylated tau protein, Renal function", "chunk": "Chronic heart failure (HF) is known to increase the risk of developing Alzheimer's dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of", "source": "PubMed"}, {"chunk_id": "36217177_1", "pmid": "36217177", "title": "Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients.", "authors": "Traub J, Otto M, Sell R et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Age, Alzheimer\u2019s dementia, Cognitive impairment, Heart failure, Neurofilament light chain, Phosphorylated tau protein, Renal function", "chunk": "single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (\u03c1 = - 0.21; p = 0.013) and pTau (\u03c1 = - 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = - 2.4 for pTau; T = - 3.4 for NfL). Markers of chronic heart failure,", "source": "PubMed"}, {"chunk_id": "36217177_2", "pmid": "36217177", "title": "Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients.", "authors": "Traub J, Otto M, Sell R et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Age, Alzheimer\u2019s dementia, Cognitive impairment, Heart failure, Neurofilament light chain, Phosphorylated tau protein, Renal function", "chunk": "= 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = - 2.4 for pTau; T = - 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = - 3.1). pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.", "source": "PubMed"}, {"chunk_id": "37042462_0", "pmid": "37042462", "title": "A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status.", "authors": "Zhou RZ, Vetrano DL, Grande G et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "APOE, Alzheimer's disease, N-glycosylation, biomarkers, blood, dementia, tau", "chunk": "There is an urgent need for novel blood biomarkers for the detection of Alzheimer's disease (AD). We previously showed that levels of the bisecting N-acetylglucosamine glycan epitope was elevated in cerebrospinal fluid in AD. However, its diagnostic value in blood is unknown. We analyzed blood levels of bisecting N-acetylglucosamine and total tau in a retrospective cohort of 233 individuals. Progression to AD was compared between the groups using Cox regression. The predictive value of the biomarkers was determined by logistic regression. Bisecting N-acetylglucosamine correlated with tau levels (p < 0.0001). Individuals with an intermediate tau/bisecting N-acetylglucosamine ratio had elevated AD risk (hazard ratio = 2.06, 95% confidence interval [CI]: 1.18-3.6). Moreover, a combined model including tau/bisecting N-acetylglucosamine ratio, apolipoprotein E (APOE) \u03b54 status, and Mini-Mental State Examination score predicted future AD (area under the curve = 0.81, 95% CI: 0.68-0.93). Bisecting N-acetylglucosamine in combination with tau is a valuable blood", "source": "PubMed"}, {"chunk_id": "37042462_1", "pmid": "37042462", "title": "A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status.", "authors": "Zhou RZ, Vetrano DL, Grande G et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "APOE, Alzheimer's disease, N-glycosylation, biomarkers, blood, dementia, tau", "chunk": "(APOE) \u03b54 status, and Mini-Mental State Examination score predicted future AD (area under the curve = 0.81, 95% CI: 0.68-0.93). Bisecting N-acetylglucosamine in combination with tau is a valuable blood biomarker for predicting AD.", "source": "PubMed"}, {"chunk_id": "41266593_0", "pmid": "41266593", "title": "APOE \u03b54 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer's disease.", "authors": "Trudel L, Therriault J, Macedo AC et al.", "year": "2025", "journal": "Communications medicine", "keywords": "None", "chunk": "Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer's disease (AD). The apolipoprotein E (APOE) \u03b54 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain. We used data from the Translational Biomarkers of Alzheimer's Disease (TRIAD) cohort (n = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE \u03b54 carriership. Statistical analyses included correlation and regression models controlling for age and sex. Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE \u03b54 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response. Our findings demonstrate", "source": "PubMed"}, {"chunk_id": "41266593_1", "pmid": "41266593", "title": "APOE \u03b54 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer's disease.", "authors": "Trudel L, Therriault J, Macedo AC et al.", "year": "2025", "journal": "Communications medicine", "keywords": "None", "chunk": "astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE \u03b54 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response. Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE \u03b54 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.", "source": "PubMed"}, {"chunk_id": "32244855_0", "pmid": "32244855", "title": "Multi-View Based Multi-Model Learning for MCI Diagnosis.", "authors": "Cao P, Gao J, Zhang Z", "year": "2020", "journal": "Brain sciences", "keywords": "CNN, alzheimer\u2019s disease, magnetic resonance imaging, multi-view", "chunk": "Mild cognitive impairment (MCI) is the early stage of Alzheimer's disease (AD). Automatic diagnosis of MCI by magnetic resonance imaging (MRI) images has been the focus of research in recent years. Furthermore, deep learning models based on 2D view and 3D view have been widely used in the diagnosis of MCI. The deep learning architecture can capture anatomical changes in the brain from MRI scans to extract the underlying features of brain disease. In this paper, we propose a multi-view based multi-model (MVMM) learning framework, which effectively combines the local information of 2D images with the global information of 3D images. First, we select some 2D slices from MRI images and extract the features representing 2D local information. Then, we combine them with the features representing 3D global information learned from 3D images to train the MVMM learning framework. We evaluate our model on the Alzheimer's Disease Neuroimaging Initiative (ADNI)", "source": "PubMed"}, {"chunk_id": "32244855_1", "pmid": "32244855", "title": "Multi-View Based Multi-Model Learning for MCI Diagnosis.", "authors": "Cao P, Gao J, Zhang Z", "year": "2020", "journal": "Brain sciences", "keywords": "CNN, alzheimer\u2019s disease, magnetic resonance imaging, multi-view", "chunk": "combine them with the features representing 3D global information learned from 3D images to train the MVMM learning framework. We evaluate our model on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our proposed model can effectively recognize MCI through MRI images (accuracy of 87.50% for MCI/HC and accuracy of 83.18% for MCI/AD).", "source": "PubMed"}, {"chunk_id": "41715194_0", "pmid": "41715194", "title": "Akkermansia muciniphila reduces neuroinflammation and A\u03b2 deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.", "authors": "Wang B, Pan M, Yang L et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "Akkermansia muciniphila, AhR/NF-\u03baB/NLRP3, Alzheimer\u2019s disease, Amyloid beta, Cognitive deficits, Gut microbiota, Neuroinflammation, Peripheral inflammation, Tryptophan metabolism", "chunk": "Akkermansia muciniphila (A. muciniphila), a beneficial gut bacterium, has increasingly attracted interests in Alzheimer's disease (AD) research, its specific role in the microbiota-gut-brain axis still remains unclear. In this study, we demonstrated that A. muciniphila administration improve cognitive deficits and reduce amyloid-beta (A\u03b2) deposition in APP/PS1 mice, a transgenic model of AD. Subsequently, it is revealed that A. muciniphila administration significantly alters gut microbiota diversity and composition. Mechanically, our metabolomics analysis of cecal contents indicates A. muciniphila administration increases short-chain fatty acids (SCFAs) derived from the intestinal microbiota, including butyric acid and acetic acid. Significantly, in APP/PS1 mice with the A. muciniphila administration, targeted metabolomics identify that the production of 62 metabolites are increased such as indole-3-acetic acid (IAA), tryptophan, acetic acid and cinnamic acid, as well as aconitic acid and threonine, et al.; the production of 28 metabolites are decreased such as isoleucine and N-acetylneuraminic acid (NANA) as well", "source": "PubMed"}, {"chunk_id": "41715194_1", "pmid": "41715194", "title": "Akkermansia muciniphila reduces neuroinflammation and A\u03b2 deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.", "authors": "Wang B, Pan M, Yang L et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "Akkermansia muciniphila, AhR/NF-\u03baB/NLRP3, Alzheimer\u2019s disease, Amyloid beta, Cognitive deficits, Gut microbiota, Neuroinflammation, Peripheral inflammation, Tryptophan metabolism", "chunk": "acetic acid and cinnamic acid, as well as aconitic acid and threonine, et al.; the production of 28 metabolites are decreased such as isoleucine and N-acetylneuraminic acid (NANA) as well as ornithine and docosapentaenoic acid (DPA), et al. It is also identified by cytokine analysis of plasma that A. muciniphila administration reduces peripheral pro-inflammatory cytokines interleukin-6 (IL-6), IL-1\u03b2, IL-17 and tumor necrosis factor-alpha (TNF-\u03b1), et al., whereas it increases anti-inflammatory cytokines, such as IL-4, IL-10 and IL-22, et al. There is no any change of other cytokines, such as interferon-gamma (IFN-g), IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), et al. Interestingly, a significant positive correlation is observed between the increased IAA, tryptophan as well as acetic acid and cognitive function indicators. At the same time, A. muciniphila administration improves cognitive deficits, alleviates neuroinflammation and A\u03b2 deposition via AhR/NF-\u03baB/NLRP3 signaling pathway in APP/PS1 mice. In summary, our findings suggest A. muciniphila is", "source": "PubMed"}, {"chunk_id": "41715194_2", "pmid": "41715194", "title": "Akkermansia muciniphila reduces neuroinflammation and A\u03b2 deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.", "authors": "Wang B, Pan M, Yang L et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "Akkermansia muciniphila, AhR/NF-\u03baB/NLRP3, Alzheimer\u2019s disease, Amyloid beta, Cognitive deficits, Gut microbiota, Neuroinflammation, Peripheral inflammation, Tryptophan metabolism", "chunk": "At the same time, A. muciniphila administration improves cognitive deficits, alleviates neuroinflammation and A\u03b2 deposition via AhR/NF-\u03baB/NLRP3 signaling pathway in APP/PS1 mice. In summary, our findings suggest A. muciniphila is a promising approach for preventing AD progression by microbiota-gut-brain axis.", "source": "PubMed"}, {"chunk_id": "41789871_0", "pmid": "41789871", "title": "Choroid plexus-glymphatic axis disruption in Alzheimer's disease: Cerebrospinal fluid expansion as a mediator of metabolic dysfunction and cognitive decline.", "authors": "Lv M, Wang Q, Yu G et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, [18F]-FDG-PET, cerebrospinal fluid dynamics, choroid plexus, glymphatic dysfunction, multiple mediation analysis, neuroimaging", "chunk": "BackgroundThe choroid plexus (ChP) and glymphatic system are crucial for cerebrospinal fluid (CSF) homeostasis and brain waste clearance. While their individual roles in Alzheimer's disease (AD) are recognized, the mechanisms linking ChP structural changes, glymphatic dysfunction, and CSF dynamics to metabolic and cognitive decline remain unclear.ObjectiveWe aimed to investigate the interrelationships among ChP volume, glymphatic function, CSF volumetric changes, cerebral glucose metabolism, and cognitive status across the AD spectrum.MethodsThis cross-sectional study included 142 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, categorized as cognitively normal (NC, n = 38), early mild cognitive impairment (EMCI, n = 31), late mild cognitive impairment (LMCI, n = 31), and AD (n = 42). We analyzed multimodal neuroimaging data, including normalized ChP volume (nChP), CSF sub-volumes, the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and [18F]-FDG-PET standardized uptake value ratios. Partial correlation and mediation analyses were performed, adjusting for covariates.ResultsIncreased nChP", "source": "PubMed"}, {"chunk_id": "41789871_1", "pmid": "41789871", "title": "Choroid plexus-glymphatic axis disruption in Alzheimer's disease: Cerebrospinal fluid expansion as a mediator of metabolic dysfunction and cognitive decline.", "authors": "Lv M, Wang Q, Yu G et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, [18F]-FDG-PET, cerebrospinal fluid dynamics, choroid plexus, glymphatic dysfunction, multiple mediation analysis, neuroimaging", "chunk": "(nChP), CSF sub-volumes, the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and [18F]-FDG-PET standardized uptake value ratios. Partial correlation and mediation analyses were performed, adjusting for covariates.ResultsIncreased nChP correlated with larger CSF (nTotal-CSF: r = 0.324, FDR-p = 0.004), lower DTI-ALPS, and reduced FDG. nChP drove cognitive decline via two paths: \"nChP\u2192nTotal-CSF\u2192 Mini-Mental State Examination (MMSE)\" (44.1% total effect) and \"nChP\u2192DTI-ALPS\u2192FDG\u2192MMSE\" (9.9%, p < 0.001). CSF showed spatial mediation: nCSF-LV (66.20% on metabolism) outperformed external CSF (38.90%); DTI-ALPS negatively correlated with nCSF-LV (r = -0.406, FDR-p < 0.01).ConclusionsOur findings demonstrate that ChP enlargement is linked to cognitive impairment through pathways involving CSF dynamics and glymphatic function, with cerebral hypometabolism as a key downstream effector. This study posits a \"CSF dynamics imbalance\" cascade in AD, highlighting the potential of targeting Choroid Plexus-CSF-glymphatic axis for early diagnosis and intervention.", "source": "PubMed"}, {"chunk_id": "41789871_2", "pmid": "41789871", "title": "Choroid plexus-glymphatic axis disruption in Alzheimer's disease: Cerebrospinal fluid expansion as a mediator of metabolic dysfunction and cognitive decline.", "authors": "Lv M, Wang Q, Yu G et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, [18F]-FDG-PET, cerebrospinal fluid dynamics, choroid plexus, glymphatic dysfunction, multiple mediation analysis, neuroimaging", "chunk": "\"CSF dynamics imbalance\" cascade in AD, highlighting the potential of targeting Choroid Plexus-CSF-glymphatic axis for early diagnosis and intervention.", "source": "PubMed"}, {"chunk_id": "37723414_0", "pmid": "37723414", "title": "SIMOA-based analysis of plasma NFL levels in MCI and AD patients: a systematic review and meta-analysis.", "authors": "Sahrai H, Norouzi A, Hamzehzadeh S et al.", "year": "2023", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease, Mild cognitive impairment, Neurofilament light chain, Serum, Single molecule array assays", "chunk": "The single-molecule array assay (SIMOA)-based detection of neurofilament light (NFL) chain could be useful in diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD). This meta-analysis aimed to evaluate the circulating concentration of NFL in AD and MCI patients compared with healthy controls using the SIMOA technique. To this end, Google Scholar, PubMed, Scopus, Web of Science, and the reference lists of relevant articles were systematically searched for studies reporting serum NFL chain levels in healthy controls, MCI, and AD patients. Appropriate statistical methods were employed to achieve the study purpose. Fifteen eligible studies including 3086 patients were pooled out of a total of 347 publications. Fixed effect model analysis showed that NFL chain level was significantly higher in the serum of patients with MCI (0.361 SMD, 95% CI, 0.286-0.435, p = 0.000, I<sup>2</sup> = 49.179) and AD (0.808 SMD, 95% CI, 0.727-0.888, p = 0.000, I<sup>2</sup> = 39.433) compared", "source": "PubMed"}, {"chunk_id": "37723414_1", "pmid": "37723414", "title": "SIMOA-based analysis of plasma NFL levels in MCI and AD patients: a systematic review and meta-analysis.", "authors": "Sahrai H, Norouzi A, Hamzehzadeh S et al.", "year": "2023", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease, Mild cognitive impairment, Neurofilament light chain, Serum, Single molecule array assays", "chunk": "serum of patients with MCI (0.361 SMD, 95% CI, 0.286-0.435, p = 0.000, I<sup>2</sup> = 49.179) and AD (0.808 SMD, 95% CI, 0.727-0.888, p = 0.000, I<sup>2</sup> = 39.433) compared with healthy individuals. The analysis also showed that the NFL chain levels in plasma were significantly different between patients with MCI and AD (0.436 SMD, 95% CI, 0.359-0.513, p = 0.000, I<sup>2</sup> = 37.44). The overall heterogeneity of the studies was modest. This study highlights the potential of serum NFL chain detected using SIMOA in differentiating MCI, AD, and healthy controls.", "source": "PubMed"}, {"chunk_id": "41822695_0", "pmid": "41822695", "title": "Social and Cardiovascular Risk Factors as Predictors of the Progression from Mild Cognitive Impairment to Dementia in a Large EHR Database.", "authors": "Miramontes S, Ferguson EL, Zimmerman S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "Progression from mild cognitive impairment (MCI) to Alzheimer's Disease and Related Dementias (AD/ADRD) varies widely across individuals, yet the mechanisms underlying this heterogeneity remain unclear. Identifying clinical and social determinants influencing this transition could enable earlier intervention. While cardiovascular and social risk factors are established contributors to dementia incidence, their role in progression from MCI to dementia may differ. Few studies using real world clinical data have evaluated these potential determinants of MCI progression. Using electronic health records (EHR) from patients with incident MCI at UCSF Health (2010-2024), we evaluated cardiovascular (blood pressure [BP], body mass index [BMI], and type II diabetes) and social (marital status, language preference, race/ethnicity, and neighborhood disadvantage) risk factors for rate of progression from MCI to AD/ADRD. Covariate-adjusted Cox proportional hazards models estimated hazard ratios for incident AD/ADRD, with evaluation of interactions by sex. Among 6,529 patients, higher systolic BP was associated with AD/ADRD incidence", "source": "PubMed"}, {"chunk_id": "41822695_1", "pmid": "41822695", "title": "Social and Cardiovascular Risk Factors as Predictors of the Progression from Mild Cognitive Impairment to Dementia in a Large EHR Database.", "authors": "Miramontes S, Ferguson EL, Zimmerman S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "to AD/ADRD. Covariate-adjusted Cox proportional hazards models estimated hazard ratios for incident AD/ADRD, with evaluation of interactions by sex. Among 6,529 patients, higher systolic BP was associated with AD/ADRD incidence (HR per 10 mmHg: 1.09, 95% CI: 1.05-1.14). BMI was inversely associated with incidence in both males (HR: 0.94; 95% CI: 0.92-0.97) and females (HR:0.98; 95% CI: 0.96-0.99). Compared to married individuals, widowed patients had a higher hazard of progression (HR: 1.15; 95% CI: 1.00-1.32). Spanish-speaking (HR: 1.38; 95% CI: 1.04-1.81), Chinese-speaking (HR: 1.19; 95% CI: 1.00-1.42), and \"Other non-English\" speaking patients (HR:1.24; 95% CI: 1.03-1.51) had a higher hazard of progression compared to English speakers. Latinx (HR:1.22; 95% CI: 1.01-1.48) and Asian patients (HR:1.14, 95% CI: 1.00-1.30; p=0.04) also had higher hazards of progression compared to White patients. Neighborhood disadvantage was not significantly associated with disease progression. Cardiovascular and social factors independently influence dementia progression, with some sex-specific patterns.", "source": "PubMed"}, {"chunk_id": "41822695_2", "pmid": "41822695", "title": "Social and Cardiovascular Risk Factors as Predictors of the Progression from Mild Cognitive Impairment to Dementia in a Large EHR Database.", "authors": "Miramontes S, Ferguson EL, Zimmerman S et al.", "year": "2026", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "had higher hazards of progression compared to White patients. Neighborhood disadvantage was not significantly associated with disease progression. Cardiovascular and social factors independently influence dementia progression, with some sex-specific patterns. Integrating clinical and social indicators highlights the potential of EHR data to identify high-risk patients earlier in the care continuum and support equitable dementia prevention.", "source": "PubMed"}, {"chunk_id": "35931049_0", "pmid": "35931049", "title": "A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.", "authors": "Ramdas S, Judd J, Graham SE et al.", "year": "2022", "journal": "American journal of human genetics", "keywords": "complex traits, fine-mapping, functional genomics, lipid biology, post-GWAS, regulatory mechanism, variant prioritization", "chunk": "A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants", "source": "PubMed"}, {"chunk_id": "35931049_1", "pmid": "35931049", "title": "A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.", "authors": "Ramdas S, Judd J, Graham SE et al.", "year": "2022", "journal": "American journal of human genetics", "keywords": "complex traits, fine-mapping, functional genomics, lipid biology, post-GWAS, regulatory mechanism, variant prioritization", "chunk": "identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.", "source": "PubMed"}, {"chunk_id": "36710671_0", "pmid": "36710671", "title": "Associations Between Insulin-Like Growth Factor-1 and Resting-State Functional Connectivity in Cognitively Unimpaired Midlife Adults.", "authors": "Li T, Pappas C, Klinedinst B et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cognitive dysfunction, functional MRI, insulin-like growth factor-1", "chunk": "Insulin-like growth factor (IGF)-1 plays an important role in Alzheimer's disease (AD) pathogenesis and increases disease risk. However, prior research examining IGF-1 levels and brain neural network activity is mixed. The present study investigated the relationship between IGF-1 levels and 21 neural networks, as measured by functional magnetic resonance imaging (fMRI) in 13,235 UK Biobank participants. Linear mixed models were used to regress IGF-1 against the intrinsic functional connectivity (i.e., degree of network activity) for each neural network. Interactions between IGF-1 and AD risk factors such as Apolipoprotein E4 (APOE4) genotype, sex, AD family history, and age were also tested. Higher IGF-1 was associated with more network activity in the right Executive Function neural network. IGF-1 interactions with APOE4 or sex implicated motor, primary/extrastriate visual, and executive function related neural networks. Neural network activity trends with increasing IGF-1 were different in different age groups. Higher IGF-1 levels relate to much", "source": "PubMed"}, {"chunk_id": "36710671_1", "pmid": "36710671", "title": "Associations Between Insulin-Like Growth Factor-1 and Resting-State Functional Connectivity in Cognitively Unimpaired Midlife Adults.", "authors": "Li T, Pappas C, Klinedinst B et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cognitive dysfunction, functional MRI, insulin-like growth factor-1", "chunk": "sex implicated motor, primary/extrastriate visual, and executive function related neural networks. Neural network activity trends with increasing IGF-1 were different in different age groups. Higher IGF-1 levels relate to much more network activity in the Sensorimotor Network and Cerebellum Network in early-life participants (40-52 years old), compared with mid-life (52-59 years old) and late-life (59-70 years old) participants. These findings suggest that sex and APOE4 genotype may modify the relationship between IGF-1 and brain network activities related to visual, motor, and cognitive processing. Additionally, IGF-1 may have an age-dependent effect on neural network connectivity.", "source": "PubMed"}, {"chunk_id": "26757041_0", "pmid": "26757041", "title": "Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in A\u03b2PP(swe)/PS1(\u0394E9) Mice.", "authors": "Qiu H, Zhong R, Liu H et al.", "year": "2016", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, apoptosis, chronic sleep deprivation, mitochondria, phosphorylated tau protein, senile plaques", "chunk": "Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in A\u03b2PP(swe)/PS1(\u0394E9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-\u03b2 protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-\u03b2(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both", "source": "PubMed"}, {"chunk_id": "26757041_1", "pmid": "26757041", "title": "Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in A\u03b2PP(swe)/PS1(\u0394E9) Mice.", "authors": "Qiu H, Zhong R, Liu H et al.", "year": "2016", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, apoptosis, chronic sleep deprivation, mitochondria, phosphorylated tau protein, senile plaques", "chunk": "plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.", "source": "PubMed"}, {"chunk_id": "41013813_0", "pmid": "41013813", "title": "Investigating the relationship between glymphatic dysfunction and motor symptoms in Parkinson's disease.", "authors": "Ma X, Yan R, Jian Y et al.", "year": "2025", "journal": "European journal of medical research", "keywords": "DTI-ALPS index, Glymphatic pathway, Motor manifestations, Parkinson\u2019s disease", "chunk": "The glymphatic system is instrumental in cerebral waste drainage, and its impairment is mechanistically linked to the pathogenesis of neurodegenerative diseases like Parkinson's disease (PD). Nevertheless, the relationship between dysfunction in the clearance processes and the intensity of motor symptoms in PD remains inadequately characterized. This study applied the non-invasive Diffusion Tensor Image Analysis along the Perivascular Space technique to quantify the clearance network activity in PD patients compared with healthy controls (HCs), probing its prospects as an imaging biomarker for motor impairment. From January 2024 to June 2025, a total of 43 PD patients, diagnosed according to the clinical diagnostic criteria, along with 31 well-matched HCs, were enrolled. All participants underwent MRI, and the waste-clearance system function was evaluated using the DTI-ALPS index. Motor manifestations in the PD group were systematically rated using the MDS-UPDRS. An independent sample t-test was carried out to compare the disparities in this imaging", "source": "PubMed"}, {"chunk_id": "41013813_1", "pmid": "41013813", "title": "Investigating the relationship between glymphatic dysfunction and motor symptoms in Parkinson's disease.", "authors": "Ma X, Yan R, Jian Y et al.", "year": "2025", "journal": "European journal of medical research", "keywords": "DTI-ALPS index, Glymphatic pathway, Motor manifestations, Parkinson\u2019s disease", "chunk": "using the DTI-ALPS index. Motor manifestations in the PD group were systematically rated using the MDS-UPDRS. An independent sample t-test was carried out to compare the disparities in this imaging metric between groups. Correlation and multiple regression analyses were further employed to explore the connections between the imaging metric and parkinsonian motor features. This study demonstrated a significantly lower MRI-derived metric in the PD group (1.19 \u00b1 0.14) relative to HCs (1.27 \u00b1 0.13; p = 0.019). The statistical significance of this difference persisted after covariance adjustment for age, years of education, and drinking history via ANCOVA (B = 0.080, 95% CI [0.015, 0.145], p = 0.016). Pearson correlation analysis revealed significant inverse associations between this radiographic measure and both the total MDS-UPDRS score (r = - 0.418, p = 0.005; Bootstrap 95% BCa CI [- 0.628, - 0.171]) and its motor subsection (Part III) score (r = - 0.424,", "source": "PubMed"}, {"chunk_id": "41013813_2", "pmid": "41013813", "title": "Investigating the relationship between glymphatic dysfunction and motor symptoms in Parkinson's disease.", "authors": "Ma X, Yan R, Jian Y et al.", "year": "2025", "journal": "European journal of medical research", "keywords": "DTI-ALPS index, Glymphatic pathway, Motor manifestations, Parkinson\u2019s disease", "chunk": "the total MDS-UPDRS score (r = - 0.418, p = 0.005; Bootstrap 95% BCa CI [- 0.628, - 0.171]) and its motor subsection (Part III) score (r = - 0.424, p = 0.005; Bootstrap 95% BCa CI [- 0.644, - 0.169]). Multiple regression indicated that the imaging metric served as an independent negative predictor of motor symptom severity (standardized \u03b2 = - 0.420, p = 0.010; B = - 42.45, Bootstrap 95% BCa CI [- 79.17, - 9.91]), accounting independently for 14.6% of the variability in motor severity (\u0394R<sup>2</sup> = 0.146, p = 0.008). These results suggest an association between the imaging metric and the function of the clearance network in PD, as well as a significant correlation with motor disability. These findings warrant further investigation into the metric's potential as a neuroimaging marker for motor impairment.", "source": "PubMed"}, {"chunk_id": "41013813_3", "pmid": "41013813", "title": "Investigating the relationship between glymphatic dysfunction and motor symptoms in Parkinson's disease.", "authors": "Ma X, Yan R, Jian Y et al.", "year": "2025", "journal": "European journal of medical research", "keywords": "DTI-ALPS index, Glymphatic pathway, Motor manifestations, Parkinson\u2019s disease", "chunk": "disability. These findings warrant further investigation into the metric's potential as a neuroimaging marker for motor impairment.", "source": "PubMed"}, {"chunk_id": "41199954_0", "pmid": "41199954", "title": "Brain virome dysbiosis in Parkinson's disease and multiple system atrophy.", "authors": "Ghorbani M, Gabarrini G, Hajikhezri Z", "year": "2025", "journal": "Frontiers in microbiology", "keywords": "Parkinson\u2019s disease, brain dysbiosis, brain virome, multiple system atrophy, putamen", "chunk": "Viral elements have been reported in human brain tissue, yet their presence in the putamen-a region critically affected in Parkinson's disease (PD) and multiple system atrophy (MSA)has not been characterized. We analyzed whole-genome sequencing data from 32 post-mortem putamen samples (PD: <i>n</i> = 10; MSA: <i>n</i> = 10; healthy controls: <i>n</i> = 12) available under NCBI BioProjects PRJNA756274, PRJNA563007, PRJNA321439, PRJNA555211, and PRJNA555099. Using MetaPhlAn4 for virome profiling, LEfSe for biomarker discovery, and Wilcoxon and ROC analyses for validation, we found that neurodegenerative samples exhibited significantly higher virome alpha diversity compared to healthy controls. LEfSe analysis revealed nine viral species enriched in the neurodegenerative group, including <i>Pestivirus A, Pestivirus Giraffe-1, Woolly monkey sarcoma virus, Abelson murine leukemia virus, Murine osteosarcoma virus, Human endogenous retrovirus K, Salmonella virus SP6, Taterapox virus</i>, and <i>Saccharomyces cerevisiae killer virus M1</i> (LDA score >2; <i>p</i> < 0.05). In contrast, <i>Alcelaphine gammaherpesvirus 1</i> was more abundant", "source": "PubMed"}, {"chunk_id": "41199954_1", "pmid": "41199954", "title": "Brain virome dysbiosis in Parkinson's disease and multiple system atrophy.", "authors": "Ghorbani M, Gabarrini G, Hajikhezri Z", "year": "2025", "journal": "Frontiers in microbiology", "keywords": "Parkinson\u2019s disease, brain dysbiosis, brain virome, multiple system atrophy, putamen", "chunk": "virus, Human endogenous retrovirus K, Salmonella virus SP6, Taterapox virus</i>, and <i>Saccharomyces cerevisiae killer virus M1</i> (LDA score >2; <i>p</i> < 0.05). In contrast, <i>Alcelaphine gammaherpesvirus 1</i> was more abundant in controls. While the functional roles of these viruses in the brain remain to be established, several have been previously linked to immunomodulatory effects, suggesting possible relevance to neurodegenerative disease processes. This pilot study provides the first evidence of a brain virome in the human putamen and suggests a potential link between virome dysbiosis and neurodegenerative disease. Distinct viral signatures identified in PD and MSA may serve as candidate biomarkers for early detection and diagnosis.", "source": "PubMed"}, {"chunk_id": "41693316_0", "pmid": "41693316", "title": "A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic biomarker for Parkinson's disease with potential prognostic value.", "authors": "Aviolat H, Mollon J, Giaisi S et al.", "year": "2026", "journal": "Journal of Parkinson's disease", "keywords": "DOPA decarboxylase (DDC), Parkinson's disease, SWEDD, biomarker, cerebrospinal fluid", "chunk": "BackgroundProteomic studies have identified cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker candidate for Parkinson's disease (PD). The aim of this study was to develop an immunoassay for CSF DDC quantification and gain further insight into its potential as a biomarker for PD.MethodsWe validated our DDC immunoassay by quantifying CSF DDC levels in the Parkinson's Progression Markers Initiative cohort, including healthy controls (n = 29), dopaminergic drug-na\u00efve PD patients (n = 27), and patients with scans without evidence for dopaminergic deficit (SWEDD) (n = 18).ResultsOur DDC assay detected elevated levels in CSF from dopaminergic drug-na\u00efve PD patients and discriminated them against SWEDD patients and controls with high sensitivity and specificity. There was an inverse correlation between DDC levels and ioflupane-[123I]-single-photon emission computed tomography-based dopamine transporter (DaT-SPECT) striatal binding ratios (SBRs) from the putamen and caudate nucleus. CSF DDC levels demonstrated prognostic potential for Movement Disorder Society Unified Parkinson's", "source": "PubMed"}, {"chunk_id": "41693316_1", "pmid": "41693316", "title": "A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic biomarker for Parkinson's disease with potential prognostic value.", "authors": "Aviolat H, Mollon J, Giaisi S et al.", "year": "2026", "journal": "Journal of Parkinson's disease", "keywords": "DOPA decarboxylase (DDC), Parkinson's disease, SWEDD, biomarker, cerebrospinal fluid", "chunk": "and ioflupane-[123I]-single-photon emission computed tomography-based dopamine transporter (DaT-SPECT) striatal binding ratios (SBRs) from the putamen and caudate nucleus. CSF DDC levels demonstrated prognostic potential for Movement Disorder Society Unified Parkinson's Disease Rating Scale total score change five to eight years post-diagnosis. DDC levels were further increased at the three-year follow-up visit in PD patients and positively correlated with the L-DOPA equivalent daily dose. There was a strong correlation between the relative CSF DDC levels determined by a proprietary immune-based proximity extension assay and absolute levels determined with our assay.ConclusionsOur assay provided further insight into the potential of CSF DDC as a diagnostic and prognostic biomarker for PD. The unchanged levels in SWEDD patients and inverse correlation with DaT-SPECT SBRs suggest that CSF DDC levels are connected to dopaminergic deficit.", "source": "PubMed"}, {"chunk_id": "41693316_2", "pmid": "41693316", "title": "A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic biomarker for Parkinson's disease with potential prognostic value.", "authors": "Aviolat H, Mollon J, Giaisi S et al.", "year": "2026", "journal": "Journal of Parkinson's disease", "keywords": "DOPA decarboxylase (DDC), Parkinson's disease, SWEDD, biomarker, cerebrospinal fluid", "chunk": "that CSF DDC levels are connected to dopaminergic deficit.", "source": "PubMed"}, {"chunk_id": "40794785_0", "pmid": "40794785", "title": "Network biomarkers of Alzheimer's disease risk derived from joint volume and texture covariance patterns in mouse models.", "authors": "Bridgeford EW, Chung J, Anderson RJ et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "Alzheimer's disease (AD) lacks effective cures and is typically detected after substantial pathological changes have occurred, making intervention challenging. Alzheimer's disease (AD) intervention requires early detection of risk factors and understanding their complex interactions before substantial pathological changes manifest. Current research often examines individual risk factors in isolation, limiting our understanding of their combined effects. We present a novel multivariate analytical framework to simultaneously assess multiple AD risk factors using mouse models expressing human ApoE alleles. Our methodological innovation lies in combining high-resolution magnetic resonance diffusion imaging with a comprehensive multifactorial analysis that integrates genotype, age, sex, diet, and immunity as interacting variables. This approach enables the simultaneous examination of regional brain volume and fractional anisotropy changes across multiple risk factors, providing a more holistic view than traditional univariate analyses. Our proposed method effectively identified how these factors converge on specific brain regions - with genotype influencing the caudate putamen,", "source": "PubMed"}, {"chunk_id": "40794785_1", "pmid": "40794785", "title": "Network biomarkers of Alzheimer's disease risk derived from joint volume and texture covariance patterns in mouse models.", "authors": "Bridgeford EW, Chung J, Anderson RJ et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "factors, providing a more holistic view than traditional univariate analyses. Our proposed method effectively identified how these factors converge on specific brain regions - with genotype influencing the caudate putamen, pons, cingulate cortex, and cerebellum; sex affecting the amygdala and piriform cortex; and immune status impacting association cortices and cerebellar nuclei. Importantly, our integrated approach revealed factor interactions that would remain undetected in single-variable studies, particularly in the amygdala, thalamus, and pons. While many findings align with previous research, our multidimensional framework offers a methodological advancement for studying AD risk factors by modeling their combined effects rather than isolated impacts. This approach creates a template for future studies to investigate mechanisms underlying coordinated changes in brain structure through network analyses of gene expression, metabolism, and structural pathways involved in neurodegeneration.", "source": "PubMed"}, {"chunk_id": "40794785_2", "pmid": "40794785", "title": "Network biomarkers of Alzheimer's disease risk derived from joint volume and texture covariance patterns in mouse models.", "authors": "Bridgeford EW, Chung J, Anderson RJ et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "of gene expression, metabolism, and structural pathways involved in neurodegeneration.", "source": "PubMed"}, {"chunk_id": "39288341_0", "pmid": "39288341", "title": "Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.", "authors": "Lorenzini L, Maranzano A, Ingala S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (A\u03b2<sub>1-42</sub>) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau<sub>181</sub>), atrophy, and cognition. This retrospective study included nondemented participants (Clinical Dementia Rating < 1) from the European Prevention of Alzheimer's Dementia (EPAD) cohort and assessed VRFs with the Framingham risk score (FRS) and cSVD features on MRI using visual scales and white matter hyperintensity volumes. After preliminary linear analysis, we used structural equation modeling (SEM) to create a \"cSVD severity\" latent variable and assess the direct and indirect effects of FRS and cSVD severity on A\u03b2<sub>1-42</sub>,", "source": "PubMed"}, {"chunk_id": "39288341_1", "pmid": "39288341", "title": "Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.", "authors": "Lorenzini L, Maranzano A, Ingala S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "preliminary linear analysis, we used structural equation modeling (SEM) to create a \"cSVD severity\" latent variable and assess the direct and indirect effects of FRS and cSVD severity on A\u03b2<sub>1-42</sub>, P-tau<sub>181</sub>, gray matter volume (baseline and longitudinal), and cognitive performance (baseline and longitudinal). A total cohort of 1,592 participants were evaluated (mean age = 65.5 \u00b1 7.4 years; 56.16% F). We observed positive associations between FRS and all cSVD features (all <i>p</i> < 0.05) and a negative association between FRS and A\u03b2<sub>1-42</sub> (\u03b2 = -0.04 \u00b1 0.01). All cSVD features were negatively associated with CSF A\u03b2<sub>1-42</sub> (all <i>p</i> < 0.05). Using SEM, the cSVD severity fully mediated the association between FRS and CSF A\u03b2<sub>1-42</sub> (indirect effect: \u03b2 = -0.03 \u00b1 0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau<sub>181</sub> (indirect effect: \u03b2 = 0.12 \u00b1 0.03), baseline and longitudinal gray matter", "source": "PubMed"}, {"chunk_id": "39288341_2", "pmid": "39288341", "title": "Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.", "authors": "Lorenzini L, Maranzano A, Ingala S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau<sub>181</sub> (indirect effect: \u03b2 = 0.12 \u00b1 0.03), baseline and longitudinal gray matter volume (indirect effect: \u03b2 = -0.10 \u00b1 0.03; \u03b2 = -0.12 \u00b1 0.05), and baseline cognitive performance (indirect effect: \u03b2 = -0.16 \u00b1 0.03) through CSF A\u03b2<sub>1-42</sub>. In a large nondemented population, our findings suggest that cSVD is a mediator of the relationship between VRFs and CSF A\u03b2<sub>1-42</sub> and affects downstream neurodegeneration and cognitive impairment. We provide evidence of VRFs indirectly affecting the pathogenesis of AD, highlighting the importance of considering cSVD burden in memory clinics for AD risk evaluation and as an early window for intervention. These results stress the role of VRFs and cerebrovascular pathology as key biomarkers for accurate design of anti-amyloid clinical trials and offer new perspectives for patient stratification.", "source": "PubMed"}, {"chunk_id": "39288341_3", "pmid": "39288341", "title": "Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.", "authors": "Lorenzini L, Maranzano A, Ingala S et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "the role of VRFs and cerebrovascular pathology as key biomarkers for accurate design of anti-amyloid clinical trials and offer new perspectives for patient stratification.", "source": "PubMed"}, {"chunk_id": "32255379_0", "pmid": "32255379", "title": "Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.", "authors": "Agnello L, Piccoli T, Vidali M et al.", "year": "2020", "journal": "Scandinavian journal of clinical and laboratory investigation", "keywords": "Alzheimer disease, CLEIA, CSF biomarkers, chemiluminescent enzyme immunoassay method, liquor", "chunk": "In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (A\u03b242), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely A\u03b242, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patients clinically diagnosed as AD (48) and non-AD (48). All CSF biomarkers levels were measured on Lumipulse G1200 fully automated platform (Fujirebio Inc. Europe, Gent, Belgium). A\u03b242 levels, 42/40 ratio, 42/tTau ratio, 42/PTau ratio were significantly reduced, and tTau and PTau levels were significantly increased in", "source": "PubMed"}, {"chunk_id": "32255379_1", "pmid": "32255379", "title": "Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.", "authors": "Agnello L, Piccoli T, Vidali M et al.", "year": "2020", "journal": "Scandinavian journal of clinical and laboratory investigation", "keywords": "Alzheimer disease, CLEIA, CSF biomarkers, chemiluminescent enzyme immunoassay method, liquor", "chunk": "Lumipulse G1200 fully automated platform (Fujirebio Inc. Europe, Gent, Belgium). A\u03b242 levels, 42/40 ratio, 42/tTau ratio, 42/PTau ratio were significantly reduced, and tTau and PTau levels were significantly increased in AD patients in comparison with non-AD patients. The receiving operator curve (ROC) analysis showed good diagnostic accuracy of all CSF biomarkers and their ratios for discriminating AD patients from non-AD patients, with 42/40 ratio having the best AUC (0.724, 95%CI 0.619-0.828; <i>p</i> < 0.001). Our findings support the use of CSF biomarkers measured by CLEIA method on a fully automated platform for AD diagnosis.", "source": "PubMed"}, {"chunk_id": "41618017_0", "pmid": "41618017", "title": "Patterns of cognitive and motor decline in Alzheimer's Disease (AD) and ageing in healthy populations.", "authors": "Beccherle M, Amato S, Facci E et al.", "year": "2026", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s Disease, Cognitive and motor decline, Healthy ageing, Nutritional status, Psychomotor abilities", "chunk": "Various patterns may apply to an individual\u2019s health-span, with quality of life deriving from a balance between physical conditions, motor and cognitive abilities (i.e. psychomotor capabilities). In this study, the Italian version of the \u00c9xamen Geronto-Psychomoteur was administered to a sample of Alzheimer\u2019s Disease (AD) patients (<i>n</i> = 94) and a group of healthy older adults (<i>n</i> = 333) to compare the patterns of psychomotor decline in pathological and physiological ageing. Three domains were considered to integrate bodily and cognitive dimensions: cognitive functions, motor abilities, and muscular tone alterations (physical constraints). Potential correlations with general cognitive functioning, autonomy in daily life, mood and nutritional status were also investigated. A correlation between cognitive, motor and physical dimensions is confirmed, and the results show that the patterns relating to healthy and pathological ageing are not only quantitatively but also qualitatively different. Besides the cognitive functions, the deterioration in AD also affects the", "source": "PubMed"}, {"chunk_id": "41618017_1", "pmid": "41618017", "title": "Patterns of cognitive and motor decline in Alzheimer's Disease (AD) and ageing in healthy populations.", "authors": "Beccherle M, Amato S, Facci E et al.", "year": "2026", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s Disease, Cognitive and motor decline, Healthy ageing, Nutritional status, Psychomotor abilities", "chunk": "results show that the patterns relating to healthy and pathological ageing are not only quantitatively but also qualitatively different. Besides the cognitive functions, the deterioration in AD also affects the physical components, precociously. Specifically, hypertonia may be present since the initial phases of illness. In healthy subjects, body representations decline early, while verbal memory, temporal and space representation resist over time. Malnutrition correlates with hypertonia in AD and with a reduction in daily life abilities in healthy people. The results highlight the importance of adopting an integrated psychomotor approach in the screening, diagnosis and treatment of ageing and AD to investigate early motor and bodily indicators, which are often not fully considered in clinical practice. The online version contains supplementary material available at 10.1007/s40520-026-03327-1.", "source": "PubMed"}, {"chunk_id": "41618017_2", "pmid": "41618017", "title": "Patterns of cognitive and motor decline in Alzheimer's Disease (AD) and ageing in healthy populations.", "authors": "Beccherle M, Amato S, Facci E et al.", "year": "2026", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s Disease, Cognitive and motor decline, Healthy ageing, Nutritional status, Psychomotor abilities", "chunk": "material available at 10.1007/s40520-026-03327-1.", "source": "PubMed"}, {"chunk_id": "41587758_0", "pmid": "41587758", "title": "Falls as a Predictor of Future Dementia in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.", "authors": "Li J, Meng Z, Zhang S et al.", "year": "2026", "journal": "Journal of the American Medical Directors Association", "keywords": "Falls, dementia, meta-analysis, older adults, prediction, systematic review", "chunk": "To systematically review and quantitatively synthesize evidence on the predictive role of falls for future dementia in middle-aged and older adults. Systematic review and meta-analysis. Middle-aged and older adults without dementia (aged \u226540 years). Systematically retrieved literature from 4 English-language databases-PubMed, Embase, Web of Science, and the Cochrane Library-from inception to July 1, 2025. Prospective and retrospective cohort studies investigating the association between falls and future development of dementia were included. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects model was applied using Stata 17.0 software to conduct a pooled analysis of the incidence of dementia in middle-aged and older adults (\u226540 years) with a history of falls, as well as the strength of the association between falls and future dementia [adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)]. A total of 7 studies were included, of which 5 were included in the meta-analysis, comprising a total", "source": "PubMed"}, {"chunk_id": "41587758_1", "pmid": "41587758", "title": "Falls as a Predictor of Future Dementia in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.", "authors": "Li J, Meng Z, Zhang S et al.", "year": "2026", "journal": "Journal of the American Medical Directors Association", "keywords": "Falls, dementia, meta-analysis, older adults, prediction, systematic review", "chunk": "and future dementia [adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)]. A total of 7 studies were included, of which 5 were included in the meta-analysis, comprising a total of 2,922,624 participants. Results indicate that among 1,246,410 middle-aged and older adults with a history of falls, the pooled incidence of future dementia was 11.6% (95% CI, 4.2%-19.0%; I<sup>2</sup> = 99.8%). Among older adults (\u226560 years), the pooled incidence was 12.3% (95% CI, 4.7%-20.0%; I<sup>2</sup> = 99.8%). Both single falls (aHR, 1.20; 95% CI, 1.07-1.36) and multiple falls (aHR, 1.74; 95% CI, 1.53-1.98) increased the risk of future all-cause dementia, and multiple falls were a more robust predictor of future dementia. Collectively, the results indicate that the frequency of falls exhibits a dose-response relationship with dementia risk. This study demonstrates that multiple falls are a significant predictor of future dementia and highlights the importance of fall frequency. Recurrent falls may", "source": "PubMed"}, {"chunk_id": "41587758_2", "pmid": "41587758", "title": "Falls as a Predictor of Future Dementia in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.", "authors": "Li J, Meng Z, Zhang S et al.", "year": "2026", "journal": "Journal of the American Medical Directors Association", "keywords": "Falls, dementia, meta-analysis, older adults, prediction, systematic review", "chunk": "exhibits a dose-response relationship with dementia risk. This study demonstrates that multiple falls are a significant predictor of future dementia and highlights the importance of fall frequency. Recurrent falls may serve as a potential clinical marker for identifying individuals at higher risk. Clinicians should maintain heightened vigilance for cognitive decline in middle-aged and older adults with a history of recurrent falls to facilitate early detection of dementia. Given the limited evidence base and high heterogeneity, further high-quality research is warranted to clarify this association and support preventive strategies in aging populations.", "source": "PubMed"}, {"chunk_id": "36630921_0", "pmid": "36630921", "title": "Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.", "authors": "Tian J, Liu RF, Li ZL et al.", "year": "2023", "journal": "Neuroendocrinology", "keywords": "Brain damage, Chronic hyperglycemia, Cognition disorders, Depression, Diabetes mellitus, Magnetic resonance imaging, Type 2", "chunk": "Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n = 47) of non-depressed T2DM (n = 59) and healthy controls (n = 41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore,", "source": "PubMed"}, {"chunk_id": "36630921_1", "pmid": "36630921", "title": "Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.", "authors": "Tian J, Liu RF, Li ZL et al.", "year": "2023", "journal": "Neuroendocrinology", "keywords": "Brain damage, Chronic hyperglycemia, Cognition disorders, Depression, Diabetes mellitus, Magnetic resonance imaging, Type 2", "chunk": "non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.", "source": "PubMed"}, {"chunk_id": "36630921_2", "pmid": "36630921", "title": "Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.", "authors": "Tian J, Liu RF, Li ZL et al.", "year": "2023", "journal": "Neuroendocrinology", "keywords": "Brain damage, Chronic hyperglycemia, Cognition disorders, Depression, Diabetes mellitus, Magnetic resonance imaging, Type 2", "chunk": "for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.", "source": "PubMed"}, {"chunk_id": "33050475_0", "pmid": "33050475", "title": "Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration.", "authors": "Gentile F, Doneddu PE, Riva N et al.", "year": "2020", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, diet, dysbiosis, metabolism", "chunk": "Increasing evidence gives support for the idea that extra-neuronal factors may affect brain physiology and its predisposition to neurodegenerative diseases. Epidemiological and experimental studies show that nutrition and metabolic disorders such as obesity and type 2 diabetes increase the risk of Alzheimer's and Parkinson's diseases after midlife, while the relationship with amyotrophic lateral sclerosis is uncertain, but suggests a protective effect of features of metabolic syndrome. The microbiota has recently emerged as a novel factor engaging strong interactions with neurons and glia, deeply affecting their function and behavior in these diseases. In particular, recent evidence suggested that gut microbes are involved in the seeding of prion-like proteins and their spreading to the central nervous system. Here, we present a comprehensive review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function. Advancing technologies may allow", "source": "PubMed"}, {"chunk_id": "33050475_1", "pmid": "33050475", "title": "Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration.", "authors": "Gentile F, Doneddu PE, Riva N et al.", "year": "2020", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, diet, dysbiosis, metabolism", "chunk": "review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function. Advancing technologies may allow researchers in the future to improve investigations in these fields, allowing the buildup of population-based preventive interventions and development of targeted therapeutics to halt progressive neurologic disability.", "source": "PubMed"}, {"chunk_id": "40270041_0", "pmid": "40270041", "title": "Associations of choroid plexus volume with white matter hyperintensity volume and susceptibility and plasma amyloid markers in cerebral small vessel disease.", "authors": "Liang P, Li M, Chen Y et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid-beta, Cerebral small vessel disease, Choroid plexus volume, Quantitative susceptibility mapping, White matter hyperintensities", "chunk": "White matter hyperintensity (WMH) is a key feature of cerebral small vessel disease (CSVD). The impact of the choroid plexus (CP) volume on disease progression remains largely unexplored. This study evaluated the relationship between CP volume and CSVD severity via WMH volume and susceptibility values. Additionally, we explored whether Alzheimer's disease (AD)-related plasma proteins influence the volume of the CP. Our study included 291 CSVD individuals, with 84 participants completing subsequent brain MRI at a mean follow-up of 20 months. To explore the potential CP-associated pathways, we assessed the relationships between AD-related plasma biomarkers and CP volume via multiple linear regression analysis. The longitudinal associations between CP volume and WMH characteristics (WMH volume and susceptibility) were analyzed via linear mixed-effects models. Finally, we employed random forest analysis with the Boruta algorithm to identify key predictors of CSVD severity. Plasma A\u03b21\u201240 levels were positively correlated with CP volume (\u03b2 = 0.115,", "source": "PubMed"}, {"chunk_id": "40270041_1", "pmid": "40270041", "title": "Associations of choroid plexus volume with white matter hyperintensity volume and susceptibility and plasma amyloid markers in cerebral small vessel disease.", "authors": "Liang P, Li M, Chen Y et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid-beta, Cerebral small vessel disease, Choroid plexus volume, Quantitative susceptibility mapping, White matter hyperintensities", "chunk": "models. Finally, we employed random forest analysis with the Boruta algorithm to identify key predictors of CSVD severity. Plasma A\u03b21\u201240 levels were positively correlated with CP volume (\u03b2 = 0.115, P = 0.009), whereas A\u03b242\u201240 ratio were negatively associated with CP volume (\u03b2 = -0.135, P = 0.03). Notably, increased CP volume was associated with both greater WMH burden (\u03b2 = 0.191, P = 0.011) and decreased WMH susceptibility (\u03b2 = -0.192, P = 0.012). Furthermore, random forest modeling identified CP volume and WMH susceptibility as the strongest predictors of CSVD severity. CP volume changes were significantly correlated with both WMH volume and WMH susceptibility in CSVD patients. These findings suggest that CP-mediated pathways may link amyloid metabolism to CSVD progression.", "source": "PubMed"}, {"chunk_id": "40270041_2", "pmid": "40270041", "title": "Associations of choroid plexus volume with white matter hyperintensity volume and susceptibility and plasma amyloid markers in cerebral small vessel disease.", "authors": "Liang P, Li M, Chen Y et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid-beta, Cerebral small vessel disease, Choroid plexus volume, Quantitative susceptibility mapping, White matter hyperintensities", "chunk": "progression.", "source": "PubMed"}, {"chunk_id": "34071634_0", "pmid": "34071634", "title": "Semi-Supervised Learning in Medical MRI Segmentation: Brain Tissue with White Matter Hyperintensity Segmentation Using FLAIR MRI.", "authors": "Rieu Z, Kim J, Kim RE et al.", "year": "2021", "journal": "Brain sciences", "keywords": "FLAIR, T1w, deep-learning, segmentation, white-matter hyperintensity", "chunk": "White-matter hyperintensity (WMH) is a primary biomarker for small-vessel cerebrovascular disease, Alzheimer's disease (AD), and others. The association of WMH with brain structural changes has also recently been reported. Although fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) provide valuable information about WMH, FLAIR does not provide other normal tissue information. The multi-modal analysis of FLAIR and T1-weighted (T1w) MRI is thus desirable for WMH-related brain aging studies. In clinical settings, however, FLAIR is often the only available modality. In this study, we thus propose a semi-supervised learning method for full brain segmentation using FLAIR. The results of our proposed method were compared with the reference labels, which were obtained by FreeSurfer segmentation on T1w MRI. The relative volume difference between the two sets of results shows that our proposed method has high reliability. We further evaluated our proposed WMH segmentation by comparing the Dice similarity coefficients of the reference", "source": "PubMed"}, {"chunk_id": "34071634_1", "pmid": "34071634", "title": "Semi-Supervised Learning in Medical MRI Segmentation: Brain Tissue with White Matter Hyperintensity Segmentation Using FLAIR MRI.", "authors": "Rieu Z, Kim J, Kim RE et al.", "year": "2021", "journal": "Brain sciences", "keywords": "FLAIR, T1w, deep-learning, segmentation, white-matter hyperintensity", "chunk": "between the two sets of results shows that our proposed method has high reliability. We further evaluated our proposed WMH segmentation by comparing the Dice similarity coefficients of the reference and the results of our proposed method. We believe our semi-supervised learning method has a great potential for use for other MRI sequences and will encourage others to perform brain tissue segmentation using MRI modalities other than T1w.", "source": "PubMed"}, {"chunk_id": "40076944_0", "pmid": "40076944", "title": "Blood Biomarkers Reflect Dementia Symptoms and Are Influenced by Cerebrovascular Lesions.", "authors": "Nakase T, Tatewaki Y, Takano Y et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, cognitive impairment, dementia, neuropsychological symptom, plasma biomarker", "chunk": "Dementia blood biomarkers are becoming increasingly important. Various factors, such as ischemic lesions and inflammation, can influence the pathomechanism of dementia. We aimed to evaluate the effects of past stroke lesions on blood biomarkers (BMs). Following approval from the institutional ethics committee, patients who were admitted to the memory clinic and were consented to written documents were enrolled (<i>n</i> = 111, average [standard deviation] age: 74.5 [9.1] years-old). Brain magnetic resonance imaging, cognitive function, and neuropsychological symptoms were analyzed. The amyloid-\u03b2 42 (A\u03b242)/A\u03b240 ratio, phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and A\u03b242/p-tau181 ratio were assessed as plasma BMs. The patients were diagnosed with Alzheimer's disease (<i>n</i> = 45), mild cognitive impairment (<i>n</i> = 56), depression (<i>n</i> = 8), and subjective cognitive impairment (<i>n</i> = 4). Bivariate analysis exhibited that all measured BM indicators were significantly associated with cognitive decline in patients without past stroke", "source": "PubMed"}, {"chunk_id": "40076944_1", "pmid": "40076944", "title": "Blood Biomarkers Reflect Dementia Symptoms and Are Influenced by Cerebrovascular Lesions.", "authors": "Nakase T, Tatewaki Y, Takano Y et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, cognitive impairment, dementia, neuropsychological symptom, plasma biomarker", "chunk": "depression (<i>n</i> = 8), and subjective cognitive impairment (<i>n</i> = 4). Bivariate analysis exhibited that all measured BM indicators were significantly associated with cognitive decline in patients without past stroke lesions. Whereas the patients with stroke lesions presented a significant association only between GFAP and cognitive decline (<i>p</i> = 0.0011). Multiple regression analysis showed that NfL significantly correlated with cognitive decline only in patients without stroke lesions (r = 0.4988, <i>p</i> = 0.0003) and with delusion only in those with stroke lesions (r = 0.5492, <i>p</i> = 0.0121). Past stroke lesions should be addressed in the assessment of the correlation between blood biomarkers and cognitive decline in dementia patients.", "source": "PubMed"}, {"chunk_id": "39922758_0", "pmid": "39922758", "title": "Effectiveness of digital screening tools in detecting cognitive impairment among community-dwelling elderly in Northern China: A large cohort study.", "authors": "Zhang X, Zhang F, Hou S et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Behavioral tool, Cognitive impairment, Digital screening tool, Machine learning model, Plasma biomarker", "chunk": "This study assessed the effectiveness of three digital screening tools in detecting cognitive impairment (CI) in a large cohort of community-dwelling elderly individuals and investigated the relationship between key digital features and plasma p-tau217 levels. This community-based cohort study included 1,083 participants aged 65 years or older, with 337 diagnosed with CI and 746 classified as normal controls (NC). We utilized two screening approaches: traditional methods (AD8, MMSE scale, and APOE genotyping) and digital tools (drawing, gait, and eye tracking). LightGBM-based machine learning models were developed for each digital screening tool and their combination, and their performance was evaluated. The correlation between key digital features and plasma p-tau217 levels was analyzed as well. A total of 21 drawing, 71 gait, and 35 eye-tracking parameters showed significant differences between the two groups (all p < 0.05). The area under the curve (AUC) values for the drawing, gait, and eye-tracking models in", "source": "PubMed"}, {"chunk_id": "39922758_1", "pmid": "39922758", "title": "Effectiveness of digital screening tools in detecting cognitive impairment among community-dwelling elderly in Northern China: A large cohort study.", "authors": "Zhang X, Zhang F, Hou S et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Behavioral tool, Cognitive impairment, Digital screening tool, Machine learning model, Plasma biomarker", "chunk": "and 35 eye-tracking parameters showed significant differences between the two groups (all p < 0.05). The area under the curve (AUC) values for the drawing, gait, and eye-tracking models in distinguishing CI from NC were 0.860, 0.848, and 0.895, respectively. The combination of eye-tracking and drawing achieved the highest classification effectiveness, with an AUC of 0.958, and accuracy, sensitivity, and specificity all exceeded 85%. The fusion model achieved an AUC of 0.928 in distinguishing mild cognitive impairment (MCI) from NC. Additionally, several digital features (including two drawing, ten gait, and one eye-tracking parameters) were significantly correlated with plasma p-tau217 levels (all |r| > 0.3, p < 0.001). Digital screening tools offer objective, accurate, and efficient alternatives for detecting CI in community settings, with the fusion of drawing and eye-tracking providing the best performance (AUC = 0.958).", "source": "PubMed"}, {"chunk_id": "39922758_2", "pmid": "39922758", "title": "Effectiveness of digital screening tools in detecting cognitive impairment among community-dwelling elderly in Northern China: A large cohort study.", "authors": "Zhang X, Zhang F, Hou S et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Behavioral tool, Cognitive impairment, Digital screening tool, Machine learning model, Plasma biomarker", "chunk": "community settings, with the fusion of drawing and eye-tracking providing the best performance (AUC = 0.958).", "source": "PubMed"}, {"chunk_id": "41639022_0", "pmid": "41639022", "title": "Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer's disease.", "authors": "Fernandes MGF, Pinard M, Sokullu E et al.", "year": "2026", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "CIMA-Q, neurodegeneration, neuroligin, synapse, tau", "chunk": "Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer's disease-Quebec (CIMA-Q), we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment (aMCI) and early-stage Alzheimer's disease (AD). Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic (ROC) curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on Mini-Mental State Examination (MMSE) scores revealed that specific plasma phosphorylated", "source": "PubMed"}, {"chunk_id": "41639022_1", "pmid": "41639022", "title": "Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer's disease.", "authors": "Fernandes MGF, Pinard M, Sokullu E et al.", "year": "2026", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "CIMA-Q, neurodegeneration, neuroligin, synapse, tau", "chunk": "individuals. Receiver operating characteristic (ROC) curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on Mini-Mental State Examination (MMSE) scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.", "source": "PubMed"}, {"chunk_id": "39672227_0", "pmid": "39672227", "title": "Pharmacological PTP1B inhibition rescues motor learning, neuroinflammation, and hyperglycaemia in a mouse model of Alzheimer's disease.", "authors": "Franklin Z, Hull C, Delibegovic M et al.", "year": "2025", "journal": "Experimental neurology", "keywords": "Alzheimer's disease, Beta-secretase, Hyperglycaemia, Neuroinflammation, PTP1B inhibitor, Type 2 diabetes mellitus", "chunk": "Patients with Alzheimer's Disease (AD) frequently suffer from comorbidities such as type 2 diabetes mellitus (T2DM), accompanied by shared common pathologies such as increased inflammation and impaired glucose homeostasis. Beta-secretase 1 (BACE1), the rate limiting enzyme in AD associated beta-amyloid (A\u03b2) production, is also implicated in metabolic dysfunction and can increase central and peripheral protein levels of protein tyrosine phosphatase 1B (PTP1B). PTP1B is a validated target in diabetes and obesity, and is a neuroinflammatory regulator involved in degenerative processes. This study investigated the effects of the PTP1B inhibitor, trodusquemine (MSI-1436) on the cognitive and metabolic phenotypes of the neuronal human BACE1 knock-in (PLB4) mouse, a co-morbidity model of AD and T2DM, and their wild-type (PLB<sub>WT</sub>) controls. Five-month-old male PLB4 and PLB<sub>WT</sub> mice received PTP1B inhibitor treatment (1 mg/kg intraperitoneal injection; 5 weeks). Activity and spatial habituation (Phenotyper), motor learning (RotaRod), glucose tolerance, and brain and liver molecular analyses were", "source": "PubMed"}, {"chunk_id": "39672227_1", "pmid": "39672227", "title": "Pharmacological PTP1B inhibition rescues motor learning, neuroinflammation, and hyperglycaemia in a mouse model of Alzheimer's disease.", "authors": "Franklin Z, Hull C, Delibegovic M et al.", "year": "2025", "journal": "Experimental neurology", "keywords": "Alzheimer's disease, Beta-secretase, Hyperglycaemia, Neuroinflammation, PTP1B inhibitor, Type 2 diabetes mellitus", "chunk": "and PLB<sub>WT</sub> mice received PTP1B inhibitor treatment (1 mg/kg intraperitoneal injection; 5 weeks). Activity and spatial habituation (Phenotyper), motor learning (RotaRod), glucose tolerance, and brain and liver molecular analyses were analysed following treatment. Inhibition of PTP1B improved motor learning alongside glucose tolerance in PLB4 mice, without affecting body weight/adiposity. MSI-1436 treatment led to lower protein levels of amyloid precursor protein (APP), reduced astrogliosis and restoration of the endoplasmic chaperone immunoglobulin heavy chain binding protein (BIP) in the brain, alongside decreased insulin receptor substrate-1 (IRS1) and dipeptidyl peptidase-4 (DPP4) proteins in the liver. We provide evidence that neuronal BACE1 contributes to neuroinflammation and hyperglycaemia in PLB4 mice, and this can be partially rescued by PTP1B inhibition. Targeting PTP1B may therefore offer an attractive therapeutic approach to ameliorate co-morbidity associated pathologies in AD and T2DM.", "source": "PubMed"}, {"chunk_id": "39672227_2", "pmid": "39672227", "title": "Pharmacological PTP1B inhibition rescues motor learning, neuroinflammation, and hyperglycaemia in a mouse model of Alzheimer's disease.", "authors": "Franklin Z, Hull C, Delibegovic M et al.", "year": "2025", "journal": "Experimental neurology", "keywords": "Alzheimer's disease, Beta-secretase, Hyperglycaemia, Neuroinflammation, PTP1B inhibitor, Type 2 diabetes mellitus", "chunk": "an attractive therapeutic approach to ameliorate co-morbidity associated pathologies in AD and T2DM.", "source": "PubMed"}, {"chunk_id": "31569571_0", "pmid": "31569571", "title": "Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer's Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy.", "authors": "Hayden MR", "year": "2019", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, aging, brain insulin resistance, db/db diabetic mouse model, diabetic cognopathy, insulin resistance, metabolic syndrome, mixed dementia, obesity, type 2 diabetes mellitus", "chunk": "Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer's disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic <i>db/db</i> models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain's neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases);", "source": "PubMed"}, {"chunk_id": "31569571_1", "pmid": "31569571", "title": "Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer's Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy.", "authors": "Hayden MR", "year": "2019", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, aging, brain insulin resistance, db/db diabetic mouse model, diabetic cognopathy, insulin resistance, metabolic syndrome, mixed dementia, obesity, type 2 diabetes mellitus", "chunk": "endeavors to demonstrate how T2DM increases the vulnerability of the brain's neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis-vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.", "source": "PubMed"}, {"chunk_id": "38984968_0", "pmid": "38984968", "title": "Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL <i>via</i> the Wnt3a/\u03b2-Catenin/GSK-3\u03b2 Pathway in a Type 2 Diabetes Mellitus Model.", "authors": "Zhao F, Guo L, Huang T et al.", "year": "2024", "journal": "Journal of agricultural and food chemistry", "keywords": "Wnt3a/\u03b2-Catenin/GSK-3\u03b2 pathway, cognitive deficiency, insulin resistance, mitochondrial function, synaptic plasticity, walnut-derived peptide", "chunk": "The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (<i>p</i> < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/\u03b2-Catenin/GSK-3\u03b2 pathway in glucose-induced insulin resistance in PC12 cells. <i>In vitro</i> LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption,", "source": "PubMed"}, {"chunk_id": "38984968_1", "pmid": "38984968", "title": "Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL <i>via</i> the Wnt3a/\u03b2-Catenin/GSK-3\u03b2 Pathway in a Type 2 Diabetes Mellitus Model.", "authors": "Zhao F, Guo L, Huang T et al.", "year": "2024", "journal": "Journal of agricultural and food chemistry", "keywords": "Wnt3a/\u03b2-Catenin/GSK-3\u03b2 pathway, cognitive deficiency, insulin resistance, mitochondrial function, synaptic plasticity, walnut-derived peptide", "chunk": "pathway in glucose-induced insulin resistance in PC12 cells. <i>In vitro</i> LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (<i>p</i> < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status <i>via</i> the Wnt3a/\u03b2-Catenin/GSK-3\u03b2 pathway.", "source": "PubMed"}, {"chunk_id": "37827850_0", "pmid": "37827850", "title": "Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.", "authors": "Acha B, Corroza J, S\u00e1nchez-Ruiz de Gordoa J et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls. A case-control study was performed. Blood DNA methylation levels at 46 cytosine-guanine sites (21 genes selected after a comprehensive literature search) were measured by bisulfite pyrosequencing in patients with \"probable AD dementia\" following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience", "source": "PubMed"}, {"chunk_id": "37827850_1", "pmid": "37827850", "title": "Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.", "authors": "Acha B, Corroza J, S\u00e1nchez-Ruiz de Gordoa J et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "\"probable AD dementia\" following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience sampling. Plasma pTau181 levels were determined by Simoa technology. Multivariable logistic regression analysis was performed to explore the optimal model to discriminate patients with AD from controls. Furthermore, we performed a stratified analysis by sex. The final study cohort consisted of 80 patients with AD (age: median [interquartile range] 79 [11] years; 58.8% female) and 100 cognitively healthy controls (age 77 [10] years; 58% female). A panel including DNA methylation levels at <i>NXN</i>, <i>ABCA7</i>, and <i>HOXA3</i> genes and plasma pTau181 significantly improved (area under the receiver operating characteristic curve 0.93, 95% CI 0.89-0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and <i>APOE</i> \u025b4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%,", "source": "PubMed"}, {"chunk_id": "37827850_2", "pmid": "37827850", "title": "Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.", "authors": "Acha B, Corroza J, S\u00e1nchez-Ruiz de Gordoa J et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "95% CI 0.89-0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and <i>APOE</i> \u025b4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%, respectively. After sex-stratified analysis, <i>HOXA3</i> DNA methylation levels showed consistent association with AD. These results highlight the potential translational value of blood-based DNA methylation biomarkers for noninvasive diagnosis of AD. Research Ethics Committee of the University Hospital of Navarre (PI17/02218).", "source": "PubMed"}, {"chunk_id": "32678803_0", "pmid": "32678803", "title": "A new method to predict anomaly in brain network based on graph deep learning.", "authors": "Mirakhorli J, Amindavar H, Mirakhorli M", "year": "2020", "journal": "Reviews in the neurosciences", "keywords": "brain function, generative model, graph theory, mild cognitive impairment (MCI), neural plasticity, posterior contraction", "chunk": "Functional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition", "source": "PubMed"}, {"chunk_id": "32678803_1", "pmid": "32678803", "title": "A new method to predict anomaly in brain network based on graph deep learning.", "authors": "Mirakhorli J, Amindavar H, Mirakhorli M", "year": "2020", "journal": "Reviews in the neurosciences", "keywords": "brain function, generative model, graph theory, mild cognitive impairment (MCI), neural plasticity, posterior contraction", "chunk": "both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain", "source": "PubMed"}, {"chunk_id": "32678803_2", "pmid": "32678803", "title": "A new method to predict anomaly in brain network based on graph deep learning.", "authors": "Mirakhorli J, Amindavar H, Mirakhorli M", "year": "2020", "journal": "Reviews in the neurosciences", "keywords": "brain function, generative model, graph theory, mild cognitive impairment (MCI), neural plasticity, posterior contraction", "chunk": "the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "40576449_0", "pmid": "40576449", "title": "LCN2 of cerebrospinal fluid: A potential biomarker for diagnosis and disease progression in Alzheimer's disease.", "authors": "Zhang QN, Yu LK, Zhang XY et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarker, cognitive impairment, lipocalin-2", "chunk": "BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder with complex pathological features and pathogenesis, involving aspects such as amyloid-\u03b2 (A\u03b2) deposition and neuroinflammation. AD lacks the specific biomarkers for diagnosis, which restricts diagnosis. Recent studies have indicated that Lipocalin-2 (LCN2) plays a direct or indirect role in the occurrence and development of AD. However, whether LCN2 can serve as a biomarker for AD diagnosis remains unclear.ObjectiveThis study aims to investigate the role of LCN2 in AD and its potential as a biomarker for diagnosis from a clinical perspective.MethodsWe analyze the participant demographic information, LCN2 and A\u03b2<sub>42</sub> levels in cerebrospinal fluid (CSF), and cortex thickness from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database with Welch ANOVA, Linear regression models and other statistical methods.ResultsLCN2 levels in the CSF of AD patients were significantly higher than those in individuals with mild cognitive impairment and no cognitive impairment. The LCN2 levels were closely associated with", "source": "PubMed"}, {"chunk_id": "40576449_1", "pmid": "40576449", "title": "LCN2 of cerebrospinal fluid: A potential biomarker for diagnosis and disease progression in Alzheimer's disease.", "authors": "Zhang QN, Yu LK, Zhang XY et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarker, cognitive impairment, lipocalin-2", "chunk": "methods.ResultsLCN2 levels in the CSF of AD patients were significantly higher than those in individuals with mild cognitive impairment and no cognitive impairment. The LCN2 levels were closely associated with cognitive decline and pathological features of AD, including A\u03b2 deposition, and reduced cortical thickness, but no tau protein phosphorylation. Age was an important confounding factor affecting the relationship between LCN2 and A\u03b2<sub>42</sub>, while gender, years of education, and <i>APOE</i> carrier status did not have a significant impact. Furthermore, LCN2 was linked to the upregulation of inflammatory markers, indicating its potential involvement in the neuroinflammatory processes of AD.ConclusionsLCN2 is not only a potential biomarker for the early diagnosis of AD but may also play a significant role in the neurodegenerative processes associated with the disease.", "source": "PubMed"}, {"chunk_id": "40576449_2", "pmid": "40576449", "title": "LCN2 of cerebrospinal fluid: A potential biomarker for diagnosis and disease progression in Alzheimer's disease.", "authors": "Zhang QN, Yu LK, Zhang XY et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarker, cognitive impairment, lipocalin-2", "chunk": "associated with the disease.", "source": "PubMed"}, {"chunk_id": "41074913_0", "pmid": "41074913", "title": "Body mass index and blood volume influence plasma biomarkers and positron emission tomography classification in preclinical Alzheimer's disease.", "authors": "Jacobs T, Brien CO, Figueredo L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, PET, amyloid, blood volume, blood\u2010based biomarkers, body mass index, dilution, glial fibrillary acidic protein, neurodegeneration, neurofilament light, obesity, plasma, p\u2010Tau181, p\u2010Tau217, tau", "chunk": "Blood-based biomarkers (BBMs) are promising tools for Alzheimer's disease (AD) diagnosis, but their accuracy may be affected by body mass index (BMI) and blood volume (BV) through dilution. We investigated how BMI and BV influence BBM concentrations and PET prediction. Data from 241 cognitively unimpaired participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were examined to evaluate the influence of BMI/BV on BBMs (A\u03b2<sub>42/40</sub>, p-Tau<sub>181</sub>, p-Tau<sub>217</sub>, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and BBM-based PET predictions. Elevated BMI/BV associated with lower BBM concentrations, especially for p-Tau<sub>217</sub> and NfL, independent of brain amyloid burden. BMI-stratified thresholds improved amyloid PET prediction, with higher BBM thresholds and area under the curve (AUC) values seen in normal weight compared to overweight or obese participants. Drastic BMI/BV declines due to weight loss increased BBM variability and systematic PET misclassification. Adjusting for BMI/BV in BBM-based diagnostics appears to improve accuracy and reliable detection", "source": "PubMed"}, {"chunk_id": "41074913_1", "pmid": "41074913", "title": "Body mass index and blood volume influence plasma biomarkers and positron emission tomography classification in preclinical Alzheimer's disease.", "authors": "Jacobs T, Brien CO, Figueredo L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, PET, amyloid, blood volume, blood\u2010based biomarkers, body mass index, dilution, glial fibrillary acidic protein, neurodegeneration, neurofilament light, obesity, plasma, p\u2010Tau181, p\u2010Tau217, tau", "chunk": "or obese participants. Drastic BMI/BV declines due to weight loss increased BBM variability and systematic PET misclassification. Adjusting for BMI/BV in BBM-based diagnostics appears to improve accuracy and reliable detection of AD pathology, especially in preclinical stages. Body mass index (BMI) and blood volume (BV) significantly influenced plasma BBM concentrations in cognitively unimpaired (CU) individuals. Blood-based biomarkers (BBMs) associated more strongly with BV than with BMI. Dilution effects were independent of brain amyloid burden. BMI-stratified BBM thresholds improved amyloid positron emission tomography (PET) classification accuracy. Declines in BMI/BV resulted in PET prediction bias and systematic errors.", "source": "PubMed"}, {"chunk_id": "39045353_0", "pmid": "39045353", "title": "The Evolution of Diagnostic Boundaries of Alzheimer's Disease and Novel Therapeutic Options: \u042d\u0432\u043e\u043b\u044e\u0446\u0438\u044f \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0433\u0440\u0430\u043d\u0438\u0446 \u0431\u043e\u043b\u0435\u0437\u043d\u0438 \u0410\u043b\u044c\u0446\u0433\u0435\u0439\u043c\u0435\u0440\u0430 \u0438 \u043d\u043e\u0432\u044b\u0435 \u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0432\u043e\u0437\u043c\u043e\u0436\u043d\u043e\u0441\u0442\u0438.", "authors": "Gavrilova S", "year": "2022", "journal": "Consortium psychiatricum", "keywords": "Alzheimer\u2019s disease, biomarkers, diagnostic boundaries, secondary prevention, treatment", "chunk": "Over the past three decades, the definition and diagnostic boundaries of Alzheimer's disease (AD) have been repeatedly revised due to significant progress in understanding of the pathogenesis of neurodegeneration associated with Alzheimer's disease and in the development of high-tech diagnostic methods. The current approach to AD diagnostics relies on the detection of biomarkers that reflect two main neuropathological processes involved in the primary neurodegeneration that underlies AD: abnormal amyloidogenesis, and neuronal degeneration. The currently available diagnostic tools are limited to the detection of cerebrospinal biomarkers and/or assessment of the abnormal amyloid and tau protein burden in the brain via amyloid and tau positron emission tomography (PET) ligands. Practical implementation (mostly in the research field) of the biological model of AD diagnosis has led to a significant expansion of its diagnostic boundaries with the inclusion of predementia AD stages: asymptomatic and symptomatic, the latter is clinically corresponding to amnestic mild cognitive", "source": "PubMed"}, {"chunk_id": "39045353_1", "pmid": "39045353", "title": "The Evolution of Diagnostic Boundaries of Alzheimer's Disease and Novel Therapeutic Options: \u042d\u0432\u043e\u043b\u044e\u0446\u0438\u044f \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0433\u0440\u0430\u043d\u0438\u0446 \u0431\u043e\u043b\u0435\u0437\u043d\u0438 \u0410\u043b\u044c\u0446\u0433\u0435\u0439\u043c\u0435\u0440\u0430 \u0438 \u043d\u043e\u0432\u044b\u0435 \u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0432\u043e\u0437\u043c\u043e\u0436\u043d\u043e\u0441\u0442\u0438.", "authors": "Gavrilova S", "year": "2022", "journal": "Consortium psychiatricum", "keywords": "Alzheimer\u2019s disease, biomarkers, diagnostic boundaries, secondary prevention, treatment", "chunk": "diagnosis has led to a significant expansion of its diagnostic boundaries with the inclusion of predementia AD stages: asymptomatic and symptomatic, the latter is clinically corresponding to amnestic mild cognitive impairment (aMCI-amnestic mild cognitive impairment). On the one hand, this approach significantly expands the possibilities to study and use preventive technologies aiming to avert or delay the progression of predementia cognitive impairment to dementia but, on the other, it is associated with a number of negative implications from both the clinical and ethical points of view. A significant limitation of purely biological diagnosis of AD based on biomarker levels is due to the low prognostic value of biomarkers, which can cause diagnostic confusion in certain circumstances. Moreover, since the future evolution of the asymptomatic stage is not yet clear and there are still no reliable ways to prevent the cognitive and behavioral symptoms associated with AD, disclosure of stressful information", "source": "PubMed"}, {"chunk_id": "39045353_2", "pmid": "39045353", "title": "The Evolution of Diagnostic Boundaries of Alzheimer's Disease and Novel Therapeutic Options: \u042d\u0432\u043e\u043b\u044e\u0446\u0438\u044f \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0433\u0440\u0430\u043d\u0438\u0446 \u0431\u043e\u043b\u0435\u0437\u043d\u0438 \u0410\u043b\u044c\u0446\u0433\u0435\u0439\u043c\u0435\u0440\u0430 \u0438 \u043d\u043e\u0432\u044b\u0435 \u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0432\u043e\u0437\u043c\u043e\u0436\u043d\u043e\u0441\u0442\u0438.", "authors": "Gavrilova S", "year": "2022", "journal": "Consortium psychiatricum", "keywords": "Alzheimer\u2019s disease, biomarkers, diagnostic boundaries, secondary prevention, treatment", "chunk": "evolution of the asymptomatic stage is not yet clear and there are still no reliable ways to prevent the cognitive and behavioral symptoms associated with AD, disclosure of stressful information about this \"terrifying\" diagnosis to patients can cause irreversible damage by triggering depressive disorder, which is a risk factor of AD itself. The current knowledge about AD prognosis in amyloid-positive cognitively unimpaired patients is insufficient.The most adequate approach to early AD diagnostics appears to be the clinical and biological model, as recommended by the International Working Group (IWG 2021), which requires a combination of the clinical AD phenotype and the detection of biomarkers specific to this disease. The article discusses the potential directions for the development of biological diagnostic methods, including those based on the so-called peripheral (serum) biomarker technologies and promising directions for the development of biological methods of secondary AD prevention.", "source": "PubMed"}, {"chunk_id": "39045353_3", "pmid": "39045353", "title": "The Evolution of Diagnostic Boundaries of Alzheimer's Disease and Novel Therapeutic Options: \u042d\u0432\u043e\u043b\u044e\u0446\u0438\u044f \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0433\u0440\u0430\u043d\u0438\u0446 \u0431\u043e\u043b\u0435\u0437\u043d\u0438 \u0410\u043b\u044c\u0446\u0433\u0435\u0439\u043c\u0435\u0440\u0430 \u0438 \u043d\u043e\u0432\u044b\u0435 \u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0432\u043e\u0437\u043c\u043e\u0436\u043d\u043e\u0441\u0442\u0438.", "authors": "Gavrilova S", "year": "2022", "journal": "Consortium psychiatricum", "keywords": "Alzheimer\u2019s disease, biomarkers, diagnostic boundaries, secondary prevention, treatment", "chunk": "including those based on the so-called peripheral (serum) biomarker technologies and promising directions for the development of biological methods of secondary AD prevention.", "source": "PubMed"}, {"chunk_id": "41603391_0", "pmid": "41603391", "title": "Independent associations of phosphorylated tau181 and neurofilament light with cognitive outcomes in the Health and Aging Brain Study-Health Disparities (HABS-HD).", "authors": "Housini M, Contreras JA, Hayes CA et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "African American, Alzheimer's disease, Hispanic, biomarkers, dementia, health disparities, neurocognition, neurofilament, non-invasive, p-tau181, plasma biomarkers", "chunk": "BackgroundThe extent to which plasma biomarkers of Alzheimer's disease and neurodegeneration capture domain-specific cognitive performance across diverse populations remains unclear.ObjectiveTo determine whether plasma phosphorylated tau181 (p-tau181) and neurofilament light (NfL) are independently associated with cognitive domains, and whether associations differ across non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic participants.MethodsWe analyzed 3023 community-dwelling older adults from the Health and Aging Brain Study-Health Disparities (38.4% NHW, 22.6% NHW, 38.9% Hispanic). We used linear regressions to test associations between plasma biomarkers and cognitive domains (memory, executive function, processing speed, language), adjusting for age, sex, education, and apolipoprotein \u03b54 carriership. We fit models including both p-tau181 and NfL to assess their independent associations, evaluate biomarker \u00d7 racial/ethnic interactions, and test p-tau181 \u00d7 NfL interactions within each racial/ethnic group.ResultsAmong NHW participants, higher p-tau181 and NfL were associated with poorer memory, executive function, processing speed, and language. In NHB participants, p-tau181 was associated with memory,", "source": "PubMed"}, {"chunk_id": "41603391_1", "pmid": "41603391", "title": "Independent associations of phosphorylated tau181 and neurofilament light with cognitive outcomes in the Health and Aging Brain Study-Health Disparities (HABS-HD).", "authors": "Housini M, Contreras JA, Hayes CA et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "African American, Alzheimer's disease, Hispanic, biomarkers, dementia, health disparities, neurocognition, neurofilament, non-invasive, p-tau181, plasma biomarkers", "chunk": "interactions within each racial/ethnic group.ResultsAmong NHW participants, higher p-tau181 and NfL were associated with poorer memory, executive function, processing speed, and language. In NHB participants, p-tau181 was associated with memory, showed attenuated associations for language, and demonstrated similar associations with executive function and processing speed as observed in NHW participants. In Hispanic participants, p-tau181 was associated with memory and processing speed but was nonsignificant for executive function and language, and NfL showed significant but attenuated associations across all domains. Higher p-tau181 and NfL were jointly associated with slower processing speed only in NHW and NHB participants.ConclusionsPlasma p-tau181 and NfL were associated with multiple cognitive domains, with the strongest effects in NHW participants and attenuated associations in NHB and Hispanic individuals.", "source": "PubMed"}, {"chunk_id": "37526237_0", "pmid": "37526237", "title": "Acute Exercise Effect on Neurocognitive Function Among Cognitively Normal Late-Middle-Aged Adults With/Without Genetic Risk of AD: The Moderating Role of Exercise Volume and APOE Genotype.", "authors": "Chang YK, Etnier JL, Li RH et al.", "year": "2024", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "APOE genotype, Aerobic exercise, ERP, Executive function, Exercise prescription", "chunk": "Acute exercise is a behavior that benefits cognitive function; however, its effect on populations with different risks for Alzheimer's disease (AD) and the role of exercise variance and Apolipoprotein E (APOE) genotype on this effect remains unknown. This study explores the acute exercise effect on behavioral and neurocognitive function, and its potential moderation by exercise intensity and duration and APOE genetic risk. Fifty-one cognitively normal adults (~36% APOE \u03b54 carriers) performed the Stroop task under a rest condition and 3 exercise conditions while electroencephalographic activity was assessed. Acute exercise improved cognitive performance assessed through both behavioral and neuroelectrical indices. These benefits were observed regardless of adjustments of intensity and duration at a predetermined exercise volume as well as being evident irrespective of APOE \u025b4 carrier status. Acute exercise could be proposed as a lifestyle intervention to benefit neurocognitive function in populations with and without genetic risk of AD. Future exploration", "source": "PubMed"}, {"chunk_id": "37526237_1", "pmid": "37526237", "title": "Acute Exercise Effect on Neurocognitive Function Among Cognitively Normal Late-Middle-Aged Adults With/Without Genetic Risk of AD: The Moderating Role of Exercise Volume and APOE Genotype.", "authors": "Chang YK, Etnier JL, Li RH et al.", "year": "2024", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "APOE genotype, Aerobic exercise, ERP, Executive function, Exercise prescription", "chunk": "irrespective of APOE \u025b4 carrier status. Acute exercise could be proposed as a lifestyle intervention to benefit neurocognitive function in populations with and without genetic risk of AD. Future exploration should further the precise exercise prescription and also the mechanisms underlying the beneficial effects of acute exercise for neurocognitive function. NCT05591313.", "source": "PubMed"}, {"chunk_id": "41337297_0", "pmid": "41337297", "title": "Barn Ruins Virtual Reality-Based Serious Game as a Rehabilitation Tool for Older Adults with Mild and Moderate Cognitive Impairment: A Pilot Study.", "authors": "Chatterjee R, Moussavi ZK", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "This study evaluates the potential of a serious game, called Barn Ruins, as a spatial learning rehabilitation tool for older adults with mild to moderate cognitive impairment (MCI). The game's user navigates a maze environment on a laptop screen using a gaming controller (a joystick). It progresses through easy, medium, and hard routes, and has an error-based spatial learning score. The intervention spanned eight weeks, during which participants played the game for 30 minutes, three times a week. Pre-and post-intervention assessments were conducted using two independent and validated spatial orientation measures: VRNHouse as the primary and the Clock Orientation Test as the secondary outcome.Seven participants (86.3 \u00b1 4.9 years, 2 males) completed the study. Although no statistically significant changes were observed in VRNHouse or Clock Orientation Test scores, 71.4% of participants improved or maintained their performance in the primary outcome measure, while 66.7% demonstrated improvement or stability in the secondary", "source": "PubMed"}, {"chunk_id": "41337297_1", "pmid": "41337297", "title": "Barn Ruins Virtual Reality-Based Serious Game as a Rehabilitation Tool for Older Adults with Mild and Moderate Cognitive Impairment: A Pilot Study.", "authors": "Chatterjee R, Moussavi ZK", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "observed in VRNHouse or Clock Orientation Test scores, 71.4% of participants improved or maintained their performance in the primary outcome measure, while 66.7% demonstrated improvement or stability in the secondary measure. Analysis of spatial learning scores within the Barn Ruins game revealed significant improvements over time (p = 0.0046, Kendall's W = 0.42), particularly in easy (p = 0.023) and hard (p = 0.01) routes. Performance on medium routes fluctuated, suggesting greater difficulty with these trials.Post-hoc comparisons revealed that by Weeks 7 and 8, participants' overall spatial learning scores were significantly higher compared to those in Week 1. Notably, easy routes exhibited a ceiling effect after Week 4, while harder routes showed consistent improvement after Week 5.Despite modest results in independent outcome measures, the game's significant performance gains suggest its utility in improving spatial skills. Future research with larger samples is needed to validate these findings.Clinical Relevance- These findings highlight", "source": "PubMed"}, {"chunk_id": "41337297_2", "pmid": "41337297", "title": "Barn Ruins Virtual Reality-Based Serious Game as a Rehabilitation Tool for Older Adults with Mild and Moderate Cognitive Impairment: A Pilot Study.", "authors": "Chatterjee R, Moussavi ZK", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "independent outcome measures, the game's significant performance gains suggest its utility in improving spatial skills. Future research with larger samples is needed to validate these findings.Clinical Relevance- These findings highlight the potential of the Barn Ruins game as a novel rehabilitation tool for enhancing spatial learning in older adults with MCI.", "source": "PubMed"}, {"chunk_id": "41636082_0", "pmid": "41636082", "title": "Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.", "authors": "Ibanez L, Pottier C, Beric A et al.", "year": "2026", "journal": "Annals of neurology", "keywords": "None", "chunk": "As the population ages, certain neurodegenerative diseases (NDs) are becoming a major health issue. For this reason, this review will focus on the most common ND with onset after 65 years old; Alzheimer's disease, Parkinson's disease, Lewy body dementia, and frontotemporal dementia. NDs are the results of multifactorial processes causing pleiotropic changes in molecular and protein networks linking a host of biological processes that lead to protein dysregulation and aggregation that ultimately leads to neurodegeneration. Genetic, transcriptomic, and proteomic studies have been instrumental to identify novel genes and proteins implicated on diseases that point to novel disease mechanism, as well as the identification of disease biomarkers. Here, we provide a review of the genomic, transcriptomic, and proteomic studies on ND so far, as well as future opportunities and challenges. ANN NEUROL 2026;99:566-587.", "source": "PubMed"}, {"chunk_id": "41636082_1", "pmid": "41636082", "title": "Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.", "authors": "Ibanez L, Pottier C, Beric A et al.", "year": "2026", "journal": "Annals of neurology", "keywords": "None", "chunk": "so far, as well as future opportunities and challenges. ANN NEUROL 2026;99:566-587.", "source": "PubMed"}, {"chunk_id": "39130642_0", "pmid": "39130642", "title": "Huanshaodan regulates microglial glucose metabolism reprogramming to alleviate neuroinflammation in AD mice through mTOR/HIF-1\u03b1 signaling pathway.", "authors": "Shang C, Su Y, Ma J et al.", "year": "2024", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Huanshaodan, mTOR/HIF-1\u03b1 signaling pathway, microglial glucose metabolism reprogramming, neuroinflammation", "chunk": "Abnormal glucose metabolism in microglial is closely associated with Alzheimer's disease (AD). Reprogramming of microglial glucose metabolism is centered on regulating the way in which microglial metabolize glucose to alter microglial function. Therefore, reprogramming microglial glucose metabolism is considered as a therapeutic strategy for AD. Huanshaodan (HSD) is a Chinese herbal compound which shows significant efficacy in treating AD, however, the precise mechanism by which HSD treats AD remains unclear. This study is aim to investigate whether HSD exerts anti-AD effects by regulating the metabolic reprogramming of microglial through the mTOR/HIF-1\u03b1 signaling pathway. SAMP8 mice and BV2 cells were used to explore the alleviative effect of HSD on AD and the molecular mechanism <i>in vivo</i> and <i>in vitro</i>. The pharmacodynamic effects of HSD was evaluated by behavioral tests. The pathological deposition of A\u03b2 in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of", "source": "PubMed"}, {"chunk_id": "39130642_1", "pmid": "39130642", "title": "Huanshaodan regulates microglial glucose metabolism reprogramming to alleviate neuroinflammation in AD mice through mTOR/HIF-1\u03b1 signaling pathway.", "authors": "Shang C, Su Y, Ma J et al.", "year": "2024", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Huanshaodan, mTOR/HIF-1\u03b1 signaling pathway, microglial glucose metabolism reprogramming, neuroinflammation", "chunk": "effects of HSD was evaluated by behavioral tests. The pathological deposition of A\u03b2 in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of HK2 and the expression of PKM2, IL-6 and TNF-\u03b1 in hippocampus and cortex tissues of mice. Meanwhile, proteins levels of p-mTOR, mTOR, HIF-1\u03b1, CD86, Arg1 and IL-1\u03b2 were detected by Western-blot. LPS-induced BV2 cells were treated with HSD-containing serum. The analysis of the expression profiles of the CD86 and CD206 markers by flow cytometry allows us to distinguish the BV2 polarization. Glucose, lactic acid, ATP, IL-6 and TNF-\u03b1 levels, as well as lactate dehydrogenase and pyruvate dehydrogenase activities were evaluated in the BV2. Western-blot analysis was employed to detect mTOR, p-mTOR, HIF-1\u03b1 and IL-1\u03b2 levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in", "source": "PubMed"}, {"chunk_id": "39130642_2", "pmid": "39130642", "title": "Huanshaodan regulates microglial glucose metabolism reprogramming to alleviate neuroinflammation in AD mice through mTOR/HIF-1\u03b1 signaling pathway.", "authors": "Shang C, Su Y, Ma J et al.", "year": "2024", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Huanshaodan, mTOR/HIF-1\u03b1 signaling pathway, microglial glucose metabolism reprogramming, neuroinflammation", "chunk": "p-mTOR, HIF-1\u03b1 and IL-1\u03b2 levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in SAMP8 mice and reduced A\u03b2 deposition, suppressed the levels of glycolysis and neuroinflammation in mice. In LPS-induced BV2 cells, HSD also regulated glycolysis and neuroinflammation, and suppressed the mTOR/HIF-1\u03b1 signaling pathway. More importantly, these effects were reversed by MHY. It is demonstrated that HSD regulated microglial glucose metabolism reprogramming by inhibiting the mTOR/HIF-1\u03b1 signaling pathway, alleviated neuroinflammation, and exerted anti-AD effects. This study provided scientific evidence for the clinical application of HSD for treating AD.", "source": "PubMed"}, {"chunk_id": "41827870_0", "pmid": "41827870", "title": "Glycyrrhizic Acid Attenuates A\u03b2<sub>42</sub>-Induced Neurodegeneration Through Coordinated Regulation of Oxidative Stress, Synaptic Markers, and Key Alzheimer's Signaling Pathways.", "authors": "Amrutha S, Prasad TSK, Modi PK", "year": "2026", "journal": "Cells", "keywords": "amyloid-beta, apoptosis, glycyrrhizic acid, mitochondrial dysfunction, neuroprotection", "chunk": "Alzheimer's disease (AD) is a catastrophic neurodegenerative disorder marked by progressive decline of cognitive function, memory loss, and neuronal death. Its pathology is characterized by the formation of extracellular amyloid-beta (A\u03b2) plaques and intracellular neurofibrillary tangles from tau hyperphosphorylation. Despite extensive research, current treatments are limited to symptomatic relief and are associated with significant side effects. This accentuates the critical need for alternative therapeutic strategies with potent neuroprotective effects and minimal toxicity. This study investigates the neuroprotective potential of glycyrrhizic acid, as the precise molecular mechanisms by which it might improve AD pathology remain poorly understood. Using an A\u03b2<sub>42</sub>-induced IMR-32 cell model of AD, our research revealed that A\u03b2<sub>42</sub> treatment caused significant protein alterations associated with AD pathology, mitochondrial dysfunction, cell cycle re-entry, and synaptic activity. Co-treatment with glycyrrhizic acid not only restored these protein levels, but also mitigated the hyperactivation of several key signaling pathways and rescued neurons from", "source": "PubMed"}, {"chunk_id": "41827870_1", "pmid": "41827870", "title": "Glycyrrhizic Acid Attenuates A\u03b2<sub>42</sub>-Induced Neurodegeneration Through Coordinated Regulation of Oxidative Stress, Synaptic Markers, and Key Alzheimer's Signaling Pathways.", "authors": "Amrutha S, Prasad TSK, Modi PK", "year": "2026", "journal": "Cells", "keywords": "amyloid-beta, apoptosis, glycyrrhizic acid, mitochondrial dysfunction, neuroprotection", "chunk": "cell cycle re-entry, and synaptic activity. Co-treatment with glycyrrhizic acid not only restored these protein levels, but also mitigated the hyperactivation of several key signaling pathways and rescued neurons from apoptosis. These findings suggest that glycyrrhizic acid exerts neuroprotective effects by preventing mitochondrial dysfunction and apoptosis via modulation of critical signaling pathways. This study provides strong evidence for glycyrrhizic acid's neuroprotective properties in AD, paving the way for further research into its potential as a promising therapeutic agent for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41313764_0", "pmid": "41313764", "title": "Neurophysiological signatures of default mode network dysfunction and cognitive decline in Alzheimer's disease.", "authors": "Ozdemir RA, Passera B, Fried PJ et al.", "year": "2025", "journal": "Science advances", "keywords": "None", "chunk": "Neural hyperexcitability and network dysfunction are neurophysiological hallmarks of Alzheimer's disease (AD) in animal studies, but their presence and clinical relevance in humans remain poorly understood. We introduce a perturbation-based approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), alongside resting-state EEG (rsEEG), to investigate neurophysiological basis of default mode network (DMN) dysfunction in early AD. While rsEEG revealed global neural slowing and disrupted synchrony, these measures reflected widespread changes in brain neurophysiology without network-specific insights. In contrast, TMS-EEG identified network-specific local hyperexcitability in the parietal DMN and disrupted connectivity with frontal DMN regions, which uniquely predicted distinct cognitive impairments and mediated the link between structural brain integrity and cognition. Our findings provide critical insights into how network-specific neurophysiological disruptions contribute to AD-related cognitive dysfunction. Perturbation-based assessments hold promise as potential markers of early detection, disease progression, and target engagement for disease-modifying therapies aiming to restore abnormal neurophysiology in AD.", "source": "PubMed"}, {"chunk_id": "41313764_1", "pmid": "41313764", "title": "Neurophysiological signatures of default mode network dysfunction and cognitive decline in Alzheimer's disease.", "authors": "Ozdemir RA, Passera B, Fried PJ et al.", "year": "2025", "journal": "Science advances", "keywords": "None", "chunk": "to AD-related cognitive dysfunction. Perturbation-based assessments hold promise as potential markers of early detection, disease progression, and target engagement for disease-modifying therapies aiming to restore abnormal neurophysiology in AD.", "source": "PubMed"}, {"chunk_id": "40735049_0", "pmid": "40735049", "title": "Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease.", "authors": "Kang MJY, Eratne D, Loi SM et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, anxiety, apathy, blood\u2010based biomarkers, depression, neurofilament light chain, neuropsychiatric symptoms, phosphorylated tau 181", "chunk": "Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia. This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models. Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration. Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression. Apathy and affective neuropsychiatric", "source": "PubMed"}, {"chunk_id": "40735049_1", "pmid": "40735049", "title": "Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease.", "authors": "Kang MJY, Eratne D, Loi SM et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, anxiety, apathy, blood\u2010based biomarkers, depression, neurofilament light chain, neuropsychiatric symptoms, phosphorylated tau 181", "chunk": "indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression. Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.", "source": "PubMed"}, {"chunk_id": "41025386_0", "pmid": "41025386", "title": "Longitudinal Blood-Biomarker-Based Assessment of Brain Injury in Patients Undergoing Deep Brain Stimulation and Magnetic Resonance-Guided Focused Ultrasound.", "authors": "Dargvainiene J, Helmers AK, Naumann J et al.", "year": "2026", "journal": "Movement disorders : official journal of the Movement Disorder Society", "keywords": "deep brain stimulation, glial fibrillary acidic protein (GFAP), magnetic resonance\u2013guided focused ultrasound (MRgFUS), neurofilament light chain (NfL)", "chunk": "Deep brain stimulation (DBS) and magnetic resonance-guided focused ultrasound (MRgFUS) are associated with neuroaxonal damage and astroglial activation; yet their extent and timing remain unclear despite clinical relevance for monitoring and outcome assessment. This study assessed neuroaxonal damage and astroglial activation after DBS (n = 21) and MRgFUS (n = 19) reflected by serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP). Samples were collected at baseline, 24 h, 7 days, and 3/6/9 months posttreatment. Biomarker levels were measured using a single-molecule array (Simoa). sNfL peaked at day 7 and sGFAP at 24 h post-intervention in both groups. sNfL normalized at 6 months in DBS and 3 months in MRgFUS. sGFAP normalized within 7 days in both groups. Biomarker elevations were higher in DBS patients. DBS and MRgFUS cause transient neuroaxonal injury and astroglial activation, with greater extent in DBS. Biomarker monitoring suggests final clinical evaluation should", "source": "PubMed"}, {"chunk_id": "41025386_1", "pmid": "41025386", "title": "Longitudinal Blood-Biomarker-Based Assessment of Brain Injury in Patients Undergoing Deep Brain Stimulation and Magnetic Resonance-Guided Focused Ultrasound.", "authors": "Dargvainiene J, Helmers AK, Naumann J et al.", "year": "2026", "journal": "Movement disorders : official journal of the Movement Disorder Society", "keywords": "deep brain stimulation, glial fibrillary acidic protein (GFAP), magnetic resonance\u2013guided focused ultrasound (MRgFUS), neurofilament light chain (NfL)", "chunk": "groups. Biomarker elevations were higher in DBS patients. DBS and MRgFUS cause transient neuroaxonal injury and astroglial activation, with greater extent in DBS. Biomarker monitoring suggests final clinical evaluation should be performed 6 months after treatment at the earliest. \u00a9 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.", "source": "PubMed"}, {"chunk_id": "41581137_0", "pmid": "41581137", "title": "Cognitive Function, Quality of Life, and Survival Outcomes in Patients with Lower Grade Gliomas Treated with Proton Radiation Therapy: A Phase II study.", "authors": "Slater JM, Horick NK, Nachtigall LB et al.", "year": "2026", "journal": "Neuro-oncology", "keywords": "Cognition, lower grade glioma, neuroendocrine, proton therapy, quality of life", "chunk": "Lower grade gliomas (LGGs) typically affect younger adults and are associated with long-term survival. Treatment-related toxicities, especially neurocognitive and neuroendocrine effects, are a concern. Proton therapy may reduce these risks by minimizing radiation exposure to healthy brain tissue. This study evaluates the safety and efficacy of proton therapy in LGG patients, focusing on neurocognitive, neuroendocrine, and quality-of-life (QOL) outcomes. This single-institution, prospective phase 2 trial enrolled 60 patients with WHO grade 1-2 gliomas or IDH-mutant grade 3 gliomas. Proton therapy was delivered at 54 Gy(RBE) or 59.4 Gy(RBE) by tumor grade. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), neurocognitive and neuroendocrine function, and QOL. Neurocognitive testing occurred at baseline and biennially. QOL was assessed using the FACT-Brain questionnaire. Toxicities were graded per CTCAE v4.0. With a median follow-up of 7.0 years, 5-year PFS and OS were 79.1% and 85.6%, respectively. PFS was highest in", "source": "PubMed"}, {"chunk_id": "41581137_1", "pmid": "41581137", "title": "Cognitive Function, Quality of Life, and Survival Outcomes in Patients with Lower Grade Gliomas Treated with Proton Radiation Therapy: A Phase II study.", "authors": "Slater JM, Horick NK, Nachtigall LB et al.", "year": "2026", "journal": "Neuro-oncology", "keywords": "Cognition, lower grade glioma, neuroendocrine, proton therapy, quality of life", "chunk": "using the FACT-Brain questionnaire. Toxicities were graded per CTCAE v4.0. With a median follow-up of 7.0 years, 5-year PFS and OS were 79.1% and 85.6%, respectively. PFS was highest in IDH-mutant, 1p/19q co-deleted gliomas (100%) and lowest in IDH-wildtype tumors (62.5%). New neurocognitive deficits occurred in 26% of patients at 5 years. Neuroendocrine dysfunction occurred in 5.3%, with only one case attributed to radiation. QOL declined transiently at 6 months, with 15% showing clinically meaningful decline at 5 years. No late grade 3 toxicities were observed; one case of grade 4 radionecrosis occurred. Proton therapy for LGG can offer effective disease control with modest long-term toxicity. These findings support its use as a standard radiation modality and highlight the need for comparative trials with photon therapy.", "source": "PubMed"}, {"chunk_id": "41581137_2", "pmid": "41581137", "title": "Cognitive Function, Quality of Life, and Survival Outcomes in Patients with Lower Grade Gliomas Treated with Proton Radiation Therapy: A Phase II study.", "authors": "Slater JM, Horick NK, Nachtigall LB et al.", "year": "2026", "journal": "Neuro-oncology", "keywords": "Cognition, lower grade glioma, neuroendocrine, proton therapy, quality of life", "chunk": "for comparative trials with photon therapy.", "source": "PubMed"}, {"chunk_id": "24215447_0", "pmid": "24215447", "title": "Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art.", "authors": "de la Monte SM", "year": "2013", "journal": "Expert opinion on drug delivery", "keywords": "None", "chunk": "Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also the ability to minimize the potentially hazardous off-target effects. This review covers the role of intranasal insulin therapy for cognitive impairment and neurodegeneration, particularly AD. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The review provides evidence that brain insulin resistance is an important and early abnormality in AD, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations", "source": "PubMed"}, {"chunk_id": "24215447_1", "pmid": "24215447", "title": "Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art.", "authors": "de la Monte SM", "year": "2013", "journal": "Expert opinion on drug delivery", "keywords": "None", "chunk": "increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy and specificity of intranasal insulin therapy.", "source": "PubMed"}, {"chunk_id": "41121334_0", "pmid": "41121334", "title": "\u03b1-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.", "authors": "Cai A, Shen D, Xiong Q et al.", "year": "2025", "journal": "Nutrition & metabolism", "keywords": "Cognitive dysfunction, Diabetes, Metabolite profiles, SLC6A14, \u03b1-MT", "chunk": "Cognitive dysfunction in diabetes significantly impairs quality of life, yet effective therapies remain limited. Our previous work showed that \u03b1-methyltryptophan (\u03b1-MT), an inhibitor of the amino acid transporter SLC6A14 and indoleamine 2,3-dioxygenase 1 (IDO1), ameliorates diabetic nephropathy by modulating renal metabolism. Given its role in metabolic regulation, we hypothesized that \u03b1-MT may also protect against cognitive decline in diabetes by influencing gut-brain metabolic crosstalk. Db/db mice were used as an in vivo model of type 2 diabetes, complemented by high-glucose-treated Caco-2 cells in vitro. Cognitive function was assessed using the Morris water maze. Gene expression related to synaptic plasticity (c-FOS, ARC, BDNF, EGR1) was measured by RT-qPCR. Colon morphology and SLC6A14 expression were evaluated by H&E, AB-PAS, immunohistochemistry, and Western blotting. \u00b9H NMR-based metabolomics was applied to profile metabolic changes in the colon and hippocampus. \u03b1-MT treatment significantly reduced hyperglycemia, restored intestinal barrier integrity, and improved cognitive performance in db/db", "source": "PubMed"}, {"chunk_id": "41121334_1", "pmid": "41121334", "title": "\u03b1-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.", "authors": "Cai A, Shen D, Xiong Q et al.", "year": "2025", "journal": "Nutrition & metabolism", "keywords": "Cognitive dysfunction, Diabetes, Metabolite profiles, SLC6A14, \u03b1-MT", "chunk": "blotting. \u00b9H NMR-based metabolomics was applied to profile metabolic changes in the colon and hippocampus. \u03b1-MT treatment significantly reduced hyperglycemia, restored intestinal barrier integrity, and improved cognitive performance in db/db mice. It also downregulated SLC6A14 overexpression under hyperglycemic conditions in both models. Metabolomic analysis revealed that \u03b1-MT induced significant metabolic reprogramming in the colon, with amino acid metabolism as the most affected pathway. Notably, metabolite alterations in the colon were positively correlated with those in the hippocampus, and both were negatively associated with increased expression of c-FOS, ARC, BDNF, and EGR1, suggesting coordinated gut-brain metabolic responses. These findings indicate that \u03b1-MT alleviates diabetes-associated cognitive impairment by promoting gut-brain metabolic remodeling. Targeting intestinal amino acid transport may represent a promising nutritional and therapeutic strategy for neuroprotection in diabetic encephalopathy (DE).", "source": "PubMed"}, {"chunk_id": "41121334_2", "pmid": "41121334", "title": "\u03b1-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.", "authors": "Cai A, Shen D, Xiong Q et al.", "year": "2025", "journal": "Nutrition & metabolism", "keywords": "Cognitive dysfunction, Diabetes, Metabolite profiles, SLC6A14, \u03b1-MT", "chunk": "and therapeutic strategy for neuroprotection in diabetic encephalopathy (DE).", "source": "PubMed"}, {"chunk_id": "16226349_0", "pmid": "16226349", "title": "Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment.", "authors": "Johnson SC, Schmitz TW, Moritz CH et al.", "year": "2006", "journal": "Neurobiology of aging", "keywords": "None", "chunk": "This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in", "source": "PubMed"}, {"chunk_id": "16226349_1", "pmid": "16226349", "title": "Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment.", "authors": "Johnson SC, Schmitz TW, Moritz CH et al.", "year": "2006", "journal": "Neurobiology of aging", "keywords": "None", "chunk": "change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD.", "source": "PubMed"}, {"chunk_id": "33924960_0", "pmid": "33924960", "title": "Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.", "authors": "Hendrix JA, Airey DC, Britton A et al.", "year": "2021", "journal": "Journal of clinical medicine", "keywords": "Alzheimer\u2019s disease, Down syndrome, amyloid \u03b2 peptide, blood biomarkers, glial fibrillary acidic protein, neurofilament light chain, phosphorylated tau protein", "chunk": "With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid \u03b2 peptides (A\u03b2<sub>1-40</sub>, A\u03b2<sub>1-42</sub>), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of", "source": "PubMed"}, {"chunk_id": "33924960_1", "pmid": "33924960", "title": "Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.", "authors": "Hendrix JA, Airey DC, Britton A et al.", "year": "2021", "journal": "Journal of clinical medicine", "keywords": "Alzheimer\u2019s disease, Down syndrome, amyloid \u03b2 peptide, blood biomarkers, glial fibrillary acidic protein, neurofilament light chain, phosphorylated tau protein", "chunk": "and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.", "source": "PubMed"}, {"chunk_id": "41085059_0", "pmid": "41085059", "title": "Cross-Cultural Adaptation of the Oral Frailty Index-8 for United States English-Speakers.", "authors": "Castillo-Allendes A, Khoury CJ, Curtis JA et al.", "year": "2026", "journal": "Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery", "keywords": "aging, cross\u2010cultural adaptation, dysphagia, oral frailty, patient\u2010reported outcomes measures", "chunk": "Oral frailty, the age-related decline in oral and pharyngeal function, is associated with physical frailty, sarcopenia, and cognitive decline. The Oral Frailty Index-8 (OFI-8) is a patient-reported outcome measure developed in Japan to assess oral frailty risk. This study aimed to culturally and linguistically adapt the OFI-8 for English-speaking older adults in the United States. Cross-cultural and cross-linguistic adaptation of the OFI-8 by an expert committee, followed by administration of the adapted OFI-8 and structured cognitive interviews with 22 English-speaking adults aged 65 years and older. Outpatient tertiary academic voice and swallowing center in New York City. Following the Professional Society for Health Economics and Outcomes Research (ISPOR) guidelines, the OFI-8 underwent forward translation, back translation, expert committee review, and reconciliation. Cognitive interviews were then conducted with 22 participants aged 65 years and older. A think-aloud and verbal-probing approach was used to evaluate comprehension, clarity, and cultural appropriateness. Interviews were", "source": "PubMed"}, {"chunk_id": "41085059_1", "pmid": "41085059", "title": "Cross-Cultural Adaptation of the Oral Frailty Index-8 for United States English-Speakers.", "authors": "Castillo-Allendes A, Khoury CJ, Curtis JA et al.", "year": "2026", "journal": "Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery", "keywords": "aging, cross\u2010cultural adaptation, dysphagia, oral frailty, patient\u2010reported outcomes measures", "chunk": "reconciliation. Cognitive interviews were then conducted with 22 participants aged 65 years and older. A think-aloud and verbal-probing approach was used to evaluate comprehension, clarity, and cultural appropriateness. Interviews were transcribed and analyzed using thematic analysis. Several cultural adaptations were made, including replacing Japanese food examples with US-familiar foods of similar texture. Three questionnaire items and the instructions were refined following participant feedback to improve syntactic flow, clarity, and understanding. The final US-English version maintained conceptual equivalence of the original OFI-8 while adapting language and examples for US cultural relevance. A culturally adapted US-English version of the OFI-8 was developed through structured translation, expert review, and cognitive interviews. Further validation studies are necessary to establish its clinimetric properties and support clinical application for early detection of oral frailty in US older adults.", "source": "PubMed"}, {"chunk_id": "41085059_2", "pmid": "41085059", "title": "Cross-Cultural Adaptation of the Oral Frailty Index-8 for United States English-Speakers.", "authors": "Castillo-Allendes A, Khoury CJ, Curtis JA et al.", "year": "2026", "journal": "Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery", "keywords": "aging, cross\u2010cultural adaptation, dysphagia, oral frailty, patient\u2010reported outcomes measures", "chunk": "clinical application for early detection of oral frailty in US older adults.", "source": "PubMed"}, {"chunk_id": "40424766_0", "pmid": "40424766", "title": "Brain Fractal Dimension and Machine Learning can predict first-episode psychosis and risk for transition to psychosis.", "authors": "Hu Y, Frisman M, Andreou C et al.", "year": "2025", "journal": "Computers in biology and medicine", "keywords": "Clinical high risk, Fractal dimension, Machine learning, Psychosis, Radiomic feature, Transition to psychosis", "chunk": "Although there are notable structural abnormalities in the brain associated with psychotic diseases, it is still unclear how these abnormalities relate to clinical presentation. However, the fractal dimension (FD), which offers details on the complexity and irregularity of brain microstructures, may be a promising feature, as demonstrated by neuropsychiatric disorders such as Parkinson's and Alzheimer's. It may offer a possible biomarker for the detection and prognosis of psychosis when paired with machine learning. The purpose of this study is to investigate FD as a structural magnetic resonance imaging (sMRI) feature from individuals with a high clinical risk of psychosis who did not transit to psychosis (CHR_NT), clinical high risk who transit to psychosis (CHR_T), patients with first-episode psychosis (FEP) and healthy controls (HC). Using a machine learning approach that ultimately classifies sMRI images, the goals are (a) to evaluate FD as a potential biomarker and (b) to investigate its ability", "source": "PubMed"}, {"chunk_id": "40424766_1", "pmid": "40424766", "title": "Brain Fractal Dimension and Machine Learning can predict first-episode psychosis and risk for transition to psychosis.", "authors": "Hu Y, Frisman M, Andreou C et al.", "year": "2025", "journal": "Computers in biology and medicine", "keywords": "Clinical high risk, Fractal dimension, Machine learning, Psychosis, Radiomic feature, Transition to psychosis", "chunk": "healthy controls (HC). Using a machine learning approach that ultimately classifies sMRI images, the goals are (a) to evaluate FD as a potential biomarker and (b) to investigate its ability to predict a subsequent transition to psychosis from the high-risk clinical condition. We obtained sMRI images from 194 subjects, including 44 HCs, 77 FEPs, 16 CHR_Ts, and 57 CHR_NTs. We extracted the FD features and analyzed them using machine learning methods under five classification schemas (a) FEP vs. HC, (b) FEP vs. CHR_NT, (c) FEP vs. CHR_T, (d) CHR_NT vs. CHR_T, (d) CHR_NT vs. HC and (e) CHR_T vs. HC. In addition, the CHR_T group was used as external validation in (a), (b) and (d) comparisons to examine whether the progression of the disorder followed the FEP or CHR_NT patterns. The proposed algorithm resulted in a balanced accuracy greater than 0.77. This study has shown that FD can function as", "source": "PubMed"}, {"chunk_id": "40424766_2", "pmid": "40424766", "title": "Brain Fractal Dimension and Machine Learning can predict first-episode psychosis and risk for transition to psychosis.", "authors": "Hu Y, Frisman M, Andreou C et al.", "year": "2025", "journal": "Computers in biology and medicine", "keywords": "Clinical high risk, Fractal dimension, Machine learning, Psychosis, Radiomic feature, Transition to psychosis", "chunk": "progression of the disorder followed the FEP or CHR_NT patterns. The proposed algorithm resulted in a balanced accuracy greater than 0.77. This study has shown that FD can function as a predictive neuroimaging marker, providing fresh information on the microstructural alterations triggered throughout the course of psychosis. The effectiveness of FD in the detection of psychosis and transition to psychosis should be established by further research using larger datasets.", "source": "PubMed"}, {"chunk_id": "39699678_0", "pmid": "39699678", "title": "A visual scale to rate amygdalar atrophy on MRI.", "authors": "Pizzini FB, Ribaldi F, Natale V et al.", "year": "2025", "journal": "European radiology", "keywords": "Amygdala, Atrophy, Dementia, MRI", "chunk": "Visual rating scales are routinely used in clinical radiology to assess brain atrophy on scans of patients with suspected neurodegenerative conditions. Limbic predominant age-related TDP-43 encephalopathy (LATE) has recently been described, featuring early and severe atrophy of the amygdala. However, there is currently no scoring system specifically designed to assess amygdalar atrophy on MRI. to develop and validate a visual rating scale for amygdalar atrophy. Stringent criteria were developed for no, mild/moderate, and severe amygdalar atrophy based on axial and coronal volumetric T1-weighted MRI scans. Inter- and intra-rater reliabilities were estimated by three independent expert neuroradiologists in 100 randomly selected scans from the Geneva Memory Center cohort selected to be representative of the variability of medial temporal atrophy. Convergent validity was evaluated versus amygdalar volumes extracted by FreeSurfer on 1943 consecutive patients. Criterion validity versus autopsy-confirmed LATE neuropathologic changes were studied in the pathological subset of the Alzheimer's Disease Neuroimaging", "source": "PubMed"}, {"chunk_id": "39699678_1", "pmid": "39699678", "title": "A visual scale to rate amygdalar atrophy on MRI.", "authors": "Pizzini FB, Ribaldi F, Natale V et al.", "year": "2025", "journal": "European radiology", "keywords": "Amygdala, Atrophy, Dementia, MRI", "chunk": "was evaluated versus amygdalar volumes extracted by FreeSurfer on 1943 consecutive patients. Criterion validity versus autopsy-confirmed LATE neuropathologic changes were studied in the pathological subset of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (N = 96). Intra- and inter-rater agreements of amygdalar visual ratings were between substantial and almost perfect (weighted Cohen's Kappa 0.71 to 0.93). Visual ratings were strongly associated with amygdalar volumes (p \u2264 0.001 on the Kruskal-Wallis test). LATE neuropathologic changes were associated with visual ratings of amygdalar atrophy (p = 0.057 on a test for trend). The proposed visual amygdalar atrophy scale is a reliable and valid tool to assess amygdalar atrophy on MRI and can be a useful adjunct in routine radiological reporting. Question Assessment of amygdalar atrophy is crucial for diagnosing neurodegenerative diseases, as the limbic predominant age-related TDP-43 encephalopathy, yet no validated visual rating scale exists. Findings The proposed amygdalar atrophy scale demonstrated", "source": "PubMed"}, {"chunk_id": "39699678_2", "pmid": "39699678", "title": "A visual scale to rate amygdalar atrophy on MRI.", "authors": "Pizzini FB, Ribaldi F, Natale V et al.", "year": "2025", "journal": "European radiology", "keywords": "Amygdala, Atrophy, Dementia, MRI", "chunk": "of amygdalar atrophy is crucial for diagnosing neurodegenerative diseases, as the limbic predominant age-related TDP-43 encephalopathy, yet no validated visual rating scale exists. Findings The proposed amygdalar atrophy scale demonstrated high intra-rater and inter-rater reliability, strong correlation with amygdalar volumetry, and association with limbic predominant age-related TDP-43 encephalopathy (LATE). Clinical relevance The amygdalar atrophy scale provides a reliable practical assessment tool that enhances diagnostic accuracy for dementia-related conditions, particularly aiding in identifying limbic predominant age-related TDP-43 encephalopathy.", "source": "PubMed"}, {"chunk_id": "36776574_0", "pmid": "36776574", "title": "Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease.", "authors": "Zhang E, Dai F, Chen T et al.", "year": "2022", "journal": "Frontiers in neurology", "keywords": "Alzheimer's disease, cuproptosis, diagnostic, drug, immune", "chunk": "Alzheimer's disease (AD) is a chronic neurodegenerative disease, and its underlying genes and treatments are unclear. Abnormalities in copper metabolism can prevent the clearance of \u03b2-amyloid peptides and promote the progression of AD pathogenesis. Therefore, the present study used a bioinformatics approach to perform an integrated analysis of the hub gene based on cuproptosis that can influence the diagnosis and treatment of AD. The gene expression profiles were obtained from the Gene Expression Omnibus database, including non-demented (ND) and AD samples. A total of 2,977 cuproptosis genes were retrieved from published articles. The seven hub genes associated with cuproptosis and AD were obtained from the differentially expressed genes and WGCNA in brain tissue from GSE33000. The GO analysis demonstrated that these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic", "source": "PubMed"}, {"chunk_id": "36776574_1", "pmid": "36776574", "title": "Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease.", "authors": "Zhang E, Dai F, Chen T et al.", "year": "2022", "journal": "Frontiers in neurology", "keywords": "Alzheimer's disease, cuproptosis, diagnostic, drug, immune", "chunk": "these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic model for AD, which was validated by GES15222, GS48350, and GSE5281. In addition, immune cell infiltration of samples was investigated for correlation with these hub genes. We identified six drugs targeting these seven cuproptosis genes in DrugBank. Hence, these cuproptosis gene signatures may be an important prognostic indicator for AD and may offer new insights into treatment options.", "source": "PubMed"}, {"chunk_id": "40990183_0", "pmid": "40990183", "title": "Sociodemographic traits as early indicators of AD, FTD, and VaD up to 10 years before diagnosis.", "authors": "Kivisild A, Rinnankoski I, Aaltonen M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "alzheimer's disease, education, frontotemporal dementia, marital status, sociodemographics, vascular dementia", "chunk": "We aimed to investigate early differences in sociodemographic factors before the onset of Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD), and mixed dementia (AD + VaD). Lifetime sociodemographic factors were collected from Statistics Finland for 1238 AD, 274 FTD, 343 VaD, and 402 AD + VaD patients with a diagnosis and visit at Kuopio and Oulu University Hospitals between January 2010 and December 2021. Comparisons were performed between dementia groups and matched controls. All patient groups showed decreased employment status compared to controls already 10 years prior to diagnosis. In particular, individuals with early-onset FTD (EOFTD; 66.9% vs. 77.6%, p < 0.01) and early-onset VaD (EOVaD; 49.0% vs. 76.5%, p < 0.001) had significantly lower employment rates than controls. Similarly, 10 years prior to diagnosis the proportion of married individuals was lower in the VaD (60.1% vs. 65.2%, p < 0.05) and EOVaD (50.0% vs. 61.6%, p <", "source": "PubMed"}, {"chunk_id": "40990183_1", "pmid": "40990183", "title": "Sociodemographic traits as early indicators of AD, FTD, and VaD up to 10 years before diagnosis.", "authors": "Kivisild A, Rinnankoski I, Aaltonen M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "alzheimer's disease, education, frontotemporal dementia, marital status, sociodemographics, vascular dementia", "chunk": "controls. Similarly, 10 years prior to diagnosis the proportion of married individuals was lower in the VaD (60.1% vs. 65.2%, p < 0.05) and EOVaD (50.0% vs. 61.6%, p < 0.05) groups versus controls, while single status was more common in early-onset AD (EOAD; 23.2% vs. 17.0%, p < 0.01) versus controls. Patients with VaD and AD + VaD had lower levels of education than controls: basic education only in 51.9% of VaD (vs. 45.0%, p < 0.05) and 65.7% of AD + VaD (vs. 60.2%, p < 0.05). Our findings may aid in the early recognition or potential risk factor evaluation for different types of dementia. Screening cognitive symptoms in individuals with unexplained long-term unemployment may help detect prodromal dementia. Employment rates were already reduced 10 years before the diagnosis of Alzheimer's disease, frontotemporal dementia, and vascular dementia. The association between education level and dementia risk appears to be", "source": "PubMed"}, {"chunk_id": "40990183_2", "pmid": "40990183", "title": "Sociodemographic traits as early indicators of AD, FTD, and VaD up to 10 years before diagnosis.", "authors": "Kivisild A, Rinnankoski I, Aaltonen M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "alzheimer's disease, education, frontotemporal dementia, marital status, sociodemographics, vascular dementia", "chunk": "dementia. Employment rates were already reduced 10 years before the diagnosis of Alzheimer's disease, frontotemporal dementia, and vascular dementia. The association between education level and dementia risk appears to be subtype specific. Lower employment may serve as an early \"social marker\" of subtle cognitive decline. Social markers could help inform models predicting progression to cognitive impairment.", "source": "PubMed"}, {"chunk_id": "39222666_0", "pmid": "39222666", "title": "Glymphotherapeutics for Alzheimer's disease: Time to move the needle.", "authors": "MohanaSundaram A, Mofatteh M, Ashraf GM et al.", "year": "2024", "journal": "Ageing research reviews", "keywords": "Alzheimer\u2019s disease, Aquaporin-4, Dementia, Glymphatic clearance, Glymphotherapeutics, Neurodegenerative disease, Neurotherapeutics", "chunk": "Alzheimer's disease (AD), the most predominant neurodegenerative disease and a quintessential entity within the dementia umbrella, is a global public health crisis. While the lack of disease modifying therapies has been a weak point in AD treatment, the success of recently approved monoclonal antibody-based therapeutics (aducanumab and lecanemab) targeted at the removal of amyloid-beta (A\u03b2) peptides in the brain is still under debate. There are multiple safety concerns about these approved neurotherapeutics including amyloid-related imaging abnormalities, stroke, meningitis, encephalitis, and even death. Novel paradigms focused on aquaporin-4-mediated neuro-perivascular A\u03b2 and Tau protein clearance pathway are garnering attention. In this paper, we argue that orchestrating the drug discovery focused on glymphatic clearance-facilitating drugs (\"glymphotherapeutics\") might be a potentially novel and viable strategy to mitigate the progression and improve the clinical outcomes of AD.", "source": "PubMed"}, {"chunk_id": "39222666_1", "pmid": "39222666", "title": "Glymphotherapeutics for Alzheimer's disease: Time to move the needle.", "authors": "MohanaSundaram A, Mofatteh M, Ashraf GM et al.", "year": "2024", "journal": "Ageing research reviews", "keywords": "Alzheimer\u2019s disease, Aquaporin-4, Dementia, Glymphatic clearance, Glymphotherapeutics, Neurodegenerative disease, Neurotherapeutics", "chunk": "strategy to mitigate the progression and improve the clinical outcomes of AD.", "source": "PubMed"}, {"chunk_id": "19276553_0", "pmid": "19276553", "title": "Brain insulin-like growth factor and neurotrophin resistance in Parkinson's disease and dementia with Lewy bodies: potential role of manganese neurotoxicity.", "authors": "Tong M, Dong M, de la Monte SM", "year": "2009", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "Parkinson's disease (PD) and dementia with Lewy bodies (DLB) frequently overlap with Alzheimer's disease, which is linked to brain impairments in insulin, insulin-like growth factor (IGF), and neurotrophin signaling. We explored whether similar abnormalities occur in PD or DLB, and examined the role of manganese toxicity in PD/DLB pathogenesis. Quantitative RT-PCR demonstrated reduced expression of insulin, IGF-II, and insulin, IGF-I, and IGF-II receptors (R) in PD and/or DLB frontal white matter and amygdala, and reduced IGF-IR and IGF-IIR mRNA in DLB frontal cortex. IGF-I and IGF-II resistance was present in DLB but not PD frontal cortex, and associated with reduced expression of Hu, nerve growth factor, and Trk neurotrophin receptors, and increased levels of glial fibrillary acidic protein, alpha-synuclein, dopamine-beta-hydroxylase, 4-hydroxy-2-nonenal (HNE), and ubiquitin immunoreactivity. MnCl2 treatment reduced survival, ATP, and insulin, IGF-I and IGF-II receptor expression, and increased alpha-synuclein, HNE, and ubiquitin immunoreactivity in cultured neurons. The results suggest", "source": "PubMed"}, {"chunk_id": "19276553_1", "pmid": "19276553", "title": "Brain insulin-like growth factor and neurotrophin resistance in Parkinson's disease and dementia with Lewy bodies: potential role of manganese neurotoxicity.", "authors": "Tong M, Dong M, de la Monte SM", "year": "2009", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "4-hydroxy-2-nonenal (HNE), and ubiquitin immunoreactivity. MnCl2 treatment reduced survival, ATP, and insulin, IGF-I and IGF-II receptor expression, and increased alpha-synuclein, HNE, and ubiquitin immunoreactivity in cultured neurons. The results suggest that: 1) IGF-I, IGF-II, and neurotrophin signaling are more impaired in DLB than PD, corresponding with DLB's more pronounced neurodegeneration, oxidative stress, and alpha-synuclein accumulation; 2) MnCl2 exposure causes PD/DLB associated abnormalities in central nervous system neurons, and therefore may contribute to their molecular pathogenesis; and 3) molecular abnormalities in PD/DLB overlap with but are distinguishable from Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "34992970_0", "pmid": "34992970", "title": "CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis.", "authors": "Angelopoulou E, Bougea A, Papadopoulos A et al.", "year": "2021", "journal": "Neurology. Clinical practice", "keywords": "None", "chunk": "To evaluate whether CSF and circulating neurofilament light chain (NfL), a marker of axonal damage, could discriminate Parkinson disease (PD) from atypical parkinsonian syndromes (APSs). MEDLINE and Scopus were systematically searched, and 15 studies were included (1,035 patients with PD and 930 patients with APS). CSF NfL levels were 1.26 SDs higher in the APS group compared to the PD group (<i>g</i> = 1.26 [95% confidence interval 0.99-1.53]), and circulating NfL levels were 1.53 SDs higher in the APS group compared to the PD group (<i>g</i> = 1.53 [95% confidence interval 1.15-1.91]); 4 studies, 307 patients with PD, 197 patients with APS. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NfL, corresponding to average sensitivities of 86% (79%-90%) and 91% (86%-95%), and specificity of 88% (82%-92%) and 76% (62%-85%), respectively. These results strongly support the high diagnostic accuracy of both CSF and circulating", "source": "PubMed"}, {"chunk_id": "34992970_1", "pmid": "34992970", "title": "CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis.", "authors": "Angelopoulou E, Bougea A, Papadopoulos A et al.", "year": "2021", "journal": "Neurology. Clinical practice", "keywords": "None", "chunk": "average sensitivities of 86% (79%-90%) and 91% (86%-95%), and specificity of 88% (82%-92%) and 76% (62%-85%), respectively. These results strongly support the high diagnostic accuracy of both CSF and circulating NfL in differentiating PD from APS, highlighting their usefulness as promising biomarkers.", "source": "PubMed"}, {"chunk_id": "36420620_0", "pmid": "36420620", "title": "Role of estrogen in women's Alzheimer's disease risk as modified by APOE.", "authors": "Valencia-Olvera AC, Maldonado Weng J, Christensen A et al.", "year": "2023", "journal": "Journal of neuroendocrinology", "keywords": "Alzheimer's disease, apolipoprotein E, dementia, estrogen, hormone responsiveness", "chunk": "Alzheimer's disease (AD) is characterized by numerous sexual dimorphisms that impact the development, progression, and probably the strategies to prevent and treat the most common form of dementia. In this review, we consider this topic from a female perspective with a specific focus on how women's vulnerability to the disease is affected by the individual and interactive effects of estrogens and apolipoprotein E (APOE) genotype. Importantly, APOE appears to modulate systemic and neural outcomes of both menopause and estrogen-based hormone therapy. In the brain, dementia risk is greater in APOE4 carriers, and the impacts of hormone therapy on cognitive decline and dementia risk vary according to both outcome measure and APOE genotype. Beyond the CNS, estrogen and APOE genotype affect vulnerability to menopause-associated bone loss, dyslipidemia and cardiovascular disease risk. An emerging concept that may link these relationships is the possibility that the effects of APOE in women interact with", "source": "PubMed"}, {"chunk_id": "36420620_1", "pmid": "36420620", "title": "Role of estrogen in women's Alzheimer's disease risk as modified by APOE.", "authors": "Valencia-Olvera AC, Maldonado Weng J, Christensen A et al.", "year": "2023", "journal": "Journal of neuroendocrinology", "keywords": "Alzheimer's disease, apolipoprotein E, dementia, estrogen, hormone responsiveness", "chunk": "vulnerability to menopause-associated bone loss, dyslipidemia and cardiovascular disease risk. An emerging concept that may link these relationships is the possibility that the effects of APOE in women interact with estrogen status by mechanisms that may include modulation of estrogen responsiveness. This review highlights the need to consider the key AD risk factors of advancing age in a sex-specific manner to optimize development of therapeutic approaches for AD, a view aligned with the principle of personalized medicine.", "source": "PubMed"}, {"chunk_id": "36034139_0", "pmid": "36034139", "title": "Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains.", "authors": "Liu C, Zhu N, Sun H et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, CBV, MRI, aging, deep-learning, gadolinium", "chunk": "While MRI contrast agents such as those based on Gadolinium are needed for high-resolution mapping of brain metabolism, these contrast agents require intravenous administration, and there are rising concerns over their safety and invasiveness. Furthermore, non-contrast MRI scans are more commonly performed than those with contrast agents and are readily available for analysis in public databases such as the Alzheimer's Disease Neuroimaging Initiative (ADNI). In this article, we hypothesize that a deep learning model, trained using quantitative steady-state contrast-enhanced structural MRI datasets, in mice and humans, can generate contrast-equivalent information from a single non-contrast MRI scan. The model was first trained, optimized, and validated in mice, and was then transferred and adapted to humans. We observe that the model can substitute for Gadolinium-based contrast agents in approximating cerebral blood volume, a quantitative representation of brain activity, at sub-millimeter granularity. Furthermore, we validate the use of our deep-learned prediction maps to", "source": "PubMed"}, {"chunk_id": "36034139_1", "pmid": "36034139", "title": "Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains.", "authors": "Liu C, Zhu N, Sun H et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, CBV, MRI, aging, deep-learning, gadolinium", "chunk": "substitute for Gadolinium-based contrast agents in approximating cerebral blood volume, a quantitative representation of brain activity, at sub-millimeter granularity. Furthermore, we validate the use of our deep-learned prediction maps to identify functional abnormalities in the aging brain using locally obtained MRI scans, and in the brain of patients with Alzheimer's disease using publicly available MRI scans from ADNI. Since it is derived from a commonly-acquired MRI protocol, this framework has the potential for broad clinical utility and can also be applied retrospectively to research scans across a host of neurological/functional diseases.", "source": "PubMed"}, {"chunk_id": "36965205_0", "pmid": "36965205", "title": "Independent role of Alzheimer's disease genetics and C-reactive protein on cognitive ability in aging.", "authors": "Supiyev A, Karlsson R, Wang Y et al.", "year": "2023", "journal": "Neurobiology of aging", "keywords": "APOE, Alzheimer's disease, Cognitive aging, Pathway-based PRS-LOAD, Polygenic risk scores, Serum CRP", "chunk": "Apolipoprotein E (APOE) \u03b54, the strongest genetic risk factor for late onset Alzheimer's disease (LOAD), has been associated with cognitive decline independent from AD pathology, but the role for other LOAD risk genes in normal cognitive aging is less studied. We examined the effect of APOE \u03b54 and several different polygenic risk scores (PRS) for LOAD on cognitive level and decline in aging, using longitudinal data from the UK Biobank. While PRS-LOAD including all variants (except APOE) predicted cognitive level, APOE \u03b54 and PRS-LOAD based on 17 non-APOE gene variants with strong association to AD (p < 5e-8) predicted age-related decline in verbal numeric reasoning. The effect on decline were partly driven by 4 variants involved in the immune system. Those variants also predicted serum levels of the inflammatory marker C-reactive protein (CRP), but CRP did not mediate the effect on decline. Those findings suggest genetic variations in immune functions", "source": "PubMed"}, {"chunk_id": "36965205_1", "pmid": "36965205", "title": "Independent role of Alzheimer's disease genetics and C-reactive protein on cognitive ability in aging.", "authors": "Supiyev A, Karlsson R, Wang Y et al.", "year": "2023", "journal": "Neurobiology of aging", "keywords": "APOE, Alzheimer's disease, Cognitive aging, Pathway-based PRS-LOAD, Polygenic risk scores, Serum CRP", "chunk": "Those variants also predicted serum levels of the inflammatory marker C-reactive protein (CRP), but CRP did not mediate the effect on decline. Those findings suggest genetic variations in immune functions play a role in aspects of cognitive aging that may be independent of LOAD pathology as well as systemic inflammation measured by CRP.", "source": "PubMed"}, {"chunk_id": "41234939_0", "pmid": "41234939", "title": "Innovations in Alzheimer's disease diagnostic technologies: clinical prospects of novel biomarkers, multimodal integration, and non-invasive detection.", "authors": "Wang R, Peng S, Zhu J et al.", "year": "2025", "journal": "Frontiers in neurology", "keywords": "Alzheimer\u2019s disease diagnosis, multimodal diagnostic technologies, non-invasive biomarkers, tau protein phosphorylation, \u03b2-amyloid", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of \u03b2-amyloid (A\u03b2) plaques and the formation of neurofibrillary tangles composed of hyperphosphorylated tau protein, ultimately leading to cognitive decline and neuronal loss. Current diagnostic methods, including clinical evaluations, neuroimaging examinations, and cerebrospinal fluid biomarker testing, face challenges such as insufficient sensitivity and specificity, as well as operational complexity. In recent years, significant advancements have been made in diagnostic technologies, with the emergence of new biomarkers and detection methods, including blood-based A\u03b2 and tau protein detection, ocular biomarker testing, and non-invasive screening through urine or breath analysis. These innovative developments, combined with multimodal diagnostic technologies that integrate imaging, genomics, and proteomics, have opened new possibilities for the early diagnosis and precise staging of Alzheimer's disease. Furthermore, advancements in microfluidic chips and biosensor technologies have enhanced the capability for rapid, efficient, and cost-effective diagnosis. As research continues to evolve, the", "source": "PubMed"}, {"chunk_id": "41234939_1", "pmid": "41234939", "title": "Innovations in Alzheimer's disease diagnostic technologies: clinical prospects of novel biomarkers, multimodal integration, and non-invasive detection.", "authors": "Wang R, Peng S, Zhu J et al.", "year": "2025", "journal": "Frontiers in neurology", "keywords": "Alzheimer\u2019s disease diagnosis, multimodal diagnostic technologies, non-invasive biomarkers, tau protein phosphorylation, \u03b2-amyloid", "chunk": "and precise staging of Alzheimer's disease. Furthermore, advancements in microfluidic chips and biosensor technologies have enhanced the capability for rapid, efficient, and cost-effective diagnosis. As research continues to evolve, the gradual application of these advanced technologies in clinical practice is expected to revolutionize the management of Alzheimer's disease, facilitating early intervention and the formulation of individualized treatment strategies.", "source": "PubMed"}, {"chunk_id": "40521751_0", "pmid": "40521751", "title": "Continuous glucose monitoring-derived time in range is associated with changes in cognitive function test scores in Japanese patients with type 2 diabetes mellitus.", "authors": "Inoue M, Kusunoki Y, Ohigashi M et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "Montreal cognitive assessment, cognitive decline, continuous glucose monitoring, digit symbol substitution test, mini\u2010mental state examination, time in range, type 2 diabetes", "chunk": "Type 2 diabetes mellitus (T2DM) is known to be a risk factor for cognitive dysfunction and dementia. Time in range (TIR), which is derived from continuous glucose monitoring (CGM), has been widely used as an indicator of the quality of glycemic control. While cross-sectional studies have reported an association between CGM-derived TIR and cognitive function scores, few studies have longitudinally investigated the relationship between the two. This study aimed to prospectively investigate the association between CGM-derived TIR and changes in multiple cognitive function scores. The present study used baseline and 2-year data from an ongoing multicenter cohort study. This study included 197 T2DM patients aged \u226560 years with undiagnosed dementia. Participants were examined with the mini-mental state examination (MMSE), the Japanese version of the Montreal cognitive assessment (MoCA-J) and the digit symbol substitution test (DSST) at both baseline and 2 years. Multiple regression analyses were performed to investigate the association", "source": "PubMed"}, {"chunk_id": "40521751_1", "pmid": "40521751", "title": "Continuous glucose monitoring-derived time in range is associated with changes in cognitive function test scores in Japanese patients with type 2 diabetes mellitus.", "authors": "Inoue M, Kusunoki Y, Ohigashi M et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "Montreal cognitive assessment, cognitive decline, continuous glucose monitoring, digit symbol substitution test, mini\u2010mental state examination, time in range, type 2 diabetes", "chunk": "Japanese version of the Montreal cognitive assessment (MoCA-J) and the digit symbol substitution test (DSST) at both baseline and 2 years. Multiple regression analyses were performed to investigate the association between TIR and changes in cognitive function test scores over 2 years. Multivariate regression analysis showed that there was a significant association between TIR and changes in MMSE (\u0394MMSE) over 2 years (standard partial regression coefficient [\u03b2] = 0.187, p = 0.005). Similarly, multivariate regression models showed a significant association between TIR and \u0394MoCA-J (\u03b2 = 0.218, p = 0.001) and \u0394DSST (\u03b2 = 0.164, p = 0.036). In patients with T2DM with undiagnosed dementia, CGM-derived TIR might be associated with overall cognitive decline and reduced processing speed.", "source": "PubMed"}, {"chunk_id": "39450675_0", "pmid": "39450675", "title": "Safety and efficacy of sodium benzoate for patients with mild Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Mansour MEM, Ali AHG, Ibrahim MHM et al.", "year": "2025", "journal": "Nutritional neuroscience", "keywords": "Alzheimer\u2019s disease, D-amino acid oxidase, N-methyl-D-aspartate, cognitive function, dementia, meta-analysis, neurodegenerative disorders, sodium benzoate", "chunk": "Alzheimer's disease (AD) is the most common neurodegenerative disorder. A key factor in its pathogenesis is the dysfunction of the N-methyl-D-aspartate (NMDA) receptor due to D-serine degradation by D-amino acid oxidase. Benzoate has been suggested to enhance NMDA receptor function, potentially benefiting early-phase AD. This study aimed to synthesize evidence from randomized clinical trials (RCTs) on the safety and efficacy of sodium benzoate in AD patients. We followed PRISMA statement guidelines during the accommodation of this systematic review and meta-analysis. A computer literature search (PubMed, Scopus, Web of Science, and Cochrane Central) was conducted. We included RCTs that compared sodium benzoate with placebo regarding cognitive functions. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale, pooled as the mean difference between the two groups from baseline to the endpoint. The secondary outcomes measures are the clinician's interview-based impression of change plus caregiver input, catalase, and superoxide dismutase antioxidants.", "source": "PubMed"}, {"chunk_id": "39450675_1", "pmid": "39450675", "title": "Safety and efficacy of sodium benzoate for patients with mild Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Mansour MEM, Ali AHG, Ibrahim MHM et al.", "year": "2025", "journal": "Nutritional neuroscience", "keywords": "Alzheimer\u2019s disease, D-amino acid oxidase, N-methyl-D-aspartate, cognitive function, dementia, meta-analysis, neurodegenerative disorders, sodium benzoate", "chunk": "mean difference between the two groups from baseline to the endpoint. The secondary outcomes measures are the clinician's interview-based impression of change plus caregiver input, catalase, and superoxide dismutase antioxidants. Three RCTs (described in four articles) with 306 patients were included in this study. Sodium benzoate significantly improved the ADAS-cog score compared with placebo (MD -2.13 points, 95% CI [-3.35 to -0.90]; <i>P</i>= 0.0007). Sodium benzoate is a safe drug that may improve cognitive function in patients with early-stage Alzheimer's disease. However, the significant effect arises primarily from one small study, highlighting the need for caution in interpretation. Further research with larger sample sizes and longer durations is necessary to validate these findings and assess safety and efficacy.", "source": "PubMed"}, {"chunk_id": "35841241_0", "pmid": "35841241", "title": "Prediction of Cognitive Decline for Enrichment of Alzheimer's Disease Clinical Trials.", "authors": "Tam A, Laurent C, Gauthier S et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, clinical trials, cognitive decline, machine learning, trial enrichment", "chunk": "A key issue to Alzheimer's disease clinical trial failures is poor participant selection. Participants have heterogeneous cognitive trajectories and many do not decline during trials, which reduces a study's power to detect treatment effects. Trials need enrichment strategies to enroll individuals who are more likely to decline. To develop machine learning models to predict cognitive trajectories in participants with early Alzheimer's disease and presymptomatic individuals over 24 and 48 months respectively. Prognostic machine learning models were trained from a combination of demographics, cognitive tests, APOE genotype, and brain imaging data. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), National Alzheimer's Coordinating Center (NACC), Open Access Series of Imaging Studies (OASIS-3), PharmaCog, and a Phase 3 clinical trial in early Alzheimer's disease were used for this study. A total of 2098 participants who had demographics, cognitive tests, APOE genotype, and brain imaging data, as well as follow-up visits for 24-48 months", "source": "PubMed"}, {"chunk_id": "35841241_1", "pmid": "35841241", "title": "Prediction of Cognitive Decline for Enrichment of Alzheimer's Disease Clinical Trials.", "authors": "Tam A, Laurent C, Gauthier S et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, clinical trials, cognitive decline, machine learning, trial enrichment", "chunk": "disease were used for this study. A total of 2098 participants who had demographics, cognitive tests, APOE genotype, and brain imaging data, as well as follow-up visits for 24-48 months were included. Baseline magnetic resonance imaging, cognitive tests, demographics, and APOE genotype were used to separate decliners, defined as individuals whose CDR-Sum of Boxes scores increased during a predefined time window, from stable individuals. A prognostic model to predict decline at 24 months in early Alzheimer's disease was trained on 1151 individuals who had baseline diagnoses of mild cognitive impairment and Alzheimer's dementia from ADNI and NACC. This model was validated on 115 individuals from a placebo arm of a Phase 3 clinical trial and 76 individuals from the PharmaCog dataset. A second prognostic model to predict decline at 48 months in presymptomatic populations was trained on 628 individuals from ADNI and NACC who were cognitively unimpaired at baseline. This", "source": "PubMed"}, {"chunk_id": "35841241_2", "pmid": "35841241", "title": "Prediction of Cognitive Decline for Enrichment of Alzheimer's Disease Clinical Trials.", "authors": "Tam A, Laurent C, Gauthier S et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, clinical trials, cognitive decline, machine learning, trial enrichment", "chunk": "dataset. A second prognostic model to predict decline at 48 months in presymptomatic populations was trained on 628 individuals from ADNI and NACC who were cognitively unimpaired at baseline. This model was validated on 128 individuals from OASIS-3. The models achieved up to 79% area under the curve (cross-validated and out-of-sample). Power analyses showed that using prognostic models to recruit enriched cohorts of predicted decliners can reduce clinical trial sample sizes by as much as 51% while maintaining the same detection power. Prognostic tools for predicting cognitive decline and enriching clinical trials with participants at the highest risk of decline can improve trial quality, derisk endpoint failures, and accelerate therapeutic development in Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41571080_0", "pmid": "41571080", "title": "Bibliometric analysis of neuroinflammation in Alzheimer's Disease: Insights from APP/PS1 mouse model research in the past two decades.", "authors": "Yan L, Wang H, Shi J et al.", "year": "2026", "journal": "Neuroscience", "keywords": "APP/PS1 mice, Alzheimer\u2019s disease, Bibliometrics, Neuroinflammation, Visual analysis.", "chunk": "The APP/PS1 transgenic mouse is a foundational model in Alzheimer's disease (AD) research, particularly for investigating the pivotal role of neuroinflammation in disease pathogenesis. Although substantial experimental work has explored inflammatory mechanisms in AD, the field still lacks a comprehensive overview of how research hotspots have evolved, which key scientific questions remain unresolved, and how global research efforts align with existing mechanistic gaps. Therefore, this investigation systematically evaluated scholarly trends, geographic contributions, institutional productivity, and thematic evolution to synthesize actionable insights that will guide subsequent experimental designs. Bibliometric analysis was conducted on peer-reviewed articles indexed in the Web of Science Core Collection (2005-2024). Analytical tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to quantify research output, collaborative networks, citation metrics, and keyword co-occurrence patterns. Annual publication numbers exhibited exponential growth post-2015, reflecting an intensified focus on neuroinflammatory mechanisms in AD. China and the United States contributed 83.4 % of total", "source": "PubMed"}, {"chunk_id": "41571080_1", "pmid": "41571080", "title": "Bibliometric analysis of neuroinflammation in Alzheimer's Disease: Insights from APP/PS1 mouse model research in the past two decades.", "authors": "Yan L, Wang H, Shi J et al.", "year": "2026", "journal": "Neuroscience", "keywords": "APP/PS1 mice, Alzheimer\u2019s disease, Bibliometrics, Neuroinflammation, Visual analysis.", "chunk": "and keyword co-occurrence patterns. Annual publication numbers exhibited exponential growth post-2015, reflecting an intensified focus on neuroinflammatory mechanisms in AD. China and the United States contributed 83.4 % of total publications, with the University of Barcelona as the most productive institution. High-impact journals such as Nature, Nature Neuroscience, and Brain Behavior Immunity. The analysis identified key scientific issues and evolving research fronts, with current hot topics focusing on oxidative stress, activated microglia releasing inflammatory cytokines, and abnormal autophagy-lysosome pathways. The APP/PS1 mice have a significantly enhanced mechanistic understanding of neuroimmune interactions in AD pathogenesis. Future research should explore microglia-mediated neuroinflammation and brain-gut microbiome interactions to uncover novel diagnostic and therapeutic strategies for AD. This study offers an evidence-based framework to guide researchers using APP/PS1 mice model.", "source": "PubMed"}, {"chunk_id": "41571080_2", "pmid": "41571080", "title": "Bibliometric analysis of neuroinflammation in Alzheimer's Disease: Insights from APP/PS1 mouse model research in the past two decades.", "authors": "Yan L, Wang H, Shi J et al.", "year": "2026", "journal": "Neuroscience", "keywords": "APP/PS1 mice, Alzheimer\u2019s disease, Bibliometrics, Neuroinflammation, Visual analysis.", "chunk": "guide researchers using APP/PS1 mice model.", "source": "PubMed"}, {"chunk_id": "38929542_0", "pmid": "38929542", "title": "Effect of Treatment of the Cholinergic Precursor Choline Alphoscerate in Mild Cognitive Dysfunction: A Randomized Controlled Trial.", "authors": "Carotenuto A, Andreone V, Amenta F et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "choline alphoscerate, cognitive dysfunction, mild cognitive impairment, randomized controlled trial, study protocol", "chunk": "<i>Background and Objectives:</i> The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer's disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer's disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving", "source": "PubMed"}, {"chunk_id": "38929542_1", "pmid": "38929542", "title": "Effect of Treatment of the Cholinergic Precursor Choline Alphoscerate in Mild Cognitive Dysfunction: A Randomized Controlled Trial.", "authors": "Carotenuto A, Andreone V, Amenta F et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "choline alphoscerate, cognitive dysfunction, mild cognitive impairment, randomized controlled trial, study protocol", "chunk": "the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. <i>Materials and Methods</i>: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. <i>Discussion</i>: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. <i>Registration</i><b>:</b> EudraCT number: 2020-000576-38.", "source": "PubMed"}, {"chunk_id": "38929542_2", "pmid": "38929542", "title": "Effect of Treatment of the Cholinergic Precursor Choline Alphoscerate in Mild Cognitive Dysfunction: A Randomized Controlled Trial.", "authors": "Carotenuto A, Andreone V, Amenta F et al.", "year": "2024", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "choline alphoscerate, cognitive dysfunction, mild cognitive impairment, randomized controlled trial, study protocol", "chunk": "cognitive dysfunction. The results of this study will be published in peer-reviewed journals. <i>Registration</i><b>:</b> EudraCT number: 2020-000576-38.", "source": "PubMed"}, {"chunk_id": "40336267_0", "pmid": "40336267", "title": "Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study.", "authors": "Cumbo E, Migliore D", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, bupropion, cognitive impairment, depression, escitalopram, paroxetine, vortioxetine", "chunk": "BackgroundDepressive symptoms are common in Alzheimer's disease (AD), leading to an increasing use of antidepressants.ObjectiveTo compare the effects of vortioxetine with other conventional antidepressants on cognition in AD patients with depressive symptoms.MethodsThis analysis is a subgroup of a 12-month, prospective, randomized, open-label, parallel-group study involving 108 outpatients receiving either vortioxetine or escitalopram, paroxetine, or bupropion as part of routine care. Data were collected at baseline, 6 and 12 months. Cognitive symptoms were assessed using the Mini-Mental State Examination (MMSE), Attentive Matrices (AM), Coloured Progressive Matrices (CPR), and Digit Span; depressive symptoms using the Hamilton Depression Scale (HAM-D) and the Cornell Scale for Depression in Dementia (CSDD). Results for patients on vortioxetine were compared to those on other antidepressants.ResultsTotal scores on cognitive measures improved in all groups. Improvements versus baseline in MMSE, AM, and CPM were statistically significant in the vortioxetine group (p < 0.001), but not in the other antidepressant", "source": "PubMed"}, {"chunk_id": "40336267_1", "pmid": "40336267", "title": "Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study.", "authors": "Cumbo E, Migliore D", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, bupropion, cognitive impairment, depression, escitalopram, paroxetine, vortioxetine", "chunk": "cognitive measures improved in all groups. Improvements versus baseline in MMSE, AM, and CPM were statistically significant in the vortioxetine group (p < 0.001), but not in the other antidepressant groups. Digit Span scores did not differ significantly from baseline. The between-group differences in MMSE, AM, and CPM changes were statistically significant in favor of vortioxetine (p < 0.05), while the Digit Span change showed a trend towards superiority with vortioxetine, but did not reach statistical significance. The between-group differences in HAM-D and CSDD changes were also statistically significant for vortioxetine (p < 0.05).ConclusionsVortioxetine was superior in improving both cognitive and depressive symptoms compared to other antidepressants. Larger studies which may also help to understand whether the beneficial effect observed with vortioxetine was a direct effect or mediated by its specific antidepressant efficacy are required.", "source": "PubMed"}, {"chunk_id": "40336267_2", "pmid": "40336267", "title": "Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study.", "authors": "Cumbo E, Migliore D", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, bupropion, cognitive impairment, depression, escitalopram, paroxetine, vortioxetine", "chunk": "with vortioxetine was a direct effect or mediated by its specific antidepressant efficacy are required.", "source": "PubMed"}, {"chunk_id": "36872781_0", "pmid": "36872781", "title": "Female APOE \u025b4 Carriers with Slow Rates of Biological Aging Have Better Memory Performances Compared to Female \u025b4 Carriers with Accelerated Aging.", "authors": "O'Shea DM, Galvin JE", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE \u025b4, Aging, epigenetic clocks, memory", "chunk": "Evidence suggests that APOE \u025b4 carriers have worse memory performances compared to APOE \u025b4 non-carriers and effects may vary by sex and age. Estimates of biological age, using DNA methylation may enhance understanding of the associations between sex and APOE \u025b4 on cognition. To investigate whether associations between APOE \u025b4 status and memory vary according to rates of biological aging, using a DNA methylation age biomarker, in older men and women without dementia. Data were obtained from 1,771 adults enrolled in the 2016 wave of the Health and Retirement Study. A series of ANCOVAs were used to test the interaction effects of APOE \u025b4 status and aging rates (defined as 1 standard deviation below (i.e., slow rate), or above (i.e., fast rate) their sex-specific mean rate of aging on a composite measure of verbal learning and memory. APOE \u025b4 female carriers with slow rates of GrimAge had significantly better memory", "source": "PubMed"}, {"chunk_id": "36872781_1", "pmid": "36872781", "title": "Female APOE \u025b4 Carriers with Slow Rates of Biological Aging Have Better Memory Performances Compared to Female \u025b4 Carriers with Accelerated Aging.", "authors": "O'Shea DM, Galvin JE", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE \u025b4, Aging, epigenetic clocks, memory", "chunk": "fast rate) their sex-specific mean rate of aging on a composite measure of verbal learning and memory. APOE \u025b4 female carriers with slow rates of GrimAge had significantly better memory performances compared to fast and average aging APOE \u025b4 female carriers. There was no effect of aging group rate on memory in the female non-carriers and no significant differences in memory according to age rate in either male APOE \u025b4 carriers or non-carriers. Slower rates of aging in female APOE \u025b4 carriers may buffer against the negative effects of the \u025b4 allele on memory. However, longitudinal studies with larger sample sizes are needed to evaluate risk of dementia/memory impairment based on rates of aging in female APOE \u025b4 carriers.", "source": "PubMed"}, {"chunk_id": "41261326_0", "pmid": "41261326", "title": "ZuoGui Pill Ameliorates Alzheimer's Disease-Like Pathology in 3xTg-AD Mice by Targeting A\u03b2 Production, Tau Phosphorylation, Synaptic Loss, and Neuroinflammation.", "authors": "Li S, Wang D, Li A et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, A\u03b2 production, Neuroinflammation, Tau phosphorylation, ZuoGui Pill", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-\u03b2 (A\u03b2) accumulation, tau hyperphosphorylation, synaptic dysfunction, and chronic neuroinflammation. Current single-target interventions fail to halt disease progression, highlighting the need for multi-target strategies. This study investigates the therapeutic potential and mechanisms of ZuoGui Pill (ZGP), a traditional Chinese medicine formula, in a transgenic AD mouse model. 3xTg-AD mice were treated with ZGP for 60 days. Behavioral performance was assessed using the Morris water maze, novel object recognition, and open field test. A\u03b2 deposition, tau phosphorylation, and synaptic integrity were evaluated via immunohistochemistry, Western blotting, RT-qPCR, and Golgi staining. Neuroinflammation and RAGE/NF-\u03baB signaling were analyzed by ELISA and protein expression profiling. Statistical analyses included ANOVA with post hoc Tukey or Bonferroni tests following Shapiro-Wilk and Bartlett's validation. ZGP significantly improved cognitive performance, reduced hippocampal A\u03b2 deposition and BACE1 expression, and suppressed tau phosphorylation at multiple pathological sites (T205, S396, S404).", "source": "PubMed"}, {"chunk_id": "41261326_1", "pmid": "41261326", "title": "ZuoGui Pill Ameliorates Alzheimer's Disease-Like Pathology in 3xTg-AD Mice by Targeting A\u03b2 Production, Tau Phosphorylation, Synaptic Loss, and Neuroinflammation.", "authors": "Li S, Wang D, Li A et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, A\u03b2 production, Neuroinflammation, Tau phosphorylation, ZuoGui Pill", "chunk": "Bonferroni tests following Shapiro-Wilk and Bartlett's validation. ZGP significantly improved cognitive performance, reduced hippocampal A\u03b2 deposition and BACE1 expression, and suppressed tau phosphorylation at multiple pathological sites (T205, S396, S404). Synaptic markers (Syn, PSD95) were restored, accompanied by increased dendritic spine density. ZGP also reduced hippocampal IL-1\u03b2, IL-6, and TNF-\u03b1 levels and inhibited the RAGE/p-NF-\u03baB pathway. ZGP exerts multi-target neuroprotective effects in 3xTg-AD mice by modulating A\u03b2 and tau pathologies, preserving synaptic structure, and attenuating RAGE-mediated neuroinflammation. These findings support ZGP as a promising integrative therapeutic strategy for AD.", "source": "PubMed"}, {"chunk_id": "41755996_0", "pmid": "41755996", "title": "Anti-IgLON5 encephalitis is associated with anti-retinal immunological reactivity without retinal alteration.", "authors": "Rafiq M, Varenne F, Pariente J et al.", "year": "2026", "journal": "Journal of translational autoimmunity", "keywords": "Anti-retinal antibodies, Autoimmune encephalitis, IgLON5 disease, Neuro-ophtalmology, Retina", "chunk": "Anti-IgLON5 disease is a recently defined autoimmune disorder of the central nervous system associated with autoantibodies against IgLON5. This progressive condition, combining features of autoimmunity and neurodegeneration, presents with highly heterogeneous symptoms, including sleep disorders, bulbar symptoms, oculomotor dysfunction, gait disturbances, and subsequent cognitive decline. Recent reports have also described cases of papillitis. The target antigen, IgLON5, is a cell adhesion protein whose role is not fully understood. In humans, it is mainly expressed in the brain and testis. IgLON5 transcripts are also expressed in the retina. However, retinal involvement is not classically explored in these patients. In this cross-sectional observational study, we investigated whether anti-IgLON5 antibodies might target retinal structures, and correlated these findings with ophthalmological assessments. Six patients were diagnosed with anti-IgLON5 antibody encephalitis at Toulouse University Hospital. Identification of the anti-IgLON5 antibody was performed by immunofluorescence on transfected cells using serum and CSF. Anti-retinal antibodies were detected", "source": "PubMed"}, {"chunk_id": "41755996_1", "pmid": "41755996", "title": "Anti-IgLON5 encephalitis is associated with anti-retinal immunological reactivity without retinal alteration.", "authors": "Rafiq M, Varenne F, Pariente J et al.", "year": "2026", "journal": "Journal of translational autoimmunity", "keywords": "Anti-retinal antibodies, Autoimmune encephalitis, IgLON5 disease, Neuro-ophtalmology, Retina", "chunk": "were diagnosed with anti-IgLON5 antibody encephalitis at Toulouse University Hospital. Identification of the anti-IgLON5 antibody was performed by immunofluorescence on transfected cells using serum and CSF. Anti-retinal antibodies were detected by an indirect immunofluorescence method on sections of monkey retina. Patients underwent a systematic ophthalmological examination including an anatomical and electrophysiological assessment. Anti-retinal antibody identification revealed specific staining of the inner plexiform layer in all patients, which was not observed in control individuals. However, morphological and electrophysiological ophthalmological examinations did not reveal any common features between the patients. Although retinal involvement is rarely reported, these findings suggest a possible role for the retina in the pathophysiology of anti-IgLON5 encephalitis. They support the relevance of considering ophthalmological monitoring in patients with IgLON5-related disease.", "source": "PubMed"}, {"chunk_id": "41755996_2", "pmid": "41755996", "title": "Anti-IgLON5 encephalitis is associated with anti-retinal immunological reactivity without retinal alteration.", "authors": "Rafiq M, Varenne F, Pariente J et al.", "year": "2026", "journal": "Journal of translational autoimmunity", "keywords": "Anti-retinal antibodies, Autoimmune encephalitis, IgLON5 disease, Neuro-ophtalmology, Retina", "chunk": "IgLON5-related disease.", "source": "PubMed"}, {"chunk_id": "41683913_0", "pmid": "41683913", "title": "Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer's Disease Revealed by Single-Nucleus RNA Sequencing.", "authors": "Yang Z, Zhang M, Zhi W et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, THY1, microglia-neuron crosstalk, microglial subtype, snRNA-seq", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60-70% of all clinically diagnosed cases worldwide. The growing focus on microglia-neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia-neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and", "source": "PubMed"}, {"chunk_id": "41683913_1", "pmid": "41683913", "title": "Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer's Disease Revealed by Single-Nucleus RNA Sequencing.", "authors": "Yang Z, Zhang M, Zhi W et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, THY1, microglia-neuron crosstalk, microglial subtype, snRNA-seq", "chunk": "leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia-neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia-neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions.", "source": "PubMed"}, {"chunk_id": "41683913_2", "pmid": "41683913", "title": "Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer's Disease Revealed by Single-Nucleus RNA Sequencing.", "authors": "Yang Z, Zhang M, Zhi W et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, THY1, microglia-neuron crosstalk, microglial subtype, snRNA-seq", "chunk": "a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions.", "source": "PubMed"}, {"chunk_id": "40491259_0", "pmid": "40491259", "title": "Integrating plasma p-tau217 and digital cognitive assessments for early detection in Alzheimer's disease.", "authors": "Vanderlip CR, Stark CEL", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, digital cognitive assessments, early detection, low\u2010burden measures, memory, phosphorylated tau 217", "chunk": "Plasma phosphorylated tau (p-tau)217 is an early Alzheimer's disease (AD) biomarker, but the timing of pathological changes and cognitive decline varies substantially. Digital cognitive assessments can detect subtle cognitive changes, suggesting they may complement p-tau217 for early detection. Here, we evaluate whether combining these tools improves the detection of individuals at risk for future decline. We analyzed 954 amyloid-positive cognitively unimpaired individuals who completed a digital cognitive assessment and a blood test for p-tau217, assessing their ability to predict future decline on the Preclinical Alzheimer Cognitive Composite (PACC) and Mini-Mental State Examination (MMSE). Combining performance on a digital cognitive assessment with p-tau217 improved identification of individuals who declined on the PACC and MMSE in the next 5 years. The predictive value was stronger in apolipoprotein E \u03b54 noncarriers but did not differ by sex. This approach offers a sensitive method for identifying individuals at high risk for AD-related cognitive decline.", "source": "PubMed"}, {"chunk_id": "40491259_1", "pmid": "40491259", "title": "Integrating plasma p-tau217 and digital cognitive assessments for early detection in Alzheimer's disease.", "authors": "Vanderlip CR, Stark CEL", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, digital cognitive assessments, early detection, low\u2010burden measures, memory, phosphorylated tau 217", "chunk": "value was stronger in apolipoprotein E \u03b54 noncarriers but did not differ by sex. This approach offers a sensitive method for identifying individuals at high risk for AD-related cognitive decline. Combining plasma phosphorylated tau 217 with baseline digital cognitive assessment improved the prediction of cognitive decline on gold-standard neuropsychological tests over the next 5 years, achieving greater accuracy than either measure alone. This combination also predicted a decline in a global cognitive screening test. Pairing a blood test with a digital cognitive assessment offers a scalable and feasible approach for Alzheimer's disease screening.", "source": "PubMed"}, {"chunk_id": "38631552_0", "pmid": "38631552", "title": "Prediction of Cognitive Progression Due to Alzheimer's Disease in Normal Participants Based on Individual Default Mode Network Metabolic Connectivity Strength.", "authors": "Zhang Q, Li F, Wei M et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "(18)F-FDG PET, Alzheimer\u2019s disease, Cognitive decline, Cognitively unimpaired, Default mode network, Metabolic connectivity", "chunk": "Predicting cognitive decline among individuals in the aging population who are already amyloid-\u03b2 (A\u03b2) positive or tau positive poses clinical challenges. In Alzheimer's disease research, intra-default mode network (DMN) connections play a pivotal role in diagnosis. In this article, we propose metabolic connectivity within the DMN as a supplementary biomarker to the A\u03b2, pathological tau, and neurodegeneration framework. Extracting data from 1292 participants in the Alzheimer's Disease Neuroimaging Initiative, we collected paired T1-weighted structural magnetic resonance imaging and <sup>18</sup>F-labeled-fluorodeoxyglucose positron emission computed tomography scans. Individual metabolic DMN networks were constructed, and metabolic connectivity (MC) strength in the DMN was assessed. In the cognitively unimpaired group, the Cox model identified cognitively unimpaired (MC+), high-risk participants, with Kaplan-Meier survival analyses and hazard ratios revealing the strength of MC's predictive performance. Spearman correlation analyses explored relationships between MC strength, and A\u03b2, pathological tau, neurodegeneration biomarkers, and clinical scales. DMN standard uptake value ratio", "source": "PubMed"}, {"chunk_id": "38631552_1", "pmid": "38631552", "title": "Prediction of Cognitive Progression Due to Alzheimer's Disease in Normal Participants Based on Individual Default Mode Network Metabolic Connectivity Strength.", "authors": "Zhang Q, Li F, Wei M et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "(18)F-FDG PET, Alzheimer\u2019s disease, Cognitive decline, Cognitively unimpaired, Default mode network, Metabolic connectivity", "chunk": "ratios revealing the strength of MC's predictive performance. Spearman correlation analyses explored relationships between MC strength, and A\u03b2, pathological tau, neurodegeneration biomarkers, and clinical scales. DMN standard uptake value ratio (SUVR) provided comparative insights in the analyses. Both MC strength and SUVR exhibited gradual declines with cognitive deterioration, displaying significant intergroup differences. Survival analyses indicated enhanced A\u03b2 and tau prediction with both metrics, with MC strength outperforming SUVR. Combined MC strength and A\u03b2 yielded optimal predictive performance (hazard ratio = 9.29), followed by MC strength and tau (hazard ratio = 8.92). Generally, the strength of MC's correlations with A\u03b2, pathological tau, and neurodegeneration biomarkers exceeded SUVR. Individuals with normal cognition and disrupted DMN metabolic connectivity face an elevated risk of cognitive decline linked to A\u03b2 that precedes metabolic issues.", "source": "PubMed"}, {"chunk_id": "38631552_2", "pmid": "38631552", "title": "Prediction of Cognitive Progression Due to Alzheimer's Disease in Normal Participants Based on Individual Default Mode Network Metabolic Connectivity Strength.", "authors": "Zhang Q, Li F, Wei M et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "(18)F-FDG PET, Alzheimer\u2019s disease, Cognitive decline, Cognitively unimpaired, Default mode network, Metabolic connectivity", "chunk": "cognitive decline linked to A\u03b2 that precedes metabolic issues.", "source": "PubMed"}, {"chunk_id": "40754677_0", "pmid": "40754677", "title": "Relationship between cerebrospinal fluid catecholamines levels and biomarkers of Alzheimer's disease, inflammation and neuronal injury.", "authors": "Portela Moreira I, Serr\u00e3o P, Sequeira L et al.", "year": "2025", "journal": "Neurological research", "keywords": "Alzheimer\u2019s disease, L-DOPA, dopamine, frontotemporal dementia, neurofilaments, norepinephrine", "chunk": "Changes in the locus coeruleus are among the earliest events in Alzheimer's disease (AD). We aimed to evaluate the relationship between cerebrospinal fluid (CSF) L-dihydroxyphenylalanine (L-DOPA), dopamine, and norepinephrine with CSF biomarkers of AD pathology (\u03b2-amyloid and p-tau), neuronal destruction (neurofilaments), and inflammation (leukocytes, IgG index, interleukin-6 and 10). We conducted a cross-sectional, observational study, including 35 patients with AD, 16 with frontotemporal dementia, and 38 normal controls (NC). L-DOPA was lower (<i>p</i> = 0.032) and neurofilaments were higher (<i>p</i> = 0.005) in AD than in NC. Norepinephrine levels were positively correlated with age (<i>r</i> = 0.260, <i>p</i> = 0.015 among all patients). L-DOPA levels were negatively correlated with neurofilaments (<i>r</i> = -0.228, <i>p</i> = 0.038 among all participants). Interleukin-6 was positively correlated with L-DOPA (<i>r</i> = 0.382, <i>p</i> = 0.026) and norepinephrine (<i>r</i> = 0.485, <i>p</i> = 0.004) levels in AD. Since neurofilaments are associated with neuronal damage, decreased", "source": "PubMed"}, {"chunk_id": "40754677_1", "pmid": "40754677", "title": "Relationship between cerebrospinal fluid catecholamines levels and biomarkers of Alzheimer's disease, inflammation and neuronal injury.", "authors": "Portela Moreira I, Serr\u00e3o P, Sequeira L et al.", "year": "2025", "journal": "Neurological research", "keywords": "Alzheimer\u2019s disease, L-DOPA, dopamine, frontotemporal dementia, neurofilaments, norepinephrine", "chunk": "was positively correlated with L-DOPA (<i>r</i> = 0.382, <i>p</i> = 0.026) and norepinephrine (<i>r</i> = 0.485, <i>p</i> = 0.004) levels in AD. Since neurofilaments are associated with neuronal damage, decreased L-DOPA levels in AD could be related to neuronal destruction. Catecholaminergic dysregulation seen in AD seems independent of \u03b2-amyloid and p-tau pathology.", "source": "PubMed"}, {"chunk_id": "35777608_0", "pmid": "35777608", "title": "Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism.", "authors": "Shi Z, Deng Z, Peng X et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "CaMMK\u03b2, Cerebral ischemia-reperfusion injury, Inflammatory reaction, Oxidative stress, Rhizoma dioscoreae", "chunk": "Rhizoma Dioscoreae (RD) is the rhizome of Dioscorea opposita Thunb., a traditional Chinese medicine, which can treat hypertension, diabetes, cerebral vasospasm headache and Alzheimer's disease. Meanwhile, RD is the main component of Liuwei Dihuang pill, a Chinese patent medicine. Rhizoma Dioscoreae polysaccharides (RDPS) are the primary active ingredient of RD. Modern medical research confirmed RDPS has multiple pharmacological effects, including neuroprotection, immunoregulation, antioxidant effect in many organs. The primary ischemia/hypoxia injury and secondary reperfusion injury are mainly caused by oxidative stress, which caused by hypoxia, such as free radical generation, energy metabolism disorder, intracellular calcium overload, excitatory amino acid release and inflammatory reaction. We have investigated the pharmacodynamic effect of RDPS on cerebral ischemia-reperfusion (IR) injury in rats and the possible mechanism in vitro. The pharmacodynamic effect of RDPS on IR injury in rats was studied by the construction of the occlusion of middle cerebral artery (MCAO) model, measuring the", "source": "PubMed"}, {"chunk_id": "35777608_1", "pmid": "35777608", "title": "Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism.", "authors": "Shi Z, Deng Z, Peng X et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "CaMMK\u03b2, Cerebral ischemia-reperfusion injury, Inflammatory reaction, Oxidative stress, Rhizoma dioscoreae", "chunk": "possible mechanism in vitro. The pharmacodynamic effect of RDPS on IR injury in rats was studied by the construction of the occlusion of middle cerebral artery (MCAO) model, measuring the volume of cerebral infarct area, the content of oxidation index, inflammatory cytokines, and the expression of CaMMK\u03b2 in brain tissue. The in vitro study was explored by oxygen-glucose deprivation/glycogen reoxygenation (OGD/R) model, construction of the CaMMK\u03b2 interference sequence, measuring the expression of CaMMK\u03b2 in BV2 cells before and after inhibition of CaMMK\u03b2, and the influence of RDPS on Nrf2/HO-1 signal pathway, in order to investigate the possible mechanism. Compared with the model group, the present study showed that RDPS with high-dose and low-dose groups could significantly reduce the volume of cerebral infarction. The content of MDA decreased and the activities of GSH and SOD increased in the two dose groups of RDPS. We confirmed that after RDPS treatment, the levels", "source": "PubMed"}, {"chunk_id": "35777608_2", "pmid": "35777608", "title": "Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism.", "authors": "Shi Z, Deng Z, Peng X et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "CaMMK\u03b2, Cerebral ischemia-reperfusion injury, Inflammatory reaction, Oxidative stress, Rhizoma dioscoreae", "chunk": "cerebral infarction. The content of MDA decreased and the activities of GSH and SOD increased in the two dose groups of RDPS. We confirmed that after RDPS treatment, the levels of IL-6, IL-1 \u03b2 and TNF-\u03b1 in brain tissue were lower than those in model group, and the expression of CaMMK\u03b2 in brain tissue of rats decreased in the model group, but increased in the groups of RDPS. In the in vitro study, compared with the control group, RDPS could regulate the OGD/R-induced apoptosis of BV2 cells and increase the level of CaMMK\u03b2, Nrf2 and HO-1 induced by OGD/R. To our surprise, these therapeutic effects are no longer present after the inhibition of CaMMK\u03b2 protein. The activity of BV2 induced by OGD/R could not be enhanced by RDPS after the inhibition of CaMMK\u03b2 protein. RDPS has the pharmacodynamic effect in IR injury, which reduce the area of cerebral infarction, up-regulate", "source": "PubMed"}, {"chunk_id": "35777608_3", "pmid": "35777608", "title": "Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism.", "authors": "Shi Z, Deng Z, Peng X et al.", "year": "2022", "journal": "Journal of ethnopharmacology", "keywords": "CaMMK\u03b2, Cerebral ischemia-reperfusion injury, Inflammatory reaction, Oxidative stress, Rhizoma dioscoreae", "chunk": "by OGD/R could not be enhanced by RDPS after the inhibition of CaMMK\u03b2 protein. RDPS has the pharmacodynamic effect in IR injury, which reduce the area of cerebral infarction, up-regulate the activity of anti-oxidant kinase, and down-regulate the inflammatory cytokine. Additionally, RDPS could affect the activation of Nrf2/HO-1 signaling pathway by regulating the expression of CaMMK\u03b2. Our observations justify the RDPS could be a new strategy for IR injury therapy, and the mechanism may be related to the improvement of antioxidant enzyme activity and inhibition of inflammatory reaction.", "source": "PubMed"}, {"chunk_id": "41373897_0", "pmid": "41373897", "title": "Oral and Periodontal Health Status, Peripheral Immune Dysregulation, and Cognitive Impairment in Alzheimer's Disease: A Clinical and Immunological Study.", "authors": "Ochnik M, Zborowski J, Leszek J et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, dysregulation of immune response, inflammation, periodontal disease, peripheral immune cells", "chunk": "Periodontal disease (PeD), a chronic oral infectious-inflammatory condition, has been linked to systemic inflammatory processes, which may contribute to the onset or progression of various systemic disorders including Alzheimer's disease (AD). We hypothesized that worsening oral and periodontal health, leading to the development of PeD, is associated with cognitive impairment and AD progression as well as peripheral immune system dysregulation. This study included 68 participants: 36 with AD and 32 cognitively healthy, age-matched controls (HCs). Periodontal assessment was performed for diagnosis of PeD (gingivitis or periodontitis). Correlations between oral and periodontal health status, cognitive impairment, and AD severity were evaluated. Peripheral immunity markers were investigated. Peripheral blood leukocytes (PBLs) were stimulated ex vivo with LPS from <i>Porphyromonas gingivalis</i> (LPS-PG) to assess cytokine IFN-\u03b3, TNF-\u03b1, IL-1\u03b2, IL-6, IL-10, and IL-15 production. The average levels of peripheral immunity markers were significantly lower in AD compared to HCs. AD severity was associated with", "source": "PubMed"}, {"chunk_id": "41373897_1", "pmid": "41373897", "title": "Oral and Periodontal Health Status, Peripheral Immune Dysregulation, and Cognitive Impairment in Alzheimer's Disease: A Clinical and Immunological Study.", "authors": "Ochnik M, Zborowski J, Leszek J et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, dysregulation of immune response, inflammation, periodontal disease, peripheral immune cells", "chunk": "assess cytokine IFN-\u03b3, TNF-\u03b1, IL-1\u03b2, IL-6, IL-10, and IL-15 production. The average levels of peripheral immunity markers were significantly lower in AD compared to HCs. AD severity was associated with poorer oral hygiene and increased periodontal tissue inflammation. PBLs from AD patients exhibited a baseline impairment in immune responsiveness reflected in decreased spontaneous TNF-\u03b1, IL-1\u03b2, IL-6, and IL-10 production. Nevertheless, stronger activation in response to LPS-PG was observed. Poorer oral health status in AD was associated with reduced levels of IL-10 and IL-6. Poor oral and periodontal health may contribute to cognitive impairment and AD progression. Even mild inflammation in periodontal tissue or gingivitis may already influence peripheral immune cell conditions, which in turn might be related to negative consequences for the brain and mental health.", "source": "PubMed"}, {"chunk_id": "41373897_2", "pmid": "41373897", "title": "Oral and Periodontal Health Status, Peripheral Immune Dysregulation, and Cognitive Impairment in Alzheimer's Disease: A Clinical and Immunological Study.", "authors": "Ochnik M, Zborowski J, Leszek J et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, dysregulation of immune response, inflammation, periodontal disease, peripheral immune cells", "chunk": "for the brain and mental health.", "source": "PubMed"}, {"chunk_id": "37762203_0", "pmid": "37762203", "title": "Treatment of Alzheimer's Disease: Beyond Symptomatic Therapies.", "authors": "Buccellato FR, D'Anca M, Tartaglia GM et al.", "year": "2023", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease (AD), disease-modifying therapy (DMT), drug, monoclonal antibody (mAb), small molecules, therapy", "chunk": "In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of \u03b2-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT)", "source": "PubMed"}, {"chunk_id": "37762203_1", "pmid": "37762203", "title": "Treatment of Alzheimer's Disease: Beyond Symptomatic Therapies.", "authors": "Buccellato FR, D'Anca M, Tartaglia GM et al.", "year": "2023", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease (AD), disease-modifying therapy (DMT), drug, monoclonal antibody (mAb), small molecules, therapy", "chunk": "efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against A\u03b2 plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.", "source": "PubMed"}, {"chunk_id": "34040574_0", "pmid": "34040574", "title": "Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?", "authors": "Ferrando R, Damian A", "year": "2021", "journal": "Frontiers in neurology", "keywords": "Alzheimer's disease, PET, SPECT, biomarkers, dementia, low- and middle-income countries, neurodegeneration", "chunk": "Biomarkers are playing a progressively leading role in both clinical practice and scientific research in dementia. Although amyloid and tau biomarkers have gained ground in the clinical community in recent years, neurodegeneration biomarkers continue to play a key role due to their ability to identify different patterns of brain involvement that sign the transition between asymptomatic and symptomatic stages of the disease with high sensitivity and specificity. Both <sup>18</sup>F-FDG positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) have proved useful to reveal the functional alterations underlying various neurodegenerative diseases. Although the focus of nuclear neuroimaging has shifted to PET, the lower cost and wider availability of SPECT make it a still valid alternative for the study of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize", "source": "PubMed"}, {"chunk_id": "34040574_1", "pmid": "34040574", "title": "Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?", "authors": "Ferrando R, Damian A", "year": "2021", "journal": "Frontiers in neurology", "keywords": "Alzheimer's disease, PET, SPECT, biomarkers, dementia, low- and middle-income countries, neurodegeneration", "chunk": "of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize patients from low- and middle-income countries, where special care of additional costs is particularly needed to meet the new recommendations for the diagnosis and characterization of patients with dementia.", "source": "PubMed"}, {"chunk_id": "41745708_0", "pmid": "41745708", "title": "Consensus Molecules Associated with Parkinson's Disease.", "authors": "Eyal S, Alfasi S, Ben Zaken K et al.", "year": "2026", "journal": "Neurology international", "keywords": "Parkinson\u2019s disease, coenzyme Q10, cofactors, tetrahydrobiopterin, vitamins", "chunk": "Parkinson's disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated", "source": "PubMed"}, {"chunk_id": "41745708_1", "pmid": "41745708", "title": "Consensus Molecules Associated with Parkinson's Disease.", "authors": "Eyal S, Alfasi S, Ben Zaken K et al.", "year": "2026", "journal": "Neurology international", "keywords": "Parkinson\u2019s disease, coenzyme Q10, cofactors, tetrahydrobiopterin, vitamins", "chunk": "droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and \u03b2-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD.", "source": "PubMed"}, {"chunk_id": "41424796_0", "pmid": "41424796", "title": "Endothelium glutamate receptors in brain pathology.", "authors": "Pirozhkov SV, Vukolova MN, Bulgakova VV et al.", "year": "2025", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, blood-brain barrier, brain microvascular endothelial cell, glutamate receptors, ischemic brain injury, multiple sclerosis, neuroinflammation, systemic lupus erythematosus", "chunk": "The endothelium in brain microcirculation functions not only as a barrier but also as a signal transduction component within a system that regulates multiple vascular processes, including muscle tone, permeability, and structural integrity. The control of local blood flow is vital to ensure adequate oxygen and nutrient supply, efficient removal of catabolic waste, and the maintenance of proper brain cell function. The role of endothelial glutamate receptors in brain pathology is an emerging area of research, particularly important for understanding how these receptors contribute to neurological diseases and disorders. Endothelial cells (ECs), which are considered active players in maintaining brain homeostasis, express glutamate receptors on their surface. Activation of these receptors can trigger a cascade of signaling events, including synthesis of nitric oxide (NO) and proinflammatory molecules. N-Methyl-D-Aspartate receptors (NMDARs) play a significant role in functional hyperemia, also known as neurovascular coupling (NVC), which is essential for maintaining the energy", "source": "PubMed"}, {"chunk_id": "41424796_1", "pmid": "41424796", "title": "Endothelium glutamate receptors in brain pathology.", "authors": "Pirozhkov SV, Vukolova MN, Bulgakova VV et al.", "year": "2025", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, blood-brain barrier, brain microvascular endothelial cell, glutamate receptors, ischemic brain injury, multiple sclerosis, neuroinflammation, systemic lupus erythematosus", "chunk": "of nitric oxide (NO) and proinflammatory molecules. N-Methyl-D-Aspartate receptors (NMDARs) play a significant role in functional hyperemia, also known as neurovascular coupling (NVC), which is essential for maintaining the energy balance in brain cells. Growing evidence suggests that disturbance of this balance is implicated in several neurological diseases, such as Alzheimer's disease, stroke, and traumatic brain injury (TBI), where endothelial dysfunction may impair blood flow regulation, contributing to further neuronal damage and cognitive decline. This review focuses on the glutamate receptor-mediated alterations in endothelial permeability and the prevention of the brain pathology through direct modulation of these receptors. Notably, the metabotropic glutamate receptor mGluR1, along with NMDARs, may cause deleterious effects in brain ischemia, as their activation increases the permeability of the vessel wall. Stimulation of NMDARs may also lead to ferroptosis in ECs. EC dysfunction results in significant blood-brain barrier (BBB) disruption, allowing infiltration by inflammatory cells and the", "source": "PubMed"}, {"chunk_id": "41424796_2", "pmid": "41424796", "title": "Endothelium glutamate receptors in brain pathology.", "authors": "Pirozhkov SV, Vukolova MN, Bulgakova VV et al.", "year": "2025", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, blood-brain barrier, brain microvascular endothelial cell, glutamate receptors, ischemic brain injury, multiple sclerosis, neuroinflammation, systemic lupus erythematosus", "chunk": "of the vessel wall. Stimulation of NMDARs may also lead to ferroptosis in ECs. EC dysfunction results in significant blood-brain barrier (BBB) disruption, allowing infiltration by inflammatory cells and the accumulation in brain of pathological proteins, such as amyloid-beta (A<sub>\u03b2</sub>) or autoantibodies. This contributes to neuronal dystrophy and apoptosis, as seen in Alzheimer's disease and autoimmune encephalopathy. Activated ECs generate proinflammatory mediators that attract leukocytes and sustain the neuroinflammatory response. Infiltrating peripheral white blood cells are key contributors to inflammatory damage following TBI. Regulation of ECs through glutamate receptors therefore represents a promising therapeutic strategy for treatment of neurodegenerative diseases, as well as ischemic and traumatic brain injuries.", "source": "PubMed"}, {"chunk_id": "33669839_0", "pmid": "33669839", "title": "From Combinations to Single-Molecule Polypharmacology-Cromolyn-Ibuprofen Conjugates for Alzheimer's Disease.", "authors": "Albertini C, Naldi M, Petralla S et al.", "year": "2021", "journal": "Molecules (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, anti-amyloid, anti-inflammatory, codrugs, drug combinations, polypharmacology", "chunk": "Despite Alzheimer's disease (AD) incidence being projected to increase worldwide, the drugs currently on the market can only mitigate symptoms. Considering the failures of the classical paradigm \"one target-one drug-one disease\" in delivering effective medications for AD, polypharmacology appears to be a most viable therapeutic strategy. Polypharmacology can involve combinations of multiple drugs and/or single chemical entities modulating multiple targets. Taking inspiration from an ongoing clinical trial, this work aims to convert a promising cromolyn-ibuprofen drug combination into single-molecule \"codrugs.\" Such codrugs should be able to similarly modulate neuroinflammatory and amyloid pathways, while showing peculiar pros and cons. By exploiting a linking strategy, we designed and synthesized a small set of cromolyn-ibuprofen conjugates (<b>4</b>-<b>6</b>). Preliminary plasma stability and neurotoxicity assays allowed us to select diamide <b>5</b> and ethanolamide <b>6</b> as promising compounds for further studies. We investigated their immunomodulatory profile in immortalized microglia cells, in vitro anti-aggregating activity towards A\u03b2<sub>42</sub>-amyloid", "source": "PubMed"}, {"chunk_id": "33669839_1", "pmid": "33669839", "title": "From Combinations to Single-Molecule Polypharmacology-Cromolyn-Ibuprofen Conjugates for Alzheimer's Disease.", "authors": "Albertini C, Naldi M, Petralla S et al.", "year": "2021", "journal": "Molecules (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, anti-amyloid, anti-inflammatory, codrugs, drug combinations, polypharmacology", "chunk": "allowed us to select diamide <b>5</b> and ethanolamide <b>6</b> as promising compounds for further studies. We investigated their immunomodulatory profile in immortalized microglia cells, in vitro anti-aggregating activity towards A\u03b2<sub>42</sub>-amyloid self-aggregation, and their cellular neuroprotective effect against A\u03b2<sub>42</sub>-induced neurotoxicity. The fact that <b>6</b> effectively reduced A\u03b2-induced neuronal death, prompted its investigation into an in vivo model. Notably, <b>6</b> was demonstrated to significantly increase the longevity of A\u03b2<sub>42</sub>-expressing <i>Drosophila</i> and to improve fly locomotor performance.", "source": "PubMed"}, {"chunk_id": "38405345_0", "pmid": "38405345", "title": "Genetic Risk for Alzheimer's Disease Alters Perceived Executive Dysfunction in Cognitively Healthy Middle-Aged and Older Adults.", "authors": "Evans SA, Paitel ER, Bhasin R et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "APOE \u025b4, Aging, Alzheimer\u2019s disease, executive function, subjective cognitive complaints", "chunk": "Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E \u025b4 allele, a primary genetic risk for Alzheimer's disease (AD). This study investigated the role of the \u025b4 allele in the consistency between subjective and objective executive functioning in 54 healthy, cognitively intact, middle-aged and older adults. Participants (<i>M</i><sub>age</sub> = 64.07, <i>SD</i> = 9.27, range = 48-84; \u025b4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into", "source": "PubMed"}, {"chunk_id": "38405345_1", "pmid": "38405345", "title": "Genetic Risk for Alzheimer's Disease Alters Perceived Executive Dysfunction in Cognitively Healthy Middle-Aged and Older Adults.", "authors": "Evans SA, Paitel ER, Bhasin R et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "APOE \u025b4, Aging, Alzheimer\u2019s disease, executive function, subjective cognitive complaints", "chunk": "48-84; \u025b4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into a single factor. After accounting for age, depression, and anxiety, objective executive functioning performance significantly predicted SEF. Importantly, \u025b4 moderated this effect. Specifically, those carrying the \u025b4 allele had significantly less accurate self-awareness of their executive functioning compared to \u025b4 non-carriers. Utilizing an approach that integrates self-evaluation of executive functioning with objective neurocognitive assessment may help identify the earliest signs of impending cognitive decline, particularly in those with genetic risk for AD. Such an approach could sensitively determine those most prone to future cognitive decline prior to symptom onset, when interventions could be most effective.", "source": "PubMed"}, {"chunk_id": "38405345_2", "pmid": "38405345", "title": "Genetic Risk for Alzheimer's Disease Alters Perceived Executive Dysfunction in Cognitively Healthy Middle-Aged and Older Adults.", "authors": "Evans SA, Paitel ER, Bhasin R et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "APOE \u025b4, Aging, Alzheimer\u2019s disease, executive function, subjective cognitive complaints", "chunk": "interventions could be most effective.", "source": "PubMed"}, {"chunk_id": "35537596_0", "pmid": "35537596", "title": "Screening neuroprotective compounds in herpes-induced Alzheimer's disease cell and 3D tissue models.", "authors": "Silveira IA, Mullis AS, Cairns DM et al.", "year": "2022", "journal": "Free radical biology & medicine", "keywords": "3D culture, Alzheimer's disease, Bioengineering, Screening", "chunk": "Alzheimer's Disease (AD) is a neurodegenerative disorder that can cause life-altering and debilitating cognitive decline. AD's etiology is poorly understood, and no disease-modifying therapeutics exist. Here, we describe the use of 2D and 3D tissue culture models of herpesvirus-induced AD, which recapitulate hallmark disease features of plaque formation, gliosis, neuroinflammation, and impaired neuronal signaling, to screen a panel of 21 medications, supplements, and nutraceuticals with purported neuroprotective benefits. This screen identified green tea catechins and resveratrol as having strong anti-plaque properties, functional neuroprotective benefits, and minimal neurotoxicity, providing support for their further investigation as AD preventives and therapies. Two other candidates, citicoline and metformin, reduced plaque formation and were minimally toxic, but did not protect against virus-induced impairments in neuronal signaling. This study establishes a simple platform for rapidly screening and characterizing AD compounds of interest in 2D and 3D human cortical tissue models representing physiologically relevant disease features.", "source": "PubMed"}, {"chunk_id": "35537596_1", "pmid": "35537596", "title": "Screening neuroprotective compounds in herpes-induced Alzheimer's disease cell and 3D tissue models.", "authors": "Silveira IA, Mullis AS, Cairns DM et al.", "year": "2022", "journal": "Free radical biology & medicine", "keywords": "3D culture, Alzheimer's disease, Bioengineering, Screening", "chunk": "signaling. This study establishes a simple platform for rapidly screening and characterizing AD compounds of interest in 2D and 3D human cortical tissue models representing physiologically relevant disease features.", "source": "PubMed"}, {"chunk_id": "37737064_0", "pmid": "37737064", "title": "Blood pressure targets for prevention of cognitive decline in patients with diabetes and hypertension: Design of the Blood Pressure Control Target in Diabetes (BPROAD) Cognitive Study.", "authors": " ", "year": "2023", "journal": "Journal of diabetes", "keywords": "2\u578b\u7cd6\u5c3f\u75c5, blood pressure, dementia, mild cognitive impairment, randomized controlled trial, type 2 diabetes, \u75f4\u5446\u75c7, \u8840\u538b, \u8f7b\u5ea6\u8ba4\u77e5\u969c\u788d, \u968f\u673a\u5bf9\u7167\u8bd5\u9a8c", "chunk": "Both hypertension and diabetes are risk factors of dementia. Proper management of blood pressure (BP) and blood glucose is critical in delaying cognitive decline in the elderly. However, little is known regarding the optimal BP target in type 2 diabetes (T2DM) for the management of cognitive decline. The Blood Pressure Control Target in Diabetes (BPROAD) study is a nationwide, multicenter, randomized controlled trial that will enroll 12 702 T2DM patients with elevated systolic BP and increased cardiovascular risk from approximately 150 study centers across mainland China to undergo randomly antihypertensive treatment achieving systolic BP <120 mm Hg or systolic BP <140 mm Hg for up to 5 years. All BPROAD participants will take part in the BPROAD Cognitive Study for the assessment of cognitive function at baseline and annual visits by blinded outcome assessors to determine whether intensive BP treatment reduces risk of dementia and mild cognitive impairment (MCI) compared", "source": "PubMed"}, {"chunk_id": "37737064_1", "pmid": "37737064", "title": "Blood pressure targets for prevention of cognitive decline in patients with diabetes and hypertension: Design of the Blood Pressure Control Target in Diabetes (BPROAD) Cognitive Study.", "authors": " ", "year": "2023", "journal": "Journal of diabetes", "keywords": "2\u578b\u7cd6\u5c3f\u75c5, blood pressure, dementia, mild cognitive impairment, randomized controlled trial, type 2 diabetes, \u75f4\u5446\u75c7, \u8840\u538b, \u8f7b\u5ea6\u8ba4\u77e5\u969c\u788d, \u968f\u673a\u5bf9\u7167\u8bd5\u9a8c", "chunk": "the assessment of cognitive function at baseline and annual visits by blinded outcome assessors to determine whether intensive BP treatment reduces risk of dementia and mild cognitive impairment (MCI) compared with standard BP treatment in patients with T2DM. In addition, approximately 1000 BPROAD participants will be enrolled in the magnetic resonance imaging (MRI) substudy to receive brain MRI at baseline and at closeout. The primary outcome of BPROAD Cognitive Study is a composite of all-cause dementia and MCI. The BPROAD Cognitive Study will provide crucial clinical trial data on the possible benefit of an intensive systolic BP lowering strategy in reducing dementia and MCI in patients with T2DM.", "source": "PubMed"}, {"chunk_id": "40559130_0", "pmid": "40559130", "title": "Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review.", "authors": "Chaple-Gil AM, Santiesteban-Vel\u00e1zquez M, Urbizo V\u00e9lez JJ", "year": "2025", "journal": "Dentistry journal", "keywords": "Alzheimer\u2019s disease, cognitive dysfunction, microbiota, mild cognitive impairment, oral health, oral microbiome", "chunk": "<b>Background/Objectives</b>: Growing evidence suggests that oral microbiota dysbiosis may contribute to the development of systemic conditions, including neurodegenerative diseases. This dysregulation promotes immunoinflammatory responses that are increasingly associated with dementia. This systematic review aimed to evaluate the association between oral microbiota dysbiosis and the risk of dementia in older adults. <b>Methods</b>: Eligible studies evaluated oral microbial composition using validated methods such as genetic sequencing, bacterial culture, or metagenomic analysis. Following PRISMA guidelines and a PICO framework, the review included cohort, case-control, and cross-sectional studies. Searches were conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane Library. Two independent reviewers screened and selected studies, resolving disagreements through a third evaluator. <b>Results</b>: This systematic review revealed that <i>Tannerella forsythia</i>, <i>Fusobacterium nucleatum</i>, <i>Porphyromonas</i>, <i>Prevotella</i>, <i>Leptotrichia</i>, <i>Fusobacteriota</i>, <i>Peptostreptococcaceae</i>, and <i>Candida</i> spp. were consistently associated with Alzheimer's disease and mild cognitive impairment, indicating their potential role in neurodegeneration. In contrast, <i>Streptococcus gordonii</i>, <i>Gemella haemolysans</i>,", "source": "PubMed"}, {"chunk_id": "40559130_1", "pmid": "40559130", "title": "Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review.", "authors": "Chaple-Gil AM, Santiesteban-Vel\u00e1zquez M, Urbizo V\u00e9lez JJ", "year": "2025", "journal": "Dentistry journal", "keywords": "Alzheimer\u2019s disease, cognitive dysfunction, microbiota, mild cognitive impairment, oral health, oral microbiome", "chunk": "<i>Porphyromonas</i>, <i>Prevotella</i>, <i>Leptotrichia</i>, <i>Fusobacteriota</i>, <i>Peptostreptococcaceae</i>, and <i>Candida</i> spp. were consistently associated with Alzheimer's disease and mild cognitive impairment, indicating their potential role in neurodegeneration. In contrast, <i>Streptococcus gordonii</i>, <i>Gemella haemolysans</i>, <i>Rothia</i>, <i>Neisseria</i>, and <i>Haemophilus</i> were reduced in cognitively impaired individuals, suggesting a link with healthy cognition. Studies also showed decreased microbial diversity in Alzheimer's disease and the possible modifying effect of the APOE4 allele. Oral health interventions improved microbial composition and slowed cognitive decline, supporting the diagnostic and therapeutic potential of oral microbiota modulation. <b>Conclusions</b>: The findings suggest that oral microbiota dysbiosis may not only result from cognitive decline but also contribute to its pathogenesis. Future studies with larger and more diverse cohorts are recommended to validate these associations.", "source": "PubMed"}, {"chunk_id": "37088045_0", "pmid": "37088045", "title": "Assessment of cognitive impairment and depressive signs in patients with type 2 diabetes treated with metformin from Southeast Mexico: A cross-sectional study.", "authors": "Nolasco-Rosales GA, Villar-Ju\u00e1rez GE, P\u00e9rez-Osorio DA et al.", "year": "2023", "journal": "Journal of psychiatric research", "keywords": "Cognitive impairment, Depression, Metformin, Type 2 diabetes mellitus", "chunk": "Multiple factors associate diabetes with cognitive impairment and depression. Antidiabetic drugs have reported antidepressant and pro-cognitive effects in diabetic and non-diabetic subjects. Antidepressant and pro-cognitive effects of metformin are reported in various studies; however, these effects are not consistent among researches. We designed a cross-sectional study. We recruited patients with T2D diagnosis from the Diabetes Clinic of the Regional Hospital of High Specialty \"Dr. Gustavo A. Rovirosa P\u00e9rez\" from January 2019 to May 2022. We included 431 subjects with T2D, 374 patients with metformin treatment and 57 subjects without metformin. These patients were on intensive therapies and had not a previous diagnosis of cognitive impairment or depression. We applied Mini-Mental State Examination (MMSE) to evaluate cognitive impairment, and Hamilton Depression Rating Scale (HAM-D) to assess depressive signs. Our sample had a mean age of 53.77 \u00b1 13.43 years. Metformin users were 374 individuals, and 57 subjects didn't use metformin. MMSE", "source": "PubMed"}, {"chunk_id": "37088045_1", "pmid": "37088045", "title": "Assessment of cognitive impairment and depressive signs in patients with type 2 diabetes treated with metformin from Southeast Mexico: A cross-sectional study.", "authors": "Nolasco-Rosales GA, Villar-Ju\u00e1rez GE, P\u00e9rez-Osorio DA et al.", "year": "2023", "journal": "Journal of psychiatric research", "keywords": "Cognitive impairment, Depression, Metformin, Type 2 diabetes mellitus", "chunk": "Rating Scale (HAM-D) to assess depressive signs. Our sample had a mean age of 53.77 \u00b1 13.43 years. Metformin users were 374 individuals, and 57 subjects didn't use metformin. MMSE found cognitive impairment in 8.3% (n = 31) of metformin users, and 14.8% (n = 8) of patients without metformin. HAM-D scale showed that 39.5% (n = 147) of patients with metformin had depression signs, subjects without metformin and depressive signs were 44.6% (n = 25). We found no differences between groups for cognitive impairment and depression grades. We did not find associations between metformin treatment, cognitive impairment measures and depression sign measures. However, chronic metformin treatment, insulin use, glycemic control and age could influence our results.", "source": "PubMed"}, {"chunk_id": "41516057_0", "pmid": "41516057", "title": "Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.", "authors": "Thangaleela S, Ali A, Tandoro Y et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease dementia, Lewy body dementia, dementia, frontotemporal dementia, neuroinflammation, vascular dementia", "chunk": "Dementia is a neurodegenerative condition marked by progressive cognitive decline, which affects people worldwide. Studies on dementia typically continue over years of uncertainty. Different types of dementia, like Alzheimer's disease dementia, Lewy body dementia, frontotemporal dementia, and vascular dementia, exhibit different pathological features, yet their downstream inflammatory pathways involve similar inflammatory mediators. As an initial trigger, microglial cells and astrocytes become activated by protein aggregates, mutations, or any other cause, and release pro-inflammatory cytokines, which can lead to synaptic dysfunction, neuronal degeneration, and impaired cognitive function. Neuroinflammation plays a critical role in the pathogenesis of all forms of dementia. Despite their distinct neuropathological features, inflammatory processes may coincide at a point and lead to neuronal degeneration and cognitive decline. Recent advancements in neuroimaging techniques and biomarker discovery revealed potential therapeutic targets that may mitigate neuroinflammation. The primary objective of this review is to explore the underlying mechanisms linking neuroinflammation to", "source": "PubMed"}, {"chunk_id": "41516057_1", "pmid": "41516057", "title": "Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.", "authors": "Thangaleela S, Ali A, Tandoro Y et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease dementia, Lewy body dementia, dementia, frontotemporal dementia, neuroinflammation, vascular dementia", "chunk": "advancements in neuroimaging techniques and biomarker discovery revealed potential therapeutic targets that may mitigate neuroinflammation. The primary objective of this review is to explore the underlying mechanisms linking neuroinflammation to various types of dementia. This review focuses on shared and distinct neuroinflammatory mechanisms to unravel significant therapeutic strategies for dementia.", "source": "PubMed"}, {"chunk_id": "41185054_0", "pmid": "41185054", "title": "Effect of melatonin on cognitive function in adults with cognitive impairment: a multi-dimensional meta-analysis of randomized trials.", "authors": "Leung LY, Tam HL, Asiamah N et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Cognitive, Alzheimer's diseases, Dementia, Melatonin, Review", "chunk": "Cognitive impairment leads to poor daily social and occupational functions and sleep disturbances. Approximately two-thirds of all individuals with mild cognitive impairment (MCI) experience sleep problems that further reduce cognitive function. Melatonin, a hormone secreted by the pineal gland, has proven effective in mitigating sleep problems and cognitive function in individuals with MCI. The current review investigated the efficacy of melatonin in improving cognitive function in adults with cognitive impairment. Seven databases were systematically searched for relevant randomized controlled trials published (in English or Chinese) until April 2025. Two reviewers independently selected studies, assessed quality (using the Physiotherapy Evidence Database scale), and extracted data. In total, 394 potentially eligible articles were identified. Finally, 8 studies (518 participants) were included. Five, one, and two studies had good, excellent, and low quality, respectively. Pooled results indicated that melatonin significantly improved cognitive function in adults with cognitive impairment (mean difference [MD]: 1.08; p", "source": "PubMed"}, {"chunk_id": "41185054_1", "pmid": "41185054", "title": "Effect of melatonin on cognitive function in adults with cognitive impairment: a multi-dimensional meta-analysis of randomized trials.", "authors": "Leung LY, Tam HL, Asiamah N et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Cognitive, Alzheimer's diseases, Dementia, Melatonin, Review", "chunk": "one, and two studies had good, excellent, and low quality, respectively. Pooled results indicated that melatonin significantly improved cognitive function in adults with cognitive impairment (mean difference [MD]: 1.08; p < 0.0001). Subgroup analyses by treatment duration, administration time, and cognitive impairment level revealed that the effects of melatonin were significant when it was administered for 13-24 weeks (MD: 2.04; p < 0.00001), between the times of 20:30 and 21:00 (MD: 2.2; p < 0.00001), and to individuals with MCI (MD: 2.63; p < 0.000001). Our findings suggest that melatonin is relatively safe for individuals with cognitive impairment. Thus, we recommend it for adults with MCI. It should be administered between 20:30 and 21:00 for 13-24 weeks.", "source": "PubMed"}, {"chunk_id": "36012501_0", "pmid": "36012501", "title": "Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer's Disease Patients.", "authors": "Gagliardi S, Truffi M, Tinelli V et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, H-Ferritin, bisdemethoxycurcumin, curcumin, drug delivery, gene expression, inflammation, nanoparticles", "chunk": "Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). We tested the BDC-HFn solubility, stability, and ability to cross a blood-brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Our data showed how BDC-Hfn could", "source": "PubMed"}, {"chunk_id": "36012501_1", "pmid": "36012501", "title": "Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer's Disease Patients.", "authors": "Gagliardi S, Truffi M, Tinelli V et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, H-Ferritin, bisdemethoxycurcumin, curcumin, drug delivery, gene expression, inflammation, nanoparticles", "chunk": "between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.", "source": "PubMed"}, {"chunk_id": "40078900_0", "pmid": "40078900", "title": "Growth-Associated Protein 43 Levels in the Cerebrospinal Fluid Correspond to the Cerebral Blood Flow Alterations in Alzheimer's Dementia Continuum: An Original Study.", "authors": "Songhori N, Goushky MS, Khaleghi MM et al.", "year": "2025", "journal": "Health science reports", "keywords": "alzheimer's disease, arterial spin labeling, biomarker, growth\u2010associated protein 43", "chunk": "Alzheimer's disease (AD) is a widespread neurodegenerative condition that has a growing impact on a global scale. This study aims to examine the relationship between cerebral blood flow (CBF) and the synaptic biomarker growth-associated protein 43 (GAP-43) through the utilization of arterial spin labeling (ASL). The research identified noteworthy correlations between cerebrospinal fluid (CSF) GAP-43 levels, CBF, and cognitive composite scores, especially among participants with mild cognitive impairment (MCI) who possess the APOE-\u03b54 gene. The study examined 92 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 36 cognitively normal (CN) and 56 MCI. The cognitive status of 42 participants was evaluated using ADNI composite scores. Independent t-tests and Mann-Whitney tests were used for the comparison of continuous variables between groups, and multiple linear regression analysis with adjustments for confounding factors was used to assess the relationship between GAP-43 and CBF values. Significant positive correlations were observed between GAP-43", "source": "PubMed"}, {"chunk_id": "40078900_1", "pmid": "40078900", "title": "Growth-Associated Protein 43 Levels in the Cerebrospinal Fluid Correspond to the Cerebral Blood Flow Alterations in Alzheimer's Dementia Continuum: An Original Study.", "authors": "Songhori N, Goushky MS, Khaleghi MM et al.", "year": "2025", "journal": "Health science reports", "keywords": "alzheimer's disease, arterial spin labeling, biomarker, growth\u2010associated protein 43", "chunk": "between groups, and multiple linear regression analysis with adjustments for confounding factors was used to assess the relationship between GAP-43 and CBF values. Significant positive correlations were observed between GAP-43 levels and (A) the executive function composite score (ADNI_EF) in CN individuals, as well as (B) the language composite score (ADNI_LAN) in individuals with MCI. CSF biomarkers and ASL regions did not show statistical significance between diagnostic groups after correction for multiple comparisons. No significant differences in baseline characteristics were found between diagnostic groups. However, associations were observed between ROI CBF and Mini Mental State Examination in various subgroups. The findings indicate a potential function for ASL perfusion in identifying early AD-related alterations and gaining insight into the pathophysiology of AD and mild cognitive impairment.The study revealed associations between CBF, cognitive scores, and APOE-\u03b54 gene status. This study contributes to the comprehension of the correlation between CSF biomarkers, regional brain", "source": "PubMed"}, {"chunk_id": "40078900_2", "pmid": "40078900", "title": "Growth-Associated Protein 43 Levels in the Cerebrospinal Fluid Correspond to the Cerebral Blood Flow Alterations in Alzheimer's Dementia Continuum: An Original Study.", "authors": "Songhori N, Goushky MS, Khaleghi MM et al.", "year": "2025", "journal": "Health science reports", "keywords": "alzheimer's disease, arterial spin labeling, biomarker, growth\u2010associated protein 43", "chunk": "AD and mild cognitive impairment.The study revealed associations between CBF, cognitive scores, and APOE-\u03b54 gene status. This study contributes to the comprehension of the correlation between CSF biomarkers, regional brain perfusion, and cognitive function in individuals with AD using ASL as a noninvasive approach.", "source": "PubMed"}, {"chunk_id": "41047765_0", "pmid": "41047765", "title": "Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.", "authors": "Jayarathne H, Manchanayake DH, Sullivan R et al.", "year": "2025", "journal": "Aging cell", "keywords": "Alzheimer's disease, Canagliflozin, aging brain, hippocampus, longevity, metabolism", "chunk": "Aging is the strongest risk factor for cognitive decline and Alzheimer's disease (AD), yet the mechanisms underlying brain aging and their modulation by pharmacological interventions remain poorly defined. The hippocampus, essential for learning and memory, is particularly vulnerable to metabolic stress and inflammation. Canagliflozin (Cana), an FDA-approved sodium-glucose co-transporter 2 inhibitor (SGLT2i) for type 2 diabetes, extends lifespan in male but not female mice, but its impact on brain aging is unknown. Here, we used a multi-omics strategy integrating transcriptomics, proteomics, and metabolomics to investigate how chronic Cana treatment reprograms brain aging in genetically diverse UM-HET3 mice. In males, Cana induced mitochondrial function, insulin and cGMP-PKG signaling, and suppressed neuroinflammatory networks across all molecular layers, resulting in improved hippocampal-dependent learning and memory. In females, transcriptional activation of neuroprotective pathways did not translate to protein or metabolite-level changes and failed to rescue cognition. In the 5xFAD AD model, Cana reduced amyloid", "source": "PubMed"}, {"chunk_id": "41047765_1", "pmid": "41047765", "title": "Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.", "authors": "Jayarathne H, Manchanayake DH, Sullivan R et al.", "year": "2025", "journal": "Aging cell", "keywords": "Alzheimer's disease, Canagliflozin, aging brain, hippocampus, longevity, metabolism", "chunk": "and memory. In females, transcriptional activation of neuroprotective pathways did not translate to protein or metabolite-level changes and failed to rescue cognition. In the 5xFAD AD model, Cana reduced amyloid plaque burden, microgliosis, and memory deficits in males only, despite comparable peripheral glucose improvements in both sexes. Our study reveals sex-specific remodeling of hippocampal aging by a clinically available SGLT2i, with implications for AD pathology and lifespan extension, and highlights Cana's potential to combat brain aging and AD through sex-specific mechanisms.", "source": "PubMed"}, {"chunk_id": "33024054_0", "pmid": "33024054", "title": "Voxel-based morphometry focusing on medial temporal lobe structures has a limited capability to detect amyloid \u03b2, an Alzheimer's disease pathology.", "authors": "Kameyama M, Ishibashi K, Toyohara J et al.", "year": "2020", "journal": "Aging", "keywords": "Pittsburgh Compound B (PiB), beta-amyloid, hippocampus, magnetic resonance imaging (MRI), positron emission tomography (PET)", "chunk": "Voxel-based morphometry (VBM) analysis of nuclear Magnetic Resonance Imaging (MRI) data allows the identification of medial temporal lobe (MTL) atrophy and is widely used to assist the diagnosis of Alzheimer's disease (AD). However, its reliability in the clinical environment has not yet been confirmed. To determine the credibility of VBM, amyloid positron emission tomography (PET) and VBM studies were compared retrospectively. Patients who underwent Pittsburgh Compound B (PiB) PET were retrospectively recruited. Ninety-seven patients were found to be amyloid negative and 116 were amyloid positive. MTL atrophy in the PiB positive group, as quantified by thin sliced 3D MRI and VBM software, was significantly more severe (p =0.0039) than in the PiB negative group. However, data histogram showed a vast overlap between the two groups. The area under the ROC curve (AUC) was 0.646. MMSE scores of patients in the amyloid negative and positive groups were also significantly different (<i>p</i>", "source": "PubMed"}, {"chunk_id": "33024054_1", "pmid": "33024054", "title": "Voxel-based morphometry focusing on medial temporal lobe structures has a limited capability to detect amyloid \u03b2, an Alzheimer's disease pathology.", "authors": "Kameyama M, Ishibashi K, Toyohara J et al.", "year": "2020", "journal": "Aging", "keywords": "Pittsburgh Compound B (PiB), beta-amyloid, hippocampus, magnetic resonance imaging (MRI), positron emission tomography (PET)", "chunk": "overlap between the two groups. The area under the ROC curve (AUC) was 0.646. MMSE scores of patients in the amyloid negative and positive groups were also significantly different (<i>p</i> = 0.0028), and the AUC was 0.672. Thus, MTL atrophy could not reliably differentiate between amyloid positive and negative patients in a clinical setting, possibly due to the wide array of dementia-type diseases that exist other than AD.", "source": "PubMed"}, {"chunk_id": "41616952_0", "pmid": "41616952", "title": "Therapeutic efficacy of synthetic analogues of gut hormones in a mouse model of Alzheimer's disease.", "authors": "Denver P, Duffy A, Kennedy RT et al.", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s, Amyloid, Cognition, GIP, GLP-1, Gliosis, Incretins, Liraglutide, Neurogenesis, Xenin-25", "chunk": "Alzheimer's disease (AD) is a neurodegenerative condition characterised by amyloid-\u03b2 pathology, neuroinflammation, synaptic dysfunction and cognitive decline. Few pharmacological interventions are available, offering only symptomatic relief, and approval for a number of anti-amyloid biologics is limited, with concerns about safety, cost and efficacy. Here we investigated the effects of 8-10 weeks treatment with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], long-lasting analogues of gut hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and xenin-25, respectively, in the APP/PS1 mouse model of AD. Cognitive function was measured in novel object recognition (NOR) and Morris water maze (MWM) tasks and amyloid burden, gliosis, synapse density and neurogenesis were assessed in brains of APP/PS1 and wild-type mice. AD-associated gene expression analysis was performed to identify potential pathways targeted by treatment. Liraglutide and NAcGIP[Lys(37)PAL] improved cognitive performance in APP/PS1 mice and, along with Xenin-25[Lys(13)PAL], reduced amyloid-\u03b2 burden in the brain. Liraglutide ameliorated gliosis and all three treatments", "source": "PubMed"}, {"chunk_id": "41616952_1", "pmid": "41616952", "title": "Therapeutic efficacy of synthetic analogues of gut hormones in a mouse model of Alzheimer's disease.", "authors": "Denver P, Duffy A, Kennedy RT et al.", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s, Amyloid, Cognition, GIP, GLP-1, Gliosis, Incretins, Liraglutide, Neurogenesis, Xenin-25", "chunk": "pathways targeted by treatment. Liraglutide and NAcGIP[Lys(37)PAL] improved cognitive performance in APP/PS1 mice and, along with Xenin-25[Lys(13)PAL], reduced amyloid-\u03b2 burden in the brain. Liraglutide ameliorated gliosis and all three treatments restored synaptophysin levels. Additionally, Xenin-25[Lys(13)PAL] increased neurogenesis in the dentate gyrus. Numerous AD-associated genes were altered in the brain following treatments. Notably, Serpina3c was upregulated in brains of APP/PS1 mice treated with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], while Map2, Adam9, Lrp8, Casp3, Abca1 and App were downregulated. These results underscore the neuroprotective effects of liraglutide and suggest that NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL] possess neuroprotective properties. Further investigation of the precise nature of these effects may support development of multi-target therapeutics based on combinations of gut hormone analogues.", "source": "PubMed"}, {"chunk_id": "39671965_0", "pmid": "39671965", "title": "A dual mode biosensor based on self-enhanced polyfluorene nanomaterial for fluorescence and electrochemiluminescence detection of Tau protein.", "authors": "Xie J, Yang G, Yuan R et al.", "year": "2025", "journal": "Biosensors & bioelectronics", "keywords": "Dual mode detection, Electrochemiluminescence, Fluorescence, Polyfluorene nanomaterials, Tau protein", "chunk": "Dual mode detection can overcome the poor anti-interference ability of single-mode detection, and greatly improve the detection accuracy. Fluorescence/electrochemiluminescence (FL/ECL) dual mode detection combines the advantages of FL and ECL, and has a promising application in bioanalysis. Common FL/ECL dual mode detection used different signal probes. Multiple signal probes inevitably have complex operation and uncontrollable differences between the two modes. In this work, poly [9,9-dioctylfluorenyl-2,7-diyl]-End-capped with 2,5-diphenyl-1,2,4-oxadiazole (PFO) was functionalized by sodium dodecyl sulfate (SDS) and polyethylenimine (PEI), and the resulting PFO-SDS-PEI nanoparticles (PSP NPs) exhibited excellent FL and ECL performance at the same time, so were creatively developed as mono-luminophore-based signal probe for FL/ECL dual-mode detection. The functional reagent SDS can significantly improve the water dispersion of luminophores, and PEI can not only provide amino functional groups for assembling biomolecules, but also significantly enhance the FL and ECL signals of the luminophores. Self-enhanced PSP NPs coupled strand displacement reaction", "source": "PubMed"}, {"chunk_id": "39671965_1", "pmid": "39671965", "title": "A dual mode biosensor based on self-enhanced polyfluorene nanomaterial for fluorescence and electrochemiluminescence detection of Tau protein.", "authors": "Xie J, Yang G, Yuan R et al.", "year": "2025", "journal": "Biosensors & bioelectronics", "keywords": "Dual mode detection, Electrochemiluminescence, Fluorescence, Polyfluorene nanomaterials, Tau protein", "chunk": "PEI can not only provide amino functional groups for assembling biomolecules, but also significantly enhance the FL and ECL signals of the luminophores. Self-enhanced PSP NPs coupled strand displacement reaction (SDR) mediated by exonuclease \u2162 (Exo \u2162) to achieve FL/ECL dual-mode detection of Tau protein, a biomarker of Alzheimer's disease (AD). The linear ranges for FL and ECL detection were 0.001-500 pg/mL and 0.00001-1.0 pg/mL and the limit of detections were 549.16 ag/mL and 5.45 ag/mL, respectively, showing good application potential. Self-enhanced PSP NPs provided an ideal mono-luminophore-based signal probe for FL/ECL dual-mode detection, and built a new method for detecting AD biomarker.", "source": "PubMed"}, {"chunk_id": "33077542_0", "pmid": "33077542", "title": "Derivation and utility of an A\u03b2-PET pathology accumulation index to estimate A\u03b2 load.", "authors": "Leuzy A, Lilja J, Buckley CJ et al.", "year": "2020", "journal": "Neurology", "keywords": "None", "chunk": "To evaluate a novel \u03b2-amyloid (A\u03b2)-PET-based quantitative measure (A\u03b2 accumulation index [A\u03b2 index]), including the assessment of its ability to discriminate between participants based on A\u03b2 status using visual read, CSF A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and post-mortem neuritic plaque burden as standards of truth. One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with A\u03b2-PET: Swedish BioFINDER, n = 392, [<sup>18</sup>F]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [<sup>18</sup>F]florbetapir; and a phase 3 end-of-life study, n = 100, [<sup>18</sup>F]flutemetamol. The relationships between A\u03b2 index and standardized uptake values ratios (SUVR) from A\u03b2-PET were assessed. The diagnostic performances of A\u03b2 index and SUVR were compared with visual reads, CSF A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and A\u03b2 histopathology used as reference standards. Strong associations were observed between A\u03b2 index and SUVR (<i>R</i> <sup>2</sup>: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating A\u03b2-positive from A\u03b2-negative participants, with areas under the", "source": "PubMed"}, {"chunk_id": "33077542_1", "pmid": "33077542", "title": "Derivation and utility of an A\u03b2-PET pathology accumulation index to estimate A\u03b2 load.", "authors": "Leuzy A, Lilja J, Buckley CJ et al.", "year": "2020", "journal": "Neurology", "keywords": "None", "chunk": "were observed between A\u03b2 index and SUVR (<i>R</i> <sup>2</sup>: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating A\u03b2-positive from A\u03b2-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and AUCs of 0.820 to 0.823 to detect abnormal A\u03b2 histopathology. Both measures also showed a similar distribution across postmortem-based A\u03b2 phases (based on anti-A\u03b2 4G8 antibodies). Compared to models using visual read alone, the addition of the A\u03b2 index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal A\u03b2 histopathology. The proposed A\u03b2 index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. A\u03b2 index may thus prove simpler", "source": "PubMed"}, {"chunk_id": "33077542_2", "pmid": "33077542", "title": "Derivation and utility of an A\u03b2-PET pathology accumulation index to estimate A\u03b2 load.", "authors": "Leuzy A, Lilja J, Buckley CJ et al.", "year": "2020", "journal": "Neurology", "keywords": "None", "chunk": "and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. A\u03b2 index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different A\u03b2-PET tracers. This study provides Class III evidence that the A\u03b2 accumulation index accurately differentiates A\u03b2-positive from A\u03b2-negative participants compared to A\u03b2-PET visual reads, CSF A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and A\u03b2 histopathology.", "source": "PubMed"}, {"chunk_id": "41295276_0", "pmid": "41295276", "title": "Methylglyoxal, a Knot to Be Untied in Brain Glucose Hypometabolism.", "authors": "Gayger-Dias V, Da Silva VF, Sobottka TM et al.", "year": "2025", "journal": "Metabolites", "keywords": "Alzheimer\u2019s, astrocyte, diabetes mellitus, insulin resistance, methylglyoxal", "chunk": "<b>Background:</b> Advanced glycation end products (AGEs) and receptors for AGEs (RAGE) have been extensively implicated in metabolic and neurodegenerative disorders due to their capacity to alter protein structure and function through non-enzymatic glycation. More recently, methylglyoxal (MG), a highly reactive glycolytic byproduct, has gained attention as a critical mediator of AGE formation and an independent contributor to cellular distress, particularly in the context of diabetes mellitus and Alzheimer's disease. <b>Objectives:</b> This review synthesizes evidence from experimental and clinical studies addressing MG generation and metabolism in brain tissue, emphasizing the glyoxalase system as the primary detoxification mechanism, the functional contribution of astrocytes, and the downstream consequences of MG accumulation. In addition, we examined the interplay between MG, RAGE signaling, unfolded protein response, and regulatory mechanisms involving the hexosamine biosynthesis pathway and O-GlcNAcylation of key proteins in glucose metabolism and insulin signaling. <b>Results and Conclusions:</b> Brain glucose hypometabolism is a consequence of", "source": "PubMed"}, {"chunk_id": "41295276_1", "pmid": "41295276", "title": "Methylglyoxal, a Knot to Be Untied in Brain Glucose Hypometabolism.", "authors": "Gayger-Dias V, Da Silva VF, Sobottka TM et al.", "year": "2025", "journal": "Metabolites", "keywords": "Alzheimer\u2019s, astrocyte, diabetes mellitus, insulin resistance, methylglyoxal", "chunk": "response, and regulatory mechanisms involving the hexosamine biosynthesis pathway and O-GlcNAcylation of key proteins in glucose metabolism and insulin signaling. <b>Results and Conclusions:</b> Brain glucose hypometabolism is a consequence of insulin resistance and results in a metabolic rearrangement that expands the glycolytic pathway and generates more MG, which, in turn, can affect insulin signaling, further compromising the molecular basis of insulin resistance and creating a vicious cycle. Astrocytes are key cells in the generation and detoxification of MG in the brain, making them a therapeutic target.", "source": "PubMed"}, {"chunk_id": "38104170_0", "pmid": "38104170", "title": "Mass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer's disease in a large clinical sample.", "authors": "de Geus MB, Leslie SN, Lam T et al.", "year": "2023", "journal": "Scientific reports", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a complex and heterogeneous neurodegenerative disorder with contributions from multiple pathophysiological pathways. One of the long-recognized and important features of AD is disrupted cerebral glucose metabolism, but the underlying molecular basis remains unclear. In this study, unbiased mass spectrometry was used to survey CSF from a large clinical cohort, comparing patients who are either cognitively unimpaired (CU; n = 68), suffering from mild-cognitive impairment or dementia from AD (MCI-AD, n = 95; DEM-AD, n = 72), or other causes (MCI-other, n = 77; DEM-other, n = 23), or Normal Pressure Hydrocephalus (NPH, n = 57). The results revealed changes related to altered glucose metabolism. In particular, two glycolytic enzymes, pyruvate kinase (PKM) and aldolase A (ALDOA), were found to be upregulated in CSF from patients with AD compared to those with other neurological conditions. Increases in full-length PKM and ALDOA levels in CSF were confirmed with", "source": "PubMed"}, {"chunk_id": "38104170_1", "pmid": "38104170", "title": "Mass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer's disease in a large clinical sample.", "authors": "de Geus MB, Leslie SN, Lam T et al.", "year": "2023", "journal": "Scientific reports", "keywords": "None", "chunk": "were found to be upregulated in CSF from patients with AD compared to those with other neurological conditions. Increases in full-length PKM and ALDOA levels in CSF were confirmed with immunoblotting. Levels of these enzymes furthermore correlated negatively with CSF glucose in matching CSF samples. PKM levels were also found to be increased in AD in publicly available brain-tissue data. These results indicate that ALDOA and PKM may act as technically-robust potential biomarkers of glucose metabolism dysregulation in AD.", "source": "PubMed"}, {"chunk_id": "38842037_0", "pmid": "38842037", "title": "Development of disease-modifying therapies against Alzheimer's disease.", "authors": "Iwatsubo T", "year": "2024", "journal": "Psychiatry and clinical neurosciences", "keywords": "Alzheimer, disease\u2010modifying therapy", "chunk": "To successfully develop disease-modifying therapies (DMT) against Alzheimer's disease (AD), it is important to target the mild stage of the disease, before the pathological changes progress and dementia symptoms are fully manifested. To this end, the AD Neuroimaging Initiative (ADNI), a large-scale observational study, was initiated in the U.S. with the goal of development of DMT that are effective in the early stages of mild cognitive impairment (MCI) by utilizing imaging and biomarkers. In Japan, J-ADNI enrolled and followed up 537 patients, mainly with MCI, and established a platform for evaluation including amyloid PET, and demonstrated a high similarity in the clinical course of amyloid-positive MCI (prodromal AD) in Japan and the U.S. In 2023, the anti-A\u03b2 antibody lecanemab successfully completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also,", "source": "PubMed"}, {"chunk_id": "38842037_1", "pmid": "38842037", "title": "Development of disease-modifying therapies against Alzheimer's disease.", "authors": "Iwatsubo T", "year": "2024", "journal": "Psychiatry and clinical neurosciences", "keywords": "Alzheimer, disease\u2010modifying therapy", "chunk": "completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also, phase III trial of donanemab was completed successful. The J-TRC study was initiated in Japan as a \"trial ready cohort (TRC)\" consisting of participants who met the eligibility criteria for participation in preclinical and prodromal AD trials. Based on such a platform, the development of DMT for AD will progress more rapidly in the future.", "source": "PubMed"}, {"chunk_id": "37480467_0", "pmid": "37480467", "title": "Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.", "authors": "Ottonelli I, Sharma A, Ruozi B et al.", "year": "2023", "journal": "Advances in neurobiology", "keywords": "Blood\u2013brain barrier, Brain edema, Brain-derived neurotrophic factor, Curcumin, Dopamine, Methamphetamine, Nanodelivery, Neuroprotection, Neurotoxicity", "chunk": "Curcumin is a well-known antioxidant used as traditional medicine in China and India since ages to treat variety of inflammatory ailments as a food supplement. Curcumin has antitumor properties with neuroprotective effects in Alzheimer's disease. Curcumin elevates brain-derived neurotrophic factor (BDNF) and dopamine (DA) levels in the brain indicating its role in substance abuse. Methamphetamine (METH) is one of the most abused substances in the world that induces profound neurotoxicity by inducing breakdown of the blood-brain barrier (BBB), vasogenic edema and cellular injuries. However, influence of curcumin on METH-induced neurotoxicity is still not well investigated. In this investigation, METH neurotoxicity and neuroprotective effects of curcumin nanodelivery were examined in a rat model. METH (20 mg/kg, i.p.) neurotoxicity is evident 4 h after its administration exhibiting breakdown of BBB to Evans blue albumin in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus associated with vasogenic brain edema as seen measured using", "source": "PubMed"}, {"chunk_id": "37480467_1", "pmid": "37480467", "title": "Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.", "authors": "Ottonelli I, Sharma A, Ruozi B et al.", "year": "2023", "journal": "Advances in neurobiology", "keywords": "Blood\u2013brain barrier, Brain edema, Brain-derived neurotrophic factor, Curcumin, Dopamine, Methamphetamine, Nanodelivery, Neuroprotection, Neurotoxicity", "chunk": "h after its administration exhibiting breakdown of BBB to Evans blue albumin in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus associated with vasogenic brain edema as seen measured using water content in all these regions. Nissl attaining exhibited profound neuronal injuries in the regions of BBB damage. Normal curcumin (50 mg/kg, i.v.) 30 min after METH administration was able to reduce BBB breakdown and brain edema partially in some of the above brain regions. However, TiO<sub>2</sub> nanowired delivery of curcumin (25 mg/kg, i.v.) significantly attenuated brain edema, neuronal injuries and the BBB leakage in all the brain areas. BDNF level showed a significant higher level in METH-treated rats as compared to saline-treated METH group. Significantly enhanced DA levels in METH-treated rats were also observed with nanowired delivery of curcumin. Normal curcumin was able to slightly elevate DA and BDNF levels in the selected brain regions. Taken together, our observations", "source": "PubMed"}, {"chunk_id": "37480467_2", "pmid": "37480467", "title": "Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.", "authors": "Ottonelli I, Sharma A, Ruozi B et al.", "year": "2023", "journal": "Advances in neurobiology", "keywords": "Blood\u2013brain barrier, Brain edema, Brain-derived neurotrophic factor, Curcumin, Dopamine, Methamphetamine, Nanodelivery, Neuroprotection, Neurotoxicity", "chunk": "METH-treated rats were also observed with nanowired delivery of curcumin. Normal curcumin was able to slightly elevate DA and BDNF levels in the selected brain regions. Taken together, our observations are the first to show that nanodelivery of curcumin induces superior neuroprotection in METH neurotoxicity probable by enhancing BDNF and DA levels in the brain, not reported earlier.", "source": "PubMed"}, {"chunk_id": "40409314_0", "pmid": "40409314", "title": "Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.", "authors": " ,  ", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "Trehalose is a disaccharide that activates autophagy pathways in animal models of neurodegenerative diseases, with the potential to catalyse clearance of toxic, misfolded proteins in motor neurons and slow disease progression in amyotrophic lateral sclerosis (ALS). We aimed to evaluate the safety and efficacy of trehalose in individuals with ALS. The HEALEY ALS Platform Trial is a perpetual, adaptive, phase 2/3, randomised, double-blind, multi-regimen trial conducted at 60 geographically diverse sites in the USA. In the current regimen, adults with clinically possible, probable, laboratory-supported probable, or definite ALS, defined by the revised El Escorial criteria, were randomly allocated (3:1), stratified by use of edaravone and riluzole, to receive trehalose 0\u00b775 g per kg intravenously weekly over 24 weeks, or matching placebo. The primary outcome was a composite of the relative rate of disease progression, as measured by the Revised ALS Functional Rating Scale (ALSFRS-R), and survival over 24 weeks, estimated", "source": "PubMed"}, {"chunk_id": "40409314_1", "pmid": "40409314", "title": "Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.", "authors": " ,  ", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "placebo. The primary outcome was a composite of the relative rate of disease progression, as measured by the Revised ALS Functional Rating Scale (ALSFRS-R), and survival over 24 weeks, estimated in a Bayesian shared-parameter model. The study included prespecified stopping rules for futility; interim analyses occurred every 12 weeks. The primary outcome was analysed according to the intention-to-treat principle in all participants in the trehalose group, the placebo group within the regimen, and placebo groups from other contributing regimens; the safety analysis population was comprised of all participants who initiated treatment. This study is registered with ClinicalTrials.gov, NCT05136885. Between Feb 21, 2022, and Feb 17, 2023, 1021 participants were screened for the platform trial and 171 were assigned to the trehalose regimen. Of these, 161 participants met eligibility criteria, with 120 randomly allocated to trehalose and 41 to regimen-specific placebo. 164 participants randomly allocated to placebo in other regimens were", "source": "PubMed"}, {"chunk_id": "40409314_2", "pmid": "40409314", "title": "Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.", "authors": " ,  ", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "trehalose regimen. Of these, 161 participants met eligibility criteria, with 120 randomly allocated to trehalose and 41 to regimen-specific placebo. 164 participants randomly allocated to placebo in other regimens were added for analysis (totalling 205 placebo recipients). The disease rate ratio for change in ALSFRS-R and survival was 0\u00b787 (95% credible interval 0\u00b7665-1\u00b7102, posterior probability of superiority 0\u00b7877). Serious adverse events occurred in 19 (16%) participants in the trehalose group and three (7%) participants in the regimen-only placebo group, leading to premature discontinuations in 14 (12%) versus one (2%), respectively. Fatal treatment-emergent adverse events occurred in seven participants in the trehalose group and none in the regimen-only placebo group. No death was considered related to the trial drug. The most common cause of death was respiratory failure, consistent with the natural history of ALS. Trehalose was well tolerated but there was no evidence to suggest a difference in ALS disease", "source": "PubMed"}, {"chunk_id": "40409314_3", "pmid": "40409314", "title": "Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.", "authors": " ,  ", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "common cause of death was respiratory failure, consistent with the natural history of ALS. Trehalose was well tolerated but there was no evidence to suggest a difference in ALS disease progression compared with placebo in this study. No statistical benefit was seen in secondary clinical or biomarker measures, suggesting that trehalose at this dosage is unlikely to be efficacious for treatment of ALS. AMG Charitable Foundation, Tackle ALS, the ALS Association, ALS Finding a Cure, the Muscular Dystrophy Association, ALS ONE, the Arthur M Blank Family Foundation, I AM ALS, Tambourine ALS Collaborative, and other community fundraising initiatives and donors. Study drug and partial regimen-related funding was provided by Seelos.", "source": "PubMed"}, {"chunk_id": "38922704_0", "pmid": "38922704", "title": "Glyceraldehyde metabolism in mouse brain and the entry of blood-borne glyceraldehyde into the brain.", "authors": "Hassel B, S\u00f8rnes K, Elsais A et al.", "year": "2024", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, advanced glycation end product, blood\u2013brain barrier, diabetes, diol dehydration, glyceraldehyde", "chunk": "D-Glyceraldehyde, a reactive aldehyde metabolite of fructose and glucose, is neurotoxic in vitro by forming advanced glycation end products (AGEs) with neuronal proteins. In Alzheimer's disease brains, glyceraldehyde-containing AGEs have been detected intracellularly and in extracellular plaques. However, little information exists on how the brain handles D-glyceraldehyde metabolically or if glyceraldehyde crosses the blood-brain barrier from the circulation into the brain. We injected [U-<sup>13</sup>C]-D-glyceraldehyde intravenously into awake mice and analyzed extracts of serum and brain by <sup>13</sup>C nuclear magnetic resonance spectroscopy. <sup>13</sup>C-Labeling of brain lactate and glutamate indicated passage of D-glyceraldehyde from blood to brain and glycolytic and oxidative D-glyceraldehyde metabolism in brain cells. <sup>13</sup>C-Labeling of serum glucose and lactate through hepatic metabolism of [U-<sup>13</sup>C]-D-glyceraldehyde could not explain the formation of <sup>13</sup>C-labeled lactate and glutamate in the brain. Cerebral glyceraldehyde dehydrogenase and reductase activities, leading to the formation of D-glycerate and glycerol, respectively, were 0.27-0.28 nmol/mg/min; triokinase, which phosphorylates D-glyceraldehyde", "source": "PubMed"}, {"chunk_id": "38922704_1", "pmid": "38922704", "title": "Glyceraldehyde metabolism in mouse brain and the entry of blood-borne glyceraldehyde into the brain.", "authors": "Hassel B, S\u00f8rnes K, Elsais A et al.", "year": "2024", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, advanced glycation end product, blood\u2013brain barrier, diabetes, diol dehydration, glyceraldehyde", "chunk": "of <sup>13</sup>C-labeled lactate and glutamate in the brain. Cerebral glyceraldehyde dehydrogenase and reductase activities, leading to the formation of D-glycerate and glycerol, respectively, were 0.27-0.28 nmol/mg/min; triokinase, which phosphorylates D-glyceraldehyde to D-glyceraldehyde-3-phosphate, has been demonstrated previously at low levels. Thus, D-glyceraldehyde metabolism toward glycolysis could proceed both through D-glycerate, glycerol, and D-glyceraldehyde-3-phosphate. The aldehyde group of D-glyceraldehyde was overwhelmingly hydrated into a diol in aqueous solution, but the diol dehydration rate greatly exceeded glyceraldehyde metabolism and did not restrict it. We conclude that (1) D-glyceraldehyde crosses the blood-brain barrier, and so blood-borne glyceraldehyde could contribute to AGE formation in the brain, (2) glyceraldehyde is taken up and metabolized by brain cells. Metabolism thus constitutes a detoxification mechanism for this reactive aldehyde, a mechanism that may be compromised in disease states.", "source": "PubMed"}, {"chunk_id": "38922704_2", "pmid": "38922704", "title": "Glyceraldehyde metabolism in mouse brain and the entry of blood-borne glyceraldehyde into the brain.", "authors": "Hassel B, S\u00f8rnes K, Elsais A et al.", "year": "2024", "journal": "Journal of neurochemistry", "keywords": "Alzheimer's disease, advanced glycation end product, blood\u2013brain barrier, diabetes, diol dehydration, glyceraldehyde", "chunk": "aldehyde, a mechanism that may be compromised in disease states.", "source": "PubMed"}, {"chunk_id": "41465589_0", "pmid": "41465589", "title": "The Role of miRNAs in Parkinson's Disease: A Systematic Review.", "authors": "Chrysanthou M, Christodoulou CC, Papanicolaou EZ", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s Disease, biomarker, miRNA, systematic review", "chunk": "Over the years, there has been extensive research conducted on Parkinson's Disease (PD), a neurodegenerative disorder known for causing motor impairment and behavioral changes. In more recent years, the roles of dysregulated microRNAs (miRNAs) in PD pathology have been studied in the hopes of developing new diagnostic methods or even treatments. This systematic review pinpoints and examines studies between 2010 and 2024 that have identified significant dysregulation of miRNAs in patients with PD. Upon filtering out the search results by a series of exclusion criteria, this review was conducted using 56 relevant studies. These studies revealed a vast array of significantly dysregulated miRNAs identified in the samples of patients with PD, when compared to healthy controls. A number of these miRNAs, such as miR-29c-3p, are likely biomarkers for more accurate PD diagnosis, and many, such as miR-485-3p, were found to be involved in PD pathogenesis. With further research, miRNAs could", "source": "PubMed"}, {"chunk_id": "41465589_1", "pmid": "41465589", "title": "The Role of miRNAs in Parkinson's Disease: A Systematic Review.", "authors": "Chrysanthou M, Christodoulou CC, Papanicolaou EZ", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s Disease, biomarker, miRNA, systematic review", "chunk": "miRNAs, such as miR-29c-3p, are likely biomarkers for more accurate PD diagnosis, and many, such as miR-485-3p, were found to be involved in PD pathogenesis. With further research, miRNAs could become a helpful diagnostic and prognostic tool for PD, with some of them even being candidate therapeutic targets for future treatments.", "source": "PubMed"}, {"chunk_id": "41235412_0", "pmid": "41235412", "title": "Bizarre astrocytes with cytoplasmic/intranuclear inclusions in an individual with alternating hemiplegia, migraine, and brain swelling associated with a GGC repeat expansion in <i>NOTCH2NLC</i>.", "authors": "Yagita K, Kanazawa K, Sano T et al.", "year": "2026", "journal": "Clinical neuropathology", "keywords": "None", "chunk": "The aberrant GGC repeat expansion in the 5'-untranslated region of the <i>NOTCH2NLC</i> gene causes neuronal intranuclear inclusion disease (NIID), a progressive neurodegenerative disorder. The clinical features of NIID are highly variable and include cognitive dysfunction, peripheral neuropathy, and episodic neurogenic symptoms. The pathogenesis of episodic symptoms in NIIDs remains unknown, and histopathological studies are limited. Here, we report an autopsy case of NIID in a 32-year-old Japanese female who developed severe episodic symptoms, including hemiplegic migraine, seizures, and impaired consciousness. Her major episodic symptoms appeared at the age of 16 years and were accompanied by alternating brain edema. She developed severe episodic symptoms with right brain edema at the age of 31. She became bedridden due to irreversible brain lesions and died 1 year later from a catheter-related bloodstream infection. Neuropathological analyses revealed numerous neuronal intranuclear inclusions and white matter lesions. In addition, bizarre astrocytes with eosinophilic cytoplasmic or intranuclear", "source": "PubMed"}, {"chunk_id": "41235412_1", "pmid": "41235412", "title": "Bizarre astrocytes with cytoplasmic/intranuclear inclusions in an individual with alternating hemiplegia, migraine, and brain swelling associated with a GGC repeat expansion in <i>NOTCH2NLC</i>.", "authors": "Yagita K, Kanazawa K, Sano T et al.", "year": "2026", "journal": "Clinical neuropathology", "keywords": "None", "chunk": "and died 1 year later from a catheter-related bloodstream infection. Neuropathological analyses revealed numerous neuronal intranuclear inclusions and white matter lesions. In addition, bizarre astrocytes with eosinophilic cytoplasmic or intranuclear inclusions were observed. GFAP immunoreactivity in the bizarre astrocytes was diminished, AQP4 showed a disorganized distribution. The histological changes observed in this case suggest an association between non-neuronal cellular disturbances and episodic neurogenic symptoms in NIIDs.", "source": "PubMed"}, {"chunk_id": "40163795_0", "pmid": "40163795", "title": "Grief and Economic Stressors by Sex, Gender, and Education: Associations With Alzheimer Disease-Related Outcomes.", "authors": "Palpatzis E, Akinci M, Garcia-Prat M et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "The prevalence and impact of stressful life events (SLEs) on age-related and Alzheimer disease (AD)-related pathways may depend on social determinants including gender and education. We investigated whether specific SLEs are associated with AD pathology and neurodegeneration and how these associations differ by gender and education. This cross-sectional study included cognitively unimpaired participants, most with a family history of sporadic AD, from the ALzheimer's and FAmilies (ALFA) cohort, based in Barcelona, Spain. Participants had available assessments on occurrence and type of lifetime SLEs and lumbar puncture and/or structural MRI. We performed multiple regression analyses to examine the associations of specific SLE type with (1) AD pathologies (CSF phosphorylated tau 181 [p-tau181] and \u03b2-amyloid [A\u03b2] 42/40) and (2) neurodegeneration markers (CSF neurogranin and GM volumes voxel-wise) including interaction and stratification analyses by gender (women/men) and education. In total, 1,290 cognitively unimpaired participants (mean age = 59.4 years, range: 48-77 years, 99%", "source": "PubMed"}, {"chunk_id": "40163795_1", "pmid": "40163795", "title": "Grief and Economic Stressors by Sex, Gender, and Education: Associations With Alzheimer Disease-Related Outcomes.", "authors": "Palpatzis E, Akinci M, Garcia-Prat M et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "neurogranin and GM volumes voxel-wise) including interaction and stratification analyses by gender (women/men) and education. In total, 1,290 cognitively unimpaired participants (mean age = 59.4 years, range: 48-77 years, 99% White participants, 61% women) were included (393 with lumbar puncture and 1,234 with spectroscopic MRI assessments). Less educated participants and women reported more grief-related and economic-related SLEs. Furthermore, women reported more abuse and reproductive SLEs. Grief-related SLEs were associated with AD and neurodegeneration CSF outcomes while economic SLEs were associated with MRI-based GM outcomes, both in an age-independent manner. Specifically, partner's death was associated with lower A\u03b242/40 (B = -5.19; 95% CI -9.61 to -0.76; <i>p</i> = 0.022) and higher p-tau181 (B = 0.18; 95% CI 0.05-0.32; <i>p</i> = 0.007) and neurogranin (B = 0.19; 95% CI 0.05-0.32; <i>p</i> = 0.007). The associations with A\u03b242/40 were driven by less educated participants and men and associations with p-tau181 and neurogranin driven", "source": "PubMed"}, {"chunk_id": "40163795_2", "pmid": "40163795", "title": "Grief and Economic Stressors by Sex, Gender, and Education: Associations With Alzheimer Disease-Related Outcomes.", "authors": "Palpatzis E, Akinci M, Garcia-Prat M et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "and neurogranin (B = 0.19; 95% CI 0.05-0.32; <i>p</i> = 0.007). The associations with A\u03b242/40 were driven by less educated participants and men and associations with p-tau181 and neurogranin driven by women. Unemployment and economic loss were associated with lower GM volumes in limbic and frontal areas, driven by more educated participants and men and by women, respectively. Older adults at risk of cognitive decline with less education and women may be more susceptible to experience more SLEs. Men who have experienced widowhood and unemployment and women who have experienced financial difficulties may benefit from interventions.", "source": "PubMed"}, {"chunk_id": "36472225_0", "pmid": "36472225", "title": "The Association of Glucose Variability and Dementia Incidence in Latinx Adults with Type 2 Diabetes: A Retrospective Study.", "authors": "Cuevas H, Mu\u00f1oz E, Nagireddy D et al.", "year": "2023", "journal": "Clinical nursing research", "keywords": "Latinx, cognitive function, glucose variability, type 2 diabetes", "chunk": "Latinx adults with both cognitive dysfunction and type 2 diabetes mellitus (T2DM) are significantly more likely than Latinx adults with diabetes alone to have complications such as cardiovascular disease. Glucose variability may be a risk for dementia, but the course of glucose variability in the time before a dementia diagnosis for Latinx adults with T2DM has not been examined. We used a 10-year retrospective cohort of medical records of Latinx patients with T2DM who had at least one use of a continuous glucose monitor. The objective was to examine how glucose variability was associated with future dementia diagnoses. A total of 116 charts were included. Mean of daily differences and mean amplitude of glycemic excursions were more strongly associated with dementia diagnoses than other variability indices (<i>p</i> < .01). Understanding the relationships between cognitive function, glucose variability, and barriers to health care can translate into improved interventions to enhance diabetes", "source": "PubMed"}, {"chunk_id": "36472225_1", "pmid": "36472225", "title": "The Association of Glucose Variability and Dementia Incidence in Latinx Adults with Type 2 Diabetes: A Retrospective Study.", "authors": "Cuevas H, Mu\u00f1oz E, Nagireddy D et al.", "year": "2023", "journal": "Clinical nursing research", "keywords": "Latinx, cognitive function, glucose variability, type 2 diabetes", "chunk": "dementia diagnoses than other variability indices (<i>p</i> < .01). Understanding the relationships between cognitive function, glucose variability, and barriers to health care can translate into improved interventions to enhance diabetes care.", "source": "PubMed"}, {"chunk_id": "35069588_0", "pmid": "35069588", "title": "Characteristics of Dysregulated Proinflammatory Cytokines and Cognitive Dysfunction in Late-Life Depression and Amnestic Mild Cognitive Impairment.", "authors": "Nie J, Fang Y, Chen Y et al.", "year": "2021", "journal": "Frontiers in immunology", "keywords": "amnestic mild cognitive impairment, chemokines, cytokines, late-life depression, neuroinflammation", "chunk": "Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are two different diseases associated with a high risk of developing Alzheimer's disease (AD). Both diseases are accompanied by dysregulation of inflammation. However, the differences and similarities of peripheral inflammatory parameters in these two diseases are not well understood. We used Luminex assays to measure 29 cytokines simultaneously in the plasma of two large cohorts of subjects at high risk for AD (23 LLD and 23 aMCI) and 23 normal controls (NCs) in the community. Demographics and lifestyle factors were also collected. Cognitive function was evaluated with the Chinese versions of the Montreal Cognitive Assessment (C-MoCA) and neuropsychological test battery (NTB). We observed a remarkably increased level of IL-6 in the plasma and reduced levels of chemokines (CXCL11 and CCL13) in the LLD group compared with the aMCI group. The LLD group also showed lower levels of CXCL16 than the NC", "source": "PubMed"}, {"chunk_id": "35069588_1", "pmid": "35069588", "title": "Characteristics of Dysregulated Proinflammatory Cytokines and Cognitive Dysfunction in Late-Life Depression and Amnestic Mild Cognitive Impairment.", "authors": "Nie J, Fang Y, Chen Y et al.", "year": "2021", "journal": "Frontiers in immunology", "keywords": "amnestic mild cognitive impairment, chemokines, cytokines, late-life depression, neuroinflammation", "chunk": "plasma and reduced levels of chemokines (CXCL11 and CCL13) in the LLD group compared with the aMCI group. The LLD group also showed lower levels of CXCL16 than the NC group. Furthermore, altered cytokine levels were associated with abnormal results in neuropsychological testing and Geriatric Depression Scale scores in both the LLD and aMCI groups. Notably, combinations of cytokines (IL-6 and CCL13) and two subitems of C-MoCA (orientation and short-term memory) generated the best area under the receiver operating characteristic curve (AUROC = 0.974). A novel model based on proinflammatory cytokines and brief screening tests performs with fair accuracy in the discrimination between LLD and aMCI. These findings will give clues to provide new therapeutic targets for interventions or markers for two diseases with similar predementia syndromes.", "source": "PubMed"}, {"chunk_id": "35069588_2", "pmid": "35069588", "title": "Characteristics of Dysregulated Proinflammatory Cytokines and Cognitive Dysfunction in Late-Life Depression and Amnestic Mild Cognitive Impairment.", "authors": "Nie J, Fang Y, Chen Y et al.", "year": "2021", "journal": "Frontiers in immunology", "keywords": "amnestic mild cognitive impairment, chemokines, cytokines, late-life depression, neuroinflammation", "chunk": "for two diseases with similar predementia syndromes.", "source": "PubMed"}, {"chunk_id": "38063257_0", "pmid": "38063257", "title": "Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer's disease.", "authors": "Salcedo C, Pozo Garcia V, Garc\u00eda-Ad\u00e1n B et al.", "year": "2024", "journal": "Journal of neurochemistry", "keywords": "APP, PSEN\u20101, energy metabolism, excitotoxicity, hiPSC astrocytes, hiPSC neurons", "chunk": "Glutamate recycling between neurons and astrocytes is essential to maintain neurotransmitter homeostasis. Disturbances in glutamate homeostasis, resulting in excitotoxicity and neuronal death, have been described as a potential mechanism in Alzheimer's disease (AD) pathophysiology. However, glutamate neurotransmitter metabolism in different human brain cells, particularly astrocytes, has been poorly investigated at the early stages of AD. We sought to investigate glucose and glutamate metabolism in AD by employing human induced pluripotent stem cell (hiPSC)-derived astrocytes and neurons carrying mutations in the amyloid precursor protein (APP) or presenilin-1 (PSEN-1) gene as found in familial types of AD (fAD). Methods such as live-cell bioenergetics and metabolic mapping using [<sup>13</sup>C]-enriched substrates were used to examine metabolism in the early stages of AD. Our results revealed greater glycolysis and glucose oxidative metabolism in astrocytes and neurons with APP or PSEN-1 mutations, accompanied by an elevated glutamate synthesis compared to control WT cells. Astrocytes with APP", "source": "PubMed"}, {"chunk_id": "38063257_1", "pmid": "38063257", "title": "Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer's disease.", "authors": "Salcedo C, Pozo Garcia V, Garc\u00eda-Ad\u00e1n B et al.", "year": "2024", "journal": "Journal of neurochemistry", "keywords": "APP, PSEN\u20101, energy metabolism, excitotoxicity, hiPSC astrocytes, hiPSC neurons", "chunk": "revealed greater glycolysis and glucose oxidative metabolism in astrocytes and neurons with APP or PSEN-1 mutations, accompanied by an elevated glutamate synthesis compared to control WT cells. Astrocytes with APP or PSEN-1 mutations exhibited reduced expression of the excitatory amino acid transporter 2 (EAAT2), and glutamine uptake increased in mutated neurons, with enhanced glutamate release specifically in neurons with a PSEN-1 mutation. These results demonstrate a hypermetabolic phenotype in astrocytes with fAD mutations possibly linked to toxic glutamate accumulation. Our findings further identify metabolic imbalances that may occur in the early phases of AD pathophysiology.", "source": "PubMed"}, {"chunk_id": "37257406_0", "pmid": "37257406", "title": "Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.", "authors": "Beydoun MA, Noren Hooten N, Beydoun HA et al.", "year": "2023", "journal": "Neurobiology of aging", "keywords": "Aging, Brain volumes, Hippocampus, Neurofilament light chain, White matter lesion", "chunk": "Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v<sub>1</sub> (2004-2009) and v<sub>2</sub> (2009-2013) plasma NfL exposure and ancillary sMRI data at v<sub>scan</sub> (2011-2015, n = 179, mean v<sub>1</sub> to v<sub>scan</sub> time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL<sub>(v1)</sub> was associated with larger WMLV (both Log<sub>e</sub> transformed), after 5-6 years' follow-up, overall (\u03b2 = +2.131 \u00b1 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv<sub>2</sub> was linked to a 125 mm<sup>3</sup> lower left hippocampal volume (p = 0.004 and q = 0.015) in", "source": "PubMed"}, {"chunk_id": "37257406_1", "pmid": "37257406", "title": "Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults.", "authors": "Beydoun MA, Noren Hooten N, Beydoun HA et al.", "year": "2023", "journal": "Neurobiology of aging", "keywords": "Aging, Brain volumes, Hippocampus, Neurofilament light chain, White matter lesion", "chunk": "+0.29, p = 0.001, and q = 0.0029) and among females. NfLv<sub>2</sub> was linked to a 125 mm<sup>3</sup> lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (\u03b4NfL<sub>bayes</sub>). Among African American adults, NfL<sub>v1</sub> was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.", "source": "PubMed"}, {"chunk_id": "41688680_0", "pmid": "41688680", "title": "Towards biomarker-based diagnosis of Parkinson disease.", "authors": "Tolosa E, Poewe W, Noyce AJ et al.", "year": "2026", "journal": "Nature reviews. Neurology", "keywords": "None", "chunk": "The current clinical diagnostic criteria for Parkinson disease (PD) have limitations and are inherently insensitive to the earliest stages of disease, when classical motor signs can be absent. Imaging and genetic tests are currently used to support or establish a diagnosis of PD, but no validated biomarker-based diagnostic framework currently exists. Substantial progress has been made in the field of molecular disease markers, most notably with the development and validation of seed amplification assays (SAAs), which enable detection of very low levels of pathological \u03b1-synuclein in the cerebrospinal fluid and other biofluids and tissue. In this Review, we discuss the potential of \u03b1-synuclein SAAs and other biomarkers to improve diagnostic accuracy and enable earlier diagnosis of PD. We consider biological disease definitions that have been proposed on the basis of these biomarkers, highlighting their merits, limitations and implications for PD research and clinical management. Research is ongoing to determine the", "source": "PubMed"}, {"chunk_id": "41688680_1", "pmid": "41688680", "title": "Towards biomarker-based diagnosis of Parkinson disease.", "authors": "Tolosa E, Poewe W, Noyce AJ et al.", "year": "2026", "journal": "Nature reviews. Neurology", "keywords": "None", "chunk": "disease definitions that have been proposed on the basis of these biomarkers, highlighting their merits, limitations and implications for PD research and clinical management. Research is ongoing to determine the predictive value of PD biomarkers in healthy people and people with prodromal PD and to develop markers that are sensitive to disease progression, both of which are key for implementation of trials involving drugs designed to modify or prevent disease. Integrating clinical, genetic, molecular and imaging biomarkers should enable earlier, more accurate diagnosis of PD and characterization of PD subtypes, thereby enabling personalized treatment to slow or even prevent PD.", "source": "PubMed"}, {"chunk_id": "38260156_0", "pmid": "38260156", "title": "Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.", "authors": "Li R, Zheng F, Xu P et al.", "year": "2023", "journal": "Frontiers in endocrinology", "keywords": "carboxymethyl lysine, interleukin-18, irisin, mild cognitive impairment, receptors for AGEs, the thickness of retinal nerve fiber layer, type 2 diabetes mellitus", "chunk": "Cognitive Impairment arising from type 2 diabetes mellitus (T2DM) has garnered significant attention in recent times. However, there are few studies on the identification and diagnosis of markers of cognitive impairment. Notably, alterations in the Retinal Nerve Fiber Layer's (RNFL) thickness can potentially serve as an indicative measure of central nervous system changes. Further investigations have indicated that the decline in cognitive function within T2DM patients is intricately linked to persistent systemic inflammation and the accumulation of advanced glycosylation end products. Comprehensive studies are warranted to unveil these complex associations. This study aims to explore the potential of utilizing the RNFL thickness and serological concentrations of IL-18, irisin, CML, and RAGE as diagnostic indicators for Mild Cognitive Impairment (MCI) among individuals with T2DM. The thickness of RNFL were determined in all patients and controls using optical coherence tomography (OCT). The serum levels of IL-18, irisin, CML and RAGE were detected", "source": "PubMed"}, {"chunk_id": "38260156_1", "pmid": "38260156", "title": "Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.", "authors": "Li R, Zheng F, Xu P et al.", "year": "2023", "journal": "Frontiers in endocrinology", "keywords": "carboxymethyl lysine, interleukin-18, irisin, mild cognitive impairment, receptors for AGEs, the thickness of retinal nerve fiber layer, type 2 diabetes mellitus", "chunk": "individuals with T2DM. The thickness of RNFL were determined in all patients and controls using optical coherence tomography (OCT). The serum levels of IL-18, irisin, CML and RAGE were detected by ELISA kit. In addition, Cognitive assessment was performed by the Mini-Mental State Examination (MMSE) and the Montreal Cognitive assessment (MoCA). The average RNFL thickness in the right eye were decreased in T2DM and T2DM combined with MCI (T2DM-MCI) patients and were positively correlated with MoCA and MMSE scores. The serum levels of IL-18, CML and RAGE in T2DM and T2DM-MCI increased significantly (p<0.05) and were negative correlated with MoCA and MMSE scores. The level of irisin in T2DM and T2DM-MCI decreased significantly (p<0.05) and were positively correlated with MoCA and MMSE scores. The area under the ROC curve of T2DM-MCI predicted by the average RNFL thickness in the right eye, CML and RAGE were 0.853, 0.874 and 0.815. The", "source": "PubMed"}, {"chunk_id": "38260156_2", "pmid": "38260156", "title": "Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.", "authors": "Li R, Zheng F, Xu P et al.", "year": "2023", "journal": "Frontiers in endocrinology", "keywords": "carboxymethyl lysine, interleukin-18, irisin, mild cognitive impairment, receptors for AGEs, the thickness of retinal nerve fiber layer, type 2 diabetes mellitus", "chunk": "and MMSE scores. The area under the ROC curve of T2DM-MCI predicted by the average RNFL thickness in the right eye, CML and RAGE were 0.853, 0.874 and 0.815. The diagnostic efficacy of the combination of average RNFL thickness in the right eye, CML, and RAGE for the diagnosis of T2DM-MCI was 0.969. The average RNFL thickness in the right eye, CML and RAGE have possible diagnostic value in T2DM-MCI patients.", "source": "PubMed"}, {"chunk_id": "41250235_0", "pmid": "41250235", "title": "Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation.", "authors": "Corbett A, Sultana J, Stych K et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s, Consensus, Delphi, Repurposing, Treatment", "chunk": "Alzheimer's disease (AD) is an escalating global challenge, with more than 40 million people affected, and this number is projected to increase to more than 100 million by 2050. While amyloid-targeting antibody treatments (lecanemab and donanemab) are a significant step forward, the benefits of these therapies remain limited. This highlights the necessity for safe and effective compounds that offer greater therapeutic benefits to the majority of individuals with or at risk of AD. Drug repurposing allows for a cost-effective, time-efficient strategy to accelerate the availability of treatments, owing to the availability of safety information. This study focuses on the third iteration of the Delphi consensus programme aimed at identifying new high-priority drug candidates for repurposing in AD. An international expert panel comprising academics, clinicians and industry representatives was convened. Through a combination of anonymized drug nominations, systemic evidence reviews, iterative consensus rankings, and lay advisory inputs, drug candidates were evaluated", "source": "PubMed"}, {"chunk_id": "41250235_1", "pmid": "41250235", "title": "Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation.", "authors": "Corbett A, Sultana J, Stych K et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s, Consensus, Delphi, Repurposing, Treatment", "chunk": "panel comprising academics, clinicians and industry representatives was convened. Through a combination of anonymized drug nominations, systemic evidence reviews, iterative consensus rankings, and lay advisory inputs, drug candidates were evaluated and ranked based on rational, non-clinical, and clinical evidence and overall safety profiles. Among the 80 candidates that were nominated by the expert panel, seven underwent review, with only three candidates meeting the following consensus criteria of relevant mechanisms for targeting neurodegenerative pathways, non-clinical efficacy, and tolerability in older individuals. The three agents were: [1] the live attenuated herpes zoster (HZ) vaccine (Zostavax) [2], sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, and [3] riluzole, a glutamate antagonist. The HZ vaccine additionally offers potential for population-level dementia risk reduction. This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform,", "source": "PubMed"}, {"chunk_id": "41250235_2", "pmid": "41250235", "title": "Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation.", "authors": "Corbett A, Sultana J, Stych K et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s, Consensus, Delphi, Repurposing, Treatment", "chunk": "three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD.", "source": "PubMed"}, {"chunk_id": "41692982_0", "pmid": "41692982", "title": "Moving Geroscience Forward in China: Proceedings of the First International Exchange Forum of the Chinese Geriatrics Society.", "authors": "Zhang L, Ji T, Bi J et al.", "year": "2026", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "Age-Related Pathology, Biology of Aging, global academic dialogue and collaboration, interventions", "chunk": "Held on 17 August 2025 in Guangzhou, the inaugural International Exchange Forum of the Chinese Geriatrics Society marked a significant milestone in advancing geroscience and fostering global collaboration in China. The forum brought together leading international experts and emerging Chinese researchers to present the latest advances in aging research. Presentations covered various topics, such as musculoskeletal aging (mitochondrial dysfunction, muscle-bone communication, and exosome-mediated mechanisms in sarcopenia and osteoporosis), cardiovascular aging (TKI- and anthracycline-induced cardiotoxicity), metabolic regulation (sarcopenic obesity and the gut-muscle axis), neurodegenerative interfaces (androgen-mediated monocyte-microglia interactions in Alzheimer's disease), and geriatric assessment (muscle-specific strength, intrinsic capacity, and gait biomarkers). There was a particular focus on novel mechanistic insights, such as RNA epitranscriptomics, mitochondrial homeostasis, and inter-organ communication, as well as on strategies for early risk prediction, intervention, and personalized management. The forum also emphasized the importance of addressing sex-specific differences and translating basic discoveries into clinical applications. As a", "source": "PubMed"}, {"chunk_id": "41692982_1", "pmid": "41692982", "title": "Moving Geroscience Forward in China: Proceedings of the First International Exchange Forum of the Chinese Geriatrics Society.", "authors": "Zhang L, Ji T, Bi J et al.", "year": "2026", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "Age-Related Pathology, Biology of Aging, global academic dialogue and collaboration, interventions", "chunk": "as on strategies for early risk prediction, intervention, and personalized management. The forum also emphasized the importance of addressing sex-specific differences and translating basic discoveries into clinical applications. As a platform designed to promote academic dialogue and collaboration, the forum successfully brought together the Chinese and global geroscience communities. It emphasized the necessity of multidisciplinary and international efforts to address the challenges posed by population aging. Moving forward, sustained partnerships, data sharing and capacity-building initiatives will be essential to accelerating the development of evidence-based, scalable solutions for healthy aging in China and beyond. This event sets a precedent for future exchanges that integrate scientific innovation with clinical practice to improve the health and quality of life of aging populations worldwide.", "source": "PubMed"}, {"chunk_id": "36325883_0", "pmid": "36325883", "title": "Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease.", "authors": "Meng X, Zhang Y, Li Z et al.", "year": "2023", "journal": "Phytotherapy research : PTR", "keywords": "Alzheimer's disease, diabetes, glucose transporter 4, peroxisome proliferator-activated receptor gamma", "chunk": "We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPAR\u03b3 agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP-75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP-75 treatment decreased the \u03b2-amyloid (A\u03b2) burden, as measured by <sup>11</sup> C-PIB PET imaging. Importantly, GP-75 treatment increased brain glucose uptake as measured by <sup>18</sup> F-FDG PET imaging. Moreover, GP-75 treatment upregulated PPAR\u03b3 and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS-1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP-75-induced", "source": "PubMed"}, {"chunk_id": "36325883_1", "pmid": "36325883", "title": "Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease.", "authors": "Meng X, Zhang Y, Li Z et al.", "year": "2023", "journal": "Phytotherapy research : PTR", "keywords": "Alzheimer's disease, diabetes, glucose transporter 4, peroxisome proliferator-activated receptor gamma", "chunk": "treatment upregulated PPAR\u03b3 and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS-1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP-75-induced increases in GLUT4 membrane translocation in primary hippocampal neurons from APP/PS1xdb/db mice was abolished by cotreatment with the selective PPAR\u03b3 antagonist GW9662 or the PI3K inhibitor LY294002. In summary, GP-75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPAR\u03b3/Akt/GLUT4 signaling pathways.", "source": "PubMed"}, {"chunk_id": "41368997_0", "pmid": "41368997", "title": "Validation status of cognitive digital assessments by the FDA BEST framework and context of use in preclinical AD studies: A systematic review.", "authors": "Porta-Mas C, Grau-Rivera O, Gispert JD et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta, biomarkers, digital biomarkers, digital cognitive assessments, preclinical Alzheimer's disease", "chunk": "Digital cognitive assessments have rapidly expanded in Alzheimer's disease (AD) research, offering a sensitive, scalable, and cost-effective alternative to traditional neuropsychological tests. This systematic review examines the validation and utility of digital cognitive assessments in cognitively normal (CN) individuals and explores their potential classification within the US Food and Drug Administration's Biomarkers, Endpoints, and other Tools (FDA BEST) framework. Additionally, we provide recommendations to consider for their implementation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed for studies validating digital cognitive tools against paper-based tests and standard AD biomarkers, including measures of amyloid beta and tau in fluid and neuroimaging biomarkers. Our findings suggest potential use as risk or monitoring biomarkers, though further longitudinal validation is needed. This review highlights the latest advancements in digital cognitive assessments, their role as novel AD biomarkers, and essential considerations for their effective use in AD. HIGHLIGHTS:", "source": "PubMed"}, {"chunk_id": "41368997_1", "pmid": "41368997", "title": "Validation status of cognitive digital assessments by the FDA BEST framework and context of use in preclinical AD studies: A systematic review.", "authors": "Porta-Mas C, Grau-Rivera O, Gispert JD et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta, biomarkers, digital biomarkers, digital cognitive assessments, preclinical Alzheimer's disease", "chunk": "longitudinal validation is needed. This review highlights the latest advancements in digital cognitive assessments, their role as novel AD biomarkers, and essential considerations for their effective use in AD. HIGHLIGHTS: Digital cognitive assessments for preclinical Alzheimer's disease (AD) are associated with established biomarkers, including paper-based neuropsychological tests and amyloid beta and tau measures in both fluid and neuroimaging techniques. These assessments have the potential to serve as novel AD biomarkers classified within the US Food and Drug Administration's Biomarkers, Endpoints, and other Tools framework and context of use, but long-term studies spanning different disease stages are needed to fully establish their validity for some of the biomarker categories. Several biases may be present when conducting digital cognitive assessments; their optimal use should follow specific recommendations to minimize them.", "source": "PubMed"}, {"chunk_id": "41368997_2", "pmid": "41368997", "title": "Validation status of cognitive digital assessments by the FDA BEST framework and context of use in preclinical AD studies: A systematic review.", "authors": "Porta-Mas C, Grau-Rivera O, Gispert JD et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta, biomarkers, digital biomarkers, digital cognitive assessments, preclinical Alzheimer's disease", "chunk": "use should follow specific recommendations to minimize them.", "source": "PubMed"}, {"chunk_id": "41225966_0", "pmid": "41225966", "title": "A Hybrid Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM)-Attention Model Architecture for Precise Medical Image Analysis and Disease Diagnosis.", "authors": "Hayat MT, Allawi YM, Alamro W et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "attention mechanism, convolutional neural networks, long short-term memory, medical image analysis, sequential features", "chunk": "<b>Background:</b> Deep learning (DL)-based medical image classification is becoming increasingly reliable, enabling physicians to make faster and more accurate decisions in diagnosis and treatment. A plethora of algorithms have been developed to classify and analyze various types of medical images. Among them, Convolutional Neural Networks (CNNs) have proven highly effective, particularly in medical image analysis and disease detection. <b>Methods:</b> To further enhance these capabilities, this research introduces MediVision, a hybrid DL-based model that integrates a vision backbone based on CNNs for feature extraction, capturing detailed patterns and structures essential for precise classification. These features are then processed through Long Short-Term Memory (LSTM), which identifies sequential dependencies to better recognize disease progression. An attention mechanism is then incorporated that selectively focuses on salient features detected by the LSTM, improving the model's ability to highlight critical abnormalities. Additionally, MediVision utilizes a skip connection, merging attention outputs with LSTM outputs along with Grad-CAM", "source": "PubMed"}, {"chunk_id": "41225966_1", "pmid": "41225966", "title": "A Hybrid Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM)-Attention Model Architecture for Precise Medical Image Analysis and Disease Diagnosis.", "authors": "Hayat MT, Allawi YM, Alamro W et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "attention mechanism, convolutional neural networks, long short-term memory, medical image analysis, sequential features", "chunk": "on salient features detected by the LSTM, improving the model's ability to highlight critical abnormalities. Additionally, MediVision utilizes a skip connection, merging attention outputs with LSTM outputs along with Grad-CAM heatmap to visualize the most important regions of the analyzed medical image and further enhance feature representation and classification accuracy. <b>Results:</b> Tested on ten diverse medical image datasets (including, Alzheimer's disease, breast ultrasound, blood cell, chest X-ray, chest CT scans, diabetic retinopathy, kidney diseases, bone fracture multi-region, retinal OCT, and brain tumor), MediVision consistently achieved classification accuracies above 95%, with a peak of 98%. <b>Conclusions:</b> The proposed MediVision model offers a robust and effective framework for medical image classification, improving interpretability, reliability, and automated disease diagnosis. To support research reproducibility, the codes and datasets used in this study have been publicly made available through an open-access repository.", "source": "PubMed"}, {"chunk_id": "41225966_2", "pmid": "41225966", "title": "A Hybrid Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM)-Attention Model Architecture for Precise Medical Image Analysis and Disease Diagnosis.", "authors": "Hayat MT, Allawi YM, Alamro W et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "attention mechanism, convolutional neural networks, long short-term memory, medical image analysis, sequential features", "chunk": "the codes and datasets used in this study have been publicly made available through an open-access repository.", "source": "PubMed"}, {"chunk_id": "40857855_0", "pmid": "40857855", "title": "Aligning personalized biomarker trajectories onto a common time axis: a connectome-based ODE model for Tau-Amyloid beta dynamics.", "authors": "Wen Z, Biros G,  ", "year": "2025", "journal": "Medical image analysis", "keywords": "Atrophy model, Computational model, PET imaging, Tau-A\u03b2 interaction", "chunk": "Abnormal tau and amyloid beta are two primary imaging biomarkers used to assist in the diagnosis of Alzheimer's disease (AD). Recent efforts have focused on developing mechanism-based biophysical models to explain the spatiotemporal dynamics of these biomarkers. In this study, we adopt a connectome-based ODE model to capture the dynamics of tau and amyloid beta (A\u03b2), aiming to predict personalized future values of these biomarkers. The ODE model includes diffusion, reaction, and clearance terms, and accounts for tau-A\u03b2 interactions. Additionally, it assumes a sparse initial condition (IC) of abnormalities, based on the assumption of localized initiation. Besides tau and A\u03b2, brain atrophy is used as a marker of neurodegeneration. We discuss the mathematical model of atrophy integrated into the tau-A\u03b2 model. A common limitation in popular models is the use of chronological age as the time axis, which prevents the unification of subject trajectories onto a common time scale and", "source": "PubMed"}, {"chunk_id": "40857855_1", "pmid": "40857855", "title": "Aligning personalized biomarker trajectories onto a common time axis: a connectome-based ODE model for Tau-Amyloid beta dynamics.", "authors": "Wen Z, Biros G,  ", "year": "2025", "journal": "Medical image analysis", "keywords": "Atrophy model, Computational model, PET imaging, Tau-A\u03b2 interaction", "chunk": "model. A common limitation in popular models is the use of chronological age as the time axis, which prevents the unification of subject trajectories onto a common time scale and hinders comprehensive cohort analysis. To address this issue, we use a normalized disease age that relates chronological age to biomarker values. In the ODE model, we use the disease age to track time and the biomarker dynamics. Furthermore, our analysis of region-of-interest-wise tau-A\u03b2 temporal correlation reveals that different regions of interest (ROIs) play distinct roles across various disease stages.", "source": "PubMed"}, {"chunk_id": "32671408_0", "pmid": "32671408", "title": "18F-MK-6240 PET for early and late detection of neurofibrillary tangles.", "authors": "Pascoal TA, Therriault J, Benedet AL et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Braak stages, neurofibrillary tangles, positron emission tomography", "chunk": "Braak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for the neuropathological diagnosis of Alzheimer's disease. It is expected that Braak staging using brain imaging can stratify living individuals according to their individual patterns of tau deposition, which may prove crucial for clinical trials and practice. However, previous studies using the first-generation tau PET agents have shown a low sensitivity to detect tau pathology in areas corresponding to early Braak histopathological stages (\u223c20% of cognitively unimpaired elderly with tau deposition in regions corresponding to Braak I-II), in contrast to \u223c80-90% reported in post-mortem cohorts. Here, we tested whether the novel high affinity tau tangles tracer 18F-MK-6240 can better identify individuals in the early stages of tau accumulation. To this end, we studied 301 individuals (30 cognitively unimpaired young, 138 cognitively unimpaired elderly, 67 with mild cognitive impairment, 54 with Alzheimer's disease dementia, and 12 with frontotemporal", "source": "PubMed"}, {"chunk_id": "32671408_1", "pmid": "32671408", "title": "18F-MK-6240 PET for early and late detection of neurofibrillary tangles.", "authors": "Pascoal TA, Therriault J, Benedet AL et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Braak stages, neurofibrillary tangles, positron emission tomography", "chunk": "accumulation. To this end, we studied 301 individuals (30 cognitively unimpaired young, 138 cognitively unimpaired elderly, 67 with mild cognitive impairment, 54 with Alzheimer's disease dementia, and 12 with frontotemporal dementia) with amyloid-\u03b2 18F-NAV4694, tau 18F-MK-6240, MRI, and clinical assessments. 18F-MK-6240 standardized uptake value ratio images were acquired at 90-110 min after the tracer injection. 18F-MK-6240 discriminated Alzheimer's disease dementia from mild cognitive impairment and frontotemporal dementia with high accuracy (\u223c85-100%). 18F-MK-6240 recapitulated topographical patterns consistent with the six hierarchical stages proposed by Braak in 98% of our population. Cognition and amyloid-\u03b2 status explained most of the Braak stages variance (P < 0.0001, R2 = 0.75). No single region of interest standardized uptake value ratio accurately segregated individuals into the six topographic Braak stages. Sixty-eight per cent of the cognitively unimpaired elderly amyloid-\u03b2-positive and 37% of the cognitively unimpaired elderly amyloid-\u03b2-negative subjects displayed tau deposition, at least in the transentorhinal", "source": "PubMed"}, {"chunk_id": "32671408_2", "pmid": "32671408", "title": "18F-MK-6240 PET for early and late detection of neurofibrillary tangles.", "authors": "Pascoal TA, Therriault J, Benedet AL et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Braak stages, neurofibrillary tangles, positron emission tomography", "chunk": "six topographic Braak stages. Sixty-eight per cent of the cognitively unimpaired elderly amyloid-\u03b2-positive and 37% of the cognitively unimpaired elderly amyloid-\u03b2-negative subjects displayed tau deposition, at least in the transentorhinal cortex (Braak I). Tau deposition solely in the transentorhinal cortex was associated with an elevated prevalence of amyloid-\u03b2, neurodegeneration, and cognitive impairment (P < 0.0001). 18F-MK-6240 deposition in regions corresponding to Braak IV-VI was associated with the highest prevalence of neurodegeneration, whereas in Braak V-VI regions with the highest prevalence of cognitive impairment. Our results suggest that the hierarchical six-stage Braak model using 18F-MK-6240 imaging provides an index of early and late tau accumulation as well as disease stage in preclinical and symptomatic individuals. Tau PET Braak staging using high affinity tracers has the potential to be incorporated in the diagnosis of living patients with Alzheimer's disease in the near future.", "source": "PubMed"}, {"chunk_id": "32671408_3", "pmid": "32671408", "title": "18F-MK-6240 PET for early and late detection of neurofibrillary tangles.", "authors": "Pascoal TA, Therriault J, Benedet AL et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Braak stages, neurofibrillary tangles, positron emission tomography", "chunk": "affinity tracers has the potential to be incorporated in the diagnosis of living patients with Alzheimer's disease in the near future.", "source": "PubMed"}, {"chunk_id": "37166562_0", "pmid": "37166562", "title": "Association of insulin resistance with delirium and CSF biomarkers of Alzheimer's disease in elderly patients with hip fracture.", "authors": "Wang J, Shuang P, Li Z et al.", "year": "2023", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s disease, CSF biomarkers, Delirium, Dementia, Hip fracture, Insulin resistance", "chunk": "Delirium is associated with dementia, which shares symptoms of cognitive dysfunctions. Notably, pathological mechanisms of Alzheimer's disease (AD) appear involved in both conditions. Insulin resistance has been reported to be a risk factor for AD, leading to neurodegeneration and cognitive impairment by affecting amyloid-beta (A\u03b2) metabolism, tau phosphorylation, and neuro-inflammation. Thus, insulin resistance may provide pathophysiological clues to the occurrence of delirium. To investigate the relationship between preoperative insulin resistance, insulin concentrations in the cerebrospinal fluid (CSF), and delirium in elderly patients with hip fracture. The study included 138 elderly patients with or without pre-existing dementia who underwent hip fracture surgery. Delirium was diagnosed with the confusion assessment method performed daily from pre-operation to 5 days post-operation. CSF and blood samples were collected at the beginning of spinal anesthesia. The concentrations of insulin, amyloid-beta1-42 (A\u03b242), total tau (t-tau), and phosphorylated tau (p-tau)<sub>181</sub> were determined by ELISA. Homeostasis model assessment (HOMA-IR)", "source": "PubMed"}, {"chunk_id": "37166562_1", "pmid": "37166562", "title": "Association of insulin resistance with delirium and CSF biomarkers of Alzheimer's disease in elderly patients with hip fracture.", "authors": "Wang J, Shuang P, Li Z et al.", "year": "2023", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s disease, CSF biomarkers, Delirium, Dementia, Hip fracture, Insulin resistance", "chunk": "samples were collected at the beginning of spinal anesthesia. The concentrations of insulin, amyloid-beta1-42 (A\u03b242), total tau (t-tau), and phosphorylated tau (p-tau)<sub>181</sub> were determined by ELISA. Homeostasis model assessment (HOMA-IR) was used to assess insulin resistance. Sixty-one (44%) of 138 hip fracture patients developed delirium peri-operatively. Compared to non-delirium group, the preoperative HOMA-IR index in delirium was much higher (median 3.3 vs 2.8, p = 0.001), but the CSF insulin concentration was significantly decreased (median 1.5 vs 2.2 mU/L, p < 0.001). Binary logistic regression analysis showed that HOMA-IR index and CSF insulin concentration were independent risk factors for delirium (p < 0.05). HOMA-IR index was negatively correlated with CSF insulin concentrations (rho = - 0.55, p < 0.001). Multiple linear regression analysis showed that AD core biomarkers were significantly correlated with HOMA-IR index and CSF insulin level (p < 0.05). This study innovatively examined insulin concentrations in serum and", "source": "PubMed"}, {"chunk_id": "37166562_2", "pmid": "37166562", "title": "Association of insulin resistance with delirium and CSF biomarkers of Alzheimer's disease in elderly patients with hip fracture.", "authors": "Wang J, Shuang P, Li Z et al.", "year": "2023", "journal": "Aging clinical and experimental research", "keywords": "Alzheimer\u2019s disease, CSF biomarkers, Delirium, Dementia, Hip fracture, Insulin resistance", "chunk": "linear regression analysis showed that AD core biomarkers were significantly correlated with HOMA-IR index and CSF insulin level (p < 0.05). This study innovatively examined insulin concentrations in serum and cerebrospinal fluid in patients with delirium. Our findings suggest that preoperative insulin resistance may affect the occurrence of delirium. The potential association between insulin resistance and delirium may be related to insulin resistance affecting the metabolism of AD biomarkers.", "source": "PubMed"}, {"chunk_id": "36203054_0", "pmid": "36203054", "title": "Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to \u03b2-amyloid clearance.", "authors": "Leng L, Yuan Z, Pan R et al.", "year": "2022", "journal": "Nature metabolism", "keywords": "None", "chunk": "Microglial cells consume adenosine triphosphate (ATP) during phagocytosis to clear neurotoxic \u03b2-amyloid in Alzheimer's disease (AD). However, the contribution of energy metabolism to microglial function in AD remains unclear. Here, we demonstrate that hexokinase 2 (HK2) is elevated in microglia from an AD mouse model (5xFAD) and AD patients. Genetic deletion or pharmacological inhibition of HK2 significantly promotes microglial phagocytosis, lowers the amyloid plaque burden and attenuates cognitive impairment in male AD mice. Notably, the ATP level is dramatically increased in HK2-deficient or inactive microglia, which can be attributed to a marked upregulation in lipoprotein lipase (LPL) expression and subsequent increase in lipid metabolism. We further show that two downstream metabolites of HK2, glucose-6-phosphate and fructose-6-phosphate, can reverse HK2-deficiency-induced upregulation of LPL, thus supporting ATP production and microglial phagocytosis. Our findings uncover a crucial role for HK2 in phagocytosis through regulation of microglial energy metabolism, suggesting a potential therapeutic strategy", "source": "PubMed"}, {"chunk_id": "36203054_1", "pmid": "36203054", "title": "Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to \u03b2-amyloid clearance.", "authors": "Leng L, Yuan Z, Pan R et al.", "year": "2022", "journal": "Nature metabolism", "keywords": "None", "chunk": "of LPL, thus supporting ATP production and microglial phagocytosis. Our findings uncover a crucial role for HK2 in phagocytosis through regulation of microglial energy metabolism, suggesting a potential therapeutic strategy for AD by targeting HK2.", "source": "PubMed"}, {"chunk_id": "41706165_0", "pmid": "41706165", "title": "Salivary total tau: a clinically practical measure of tau neuropathology in Alzheimer's disease.", "authors": "Bamford AR, Logan C, Do QT et al.", "year": "2026", "journal": "Journal of neurology", "keywords": "Biomarker, Dementia, Neurodegenerative, Saliva, Tau", "chunk": "Neurofibrillary tangles, consisting of intracellular accumulations of the protein tau, are a hallmark feature of Alzheimer's disease (AD), and are thought to contribute to neuronal dysfunction and death during the disease process. The quantification of tau proteins in cerebrospinal fluid (CSF) or plasma has enormous utility for AD diagnosis; however, validated non-invasive measures of tau protein are lacking and would have added value for widespread screening. In this study, we quantified the levels of total tau (t-tau), along with neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), in saliva samples from 111 participants, including those with CSF biomarker-confirmed AD, mild AD, non-AD cognitively impaired (CI) and cognitively unimpaired (CU) older adults, using immunoassays on the Meso Scale Discovery platform. We find that salivary levels of t-tau were significantly elevated in AD and mild AD, but not other CI patients, compared to CU adults, while salivary levels of NfL and", "source": "PubMed"}, {"chunk_id": "41706165_1", "pmid": "41706165", "title": "Salivary total tau: a clinically practical measure of tau neuropathology in Alzheimer's disease.", "authors": "Bamford AR, Logan C, Do QT et al.", "year": "2026", "journal": "Journal of neurology", "keywords": "Biomarker, Dementia, Neurodegenerative, Saliva, Tau", "chunk": "We find that salivary levels of t-tau were significantly elevated in AD and mild AD, but not other CI patients, compared to CU adults, while salivary levels of NfL and GFAP showed no significant differences across cohorts. In addition, we found that salivary t-tau was significantly correlated with CSF biomarker measures, including significant positive correlations with CSF t-tau and p-tau 181 (0.257; p = 0.016 and 0.276; p = 0.009 for t-tau and p-tau 181, respectively). Salivary t-tau was also found to predict AD cases compared to CU individuals with an area under the curve of 0.834 (95% CI 0.74-0.93; p < 0.0001). Finally, we observed that salivary t-tau levels were significantly negatively correlated with cognitive performance in AD patients, as well as all individuals together. These findings suggest that salivary t-tau might represent a non-invasive biomarker specific to AD pathology and could aid in early detection of AD or", "source": "PubMed"}, {"chunk_id": "41706165_2", "pmid": "41706165", "title": "Salivary total tau: a clinically practical measure of tau neuropathology in Alzheimer's disease.", "authors": "Bamford AR, Logan C, Do QT et al.", "year": "2026", "journal": "Journal of neurology", "keywords": "Biomarker, Dementia, Neurodegenerative, Saliva, Tau", "chunk": "as well as all individuals together. These findings suggest that salivary t-tau might represent a non-invasive biomarker specific to AD pathology and could aid in early detection of AD or for clinical screening purposes.", "source": "PubMed"}, {"chunk_id": "40064805_0", "pmid": "40064805", "title": "Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.", "authors": "Dahiya M, Yadav M, Goyal C et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Insulin resistance, Insulin signalling, Treatment strategy", "chunk": "Alzheimer's disease (AD), one of the most common neurodegenerative disorders, is characterised by hallmark abnormalities such as amyloid-\u03b2 plaques and neurofibrillary tangles (NFTs). Emerging evidence suggests that faulty insulin signalling contributes to these pathological features, impairing critical cellular and metabolic processes. This review aims to elucidate the role of insulin signalling in the central nervous system (CNS) under normal and pathological conditions and to explore therapeutic approaches targeting insulin pathways in AD and other neurodegenerative diseases. We reviewed studies highlighting the involvement of insulin-signalling pathways in neuronal health, with a particular focus on the key components-IRS, PI3K, Akt, and GSK-3\u03b2-predominantly expressed in cortical and hippocampal regions. Insulin, an essential growth factor, regulates numerous cellular functions, including glucose metabolism, mitochondrial activity, oxidative stress response, autophagy, synaptic plasticity, and cognitive processes. Altered phosphorylation of signalling molecules in insulin pathways contributes to oxidative stress, inflammation, and the formation of AD hallmarks. Indirect modulators", "source": "PubMed"}, {"chunk_id": "40064805_1", "pmid": "40064805", "title": "Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.", "authors": "Dahiya M, Yadav M, Goyal C et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Insulin resistance, Insulin signalling, Treatment strategy", "chunk": "oxidative stress response, autophagy, synaptic plasticity, and cognitive processes. Altered phosphorylation of signalling molecules in insulin pathways contributes to oxidative stress, inflammation, and the formation of AD hallmarks. Indirect modulators such as NF-\u03baB and caspases further exacerbate neuronal damage, linking impaired insulin signalling to neurodegeneration. Insulin signalling plays a crucial role in maintaining neuronal health and mitigating neurodegenerative processes. Targeting insulin pathways and associated molecules offers promising therapeutic avenues for AD and other neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "39225907_0", "pmid": "39225907", "title": "Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.", "authors": "Hu H, Yu L, Cheng Y et al.", "year": "2025", "journal": "Molecular diversity", "keywords": "Diagnostic markers, Oxidative stress, Recurrent pregnancy loss", "chunk": "It has been recognized that oxidative stress (OS) is implicated in the etiology of recurrent pregnancy loss (RPL), yet the biomarkers reflecting oxidative stress in association with RPL remain scarce. The dataset GSE165004 was retrieved from the Gene Expression Omnibus (GEO) database. From the GeneCards database, a compendium of 789 genes related to oxidative stress-related genes (OSRGs) was compiled. By intersecting differentially expressed genes (DEGs) in normal and RPL samples with OSRGs, differentially expressed OSRGs (DE-OSRGs) were identified. In addition, four machine learning algorithms were employed for the selection of diagnostic markers for RPL. The Receiver Operating Characteristic (ROC) curves for these genes were generated and a predictive nomogram for the diagnostic markers was established. The functions and pathways associated with the diagnostic markers were elucidated, and the correlations between immune cells and diagnostic markers were examined. Potential therapeutics targeting the diagnostic markers were proposed based on data from the", "source": "PubMed"}, {"chunk_id": "39225907_1", "pmid": "39225907", "title": "Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.", "authors": "Hu H, Yu L, Cheng Y et al.", "year": "2025", "journal": "Molecular diversity", "keywords": "Diagnostic markers, Oxidative stress, Recurrent pregnancy loss", "chunk": "with the diagnostic markers were elucidated, and the correlations between immune cells and diagnostic markers were examined. Potential therapeutics targeting the diagnostic markers were proposed based on data from the Comparative Toxicogenomics Database and ClinicalTrials.gov. The candidate biomarker genes from the four models were further validated in RPL tissue samples using RT-PCR and immunohistochemistry. A set of 20 DE-OSRGs was identified, with 4 genes (KRAS, C2orf69, CYP17A1, and UCP3) being recognized by machine learning algorithms as diagnostic markers exhibiting robust diagnostic capabilities. The nomogram constructed demonstrated favorable predictive accuracy. Pathways including ribosome, peroxisome, Parkinson's disease, oxidative phosphorylation, Huntington's disease, and Alzheimer's disease were co-enriched by KRAS, C2orf69, and CYP17A1. Cell chemotaxis terms were commonly enriched by all four diagnostic markers. Significant differences in the abundance of five cell types, namely eosinophils, monocytes, natural killer cells, regulatory T cells, and T follicular helper cells, were observed between normal and RPL samples.", "source": "PubMed"}, {"chunk_id": "39225907_2", "pmid": "39225907", "title": "Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.", "authors": "Hu H, Yu L, Cheng Y et al.", "year": "2025", "journal": "Molecular diversity", "keywords": "Diagnostic markers, Oxidative stress, Recurrent pregnancy loss", "chunk": "Significant differences in the abundance of five cell types, namely eosinophils, monocytes, natural killer cells, regulatory T cells, and T follicular helper cells, were observed between normal and RPL samples. A total of 180 drugs were predicted to target the diagnostic markers, including C544151, D014635, and CYP17A1. In the validation cohort of RPL patients, the LASSO model demonstrated superiority over other models. The expression levels of KRAS, C2orf69, and CYP17A1 were significantly reduced in RPL, while UCP3 levels were elevated, indicating their suitability as molecular markers for RPL. Four oxidative stress-related diagnostic markers (KRAS, C2orf69, CYP17A1, and UCP3) have been proposed to diagnose and potentially treat RPL.", "source": "PubMed"}, {"chunk_id": "40743680_0", "pmid": "40743680", "title": "Early diagnosis of mild cognitive impairment and Alzheimer's disease using multimodal feature-based deep learning models in a Chinese elderly population.", "authors": "Wang C, Wang Z, Herrero MT et al.", "year": "2025", "journal": "Asian journal of psychiatry", "keywords": "Alzheimer\u2019s disease, Deep learning, Early diagnosis, Event-related potentials, Mild cognitive impairment", "chunk": "Alzheimer's disease (AD) and mild cognitive impairment (MCI) are progressive neurodegenerative disorders with no effective treatments currently, underscoring the urgent need for early diagnosis. Electroencephalography and event-related potentials (ERP) provide noninvasive, cost-effective methods with high temporal resolution for detecting cognitive decline, while traditional Chinese medicine (TCM) features such as body constitutions have been identified as risk factors for MCI. Recent developments in artificial intelligence (AI) especially deep learning architectures have further improved the diagnostic accuracies of AD and MCI. This study aimed to assess the efficacy of deep learning models based on fused ERP and TCM features in the cross-subject classification of cognitive impairment. Visual oddball ERP tasks under Neutral, Happiness, or Sadness stimulus were conducted among 30 healthy controls (HC, 12 males and 18 females), 30 MCI (10 males and 20 females), and 30 AD (10 males and 20 females) patients. Deep learning models, including EEGNet, Convolutional Neural Network", "source": "PubMed"}, {"chunk_id": "40743680_1", "pmid": "40743680", "title": "Early diagnosis of mild cognitive impairment and Alzheimer's disease using multimodal feature-based deep learning models in a Chinese elderly population.", "authors": "Wang C, Wang Z, Herrero MT et al.", "year": "2025", "journal": "Asian journal of psychiatry", "keywords": "Alzheimer\u2019s disease, Deep learning, Early diagnosis, Event-related potentials, Mild cognitive impairment", "chunk": "(HC, 12 males and 18 females), 30 MCI (10 males and 20 females), and 30 AD (10 males and 20 females) patients. Deep learning models, including EEGNet, Convolutional Neural Network - Long Short-Term Memory, Graph Convolutional Network, (GCN), and multi-scale feature reconstruction GCN, were employed to extract differential entropy features from ERP data, and multilayer perceptron was utilized to extract features from TCM questionnaires. After feature fusion, 10-fold cross-subject binary (HC vs. MCI+AD; MCI vs. AD) and ternary (HC, MCI, AD) classification tasks were performed subsequently. GCN significantly outperformed other models in all three cross-subject classification tasks. In binary classification tasks distinguishing HC from MCI and AD, GCN achieved accuracies of 90.17 \u00b1 5.58 %, 86.73 \u00b1 2.34 %, and 84.73 \u00b1 4.28 % under Neutral, Happiness, and Sadness, respectively. Similarly, in ternary classification of HC, MCI, and AD, GCN reached the highest accuracy of 72.67 \u00b1 1.89 % under", "source": "PubMed"}, {"chunk_id": "40743680_2", "pmid": "40743680", "title": "Early diagnosis of mild cognitive impairment and Alzheimer's disease using multimodal feature-based deep learning models in a Chinese elderly population.", "authors": "Wang C, Wang Z, Herrero MT et al.", "year": "2025", "journal": "Asian journal of psychiatry", "keywords": "Alzheimer\u2019s disease, Deep learning, Early diagnosis, Event-related potentials, Mild cognitive impairment", "chunk": "84.73 \u00b1 4.28 % under Neutral, Happiness, and Sadness, respectively. Similarly, in ternary classification of HC, MCI, and AD, GCN reached the highest accuracy of 72.67 \u00b1 1.89 % under Neutral stimulus. Leveraging fused ERP and TCM features, deep learning models have demonstrated robust cross-subject efficacy in the early diagnosis of cognitive decline. Particularly in distinguishing HC from MCI and AD, the performance of GCN was comparable to that of hematological biomarkers. Our study, therefore, highlights a reliable and effective AI-driven methodology for the early diagnosis of cognitive impairment in clinical settings.", "source": "PubMed"}, {"chunk_id": "41328628_0", "pmid": "41328628", "title": "Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis.", "authors": "Ren S, Singh J, Gsteiger S et al.", "year": "2026", "journal": "Journal of comparative effectiveness research", "keywords": "Alzheimer's disease, amyloid-beta, clinical outcomes, meta-analysis, surrogate endpoint", "chunk": "<b>Aim:</b> The use of amyloid-beta (A\u03b2) clearance to support regulatory approvals of drugs in Alzheimer's disease (AD) remains controversial. We evaluate A\u03b2 as a potential trial-level surrogate endpoint for clinical function in AD. <b>Materials & methods:</b> Data on the effectiveness of anti-A\u03b2 monoclonal antibodies (MABs) on A\u03b2 and multiple clinical outcomes were identified from randomized controlled trials through a literature review. A Bayesian bivariate meta-analysis was used to evaluate A\u03b2 as a surrogate endpoint for clinical function across all MABs and for each individual anti-A\u03b2 MAB. The analysis for individual therapies was conducted in subgroups of treatments and by applying Bayesian hierarchical models to borrow information across treatments. <b>Results:</b> We identified 23 randomized controlled trials with 39 treatment contrasts for seven MABs. The surrogate relationship between treatment effects on A\u03b2 and Clinical Dementia Rating-Sum of Boxes (CDR-SOB) across all MABs was strong: with a meaningful slope of 1.41 (0.60, 2.21)", "source": "PubMed"}, {"chunk_id": "41328628_1", "pmid": "41328628", "title": "Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis.", "authors": "Ren S, Singh J, Gsteiger S et al.", "year": "2026", "journal": "Journal of comparative effectiveness research", "keywords": "Alzheimer's disease, amyloid-beta, clinical outcomes, meta-analysis, surrogate endpoint", "chunk": "seven MABs. The surrogate relationship between treatment effects on A\u03b2 and Clinical Dementia Rating-Sum of Boxes (CDR-SOB) across all MABs was strong: with a meaningful slope of 1.41 (0.60, 2.21) and small variance of 0.02 (0.00, 0.05). For individual treatments, the surrogate relationships were suboptimal, displaying large uncertainty. Sharing information across treatments considerably reduced the uncertainty, resulting in moderate surrogate relationships for aducanumab and lecanemab. No meaningful association was detected for other clinical outcomes, including Mini Mental State Examination and Alzheimer's Disease Assessment Scale-Cognitive Subscale. <b>Conclusion:</b> Although our results from the analysis of data across all MABs suggested that A\u03b2 was a potential surrogate endpoint for CDR-SOB, individually the surrogacy patterns varied across treatments and showed no evidence of association. Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab.", "source": "PubMed"}, {"chunk_id": "41328628_2", "pmid": "41328628", "title": "Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis.", "authors": "Ren S, Singh J, Gsteiger S et al.", "year": "2026", "journal": "Journal of comparative effectiveness research", "keywords": "Alzheimer's disease, amyloid-beta, clinical outcomes, meta-analysis, surrogate endpoint", "chunk": "Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab.", "source": "PubMed"}, {"chunk_id": "35908307_0", "pmid": "35908307", "title": "Determining the OPTIMAL DTI analysis method for application in cerebral small vessel disease.", "authors": "Egle M, Hilal S, Tuladhar AM et al.", "year": "2022", "journal": "NeuroImage. Clinical", "keywords": "Cognition, Dementia, Diffusion tensor imaging, Small vessel disease, Surrogate marker", "chunk": "DTI is sensitive to white matter (WM) microstructural damage and has been suggested as a surrogate marker for phase 2 clinical trials in cerebral small vessel disease (SVD). The study's objective is to establish the best way to analyse the diffusion-weighted imaging data in SVD for this purpose. The ideal method would be sensitive to change and predict dementia conversion, but also straightforward to implement and ideally automated. As part of the OPTIMAL collaboration, we evaluated five different DTI analysis strategies across six different cohorts with differing SVD severity. Those 5 strategies were: (1) conventional mean diffusivity WM histogram measure (MD median), (2) a principal component-derived measure based on conventional WM histogram measures (PC1), (3) peak width skeletonized mean diffusivity (PSMD), (4) diffusion tensor image segmentation \u03b8 (DSEG \u03b8) and (5) a WM measure of global network efficiency (Geff). The association between each measure and cognitive function was tested using", "source": "PubMed"}, {"chunk_id": "35908307_1", "pmid": "35908307", "title": "Determining the OPTIMAL DTI analysis method for application in cerebral small vessel disease.", "authors": "Egle M, Hilal S, Tuladhar AM et al.", "year": "2022", "journal": "NeuroImage. Clinical", "keywords": "Cognition, Dementia, Diffusion tensor imaging, Small vessel disease, Surrogate marker", "chunk": "(PSMD), (4) diffusion tensor image segmentation \u03b8 (DSEG \u03b8) and (5) a WM measure of global network efficiency (Geff). The association between each measure and cognitive function was tested using a linear regression model adjusted by clinical markers. Changes in the imaging measures over time were determined. In three cohort studies, repeated imaging data together with data on incident dementia were available. The association between the baseline measure, change measure and incident dementia conversion was examined using Cox proportional-hazard regression or logistic regression models. Sample size estimates for a hypothetical clinical trial were furthermore computed for each DTI analysis strategy. There was a consistent cross-sectional association between the imaging measures and impaired cognitive function across all cohorts. All baseline measures predicted dementia conversion in severe SVD. In mild SVD, PC1, PSMD and Geff predicted dementia conversion. In MCI, all markers except Geff predicted dementia conversion. Baseline DTI was significantly different", "source": "PubMed"}, {"chunk_id": "35908307_2", "pmid": "35908307", "title": "Determining the OPTIMAL DTI analysis method for application in cerebral small vessel disease.", "authors": "Egle M, Hilal S, Tuladhar AM et al.", "year": "2022", "journal": "NeuroImage. Clinical", "keywords": "Cognition, Dementia, Diffusion tensor imaging, Small vessel disease, Surrogate marker", "chunk": "predicted dementia conversion in severe SVD. In mild SVD, PC1, PSMD and Geff predicted dementia conversion. In MCI, all markers except Geff predicted dementia conversion. Baseline DTI was significantly different in patients converting to vascular dementia than to Alzheimer' s disease. Significant change in all measures was associated with dementia conversion in severe but not in mild SVD. The automatic and semi-automatic measures PSMD and DSEG \u03b8 required the lowest minimum sample sizes for a hypothetical clinical trial in single-centre sporadic SVD cohorts. DTI parameters obtained from all analysis methods predicted dementia, and there was no clear winner amongst the different analysis strategies. The fully automated analysis provided by PSMD offers advantages particularly for large datasets.", "source": "PubMed"}, {"chunk_id": "40675424_0", "pmid": "40675424", "title": "Future of Alzheimer's detection: Advancing diagnostic accuracy through the integration of qEEG and artificial intelligence.", "authors": "Rezaei S, Asadirad F, Motamedi A et al.", "year": "2025", "journal": "NeuroImage", "keywords": "Alzheimer's disease, Artificial intelligence, Early detection, Machine learning, Quantitative electroencephalography", "chunk": "This comprehensive review examines the integration of Quantitative Electroencephalography (qEEG) and Artificial Intelligence (AI) in the detection and diagnosis of Alzheimer's Disease (AD). Through systematic analysis of 11 key studies across multiple international databases, we evaluated various AI architectures, including machine learning algorithms and deep learning networks, applied to qEEG data for AD detection. The review encompasses studies with diverse subject populations, ranging from 35 to 890 participants, with mean ages between 66.94 and 74.8 years. Results demonstrate that AI-enhanced qEEG analysis achieves remarkable diagnostic accuracy, with Linear Discriminant Analysis (LDA) reaching 93.18% accuracy and 97.92% Area Under Curve (AUC). Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) also showed promising results, with some models achieving up to 100% sensitivity in specific classifications. The integration of multiple data types and advanced feature extraction methods significantly improved diagnostic precision. Geographic diversity in research origins, spanning from Asia to Europe and", "source": "PubMed"}, {"chunk_id": "40675424_1", "pmid": "40675424", "title": "Future of Alzheimer's detection: Advancing diagnostic accuracy through the integration of qEEG and artificial intelligence.", "authors": "Rezaei S, Asadirad F, Motamedi A et al.", "year": "2025", "journal": "NeuroImage", "keywords": "Alzheimer's disease, Artificial intelligence, Early detection, Machine learning, Quantitative electroencephalography", "chunk": "sensitivity in specific classifications. The integration of multiple data types and advanced feature extraction methods significantly improved diagnostic precision. Geographic diversity in research origins, spanning from Asia to Europe and the Americas, provides robust cross-cultural validation of findings. However, challenges persist in data quality, computational resources, and standardization of methodologies. This review highlights the significant potential of AI-enhanced qEEG as a non-invasive, cost-effective tool for the diagnosis of AD in its prodromal and dementia stages, while also identifying areas requiring further research to optimize its clinical application. These findings suggest that AI-enhanced qEEG analysis could revolutionize AD diagnosis, enabling earlier intervention and improved patient outcomes.", "source": "PubMed"}, {"chunk_id": "41762057_0", "pmid": "41762057", "title": "Caudate-Centric Triphasic Network Reconfiguration Characterizes the Early Progression of Cognitive Impairment in Parkinson's Disease: A Simultaneous PET/fMRI Study.", "authors": "Zhang W, Li G, Mao F et al.", "year": "2026", "journal": "Journal of integrative neuroscience", "keywords": "Parkinson\u2019s disease, cognitive dysfunction, dopamine, functional neuroimaging, positron-emission tomography", "chunk": "The stage-specific dynamics of functional brain networks in early Parkinson's disease cognitive impairment (PD-CI) remain unclear. This study investigated caudate-centric hierarchical functional network reconfiguration across early PD-CI stages using simultaneous [<sup>18</sup>F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography (<sup>18</sup>F-FP-DTBZ PET) and resting-state functional magnetic resonance imaging (rs-fMRI). Forty-six Parkinson's disease (PD) patients underwent simultaneous <sup>18</sup>F-FP-DTBZ PET/MR with rs-fMRI sequences. Patients were categorized as normal cognition (PD-NC, n = 15), subjective cognitive decline (PD-SCD, n = 16), and mild cognitive impairment (PD-MCI, n = 15). PET-identified striatal regions with significant dopaminergic deficits were used as seeds for stepwise functional connectivity (SFC) analysis. Associations with cognitive factors and network coupling in early PD-CI were evaluated. <sup>18</sup>F-FP-DTBZ PET revealed that the caudate nucleus was a critical dopaminergic hub in early PD-CI. Caudate seed-based SFC analysis revealed a triphasic reconfiguration: stable integration in PD-NC, compensatory hyperconnectivity in PD-SCD, and global inefficiency with rigidity in PD-MCI. Key circuits showed", "source": "PubMed"}, {"chunk_id": "41762057_1", "pmid": "41762057", "title": "Caudate-Centric Triphasic Network Reconfiguration Characterizes the Early Progression of Cognitive Impairment in Parkinson's Disease: A Simultaneous PET/fMRI Study.", "authors": "Zhang W, Li G, Mao F et al.", "year": "2026", "journal": "Journal of integrative neuroscience", "keywords": "Parkinson\u2019s disease, cognitive dysfunction, dopamine, functional neuroimaging, positron-emission tomography", "chunk": "hub in early PD-CI. Caudate seed-based SFC analysis revealed a triphasic reconfiguration: stable integration in PD-NC, compensatory hyperconnectivity in PD-SCD, and global inefficiency with rigidity in PD-MCI. Key circuits showed reduced connectivity in PD-MCI including caudate linkages with the globus pallidus, thalamus, right superior frontal gyrus, left inferior temporal gyrus, right superior orbitofrontal cortex, supplementary motor area, and right hippocampus. Clinical analysis showed that both global cognitive efficiency and memory control were associated with specific short- and long-range caudate connectivity. The caudate nucleus is central to the interplay between dopaminergic metabolic deficits and functional network reconfiguration during early PD-CI progression, shifting from compensatory hyperconnectivity to network rigidity. These findings provide a mechanistic framework for targeted neuromodulation strategies in early PD-CI.", "source": "PubMed"}, {"chunk_id": "36872303_0", "pmid": "36872303", "title": "Cellular response to \u03b2-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.", "authors": "Zhang H, Li X, Wang X et al.", "year": "2023", "journal": "Animal models and experimental medicine", "keywords": "Alzheimer's disease (AD), astrocytes, endopeptidase, glutaminyl cyclase (QC), microglia, p75 neurotrophin receptor (p75NTR), proteolysis targeting chimeras (PROTACs), \u03b2-Amyloid (A\u03b2)", "chunk": "\u03b2-Amyloid (A\u03b2) is a specific pathological hallmark of Alzheimer's disease (AD). Because of its neurotoxicity, AD patients exhibit multiple brain dysfunctions. Disease-modifying therapy (DMT) is the central concept in the development of AD therapeutics today, and most DMT drugs that are currently in clinical trials are anti-A\u03b2 drugs, such as aducanumab and lecanemab. Therefore, understanding A\u03b2's neurotoxic mechanism is crucial for A\u03b2-targeted drug development. Despite its total length of only a few dozen amino acids, A\u03b2 is incredibly diverse. In addition to the well-known A\u03b2<sub>1-42</sub> , N-terminally truncated, glutaminyl cyclase (QC) catalyzed, and pyroglutamate-modified A\u03b2 (pEA\u03b2) is also highly amyloidogenic and far more cytotoxic. The extracellular monomeric A\u03b2<sub>x-42</sub> (x = 1-11) initiates the aggregation to form fibrils and plaques and causes many abnormal cellular responses through cell membrane receptors and receptor-coupled signal pathways. These signal cascades further influence many cellular metabolism-related processes, such as gene expression, cell cycle, and cell", "source": "PubMed"}, {"chunk_id": "36872303_1", "pmid": "36872303", "title": "Cellular response to \u03b2-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.", "authors": "Zhang H, Li X, Wang X et al.", "year": "2023", "journal": "Animal models and experimental medicine", "keywords": "Alzheimer's disease (AD), astrocytes, endopeptidase, glutaminyl cyclase (QC), microglia, p75 neurotrophin receptor (p75NTR), proteolysis targeting chimeras (PROTACs), \u03b2-Amyloid (A\u03b2)", "chunk": "causes many abnormal cellular responses through cell membrane receptors and receptor-coupled signal pathways. These signal cascades further influence many cellular metabolism-related processes, such as gene expression, cell cycle, and cell fate, and ultimately cause severe neural cell damage. However, endogenous cellular anti-A\u03b2 defense processes always accompany the A\u03b2-induced microenvironment alterations. A\u03b2-cleaving endopeptidases, A\u03b2-degrading ubiquitin-proteasome system (UPS), and A\u03b2-engulfing glial cell immune responses are all essential self-defense mechanisms that we can leverage to develop new drugs. This review discusses some of the most recent advances in understanding A\u03b2-centric AD mechanisms and suggests prospects for promising anti-A\u03b2 strategies.", "source": "PubMed"}, {"chunk_id": "40566800_0", "pmid": "40566800", "title": "Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.", "authors": "Germann J, Amaral RSC, Tomaszczyk J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease biomarker, amyloid clearance, fornix DBS, hippocampal atrophy, neuromodulation therapy", "chunk": "Deep brain stimulation of the fornix (fx-DBS) is being investigated for treatment of Alzheimer's disease (AD). The therapy aims at alleviating memory and cognitive circuit dysfunction. In preclinical models of AD, electrical stimulation of the memory circuit has demonstrated a possible disease-modifying potential. Here we examined changes resulting from fx-DBS in hippocampal atrophy and amyloid accumulation in AD patients with fx-DBS. Repeated magnetic resonance imaging and positron emission tomography (PET) images acquired over the course of 12 months were used to assess changes in hippocampal volume in 36 ADvance trial patients compared to 40 matched untreated AD patients from the Alzheimer's Disease Neuroimaging Initiative, and in 10 separate patients with repeated flutemetamol PET and cerebrospinal fluid (CSF) markers. We observed a reduction of hippocampal atrophy and amyloid beta (A\u03b2) PET binding, and an increase in the CSF A\u03b2/total-tau ratio in DBS patients. These findings highlight the potential of fornix deep", "source": "PubMed"}, {"chunk_id": "40566800_1", "pmid": "40566800", "title": "Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.", "authors": "Germann J, Amaral RSC, Tomaszczyk J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease biomarker, amyloid clearance, fornix DBS, hippocampal atrophy, neuromodulation therapy", "chunk": "a reduction of hippocampal atrophy and amyloid beta (A\u03b2) PET binding, and an increase in the CSF A\u03b2/total-tau ratio in DBS patients. These findings highlight the potential of fornix deep brain stimulation to modify AD biomarkers and possibly progression in some patients. Fornix deep brain stimulation (fx-DBS) is being investigated to treat Alzheimer's disease (AD). Results show that fx-DBS modifies imaging and cerebrospinal fluid (CSF) markers. It reduces hippocampal atrophy and increases the amyloid beta/total-tau CSF ratio. These findings highlight the potential of fx-DBS to modify AD.", "source": "PubMed"}, {"chunk_id": "39570569_0", "pmid": "39570569", "title": "Cognitive aging and reserve factors in the Metropolit 1953 Danish male cohort.", "authors": "Mehdipour Ghazi M, Urdanibia-Centelles O, Bakhtiari A et al.", "year": "2025", "journal": "GeroScience", "keywords": "Aging risk factors, Cognitive decline, Cognitive reserve, Electroencephalography, Machine learning, Magnetic resonance imaging", "chunk": "Identifying early predictors of cognitive decline and at-risk individuals is essential for timely intervention and prevention of dementia. This study aimed to detect neurobiological changes and factors related to cognitive performance in the Metropolit 1953 Danish male birth cohort. We analyzed data from 582 participants, aged 57-68 years, using machine learning techniques to group cognitive trajectories into four clusters differentiating high- and low-performing groups. These clusters were then evaluated with MRI, EEG, and lifestyle/familial risk factors to identify predictors of cognitive decline. Low education and occupation, alcohol consumption, and type 2 diabetes were associated with lower cognitive performance. Declines in neocortical volume and increases in frontotemporal alpha and temporoparietal gamma activity preceded clinical symptoms of cognitive decline. Neocortical atrophy and disruptions in network activity were prominent in lower-performing groups, with higher education and IQ scores and a lower prevalence of lifestyle factors moderating cognitive decline.", "source": "PubMed"}, {"chunk_id": "39570569_1", "pmid": "39570569", "title": "Cognitive aging and reserve factors in the Metropolit 1953 Danish male cohort.", "authors": "Mehdipour Ghazi M, Urdanibia-Centelles O, Bakhtiari A et al.", "year": "2025", "journal": "GeroScience", "keywords": "Aging risk factors, Cognitive decline, Cognitive reserve, Electroencephalography, Machine learning, Magnetic resonance imaging", "chunk": "disruptions in network activity were prominent in lower-performing groups, with higher education and IQ scores and a lower prevalence of lifestyle factors moderating cognitive decline.", "source": "PubMed"}, {"chunk_id": "38087143_0", "pmid": "38087143", "title": "Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.", "authors": "Ferini-Strambi L, Liguori C, Lucey BP et al.", "year": "2024", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dementia, Neurodegeneration, Obstructive sleep apnea, Rem sleep behavior disorder, Sleep", "chunk": "Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-\u03b2 (A\u03b2) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases A\u03b2. Obstructive sleep apnea (OSA) is a risk", "source": "PubMed"}, {"chunk_id": "38087143_1", "pmid": "38087143", "title": "Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.", "authors": "Ferini-Strambi L, Liguori C, Lucey BP et al.", "year": "2024", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dementia, Neurodegeneration, Obstructive sleep apnea, Rem sleep behavior disorder, Sleep", "chunk": "increases amyloid-\u03b2 (A\u03b2) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases A\u03b2. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying", "source": "PubMed"}, {"chunk_id": "38087143_2", "pmid": "38087143", "title": "Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.", "authors": "Ferini-Strambi L, Liguori C, Lucey BP et al.", "year": "2024", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dementia, Neurodegeneration, Obstructive sleep apnea, Rem sleep behavior disorder, Sleep", "chunk": "recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.", "source": "PubMed"}, {"chunk_id": "40058720_0", "pmid": "40058720", "title": "SNAP-25: A biomarker of synaptic loss in neurodegeneration.", "authors": "Zhang C, Xie S, Malek M", "year": "2025", "journal": "Clinica chimica acta; international journal of clinical chemistry", "keywords": "Biomarker, Diagnosis, Neurodegenerative diseases, Prognostic factor, SNAP-25", "chunk": "Synaptic dysfunction is one of the most important markers of neurodegenerative diseases, which contribute to cognitive decline and the loss of neurons. Synaptosomal-associated protein 25 (SNAP-25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which plays a significant role in the exocytosis of synaptic vesicles and the release of neurotransmitters. Recent studies have shown that expression levels of SNAP-25 are altered in various neurodegenerative disorders, including Alzheimer's disease (AD), Huntington's disease (HD), and Creutzfeldt-Jakob disease (CJD). These investigations led to the consideration of SNAP-25 as a potential biomarker of synaptic degeneration. Understanding the role of SNAP-25 in neurodegeneration will aid in early diagnosis, disease monitoring, and therapeutic development, and will also provide new insights into synaptic dysfunction as a main feature of neurodegenerative diseases. Therefore, this paper explores the physiological role of SNAP-25, its involvement in synaptic pathology, and the implications of its dysregulation in", "source": "PubMed"}, {"chunk_id": "40058720_1", "pmid": "40058720", "title": "SNAP-25: A biomarker of synaptic loss in neurodegeneration.", "authors": "Zhang C, Xie S, Malek M", "year": "2025", "journal": "Clinica chimica acta; international journal of clinical chemistry", "keywords": "Biomarker, Diagnosis, Neurodegenerative diseases, Prognostic factor, SNAP-25", "chunk": "synaptic dysfunction as a main feature of neurodegenerative diseases. Therefore, this paper explores the physiological role of SNAP-25, its involvement in synaptic pathology, and the implications of its dysregulation in neurodegenerative conditions, such as AD, HD, and CJD. Literature regarding cerebrospinal fluid (CSF) SNAP-25 levels as a diagnostic marker were reviewed and its applications in detecting the progression of the disease have been discussed. Additionally, the limitations of SNAP-25 as a biomarker, including variability across studies and the need for further validation have been addressed.", "source": "PubMed"}, {"chunk_id": "41623597_0", "pmid": "41623597", "title": "Gingival crevicular fluid as a functionalized point of care for the early detection of dementia or the asymptomatic phase of neurodegeneration.", "authors": "Leanza Y, Belmonte A, Polizzi A et al.", "year": "2025", "journal": "Frontiers in dental medicine", "keywords": "biomarkers, gingival crevicular fluid, neurodegenerative diseases, oralmicrobiome, periodontitis", "chunk": "Growing evidence links chronic systemic inflammation, particularly from periodontitis, to neurodegenerative processes, which have been reported to share common pathways. Early detection of neurodegenerative diseases such as Alzheimer's disease is crucial, given that underlying neuropathological processes evolve silently for decades before diagnosis. The gingival crevicular fluid (GCF), a serum-derived exudate from the gingival sulcus, mirrors both local periodontal inflammation and systemic conditions. Its molecular composition-rich in cytokines, enzymes, oxidative stress markers, and microbial metabolites-makes it a potential source of biomarkers reflecting neuroinflammatory pathways. This review discusses the biological rationale and emerging evidence supporting the use of GCF as a functionalized biofluid for early detection of dementia or asymptomatic neurodegeneration. By integrating advances in biosensing and lab-on-a-chip technologies, GCF analysis could become a minimally invasive, point-of-care approach to identify individuals at risk of neurodegenerative diseases. Exploring this oral-brain connection may open new perspectives in preventive medicine and personalized diagnostics.", "source": "PubMed"}, {"chunk_id": "41623597_1", "pmid": "41623597", "title": "Gingival crevicular fluid as a functionalized point of care for the early detection of dementia or the asymptomatic phase of neurodegeneration.", "authors": "Leanza Y, Belmonte A, Polizzi A et al.", "year": "2025", "journal": "Frontiers in dental medicine", "keywords": "biomarkers, gingival crevicular fluid, neurodegenerative diseases, oralmicrobiome, periodontitis", "chunk": "become a minimally invasive, point-of-care approach to identify individuals at risk of neurodegenerative diseases. Exploring this oral-brain connection may open new perspectives in preventive medicine and personalized diagnostics.", "source": "PubMed"}, {"chunk_id": "41249712_0", "pmid": "41249712", "title": "Long term cognitive outcome of prodromal and mild dementia with Lewy bodies: a cohort study.", "authors": "Blanc F, Cretin B, Muller C et al.", "year": "2025", "journal": "GeroScience", "keywords": "Alzheimer\u2019s disease, Dementia with Lewy bodies, Lewy body disease, MMSE, Mild cognitive impairment, Outcome", "chunk": "The cognitive evolution of early dementia with Lewy bodies (DLB) is less well known than that of Alzheimer's disease (AD). During dementia, DLB progresses like AD. The aim of this study was to analyze the long-term cognitive decline of early DLB. Participants were recruited for either mild cognitive impairment or mild dementia with a suspicion of DLB or AD, or as healthy older subjects (AlphaLewyMA study, NCT01876459, 2013). Using beta regression, we compared the slope of the Mini-Mental State Examination (MMSE) score of 110 DLB patients (DLB group), 57 AD patients (AD group), 19 DLB and AD patients (DLB + AD group), 30 patients with other cognitive diseases (DC group), and 31 healthy older controls (HC group). The mean follow-up was 4.8 years. All patients' groups had a significant decrease in MMSE score. The slope of MMSE decline of the DLB group (-0.49 point a year) was higher than the", "source": "PubMed"}, {"chunk_id": "41249712_1", "pmid": "41249712", "title": "Long term cognitive outcome of prodromal and mild dementia with Lewy bodies: a cohort study.", "authors": "Blanc F, Cretin B, Muller C et al.", "year": "2025", "journal": "GeroScience", "keywords": "Alzheimer\u2019s disease, Dementia with Lewy bodies, Lewy body disease, MMSE, Mild cognitive impairment, Outcome", "chunk": "was 4.8 years. All patients' groups had a significant decrease in MMSE score. The slope of MMSE decline of the DLB group (-0.49 point a year) was higher than the HC group (+ 0.03; P < .0001), lower than that of the AD (-2.78; P < .0001) and DLB + AD (-2.92; P < .0001) groups and not different from the DC group (-0.29; P = .8000). The variability of annual variations in MMSE score was greater in the DLB group (2.13 points) than in the AD group (1.73 points). There was no difference between patients' group in terms of death or admission to a nursing home. Patients with early DLB decline cognitively more slowly while fluctuating, whereas AD and DLB + AD patients decline markedly. These results suggest that there is a more dysfunctional than neurodegenerative phase at the beginning of DLB.", "source": "PubMed"}, {"chunk_id": "41249712_2", "pmid": "41249712", "title": "Long term cognitive outcome of prodromal and mild dementia with Lewy bodies: a cohort study.", "authors": "Blanc F, Cretin B, Muller C et al.", "year": "2025", "journal": "GeroScience", "keywords": "Alzheimer\u2019s disease, Dementia with Lewy bodies, Lewy body disease, MMSE, Mild cognitive impairment, Outcome", "chunk": "DLB + AD patients decline markedly. These results suggest that there is a more dysfunctional than neurodegenerative phase at the beginning of DLB.", "source": "PubMed"}, {"chunk_id": "41047224_0", "pmid": "41047224", "title": "Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players.", "authors": "Graham N, Zimmerman K, Hain J et al.", "year": "2025", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "DEMENTIA, HEAD INJURY, NEUROBIOLOGY, TRAUMATIC BRAIN INJURY", "chunk": "Contact sports, including rugby union, are associated with higher rates of neurodegenerative dementia, due to various underlying pathologies such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). New ultrasensitive multiplexed immunoassays may clarify disease mechanisms after repetitive head impacts (RHI) and traumatic brain injury, potentially aiding risk-stratification, early diagnosis and dementia treatment. Midlife participants in the ABHC cohort underwent plasma biomarker quantification (NULISA - NUcleic acid Linked Immuno-Sandwich Assay; n=124 markers), 3T MRI, trauma exposure ascertainment and phenotyping. Regressions quantified exposure-specific protein expression, relationship to trauma (including position) and brain atrophy, using cluster analysis to test correlates of traumatic encephalopathy syndrome (TES). 197 former elite rugby players and 33 controls were assessed. 24 (12.2%) met criteria for TES but none had dementia. Ex-players returned reduced plasma glial fibrillary acidic protein (GFAP), kallikrein-6 (KLK6) and synaptosomal-associated protein 25 (SNAP25). Ex-forwards specifically showed reduced plasma beta-site amyloid precursor protein cleaving enzyme", "source": "PubMed"}, {"chunk_id": "41047224_1", "pmid": "41047224", "title": "Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players.", "authors": "Graham N, Zimmerman K, Hain J et al.", "year": "2025", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "DEMENTIA, HEAD INJURY, NEUROBIOLOGY, TRAUMATIC BRAIN INJURY", "chunk": "none had dementia. Ex-players returned reduced plasma glial fibrillary acidic protein (GFAP), kallikrein-6 (KLK6) and synaptosomal-associated protein 25 (SNAP25). Ex-forwards specifically showed reduced plasma beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), amyloid beta-38 (A\u03b238), and increased phospho-tau<sub>181</sub> (p-tau<sub>181</sub>). KLK6 was lower in ex-backs than controls. No biomarkers related to career duration, concussion load or regional brain volume, nor did clustering relate to TES. Ex-players showed distinctive plasma biomarker changes, more prominently in ex-forwards, possibly reflecting greater RHI exposure. Plasma KLK6, an endothelial serine protease, was reduced across the ex-player group, with potential diagnostic or prognostic utility in future. Reduced GFAP and SNAP25 in ex-forwards has an uncertain basis, while elevated p-tau-<sub>181</sub> more so than p-tau<sub>217</sub> points towards non-AD tau pathology. Our findings motivate longitudinal characterisation, including comparison with other neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "41047224_2", "pmid": "41047224", "title": "Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players.", "authors": "Graham N, Zimmerman K, Hain J et al.", "year": "2025", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "DEMENTIA, HEAD INJURY, NEUROBIOLOGY, TRAUMATIC BRAIN INJURY", "chunk": "pathology. Our findings motivate longitudinal characterisation, including comparison with other neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "30704251_0", "pmid": "30704251", "title": "[Current views on metabolic syndrome].", "authors": "Sva\u010dina \u0160", "year": "2019", "journal": "Vnitrni lekarstvi", "keywords": "adipose tissue inflammation\u00a0- definition of metabolic syndrome\u00a0- insulin resistance\u00a0- myokines\u00a0- systemic inflammation", "chunk": "The theory of metabolic syndrome originated 30 years ago. Several definitions try to explain the frequent common incidence of the risk factors for atherosclerosis. At first the syndrome of insulin resistance was involved. It was only later that the relation of the metabolic syndrome was described to what is known as systemic inflammation arising in adipose tissue and inflammatory diseases such as chronic bronchitis or psoriasis, or to degenerative diseases such as Alzheimers disease. The views on the metabolic syndrome are thus constantly changing. Key words: adipose tissue inflammation - definition of metabolic syndrome - insulin resistance - myokines - systemic inflammation.", "source": "PubMed"}, {"chunk_id": "39164754_0", "pmid": "39164754", "title": "Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies.", "authors": "Jicha GA, Tucker TC, Arnold SM et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Donanemab, Epidemiology, Immunotherapy, Lecanemab, Neuropathology, Neuropsychiatric, Non-amnestic, Polling, Side effects", "chunk": "Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical interventions, either standard of care or experimental, even if the benefits are not certain and the therapy's side effects are potentially severe. The prognosis for many individuals at risk for dementia carries a correspondingly high level of risk for both mortality and severe morbidity, particularly if one focuses on \"health-span\"", "source": "PubMed"}, {"chunk_id": "39164754_1", "pmid": "39164754", "title": "Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies.", "authors": "Jicha GA, Tucker TC, Arnold SM et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Donanemab, Epidemiology, Immunotherapy, Lecanemab, Neuropathology, Neuropsychiatric, Non-amnestic, Polling, Side effects", "chunk": "potentially severe. The prognosis for many individuals at risk for dementia carries a correspondingly high level of risk for both mortality and severe morbidity, particularly if one focuses on \"health-span\" rather than lifespan. Caregivers and patients can be strongly impacted by dementia and the many troubling associated symptoms that often go well beyond amnesia. Polls, surveys, and a literature on \"dementia worry\" strongly underscore that the public fears dementia. While there are institutional and industry hurdles that complicate enrollment in randomized trials, the gravity of the future morbidity and mortality inherent in a dementia diagnosis may require reconsideration of the current protective stance that limits the freedom of at-risk individuals (either symptomatic or asymptomatic) to participate and potentially benefit from ongoing clinical research. There is also evidence from both cancer and dementia research that individuals enrolled in the placebo arms of clinical trials have unexpectedly good outcomes, indicating that participation", "source": "PubMed"}, {"chunk_id": "39164754_2", "pmid": "39164754", "title": "Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies.", "authors": "Jicha GA, Tucker TC, Arnold SM et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Donanemab, Epidemiology, Immunotherapy, Lecanemab, Neuropathology, Neuropsychiatric, Non-amnestic, Polling, Side effects", "chunk": "ongoing clinical research. There is also evidence from both cancer and dementia research that individuals enrolled in the placebo arms of clinical trials have unexpectedly good outcomes, indicating that participation in clinical trial can have medical benefits to enrollees. To highlight aspects of cancer clinical research that may inform present and future dementia clinical research, this review highlights three main themes: the risk of side effects should be weighed against the often dire consequences of non-treatment; the desirability of long-term incremental (rather than \"magic bullet\") clinical advances; and, the eventual importance of combination therapies, reflecting that the dementia clinical syndrome has many underlying biological pathways.", "source": "PubMed"}, {"chunk_id": "39661323_0", "pmid": "39661323", "title": "Impact of acute sleep restriction on cerebrovascular reactivity and neurovascular coupling in young men and women.", "authors": "McDonald MJ, Marsh ML, Fears SD et al.", "year": "2025", "journal": "Journal of applied physiology (Bethesda, Md. : 1985)", "keywords": "brain blood flow, carbon dioxide, middle cerebral artery, sleep", "chunk": "Chronic exposure to shortened sleep is associated with an increased risk of Alzheimer's disease and dementia. Previous studies show insufficient (e.g., poor or fragmented) sleep impairs cerebrovascular reactivity to metabolic stress and may have a detrimental effect on the link between cerebral blood flow (CBF) and neural activity (i.e., neurovascular coupling, NVC). The purpose of this study was to examine the effect of acute sleep restriction on CBF in response to a metabolic (carbon dioxide, CO<sub>2</sub>) and a cognitive stressor. We hypothesized sleep restriction (4-h time in bed) would attenuate CBF and NVC. Sixteen young adults (8 M/8 F, 28 \u00b1 8 yr, 25 \u00b1 3 kg/m<sup>2</sup>) completed two morning visits following a night of normal (7.38 \u00b1 0.82 h) or restricted (4.27 \u00b1 0.93 h, <i>P</i> < 0.001) sleep duration. Middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) was measured at rest and during <i>1</i>) 5 min of carbogen", "source": "PubMed"}, {"chunk_id": "39661323_1", "pmid": "39661323", "title": "Impact of acute sleep restriction on cerebrovascular reactivity and neurovascular coupling in young men and women.", "authors": "McDonald MJ, Marsh ML, Fears SD et al.", "year": "2025", "journal": "Journal of applied physiology (Bethesda, Md. : 1985)", "keywords": "brain blood flow, carbon dioxide, middle cerebral artery, sleep", "chunk": "or restricted (4.27 \u00b1 0.93 h, <i>P</i> < 0.001) sleep duration. Middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) was measured at rest and during <i>1</i>) 5 min of carbogen air-breathing and <i>2</i>) five trials consisting of a period of eyes closed (30 s), followed by eyes open (40 s) while being challenged with a validated visual paradigm (Where's Waldo). Baseline MCAv was unaffected by acute sleep restriction (control: 64 \u00b1 14 cm/s; restricted 61 \u00b1 13 cm/s; <i>P</i> = 0.412). MCAv increased with CO<sub>2</sub>; however, there was no effect of restricted sleep (<i>P</i> = 0.488). MCAv increased in response to visual stimulation; the peak NVC response was reduced from control following restricted sleep (control: 16 \u00b1 12%; restricted: 9 \u00b1 7%; <i>P</i> = 0.008). Despite no effect of acute sleep restriction on resting CBF or the response to CO<sub>2</sub> in young men and women, NVC was attenuated following a", "source": "PubMed"}, {"chunk_id": "39661323_2", "pmid": "39661323", "title": "Impact of acute sleep restriction on cerebrovascular reactivity and neurovascular coupling in young men and women.", "authors": "McDonald MJ, Marsh ML, Fears SD et al.", "year": "2025", "journal": "Journal of applied physiology (Bethesda, Md. : 1985)", "keywords": "brain blood flow, carbon dioxide, middle cerebral artery, sleep", "chunk": "\u00b1 7%; <i>P</i> = 0.008). Despite no effect of acute sleep restriction on resting CBF or the response to CO<sub>2</sub> in young men and women, NVC was attenuated following a night of shortened sleep. These data support an important role for sleep in NVC and may have implications for the development of neurodegenerative disease states, such as Alzheimer's and dementia.<b>NEW & NOTEWORTHY</b> Chronic exposure to shortened sleep is associated with an increased risk of Alzheimer's disease and dementia. We examined the effect of acute sleep restriction (4-h time in bed) on cerebral blood flow in response to a metabolic (carbon dioxide) and a cognitive stimulus. Despite no effect of acute sleep restriction on resting cerebral blood flow or the response to carbon dioxide in young men and women, neurovascular coupling was attenuated following a night of shortened sleep.", "source": "PubMed"}, {"chunk_id": "39661323_3", "pmid": "39661323", "title": "Impact of acute sleep restriction on cerebrovascular reactivity and neurovascular coupling in young men and women.", "authors": "McDonald MJ, Marsh ML, Fears SD et al.", "year": "2025", "journal": "Journal of applied physiology (Bethesda, Md. : 1985)", "keywords": "brain blood flow, carbon dioxide, middle cerebral artery, sleep", "chunk": "to carbon dioxide in young men and women, neurovascular coupling was attenuated following a night of shortened sleep.", "source": "PubMed"}, {"chunk_id": "41440112_0", "pmid": "41440112", "title": "A Longitudinal Observational Study to Monitor the Outpatient-Caregiver Dyad in a Rehabilitation Hospital: Sociodemographic Characteristics and the Impact of Cognitive and Functional Impairment.", "authors": "Mancini D, Torlaschi V, Maffoni M et al.", "year": "2025", "journal": "Brain sciences", "keywords": "MCI, burden, caregiver, dementia, dyad, rehabilitation", "chunk": "<b>Background and objectives:</b> This study examines how sociodemographic, clinical, and psychological factors within the patient-caregiver dyad affect caregiver burden and health-related quality of life (HRQoL) in cognitive impairment. By comparing baseline data with a 1-year follow-up, the research aims to identify key predictors of caregiver burden and well-being. <b>Methods</b>: A longitudinal observational study was conducted in an Italian rehabilitation hospital, recruiting 132 outpatients and their caregivers at baseline, categorized as (a) Mild Cognitive Impairment (MCI, n = 33); (b) dementia (DEM, n = 58); (c) healthy subjects (No-CI, n = 41). One year after baseline assessment (T0), patients were contacted and invited for an in-person follow-up re-evaluation (T1). Most attrition was related to the COVID-19 pandemic. Statistical analyses included non-parametric tests for group comparisons and stepwise multiple linear regression to identify predictors of burden, adjusting for confounders (e.g., age, gender, education, employment, co-residence). <b>Results:</b> A total of 51 subjects (age:", "source": "PubMed"}, {"chunk_id": "41440112_1", "pmid": "41440112", "title": "A Longitudinal Observational Study to Monitor the Outpatient-Caregiver Dyad in a Rehabilitation Hospital: Sociodemographic Characteristics and the Impact of Cognitive and Functional Impairment.", "authors": "Mancini D, Torlaschi V, Maffoni M et al.", "year": "2025", "journal": "Brain sciences", "keywords": "MCI, burden, caregiver, dementia, dyad, rehabilitation", "chunk": "tests for group comparisons and stepwise multiple linear regression to identify predictors of burden, adjusting for confounders (e.g., age, gender, education, employment, co-residence). <b>Results:</b> A total of 51 subjects (age: 80.0 \u00b1 6.1) and 34 caregivers (age: 58.8 \u00b1 15.9) were evaluated. Patients were balanced by gender (53% males); most were retired (96%), married (62.7%), and cared for by sons (47%) or wife-husband (47%). Caregivers (females: 85%) were married (68.3%) and active workers (46.4%). Over one year, 17 No-CI subjects developed MCI or DEM; 15 MCI patients progressed to DEM. Caregiver HRQoL negatively correlated with distress and burden in MCI and DEM groups. Patient cognitive status, functional abilities, neuropsychiatric symptoms, and gender predicted caregiver burden, emphasizing the interplay between clinical and demographic factors. <b>Conclusions:</b> It is essential to monitor psychosocial factors in both the patient and the caregiver to develop effective prevention and support strategies.", "source": "PubMed"}, {"chunk_id": "41440112_2", "pmid": "41440112", "title": "A Longitudinal Observational Study to Monitor the Outpatient-Caregiver Dyad in a Rehabilitation Hospital: Sociodemographic Characteristics and the Impact of Cognitive and Functional Impairment.", "authors": "Mancini D, Torlaschi V, Maffoni M et al.", "year": "2025", "journal": "Brain sciences", "keywords": "MCI, burden, caregiver, dementia, dyad, rehabilitation", "chunk": "and demographic factors. <b>Conclusions:</b> It is essential to monitor psychosocial factors in both the patient and the caregiver to develop effective prevention and support strategies.", "source": "PubMed"}, {"chunk_id": "28159472_0", "pmid": "28159472", "title": "Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs.", "authors": "Chung MM, Nicol CJ, Cheng YC et al.", "year": "2017", "journal": "Experimental cell research", "keywords": "AGE, AMPK, Inflammatory response, Metformin, hNSCs", "chunk": "A growing body of evidence suggests type 2 diabetes mellitus (T2DM) is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanisms remain unclear, T2DM may exacerbate neurodegenerative processes. AMP-activated protein kinase (AMPK) signaling is an evolutionary preserved pathway that is important during homeostatic energy biogenesis responses at both the cellular and whole-body levels. Metformin, a ubiquitously prescribed anti-diabetic drug, exerts its effects by AMPK activation. However, while the roles of AMPK as a metabolic mediator are generally well understood, its performance in neuroprotection and neurodegeneration are not yet well defined. Given hyperglycemia is accompanied by an accelerated rate of advanced glycosylation end product (AGE) formation, which is associated with the pathogenesis of diabetic neuronal impairment and, inflammatory response, clarification of the role of AMPK signaling in these processes is needed. Therefore, we tested the hypothesis that metformin, an AMPK activator, protects against diabetic AGE induced neuronal", "source": "PubMed"}, {"chunk_id": "28159472_1", "pmid": "28159472", "title": "Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs.", "authors": "Chung MM, Nicol CJ, Cheng YC et al.", "year": "2017", "journal": "Experimental cell research", "keywords": "AGE, AMPK, Inflammatory response, Metformin, hNSCs", "chunk": "inflammatory response, clarification of the role of AMPK signaling in these processes is needed. Therefore, we tested the hypothesis that metformin, an AMPK activator, protects against diabetic AGE induced neuronal impairment in human neural stem cells (hNSCs). In the present study, hNSCs exposed to AGE had significantly reduced cell viability, which correlated with elevated inflammatory cytokine expression, such as IL-1\u03b1, IL-1\u03b2, IL-2, IL-6, IL-12 and TNF-\u03b1. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. In addition, metformin rescued the transcript and protein expression levels of acetyl-CoA carboxylase (ACC) and inhibitory kappa B kinase (IKK) in AGE-treated hNSCs. NF-\u03baB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses, and metformin did prevent the AGE-mediated increase in NF-\u03baB mRNA and protein levels in the hNSCs exposed to AGE. Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS)", "source": "PubMed"}, {"chunk_id": "28159472_2", "pmid": "28159472", "title": "Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs.", "authors": "Chung MM, Nicol CJ, Cheng YC et al.", "year": "2017", "journal": "Experimental cell research", "keywords": "AGE, AMPK, Inflammatory response, Metformin, hNSCs", "chunk": "and metformin did prevent the AGE-mediated increase in NF-\u03baB mRNA and protein levels in the hNSCs exposed to AGE. Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs. These findings extend our understanding of the central role of AMPK in AGE induced inflammatory responses, which increase the risk of neurodegeneration in diabetic patients.", "source": "PubMed"}, {"chunk_id": "41023536_0", "pmid": "41023536", "title": "Associations of neurodegenerative proteins with brain iron deposition and cognition in cerebral small vessel disease: a quantitative susceptibility mapping and plasma biomarker study.", "authors": "Chen Y, Li M, Li J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "cerebral small vessel disease, iron, neurodegeneration, quantitative susceptibility mapping, tau", "chunk": "Cerebral small vessel disease (CSVD) is a common neurological disorder with limited pathology on conventional magnetic resonance imaging. This study uses quantitative susceptibility mapping (QSM) to investigate links among brain iron, plasma neurodegenerative proteins, and cognition in CSVD. This study enrolled 319 CSVD patients, grouped into CSVD-M and CSVD-S. Plasma proteins were measured in 178 participants, with 80 being followed up after 2 years. QSM-based voxel-wise analysis assessed brain iron, CSVD severity, and protein correlations. A cross-lagged panel model was used to analyze the temporal association between plasma protein levels and brain iron levels. In CSVD-S, elevated QSM values in the right Rolandic operculum/superior temporal gyrus negatively correlated with plasma A\u03b242 and executive function. A\u03b242 also negatively correlated with QSM in cortical regions, tied to episodic memory decline. Higher baseline A\u03b240 predicted increased QSM in the left putamen at follow-up. Plasma A\u03b242 and A\u03b240 may drive brain iron deposition and", "source": "PubMed"}, {"chunk_id": "41023536_1", "pmid": "41023536", "title": "Associations of neurodegenerative proteins with brain iron deposition and cognition in cerebral small vessel disease: a quantitative susceptibility mapping and plasma biomarker study.", "authors": "Chen Y, Li M, Li J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "cerebral small vessel disease, iron, neurodegeneration, quantitative susceptibility mapping, tau", "chunk": "in cortical regions, tied to episodic memory decline. Higher baseline A\u03b240 predicted increased QSM in the left putamen at follow-up. Plasma A\u03b242 and A\u03b240 may drive brain iron deposition and cognitive impairment in CSVD, serving as potential early biomarkers for disease progression. QSM reveals brain iron links to A\u03b242, cognition in CSVD. Plasma A\u03b242 correlates with iron in motor and frontal areas. High A\u03b240 predicts putamen iron increase in CSVD follow-up. Iron deposition is tied to executive, memory deficits in CSVD.", "source": "PubMed"}, {"chunk_id": "37216716_0", "pmid": "37216716", "title": "An extensible hierarchical graph convolutional network for early Alzheimer's disease identification.", "authors": "Tian X, Liu Y, Wang L et al.", "year": "2023", "journal": "Computer methods and programs in biomedicine", "keywords": "Alzheimer\u2019S disease, Computer-aided disease diagnosis, Deep learning, Graph convolutional networks, Magnetic resonance imaging (MRI)", "chunk": "For early identification of Alzheimer's disease (AD) based on multi-modal magnetic resonance imaging (MRI) data, it is important to make comprehensive use of image features and non-image information to analyze the gray matter atrophy and the structural/functional connectivity abnormalities for different courses of AD. In this study, we propose an extensible hierarchical graph convolutional network (EH-GCN) for early AD identification. Based on the extracted image features from multi-modal MRI data using the presented multi-branch residual network (ResNet), the brain regions-of-interests (ROIs) based GCN is built to extract structural and functional connectivity features between different ROIs of the brain. In order to further improve the performance of AD identification, an optimized spatial GCN is proposed as convolution operator in the population-based GCN to avoid rebuilding the graph network and take advantage of relationships between subjects. Finally, the proposed EH-GCN is built by embedding the image features and internal brain connectivity features", "source": "PubMed"}, {"chunk_id": "37216716_1", "pmid": "37216716", "title": "An extensible hierarchical graph convolutional network for early Alzheimer's disease identification.", "authors": "Tian X, Liu Y, Wang L et al.", "year": "2023", "journal": "Computer methods and programs in biomedicine", "keywords": "Alzheimer\u2019S disease, Computer-aided disease diagnosis, Deep learning, Graph convolutional networks, Magnetic resonance imaging (MRI)", "chunk": "GCN to avoid rebuilding the graph network and take advantage of relationships between subjects. Finally, the proposed EH-GCN is built by embedding the image features and internal brain connectivity features into the spatial population-based GCN, which provides an extensible way to improve early AD identification performance by adding imaging features and non-image information from multi-modal data. Experiments are performed on two datasets, which illustrate the effectiveness of the extracted structural/functional connectivity features and the high computational efficiency of the proposed method. The classification accuracy of AD vs NC, AD vs MCI and MCI vs NC classification tasks reaches 88.71%, 82.71% and 79.68% respectively. The extracted connectivity features between ROIs indicate that functional abnormalities are earlier than gray matter atrophy and abnormalities of structural connections, which is consistent with the clinical manifestations. The proposed method allows for the addition of other modal image features and non-image information from multi-modal data to", "source": "PubMed"}, {"chunk_id": "37216716_2", "pmid": "37216716", "title": "An extensible hierarchical graph convolutional network for early Alzheimer's disease identification.", "authors": "Tian X, Liu Y, Wang L et al.", "year": "2023", "journal": "Computer methods and programs in biomedicine", "keywords": "Alzheimer\u2019S disease, Computer-aided disease diagnosis, Deep learning, Graph convolutional networks, Magnetic resonance imaging (MRI)", "chunk": "abnormalities of structural connections, which is consistent with the clinical manifestations. The proposed method allows for the addition of other modal image features and non-image information from multi-modal data to continuously improve the performance of clinical data analysis. The proposed method can help us comprehensively analyze the role of gray matter atrophy, the damage of white matter nerve fiber tracts and the degradation of functional connectivity for different courses of AD, which could be useful for further extraction of clinical biomarkers for early AD identification.", "source": "PubMed"}, {"chunk_id": "40801838_0", "pmid": "40801838", "title": "Reducing ARIA risk in Alzheimer's disease: Real-world impact of <i>APOE</i> genotype-guided slow titration with aducanumab and lecanemab.", "authors": "Mervosh N, Bilici N, Wisniewski T et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE genotype, Alzheimer's disease, aducanumab, amyloid-related imaging abnormalities, lecanemab, monoclonal antibodies, real-world evidence, slow titration", "chunk": "We evaluated whether apolipoprotein E (<i>APOE</i>) genotype-guided slow titration of monoclonal antibodies reduced amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease. We retrospectively analyzed ARIA incidence in 25 patients on aducanumab and 19 patients on lecanemab on a genotype-informed protocol in a private practice setting. ARIA-E and ARIA-H each occurred in 4% of the aducanumab group and 5% of the lecanemab group. Plaque clearance was achieved in 50% of evaluable aducanumab patients and 26.3% of lecanemab patients. Compared to clinical trial ARIA rates, our results suggest that individualized, genotype-informed titration improves safety although plaque clearance rates were less robust.", "source": "PubMed"}, {"chunk_id": "41249905_0", "pmid": "41249905", "title": "A case report of CLIPPERS syndrome with gait and cognitive impairment.", "authors": "Shrestha AM, Bashyal S, Kharbuja N et al.", "year": "2025", "journal": "BMC neurology", "keywords": "CLIPPERS, Cognitive impairment, Corticosteroids, Inflammation, Pontocerebellar", "chunk": "Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) syndrome is a rare, chronic inflammatory central nervous system (CNS) disorder. It primarily involves the brainstem and cerebellum, presenting with subacute neurological symptoms. A 44-year-old male presented with progressive gait imbalance, cognitive dysfunction, and behavioral changes over six weeks. Neurological examination revealed a wide-based unsteady gait, cerebellar dysmetria, and mild cognitive deficits. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis and elevated protein, while infectious and neoplastic causes were ruled out. Brain MRI demonstrated nodular and patchy lesions involving the cerebellum, brainstem, and thalamus, with characteristic pepper-like post-contrast enhancement consistent with CLIPPERS syndrome. High-dose intravenous methylprednisolone (1 g/day for 5 days) led to significant clinical improvement, including resolution of gait disturbance and cognitive deficits. Follow-up MRI showed a marked reduction in lesion size. Maintenance therapy with oral methotrexate was initiated to sustain remission. CLIPPERS syndrome should be considered in patients", "source": "PubMed"}, {"chunk_id": "41249905_1", "pmid": "41249905", "title": "A case report of CLIPPERS syndrome with gait and cognitive impairment.", "authors": "Shrestha AM, Bashyal S, Kharbuja N et al.", "year": "2025", "journal": "BMC neurology", "keywords": "CLIPPERS, Cognitive impairment, Corticosteroids, Inflammation, Pontocerebellar", "chunk": "disturbance and cognitive deficits. Follow-up MRI showed a marked reduction in lesion size. Maintenance therapy with oral methotrexate was initiated to sustain remission. CLIPPERS syndrome should be considered in patients presenting with subacute pontocerebellar dysfunction and characteristic MRI findings. Early diagnosis and prompt corticosteroid therapy can lead to favorable outcomes. Long-term immunosuppressive treatment is essential to prevent relapse. Careful follow-up is required to monitor for recurrence and potential malignant transformation.", "source": "PubMed"}, {"chunk_id": "41761793_0", "pmid": "41761793", "title": "Comparative assessment of donepezil memantine and sodium oligomannate on cognitive decline and neuroinflammation in early Alzheimer's disease.", "authors": "Deng X, Zeng Y, Ding D", "year": "2026", "journal": "Pakistan journal of pharmaceutical sciences", "keywords": "Donepezil, Early Alzheimer's disease, Memantine, Sodium oligomannate", "chunk": "Early Alzheimer's disease (AD) treatments include donepezil, memantine and sodium oligomannate, but their comparative effects on cognitive decline and neuroinflammation are understudied. This study compares three drugs' validity in improving two aspects in early AD patients. 132 early AD patients from XX Hospital (Jan 2022-Dec 2024) were retrospectively included. After exclusion, 126 patients were divided into 3 groups (42 each): Group A (donepezil), Group B (memantine), Group C (sodium oligomannate). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-cog), the Activity of Daily Living Scale (ADL), the Montreal Cognitive Assessment Scale (MoCA), levels of inflammatory mediators, including Tumour Necrosis Factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), interleukin-8 (IL-8), neuronal marker levels including \u03b2-Amyloid (1-42) (A\u03b242), Total tau protein (T-tau protein) and adverse reaction incidence. After treatment, compared with Group A, Groups B/C had significantly higher MMSE, ADL, MoCA, A\u03b242 (all P<0.05) and lower ADAS-cog, TNF-\u03b1,", "source": "PubMed"}, {"chunk_id": "41761793_1", "pmid": "41761793", "title": "Comparative assessment of donepezil memantine and sodium oligomannate on cognitive decline and neuroinflammation in early Alzheimer's disease.", "authors": "Deng X, Zeng Y, Ding D", "year": "2026", "journal": "Pakistan journal of pharmaceutical sciences", "keywords": "Donepezil, Early Alzheimer's disease, Memantine, Sodium oligomannate", "chunk": "Total tau protein (T-tau protein) and adverse reaction incidence. After treatment, compared with Group A, Groups B/C had significantly higher MMSE, ADL, MoCA, A\u03b242 (all P<0.05) and lower ADAS-cog, TNF-\u03b1, IL-6, IL-8, T-tau (all P<0.05); compared with Group B, Group C had no significant difference in MMSE, ADAS-cog, ADL, MoCA (all P>0.05), but higher A\u03b242 and lower TNF-\u03b1, IL-6, IL-8, T-tau (all P<0.05); adverse reaction incidence did not differ significantly among the three groups (P>0.05). Memantine and sodium oligomannate outperform donepezil in improving cognitive function and neuroinflammation, with sodium oligomannate suggesting the best effect on neuroinflammation. This study provides a scientific basis for optimizing early AD medication.", "source": "PubMed"}, {"chunk_id": "33916835_0", "pmid": "33916835", "title": "High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer's Disease Signatures.", "authors": "Zuliani I, Lanzillotta C, Tramutola A et al.", "year": "2021", "journal": "International journal of molecular sciences", "keywords": "brain insulin resistance, high-fat diet, mitochondria, neurodegeneration, protein O-GlcNAcylation", "chunk": "The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer's disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling", "source": "PubMed"}, {"chunk_id": "33916835_1", "pmid": "33916835", "title": "High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer's Disease Signatures.", "authors": "Zuliani I, Lanzillotta C, Tramutola A et al.", "year": "2021", "journal": "International journal of molecular sciences", "keywords": "brain insulin resistance, high-fat diet, mitochondria, neurodegeneration, protein O-GlcNAcylation", "chunk": "(HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.", "source": "PubMed"}, {"chunk_id": "32680941_0", "pmid": "32680941", "title": "NfL as a biomarker for neurodegeneration and survival in Parkinson disease.", "authors": "B\u00e4ckstr\u00f6m D, Linder J, Jakobson Mo S et al.", "year": "2020", "journal": "Neurology", "keywords": "None", "chunk": "To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD). We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Ume\u00e5 (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years. Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death", "source": "PubMed"}, {"chunk_id": "32680941_1", "pmid": "32680941", "title": "NfL as a biomarker for neurodegeneration and survival in Parkinson disease.", "authors": "B\u00e4ckstr\u00f6m D, Linder J, Jakobson Mo S et al.", "year": "2020", "journal": "Neurology", "keywords": "None", "chunk": "symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts. cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials. This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.", "source": "PubMed"}, {"chunk_id": "40869398_0", "pmid": "40869398", "title": "The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson's Disease: A Systematic Review.", "authors": "Zeidan O, Jaragh N, Tama M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, cognitive decline, dementia, insulin resistance, type 2 diabetes", "chunk": "Parkinson's disease (PD) is a common neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. While PD is most recognized by its motor symptoms (resting tremor, rigidity, bradykinesia, and postural instability), cognitive decline (CD) may become apparent as PD progresses, leading to Parkinson's disease dementia (PDD). Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are risk factors for dementia, especially Alzheimer's disease; however, their influence on dementia in PD is underexplored. Therefore, we sought to determine the effect of T2DM and IR on dementia in PD. A systematic search of articles from 2005 to March 2025 was undertaken using Embase, PubMed, Scopus, Web of Science, and citation searching. Case-control, cross-sectional, longitudinal, and non-human population studies assessing cognitive outcomes in individuals with PD, with and without T2DM and IR, were included (PROSPERO registration number CRD420251013367). In total, 27 studies met", "source": "PubMed"}, {"chunk_id": "40869398_1", "pmid": "40869398", "title": "The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson's Disease: A Systematic Review.", "authors": "Zeidan O, Jaragh N, Tama M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, cognitive decline, dementia, insulin resistance, type 2 diabetes", "chunk": "cross-sectional, longitudinal, and non-human population studies assessing cognitive outcomes in individuals with PD, with and without T2DM and IR, were included (PROSPERO registration number CRD420251013367). In total, 27 studies met the inclusion criteria, with clinical sample sizes ranging from 23 to 544,162 participants. Among the 23 clinical studies, 15 identified T2DM as a contributor to cognitive decline (CD) in PD, and 4 specifically examined insulin resistance (IR). Elevated HbA1c was consistently associated with poorer cognitive performance and increased risk of Parkinson's disease dementia (PDD); HbA1c \u2265 7% independently predicted cognitive impairment (OR = 4.25, 95% CI: 1.59-11.34). Vascular and inflammatory markers, including elevated LDL-C, fibrinogen, and hs-CRP, further exacerbated CD. MoCA and MMSE scores were the most common cognitive measures, consistently showing worse outcomes in PD patients with T2DM. Preclinical studies supported these associations, showing that high-fat-diet-induced T2DM and IR aggravated dopaminergic neuronal loss by 38-45%, increased \u03b1-synuclein by 35%,", "source": "PubMed"}, {"chunk_id": "40869398_2", "pmid": "40869398", "title": "The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson's Disease: A Systematic Review.", "authors": "Zeidan O, Jaragh N, Tama M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, cognitive decline, dementia, insulin resistance, type 2 diabetes", "chunk": "consistently showing worse outcomes in PD patients with T2DM. Preclinical studies supported these associations, showing that high-fat-diet-induced T2DM and IR aggravated dopaminergic neuronal loss by 38-45%, increased \u03b1-synuclein by 35%, and heightened microglial activation, providing mechanistic evidence for the observed clinical associations. This systematic review, the first to examine the impact of T2DM and IRs on the occurrence and advancement of CD in PD patients, demonstrates a possible association between the two. However, these results demonstrate the need for larger sample sizes and the inclusion of additional clinical variables, such as HbA1c levels and pharmacological interventions, providing further information about the link between metabolic dysfunction and CD in PD. To further strengthen this link, longitudinal studies with systematic follow-ups are essential to establish causal links and avoid misdiagnosis in clinical practice.", "source": "PubMed"}, {"chunk_id": "40869398_3", "pmid": "40869398", "title": "The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson's Disease: A Systematic Review.", "authors": "Zeidan O, Jaragh N, Tama M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, cognitive decline, dementia, insulin resistance, type 2 diabetes", "chunk": "essential to establish causal links and avoid misdiagnosis in clinical practice.", "source": "PubMed"}, {"chunk_id": "36797344_0", "pmid": "36797344", "title": "Bidirectional alterations in brain temperature profoundly modulate spatiotemporal neurovascular responses in-vivo.", "authors": "Boorman LW, Harris SS, Shabir O et al.", "year": "2023", "journal": "Communications biology", "keywords": "None", "chunk": "Neurovascular coupling (NVC) is a mechanism that, amongst other known and latent critical functions, ensures activated brain regions are adequately supplied with oxygen and glucose. This biological phenomenon underpins non-invasive perfusion-related neuroimaging techniques and recent reports have implicated NVC impairment in several neurodegenerative disorders. Yet, much remains unknown regarding NVC in health and disease, and only recently has there been burgeoning recognition of a close interplay with brain thermodynamics. Accordingly, we developed a novel multi-modal approach to systematically modulate cortical temperature and interrogate the spatiotemporal dynamics of sensory-evoked NVC. We show that changes in cortical temperature profoundly and intricately modulate NVC, with low temperatures associated with diminished oxygen delivery, and high temperatures inducing a distinct vascular oscillation. These observations provide novel insights into the relationship between NVC and brain thermodynamics, with important implications for brain-temperature related therapies, functional biomarkers of elevated brain temperature, and in-vivo methods to study neurovascular coupling.", "source": "PubMed"}, {"chunk_id": "36797344_1", "pmid": "36797344", "title": "Bidirectional alterations in brain temperature profoundly modulate spatiotemporal neurovascular responses in-vivo.", "authors": "Boorman LW, Harris SS, Shabir O et al.", "year": "2023", "journal": "Communications biology", "keywords": "None", "chunk": "novel insights into the relationship between NVC and brain thermodynamics, with important implications for brain-temperature related therapies, functional biomarkers of elevated brain temperature, and in-vivo methods to study neurovascular coupling.", "source": "PubMed"}, {"chunk_id": "34024834_0", "pmid": "34024834", "title": "Cerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer's Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.", "authors": "Duan W, Zhou GD, Balachandrasekaran A et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, arterial spin labeling, cerebral blood flow, longitudinal study, mild cognitive impairment, prediction", "chunk": "This is the first longitudinal study to assess regional cerebral blood flow (rCBF) changes during the progression from normal control (NC) through mild cognitive impairment (MCI) and Alzheimer's disease (AD). We aim to determine if perfusion MRI biomarkers, derived from our prior cross-sectional study, can predict the onset and cognitive decline of AD. Perfusion MRIs using arterial spin labeling (ASL) were acquired in 15 stable-NC, 14 NC-to-MCI, 16 stable-MCI, and 18 MCI/AD-to-AD participants from the Cardiovascular Health Study (CHS) cognition study. Group comparisons, predictions of AD conversion and time to conversion, and Modified Mini-Mental State Examination (3MSE) from rCBF were performed. Compared to the stable-NC group: 1) the stable-MCI group exhibited rCBF decreases in the right temporoparietal (p = 0.00010) and right inferior frontal and insula (p = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p = 0.00062 and 0.0035). Compared to", "source": "PubMed"}, {"chunk_id": "34024834_1", "pmid": "34024834", "title": "Cerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer's Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.", "authors": "Duan W, Zhou GD, Balachandrasekaran A et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, arterial spin labeling, cerebral blood flow, longitudinal study, mild cognitive impairment, prediction", "chunk": "and right inferior frontal and insula (p = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p = 0.00062 and 0.0035). Compared to the NC-to-MCI group, the stable-MCI group exhibited a rCBF decrease in the right hippocampus region (p = 0.0053). The baseline rCBF values in the posterior cingulate cortex (PCC) (p = 0.0043), bilateral superior medial frontal regions (BSMF) (p = 0.012), and left inferior frontal (p = 0.010) regions predicted the 3MSE scores for all the participants at follow-up. The baseline rCBF in the PCC and BSMF regions predicted the conversion and time to conversion from MCI to AD (p < 0.05; not significant after multiple corrections). We demonstrated the feasibility of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline.", "source": "PubMed"}, {"chunk_id": "34024834_2", "pmid": "34024834", "title": "Cerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer's Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.", "authors": "Duan W, Zhou GD, Balachandrasekaran A et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, arterial spin labeling, cerebral blood flow, longitudinal study, mild cognitive impairment, prediction", "chunk": "of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline.", "source": "PubMed"}, {"chunk_id": "36627944_0", "pmid": "36627944", "title": "Type 2 Diabetes Mellitus, Platelet Activation and Alzheimer's Disease: A Possible Connection.", "authors": "Carbone MG, Pomara N, Callegari C et al.", "year": "2022", "journal": "Clinical neuropsychiatry", "keywords": "Alzheimer\u2019s disease, neuroinflammation, perivascular inflammation, platelet activation, type 2 diabetes mellitus, \u03b2-amyloid", "chunk": "Type 2 diabetes mellitus DM (T2DM) is associated with a 70% increased risk for dementia, including Alzheimer's disease (AD). Insulin resistance has been proposed to play a pivotal role in both T2DM and AD and the concept of \"brain insulin resistance\" has been suggested as an interpretation to the growing literature regarding cognitive impairment and T2DM. Subjects with T2DM present an abnormal platelet reactivity that together with insulin resistance, hyperglycaemia and dyslipidaemia effect the vascular wall by a series of events including endothelial dysfunction, oxidative stress and low-grade inflammation. Activated platelets directly contribute to cerebral amyloid angiopathy (CAA) by promoting the formation of \u03b2-amyloid (A\u03b2) aggregates and that A\u03b2, in turn, activates platelets, creating a feed-forward loop suggesting the involvement of platelets in the AD pathogenesis. Moreover, islet amyloid polypeptide deposition, co-localized with A\u03b2 deposits, is a common finding in the brain of patients with T2DM. These observations raise the", "source": "PubMed"}, {"chunk_id": "36627944_1", "pmid": "36627944", "title": "Type 2 Diabetes Mellitus, Platelet Activation and Alzheimer's Disease: A Possible Connection.", "authors": "Carbone MG, Pomara N, Callegari C et al.", "year": "2022", "journal": "Clinical neuropsychiatry", "keywords": "Alzheimer\u2019s disease, neuroinflammation, perivascular inflammation, platelet activation, type 2 diabetes mellitus, \u03b2-amyloid", "chunk": "of platelets in the AD pathogenesis. Moreover, islet amyloid polypeptide deposition, co-localized with A\u03b2 deposits, is a common finding in the brain of patients with T2DM. These observations raise the intriguing prospect that traditional or novel antiplatelet therapeutic strategies may alleviate fibril formation and could be used in the prevention or treatment of AD subjects with diabetes.", "source": "PubMed"}, {"chunk_id": "40542388_0", "pmid": "40542388", "title": "Sleep disorders and Alzheimer's disease: relationship and mechanisms involving neuroinflammation, orexin and A\u03b2.", "authors": "Zhang W, Lian T, He M et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "Alzheimer\u2019s disease, Cerebrospinal fluid, Neuroinflammation, Orexin, Short sleep duration, \u03b2 amyloid", "chunk": "Sleep disorders are common in Alzheimer's disease (AD), but the underlying mechanisms are unknown. This study aimed to specifically investigate the relationship between a specific sleep disorder of short sleep duration (SSD) and AD, and related mechanisms involving neuroinflammation, orexin and AD biomarkers in both AD patients and mice. In part I, total 247 AD patients were consecutively recruited and categorized into AD with SSD (AD-SSD, < 6 h) and AD with no SSD (AD-nSSD, 7-8 h). Comparisons were made between the two groups in cognitive function, neuroinflammatory factors, orexinergic factors and AD biomarkers in cerebrospinal fluid (CSF). The correlations of orexinergic factors with the neuroinflammatory factors and AD biomarkers in CSF from AD-SSD group were investigated. In part II, the spatiotemporal relationships among glial activation, orexin expression, AD pathology, sleep architecture disturbance and cognitive function in 5XFAD mice were dynamically explored and the potential mechanisms underlying their relationships were", "source": "PubMed"}, {"chunk_id": "40542388_1", "pmid": "40542388", "title": "Sleep disorders and Alzheimer's disease: relationship and mechanisms involving neuroinflammation, orexin and A\u03b2.", "authors": "Zhang W, Lian T, He M et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "Alzheimer\u2019s disease, Cerebrospinal fluid, Neuroinflammation, Orexin, Short sleep duration, \u03b2 amyloid", "chunk": "the spatiotemporal relationships among glial activation, orexin expression, AD pathology, sleep architecture disturbance and cognitive function in 5XFAD mice were dynamically explored and the potential mechanisms underlying their relationships were analyzed. In part I, compared to AD-nSSD group, AD-SSD group exhibited significantly poorer cognitive performance on the Montreal Cognitive Assessment and the Auditory Verbal Learning Test-delayed recall scales, higher orexin A level in CSF and lower \u03b2 amyloid (A\u03b2) 42 level in CSF (all P < 0.05). Furthermore, orexin A had a positive correlation with prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) (r = 0.322, P = 0.002) and a negative correlation with A\u03b242 (r = -0.223, P = 0.027) levels in CSF from AD-SSD group. In part II, compared with WT mice, 5XFAD mice displayed elevated hippocampal glial fibrillary acidic protein level at 3.5 months, increased hippocampal/cortical Chitinase-3-like protein 1 level, hypothalamic orexin A level and sleep architecture disturbance at 4.5 months, elevated", "source": "PubMed"}, {"chunk_id": "40542388_2", "pmid": "40542388", "title": "Sleep disorders and Alzheimer's disease: relationship and mechanisms involving neuroinflammation, orexin and A\u03b2.", "authors": "Zhang W, Lian T, He M et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "Alzheimer\u2019s disease, Cerebrospinal fluid, Neuroinflammation, Orexin, Short sleep duration, \u03b2 amyloid", "chunk": "mice displayed elevated hippocampal glial fibrillary acidic protein level at 3.5 months, increased hippocampal/cortical Chitinase-3-like protein 1 level, hypothalamic orexin A level and sleep architecture disturbance at 4.5 months, elevated insoluble A\u03b242 deposition in hippocampus, orexinergic neuronal numbers in lateral hypothalamus, colocalization of their fibers with A\u03b2 in cerebral cortex and cognitive impairment at 5.5 months old (all P < 0.05). SSD in AD is associated with significant cognitive impairment, neuroinflammation, orexin elevation and A\u03b2 deposition. Hippocampal astroglial activation, hypothalamic orexin elevation and sleep architecture disturbance precede A\u03b2 deposition in hippocampus and cognitive impairment in 5XFAD mice.", "source": "PubMed"}, {"chunk_id": "39878109_0", "pmid": "39878109", "title": "Associations Between Metabolomics Findings and Brain Hypometabolism in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Mir M, Khosravani P, Ramezannezhad E et al.", "year": "2024", "journal": "Current Alzheimer research", "keywords": "ADNI., Alzheimer's Disease, biomarkers, dementia, fluorodeoxyglucose-positron emission tomography (FDG PET), metabolomics", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disease with rising prevalence due to the aging global population. Existing methods for diagnosing AD are struggling to detect the condition in its earliest and most treatable stages. One early indicator of AD is a substantial decrease in the brain's glucose metabolism. Metabolomics can detect disturbances in biofluids, which may be advantageous for early detection of some AD-related changes. The study aims to predict brain hypometabolism in Alzheimer's disease using metabolomics findings and develop a predictive model based on metabolomic data. The data used in this study were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. We conducted a longitudinal study with three assessment time points to investigate the predictive power of baseline metabolomics for modeling longitudinal fluorodeoxyglucose- positron emission tomography (FDG-PET) trajectory changes in AD patients. A total of 44 participants with AD were included. The Alzheimer's Disease Assessment Scale (ADAS),", "source": "PubMed"}, {"chunk_id": "39878109_1", "pmid": "39878109", "title": "Associations Between Metabolomics Findings and Brain Hypometabolism in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Mir M, Khosravani P, Ramezannezhad E et al.", "year": "2024", "journal": "Current Alzheimer research", "keywords": "ADNI., Alzheimer's Disease, biomarkers, dementia, fluorodeoxyglucose-positron emission tomography (FDG PET), metabolomics", "chunk": "baseline metabolomics for modeling longitudinal fluorodeoxyglucose- positron emission tomography (FDG-PET) trajectory changes in AD patients. A total of 44 participants with AD were included. The Alzheimer's Disease Assessment Scale (ADAS), the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) were used for cognitive assessments. A single global brain hypo-metabolism index was used as the outcome variable. Across models, we observed consistent positive relationships between specific cholesterol esters - CE (20:3) (p = 0.005) and CE (18:3) (p = 0.0039) - and FDG-PET metrics, indicating these baseline metabolites may be valuable indicators of future PET score changes. Selected triglycerides like DG-O (16:0-20:4) also showed time-specific positive associations (p = 0.017). This research provides new insights into the disruptions in the metabolic network linked to AD pathology. These findings could pave the way for identifying novel biomarkers and potential treatment targets for AD.", "source": "PubMed"}, {"chunk_id": "39878109_2", "pmid": "39878109", "title": "Associations Between Metabolomics Findings and Brain Hypometabolism in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Mir M, Khosravani P, Ramezannezhad E et al.", "year": "2024", "journal": "Current Alzheimer research", "keywords": "ADNI., Alzheimer's Disease, biomarkers, dementia, fluorodeoxyglucose-positron emission tomography (FDG PET), metabolomics", "chunk": "the disruptions in the metabolic network linked to AD pathology. These findings could pave the way for identifying novel biomarkers and potential treatment targets for AD.", "source": "PubMed"}, {"chunk_id": "38058357_0", "pmid": "38058357", "title": "Blood-based biomarkers in Alzheimer's disease: Future directions for implementation.", "authors": "Suridjan I, van der Flier WM, Monsch AU et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, amyloid pathology, blood\u2010based biomarker, clinical practice, diagnosis, qualitative, screening", "chunk": "Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) will increase diagnostic demand. A non-invasive blood-based biomarker (BBBM) test for detection of amyloid-\u03b2 pathology may reduce diagnostic barriers and facilitate DMT initiation. To explore heterogeneity in AD care pathways and potential role of BBBM tests. Survey of 213 healthcare professionals/payers in US/China/UK/Germany/Spain/France and two advisory boards (US/Europe). Current diagnostic pathways are heterogeneous, meaning many AD patients are missed while low-risk patients undergo unnecessary procedures. Confirmatory amyloid testing (cerebrospinal fluid biomarkers/positron emission tomography) is utilized in few patients, resulting in diagnostic/treatment delays. A high negative-predictive-value test could streamline the diagnostic pathway by reducing unnecessary procedures in low-risk patients; supporting confirmatory testing where needed. Imminent approval of DMTs will increase need for fast and reliable AD diagnostic tests. An easy-to-use, accurate, non-invasive BBBM test for amyloid pathology could guide diagnostic procedures or referral, streamlining early diagnosis and DMT initiation. This study explored AD care", "source": "PubMed"}, {"chunk_id": "38058357_1", "pmid": "38058357", "title": "Blood-based biomarkers in Alzheimer's disease: Future directions for implementation.", "authors": "Suridjan I, van der Flier WM, Monsch AU et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, amyloid pathology, blood\u2010based biomarker, clinical practice, diagnosis, qualitative, screening", "chunk": "reliable AD diagnostic tests. An easy-to-use, accurate, non-invasive BBBM test for amyloid pathology could guide diagnostic procedures or referral, streamlining early diagnosis and DMT initiation. This study explored AD care pathways and how BBBM may meet diagnostic demandsCurrent diagnostic pathways are heterogeneous, with country and setting variationsMany AD patients are missed, while low-risk patients undergo unnecessary proceduresAn easy-to-use, accurate, non-invasive BBBM test for amyloid pathology is neededThis test could streamline early diagnosis of amyloid pathology and DMT initiation.", "source": "PubMed"}, {"chunk_id": "40566796_0", "pmid": "40566796", "title": "Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.", "authors": "Burns JM, Morris JK, Vidoni ED et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's, MRS, SGLT2, dapagliflozin, glucose, metabolism", "chunk": "Due to its metabolic effects, dapagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, holds potential as an Alzheimer's disease (AD) therapeutic. We conducted a double-blind, randomized, placebo-controlled, parallel-group, 12-week single-site study to investigate the effect of dapagliflozin in participants with probable AD (Mini-Mental State Examination [MMSE] score 15-26). We planned to enroll 48 participants with 2:1 randomization to 10 mg dapagliflozin once daily (n = 32) versus matching placebo (n = 16). The primary objective was the effect of dapagliflozin on cerebral N-acetylaspartate (NAA). We also assessed safety, glycemic control, body composition, brain metabolism, and cognition. There was no change in the primary outcome. There were no significant adverse event differences. Hemoglobin A1c, fat mass, and fat-free lean mass decreased; brain glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved. Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may", "source": "PubMed"}, {"chunk_id": "40566796_1", "pmid": "40566796", "title": "Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.", "authors": "Burns JM, Morris JK, Vidoni ED et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's, MRS, SGLT2, dapagliflozin, glucose, metabolism", "chunk": "glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved. Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may affect the brain. Dapagliflozin did not alter magnetic resonance spectroscopy N-acetylaspartate (primary outcome) in this exploratory Alzheimer's disease (AD) trial. Dapagliflozin-induced glucose disposal is sufficient to alter systemic metabolism. AD patients taking dapagliflozin exhibited metabolic effects seen in diabetics.", "source": "PubMed"}, {"chunk_id": "41135100_0", "pmid": "41135100", "title": "Potential Risk to Brain Health after Surgical Interventions: Biomarkers to Predict the Occurrence of Cognitive Decline.", "authors": "Rey-Picazo J, Pita J, Pe\u00f1a L et al.", "year": "2025", "journal": "Aging and disease", "keywords": "None", "chunk": "As the global population ages, the number of people living with dementia is projected to increase significantly. Estimations indicate that over 150 million people worldwide will be living with dementia by 2050, with Alzheimer's disease being the most common cause. Elderly people are also at greater risk of undergoing surgery, either elective or emergency, escalating the associated likelihood leading to cognitive decline, especially if accumulative. However, the relationship between surgery and dementia development remains controversial. The cause seems to lie in the heterogeneous preoperative state of subjects participating in research studies. Interpreting and comparing the results of these studies could be an arduous task due to variables such as medication, follow-up time, type of surgery and anesthesia, duration and invasiveness of the surgical intervention, differential neuroinflammatory response, the patient metabolic/biochemical status or if there are comorbidities. Considering the complexity of this type of studies, the present review summarizes the most", "source": "PubMed"}, {"chunk_id": "41135100_1", "pmid": "41135100", "title": "Potential Risk to Brain Health after Surgical Interventions: Biomarkers to Predict the Occurrence of Cognitive Decline.", "authors": "Rey-Picazo J, Pita J, Pe\u00f1a L et al.", "year": "2025", "journal": "Aging and disease", "keywords": "None", "chunk": "of the surgical intervention, differential neuroinflammatory response, the patient metabolic/biochemical status or if there are comorbidities. Considering the complexity of this type of studies, the present review summarizes the most important factors/biomarkers that could provide useful information for pre- and post-operative medical decision making in relation to the development of dementia. Emphasis will be placed on the relationship between temperature, Tau phosphorylation, whose plasma detection as an early diagnostic factor is gaining great relevance, and other neurodegenerative biomarker interplay. The prolonged maintenance of key biomarkers in blood could be detrimental and, therefore, a more comprehensive individualized hospital study may improve the prevention of postoperative complications.", "source": "PubMed"}, {"chunk_id": "41169480_0", "pmid": "41169480", "title": "Mechanisms underlying cognitive impairment and management strategies in type 2 diabetes.", "authors": "Chen X, Huang Y, Xiong X", "year": "2025", "journal": "Frontiers in endocrinology", "keywords": "cognitive impairment, glycemic control, insulin resistance, neuroinflammation, neuroprotection, type 2 diabetes", "chunk": "Type 2 diabetes (T2D) is increasingly recognized as a risk factor for cognitive impairment, ranging from mild cognitive impairment (MCI) to dementia. The underlying mechanisms involve a complex interplay of hyperglycemia, insulin resistance, neuroinflammation, oxidative stress, vascular dysfunction, and amyloid pathology. Effective management strategies remain an area of active investigation. This review explores the pathophysiological mechanisms linking T2D to cognitive dysfunction and evaluates current and emerging therapeutic strategies to preserve cognitive function in diabetic patients. Chronic hyperglycemia and insulin resistance impair neuronal function and synaptic plasticity, while microvascular complications contribute to cerebral hypoperfusion and white matter lesions. Additionally, metabolic disturbances exacerbate neurodegenerative processes, further compromising cognitive health. Effective management strategies for cognitive impairment in T2D include regular cognitive screening, stringent glycemic control, lifestyle modifications, comprehensive cardiovascular risk management, patient education and pharmacological interventions such as metformin, GLP-1 receptor agonists (GLP1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, which may offer neuroprotective", "source": "PubMed"}, {"chunk_id": "41169480_1", "pmid": "41169480", "title": "Mechanisms underlying cognitive impairment and management strategies in type 2 diabetes.", "authors": "Chen X, Huang Y, Xiong X", "year": "2025", "journal": "Frontiers in endocrinology", "keywords": "cognitive impairment, glycemic control, insulin resistance, neuroinflammation, neuroprotection, type 2 diabetes", "chunk": "glycemic control, lifestyle modifications, comprehensive cardiovascular risk management, patient education and pharmacological interventions such as metformin, GLP-1 receptor agonists (GLP1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, which may offer neuroprotective benefits. In this review, we conclude that cognitive impairment in T2D results from complex, interrelated mechanisms requiring early intervention and personalized strategies. While current therapies focus on metabolic and vascular risk reduction, future research should prioritize biomarker discovery, mechanism-driven treatments, and long-term clinical trials to optimize outcomes. A proactive, integrated care model is essential to mitigate cognitive decline in this high-risk population.", "source": "PubMed"}, {"chunk_id": "40193122_0", "pmid": "40193122", "title": "Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis.", "authors": "Seminer A, Mulihano A, O'Brien C et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "Although diabetes is a risk factor for dementia, the effect of glucose-lowering therapy for prevention of incident dementia is uncertain. To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes. The PubMed and Embase databases were searched for studies published from inception of the database to July 11, 2024. Randomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores. Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials. Inclusion criteria were assessed independently and inconsistencies were resolved by consensus. Data were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models", "source": "PubMed"}, {"chunk_id": "40193122_1", "pmid": "40193122", "title": "Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis.", "authors": "Seminer A, Mulihano A, O'Brien C et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "criteria were assessed independently and inconsistencies were resolved by consensus. Data were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models were used to estimate a pooled treatment effect. The primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia, and change in cognitive scores. Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR],", "source": "PubMed"}, {"chunk_id": "40193122_2", "pmid": "40193122", "title": "Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis.", "authors": "Seminer A, Mulihano A, O'Brien C et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04). While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.", "source": "PubMed"}, {"chunk_id": "41055720_0", "pmid": "41055720", "title": "Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish.", "authors": "Minz R, Sharma PK", "year": "2025", "journal": "Acta diabetologica", "keywords": "Behaviour, Cortisol, Diabetes, Hyperglycemia, SOD and CAT, Sucrose, Zebrafish", "chunk": "Emerging evidence links hyperglycemia, a \"hallmark of diabetes mellitus\" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-related pathologies such as depression and cognitive decline. Zebrafish, with their well-characterized vascular system and behavioral assays, offer a unique model to study the impacts of sucrose-induced hyperglycemia. This study aims to investigates the effects of sucrose-induced hyperglycemia on stress mechanisms in type 2 diabetes using the zebrafish. Male zebrafish were divided into two groups: control, and 55.5mM sucrose immersed. Over two weeks, these were subjected to behavioural assays- the novel tank test (NTT) and the light/dark test (LDT). The NTT assessed anxiety-related behaviour by measuring the time spent in different vertical zones of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using", "source": "PubMed"}, {"chunk_id": "41055720_1", "pmid": "41055720", "title": "Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish.", "authors": "Minz R, Sharma PK", "year": "2025", "journal": "Acta diabetologica", "keywords": "Behaviour, Cortisol, Diabetes, Hyperglycemia, SOD and CAT, Sucrose, Zebrafish", "chunk": "of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using ZebraZoom software to asses locomotor metrics status. Cortisol levels were measured to assess HPA axis function. Antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), were quantified to evaluate oxidative stress. The results revealed that zebrafish exposed to sucrose exhibited significant hyperglycemia (**p < 0.01) and behavioural changes compared to those on control. Specifically, in the NTT, the hyperglycemic group demonstrated heightened anxiety-like behaviour, spending more time at the bottom zone of the tank. In the light/dark test, male zebrafish showed increased anxiety by spending more time in the dark compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative", "source": "PubMed"}, {"chunk_id": "41055720_2", "pmid": "41055720", "title": "Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish.", "authors": "Minz R, Sharma PK", "year": "2025", "journal": "Acta diabetologica", "keywords": "Behaviour, Cortisol, Diabetes, Hyperglycemia, SOD and CAT, Sucrose, Zebrafish", "chunk": "compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative defense mechanisms. The zebrafish system effectively models the negative impacts of sucrose-induced hyperglycemia, providing valuable insights into the stress mechanisms associated with type 2 diabetes. These findings demonstrate that hyperglycemia alters both endocrine stress response and antioxidant systems, potentially serving as biomarkers of systemic stress.", "source": "PubMed"}, {"chunk_id": "40086910_0", "pmid": "40086910", "title": "Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).", "authors": "Sankhe K, Tumati S, Perin J et al.", "year": "2025", "journal": "International psychogeriatrics", "keywords": "Alzheimer\u2019s disease, Apathy, Cognition, Methylphenidate", "chunk": "Previous trials have shown improvements in both apathy and cognition with methylphenidate (MPH). To assess whether changes in apathy correlated with changes in cognition in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2). Mild to moderate AD patients with clinically significant apathy randomized to MPH (20 mg/day) or placebo for 6 months. Apathy was measured with the Neuropsychiatric Inventory-apathy (NPI-A) domain. Cognition was measured using the Mini-Mental State Exam (MMSE), Hopkins Verbal Learning (immediate [HVLT-I], delayed [HVLT-D] recall), Digit Span (Forward [DF], Backward [DB]), Trail Making (TMT-A, TMT-B), Action Verbal Fluency (AV), Category Fluency (CF), and the Short Boston Naming Test (BNT). Linear mixed models included cognitive change scores as dependent variables and time, treatment, change in NPI-A and the interaction between treatment and change in NPI-A as independent variables, which were additionally adjusted for baseline NPI-A and cognitive scores, age, sex, level of education and presence of diabetes.", "source": "PubMed"}, {"chunk_id": "40086910_1", "pmid": "40086910", "title": "Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).", "authors": "Sankhe K, Tumati S, Perin J et al.", "year": "2025", "journal": "International psychogeriatrics", "keywords": "Alzheimer\u2019s disease, Apathy, Cognition, Methylphenidate", "chunk": "the interaction between treatment and change in NPI-A as independent variables, which were additionally adjusted for baseline NPI-A and cognitive scores, age, sex, level of education and presence of diabetes. 199 participants (66 % male) were included (98-MPH, 101-placebo). Among all participants, worsening CF was associated with worsening apathy (-0.15 (0.05), p = .003). In addition, change in HVLT-I was associated with the interaction between changes in apathy and treatment (-0.31 (0.07), p = 0.0000158). Changes in apathy are mostly independent of cognitive changes and apathy response to MPH may be independent from cognition. These results are consistent with the view that apathy as a syndrome is related to but distinct from cognition.", "source": "PubMed"}, {"chunk_id": "39449522_0", "pmid": "39449522", "title": "Pathways to Alzheimer's Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-\u03b2 Regulation and Neuronal Health.", "authors": "Laslo A, Laslo L, Arb\u0103na\u0219i EM et al.", "year": "2024", "journal": "Pathophysiology : the official journal of the International Society for Pathophysiology", "keywords": "Alzheimer disease, amyloid-\u03b2, apolipoprotein E, cerebral amyloid angiopathy, clusterin", "chunk": "One of the hallmarks of Alzheimer's disease (AD) is the deposition of amyloid-\u03b2 (A\u03b2) within the extracellular spaces of the brain as plaques and along the blood vessels in the brain, a condition also known as cerebral amyloid angiopathy (CAA). Clusterin (CLU), or apolipoprotein J (APOJ), is a multifunctional glycoprotein that has a role in many physiological and neurological conditions, including AD. The apolipoprotein E (APOE) is a significant genetic factor in AD, and while the primary physiological role of APOE in the brain and peripheral tissues is to regulate lipid transport, it also participates in various other biological processes, having three basic human forms: APOE2, APOE3, and APOE4. Notably, the APOE4 allele substantially increases the risk of developing late-onset AD. The main purpose of this review is to examine the roles of CLU and APOE in AD pathogenesis in order to acquire a better understanding of AD pathogenesis from", "source": "PubMed"}, {"chunk_id": "39449522_1", "pmid": "39449522", "title": "Pathways to Alzheimer's Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-\u03b2 Regulation and Neuronal Health.", "authors": "Laslo A, Laslo L, Arb\u0103na\u0219i EM et al.", "year": "2024", "journal": "Pathophysiology : the official journal of the International Society for Pathophysiology", "keywords": "Alzheimer disease, amyloid-\u03b2, apolipoprotein E, cerebral amyloid angiopathy, clusterin", "chunk": "AD. The main purpose of this review is to examine the roles of CLU and APOE in AD pathogenesis in order to acquire a better understanding of AD pathogenesis from which to develop targeted therapeutic approaches.", "source": "PubMed"}, {"chunk_id": "37199592_0", "pmid": "37199592", "title": "Oligomers and Neurodegeneration: New Evidence.", "authors": "Forloni G", "year": "2023", "journal": "Aging and disease", "keywords": "None", "chunk": "In the last few months new results in Alzheimer's (AD) and Parkinson's disease (PD) have converged, attracting attention to oligomer species of misfolded proteins, \u03b2-amyloid (A\u03b2 and \u03b1-synuclein (\u03b1-Syn), in the pathogenesis. The high affinity for A\u03b2 protofibrils and oligomers of lecanemab, an antibody recently approved as a disease-modifying drug in AD, and the identification of A\u03b2-oligomers in blood samples as early biomarkers in subjects with cognitive decline, indicate the oligomers as a therapeutic target and diagnostic tool in AD. \u03b1-Syn oligomers were identified by new histopathological techniques in the hippocampus and visual cortex of PD subjects with a distribution distinct from the Lewy body pathologies but associated with cognitive impairment; these species purified from PD brain were highly neurotoxic. In a PD experimental model, we confirmed the presence of \u03b1-Syn oligomers associated with cognitive decline and sensitive to drug treatment.", "source": "PubMed"}, {"chunk_id": "37199592_1", "pmid": "37199592", "title": "Oligomers and Neurodegeneration: New Evidence.", "authors": "Forloni G", "year": "2023", "journal": "Aging and disease", "keywords": "None", "chunk": "In a PD experimental model, we confirmed the presence of \u03b1-Syn oligomers associated with cognitive decline and sensitive to drug treatment.", "source": "PubMed"}, {"chunk_id": "41828418_0", "pmid": "41828418", "title": "The Progress of Active Immunotherapy for Parkinson's Disease.", "authors": "Busot D, Yang H, Sawmiller D et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, alpha synuclein, antibody, dendritic cells, immunotherapy, vaccine", "chunk": "Parkinson's disease (PD) is a multifactorial neurodegenerative disorder defined by nigrostriatal dopaminergic neuron loss and the pathological aggregation of alpha synuclein, yet current clinical interventions remain largely symptomatic and fail to alter long-term disease progression. Emerging evidence demonstrates that immune dysregulation and chronic neuroinflammation contribute significantly to PD pathology, supporting the rationale for active immunotherapy as a disease modifying strategy. This review examines contemporary active immunotherapy platforms including peptide vaccines, genetic vaccination strategies, and antigen sensitized dendritic cell (DC) vaccines with emphasis on the dual capacity of DC based approaches to enhance pathological protein clearance and restore immune homeostasis. Technical limitations and translational barriers are evaluated such as immune heterogeneity among patients, the blood-brain barrier, and variability in DC vaccine manufacturing. Finally, future research directions are proposed including individualized immunologic profiling for treatment stratification, long-acting immunomodulatory formulations, and development of isoform specific DC powder vaccines capable of targeted alpha synuclein", "source": "PubMed"}, {"chunk_id": "41828418_1", "pmid": "41828418", "title": "The Progress of Active Immunotherapy for Parkinson's Disease.", "authors": "Busot D, Yang H, Sawmiller D et al.", "year": "2026", "journal": "International journal of molecular sciences", "keywords": "Parkinson\u2019s disease, alpha synuclein, antibody, dendritic cells, immunotherapy, vaccine", "chunk": "manufacturing. Finally, future research directions are proposed including individualized immunologic profiling for treatment stratification, long-acting immunomodulatory formulations, and development of isoform specific DC powder vaccines capable of targeted alpha synuclein engagement. Collectively, these advances highlight active immunotherapy as a promising pathway toward disease modification in Parkinson's disease.", "source": "PubMed"}, {"chunk_id": "36139002_0", "pmid": "36139002", "title": "Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer's Disease Cohort.", "authors": "Valcic M, Khoury MA, Kim J et al.", "year": "2022", "journal": "Brain sciences", "keywords": "APOE, Alzheimer\u2019s disease, Lewy body, neuropsychiatric, psychosis", "chunk": "The APOE4 allele is a genetic risk factor for developing late-onset Alzheimer's disease (AD). Previous work by our group revealed that female APOE4 homozygotes with Lewy body (LB) pathology were more likely to experience psychosis compared to female APOE4 non-carriers, whereas in males there was no APOE4 dose-dependent significant effect. The objective of this study was to refine our previous findings by adjusting for covariates and determining the probability of an APOE4 sex-mediated effect on psychosis. Neuropathologically confirmed AD patients with LB pathology (n = 491) and without LB pathology (n = 716) were extracted from the National Alzheimer's Coordinating Center (NACC). Patients were classified as psychotic if they scored positively for delusions and/or hallucinations on the Neuropsychiatric Inventory. Analysis consisted of a preliminary unadjusted binary logistic regression and a Generalized Additive binary logistic regression Model (GAM) to predict the relationship between APOE4 status and sex on the presence of", "source": "PubMed"}, {"chunk_id": "36139002_1", "pmid": "36139002", "title": "Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer's Disease Cohort.", "authors": "Valcic M, Khoury MA, Kim J et al.", "year": "2022", "journal": "Brain sciences", "keywords": "APOE, Alzheimer\u2019s disease, Lewy body, neuropsychiatric, psychosis", "chunk": "consisted of a preliminary unadjusted binary logistic regression and a Generalized Additive binary logistic regression Model (GAM) to predict the relationship between APOE4 status and sex on the presence of psychosis in both cohorts, adjusting for age, education and MMSE. In the cohort with LB pathology, female APOE4 homozygotes were significantly more likely to experience psychosis compared to female APOE4 non-carriers (OR = 4.15, 95%CI [1.21, 14.2], <i>p</i> = 0.023). Female heterozygotes were also more likely to experience psychosis compared to female APOE4 non-carriers, but to a lesser extent (OR = 2.37, 95%CI [1.01, 5.59], <i>p</i> = 0.048). There was no significant difference in males with LB pathology or in any sex in the cohort without LB pathology. Sex and zygosity influence the effect of APOE4 on psychosis in neuropathologically confirmed AD patients, with the effect being limited to females with LB pathology.", "source": "PubMed"}, {"chunk_id": "36139002_2", "pmid": "36139002", "title": "Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer's Disease Cohort.", "authors": "Valcic M, Khoury MA, Kim J et al.", "year": "2022", "journal": "Brain sciences", "keywords": "APOE, Alzheimer\u2019s disease, Lewy body, neuropsychiatric, psychosis", "chunk": "zygosity influence the effect of APOE4 on psychosis in neuropathologically confirmed AD patients, with the effect being limited to females with LB pathology.", "source": "PubMed"}, {"chunk_id": "40634782_0", "pmid": "40634782", "title": "Plasma proteomics links brain and immune system aging with healthspan and longevity.", "authors": "Oh HS, Le Guen Y, Rappoport N et al.", "year": "2025", "journal": "Nature medicine", "keywords": "None", "chunk": "Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17 years' follow-up) of a range of diseases, including heart failure, chronic obstructive pulmonary disease, type 2 diabetes and Alzheimer's disease. Notably, having an especially aged brain posed a risk of Alzheimer's disease (hazard ratio (HR) = 3.1) that was similar to carrying one copy of APOE4, the strongest genetic risk factor for sporadic Alzheimer's disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2, independent of APOE", "source": "PubMed"}, {"chunk_id": "40634782_1", "pmid": "40634782", "title": "Plasma proteomics links brain and immune system aging with healthspan and longevity.", "authors": "Oh HS, Le Guen Y, Rappoport N et al.", "year": "2025", "journal": "Nature medicine", "keywords": "None", "chunk": "the strongest genetic risk factor for sporadic Alzheimer's disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2, independent of APOE genotype. Accrual of aged organs progressively increased mortality risk (2-4 aged organs, HR = 2.3; 5-7 aged organs, HR = 4.5; 8+ aged organs, HR = 8.3), whereas youthful brains and immune systems were uniquely associated with longevity (youthful brain, HR = 0.60 for mortality risk; youthful immune system, HR = 0.58; youthful both, HR = 0.44). Altogether, these findings support the use of plasma proteins for monitoring of organ health and point to the brain and immune systems as key targets for longevity interventions.", "source": "PubMed"}, {"chunk_id": "40938528_0", "pmid": "40938528", "title": "Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies.", "authors": "H\u00f6lscher C", "year": "2025", "journal": "CNS drugs", "keywords": "None", "chunk": "Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative disorders with few effective drug treatments available. An underrated element of these diseases is that glucose uptake and energy utilization is much reduced in neurons. In the brains of patients, signaling of insulin, insulin-like growth factor 1, and other growth factors is downregulated early on. This leads to reduced glucose utilization and impaired mitochondrial function. In an attempt to compensate for the loss, other pathways are upregulated, e.g., the increased use of ketones produced from fatty acids by astrocytes that are shuttled to neurons. In addition, amino acids are increasingly used to generate energy. Despite this, neurons generate less and less energy over time, leading to impaired synaptic activity, reduced cell repair, mitogenesis, autophagy, the accumulation of misfolded proteins, and finally, to cell death. At the same time, the chronic inflammation response in the brain that is part of these", "source": "PubMed"}, {"chunk_id": "40938528_1", "pmid": "40938528", "title": "Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies.", "authors": "H\u00f6lscher C", "year": "2025", "journal": "CNS drugs", "keywords": "None", "chunk": "cell repair, mitogenesis, autophagy, the accumulation of misfolded proteins, and finally, to cell death. At the same time, the chronic inflammation response in the brain that is part of these diseases continues to damage neurons. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are peptide hormones and growth factors that have shown neuroprotective effects in animal studies and in clinical trials. GLP-1 and GIP receptor agonists were able to reduce inflammation while normalizing growth factor signaling and energy utilization in the brain. Insulin signaling was improved and energy utilization, glucose uptake, mitogenesis, and mitochondrial functionality was brought back to physiological levels. In addition, the chronic inflammation response and the levels of proinflammatory cytokines in the brain were much reduced. Clinical trials testing GLP-1 receptor agonists in patients with AD or PD have been conducted and have shown first successes, serving as proof of concept that activating GLP-1 receptor is", "source": "PubMed"}, {"chunk_id": "40938528_2", "pmid": "40938528", "title": "Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies.", "authors": "H\u00f6lscher C", "year": "2025", "journal": "CNS drugs", "keywords": "None", "chunk": "Clinical trials testing GLP-1 receptor agonists in patients with AD or PD have been conducted and have shown first successes, serving as proof of concept that activating GLP-1 receptor is a sensible strategy to treat AD/PD. A phase II study testing liraglutide in patients with AD showed first improvements, and two phase II trials testing exendin-4 (exenatide, Bydureon<sup>\u00ae</sup>) or lixisenatide showed improvements in patients with PD. A recent phase III trial testing exendin-4 did not show an improvement, which may be linked to the lack of insulin desensitization in the study participants. Semaglutide (Rybelsus<sup>\u00ae</sup>; Wegovy<sup>\u00ae</sup>; Ozempic<sup>\u00ae</sup>) is currently in two phase III trials for AD. Current drugs that are on the market have a long half-life in the blood and do not readily cross the blood-brain barrier (BBB). Newer dual GLP-1/GIP receptor agonists have been developed that can more easily cross the BBB and that show improved protection in animal", "source": "PubMed"}, {"chunk_id": "40938528_3", "pmid": "40938528", "title": "Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies.", "authors": "H\u00f6lscher C", "year": "2025", "journal": "CNS drugs", "keywords": "None", "chunk": "do not readily cross the blood-brain barrier (BBB). Newer dual GLP-1/GIP receptor agonists have been developed that can more easily cross the BBB and that show improved protection in animal models of AD and PD. Therefore, GLP-1 and GIP receptor agonists that can cross the BBB show promise as treatments for chronic neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "40345320_0", "pmid": "40345320", "title": "Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study.", "authors": "Zhou J, Ni C, Wang Z et al.", "year": "2025", "journal": "Microvascular research", "keywords": "Activated partial thromboplastin time, Coronary artery lesions, Kawasaki disease", "chunk": "Kawasaki disease (KD) is an acute systemic inflammation, that affects medium-sized arteries. Coronary artery lesions (CALs) were the most serious complication or sequelae of KD. The intense inflammatory response leads to platelet activation, further exacerbating inflammation, which plays an important role in the pathogenesis of CALs in KD patients. Plus, coagulation factors are closely related to platelet activation. Therefore, we speculate that the activated partial thromboplastin time (APTT), an indicator of coagulation factor function, may be involved in the occurrence of CALs, but it has not been explored yet. This study aims to investigate the effect of the APTT level on CALs occurrence in the acute phase of KD. A total of 2303 KD patients during a 10-year period were recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the", "source": "PubMed"}, {"chunk_id": "40345320_1", "pmid": "40345320", "title": "Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study.", "authors": "Zhou J, Ni C, Wang Z et al.", "year": "2025", "journal": "Microvascular research", "keywords": "Activated partial thromboplastin time, Coronary artery lesions, Kawasaki disease", "chunk": "recruited at the Wenzhou Medical University affiliated Yuying Children's Hospital. A total of 1715 patients who completed the follow-up were enrolled in the final analysis and were divided into the low APTT group and the high APTT group at a 46 s cutoff before receiving intravenous immunoglobulin (IVIG) treatment. Multiple logistic regression analysis and stratified analysis were utilized to evaluate the independent impact of APTT levels on the occurrence of CALs and to determine the impact of APTT levels on the occurrence of CALs in different subgroups, respectively. The incidence of CALs in the low APTT group and the high APTT group was 12.5 % and 17.5 %, respectively (P = 0.005). Patients with high APTT levels had higher CRP levels (P < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar", "source": "PubMed"}, {"chunk_id": "40345320_2", "pmid": "40345320", "title": "Activated partial thromboplastin time levels and coronary artery lesions in Kawasaki disease: A retrospective cohort study.", "authors": "Zhou J, Ni C, Wang Z et al.", "year": "2025", "journal": "Microvascular research", "keywords": "Activated partial thromboplastin time, Coronary artery lesions, Kawasaki disease", "chunk": "levels (P < 0.001). High APTT levels were the independent risk factor on the occurrence of CALs; the adjusted odds ratio (OR) was 1.523 (95 % CI: 1.144, 2.028). Similar results were found in stratification analysis and sensitivity analysis. KD patients with high APTT levels (\u226546 s) before IVIG treatment may be more prone to developing CALs in the acute phase of KD.", "source": "PubMed"}, {"chunk_id": "36385529_0", "pmid": "36385529", "title": "APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.", "authors": "Blanchard JW, Akay LA, Davila-Velderrain J et al.", "year": "2022", "journal": "Nature", "keywords": "None", "chunk": "APOE4 is the strongest genetic risk factor for Alzheimer's disease<sup>1-3</sup>. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer's disease<sup>4-8</sup>. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE<sup>2-6</sup>, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and transport. Confirming these findings with histological and lipidomic analysis of the post-mortem human brain, induced pluripotent stem-cell-derived cells and targeted-replacement mice, we show that cholesterol is aberrantly deposited in oligodendrocytes-myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We", "source": "PubMed"}, {"chunk_id": "36385529_1", "pmid": "36385529", "title": "APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.", "authors": "Blanchard JW, Akay LA, Davila-Velderrain J et al.", "year": "2022", "journal": "Nature", "keywords": "None", "chunk": "induced pluripotent stem-cell-derived cells and targeted-replacement mice, we show that cholesterol is aberrantly deposited in oligodendrocytes-myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We show that altered cholesterol localization in the APOE4 brain coincides with reduced myelination. Pharmacologically facilitating cholesterol transport increases axonal myelination and improves learning and memory in APOE4 mice. We provide a single-cell atlas describing the transcriptional effects of APOE4 on the aging human brain and establish a functional link between APOE4, cholesterol, myelination and memory, offering therapeutic opportunities for Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "32471175_0", "pmid": "32471175", "title": "The Pluripotency Factor Nanog Protects against Neuronal Amyloid \u03b2-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration.", "authors": "Chang CC, Li HH, Tsou SH et al.", "year": "2020", "journal": "Cells", "keywords": "Nanog, amyloid \u03b2, insulin signaling, oxidative stress, senescence", "chunk": "Amyloid \u03b2 (A\u03b2) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer's Disease (AD). It is believed that A\u03b2 contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from A\u03b2-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate A\u03b2-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog-both in vitro and in vivo-and investigated the protective effects and underlying mechanisms against A\u03b2. We found that overexpression of Nanog is responsible for attenuating", "source": "PubMed"}, {"chunk_id": "32471175_1", "pmid": "32471175", "title": "The Pluripotency Factor Nanog Protects against Neuronal Amyloid \u03b2-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration.", "authors": "Chang CC, Li HH, Tsou SH et al.", "year": "2020", "journal": "Cells", "keywords": "Nanog, amyloid \u03b2, insulin signaling, oxidative stress, senescence", "chunk": "present study, we transiently overexpressed Nanog-both in vitro and in vivo-and investigated the protective effects and underlying mechanisms against A\u03b2. We found that overexpression of Nanog is responsible for attenuating A\u03b2-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of A\u03b2 neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of A\u03b2, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing A\u03b2 neurotoxicity in the AD brain.", "source": "PubMed"}, {"chunk_id": "32471175_2", "pmid": "32471175", "title": "The Pluripotency Factor Nanog Protects against Neuronal Amyloid \u03b2-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration.", "authors": "Chang CC, Li HH, Tsou SH et al.", "year": "2020", "journal": "Cells", "keywords": "Nanog, amyloid \u03b2, insulin signaling, oxidative stress, senescence", "chunk": "used as a novel intervention for reducing A\u03b2 neurotoxicity in the AD brain.", "source": "PubMed"}, {"chunk_id": "35388950_0", "pmid": "35388950", "title": "Hippocampal-amygdalo-ventricular atrophy score: Alzheimer disease detection using normative and pathological lifespan models.", "authors": "Coup\u00e9 P, Manj\u00f3n JV, Mansencal B et al.", "year": "2022", "journal": "Human brain mapping", "keywords": "None", "chunk": "In this article, we present an innovative MRI-based method for Alzheimer disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3,032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Atrophy score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1,039 subjects, our approach showed very accurate detection (AUC \u2265 94%) of patients with AD compared to control subjects and accurate discrimination (AUC = 78%) between progressive MCI and stable MCI (during a 3-year follow-up). Compared to normative modeling, classical machine learning methods and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.", "source": "PubMed"}, {"chunk_id": "35388950_1", "pmid": "35388950", "title": "Hippocampal-amygdalo-ventricular atrophy score: Alzheimer disease detection using normative and pathological lifespan models.", "authors": "Coup\u00e9 P, Manj\u00f3n JV, Mansencal B et al.", "year": "2022", "journal": "Human brain mapping", "keywords": "None", "chunk": "learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.", "source": "PubMed"}, {"chunk_id": "41759439_0", "pmid": "41759439", "title": "Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.", "authors": "Paul S, Verma J, Mehan S", "year": "2026", "journal": "Neuropeptides", "keywords": "Nanotechnology drug delivery, Neurodegenerative disorders, Neuroprotection, Oxytocin, Therapeutic potential, neuropsychiatric disorders", "chunk": "Oxytocin, a neuropeptide predominantly produced in the hypothalamus, has garnered significant attention for its multifaceted roles extending beyond social bonding and reproduction to therapeutic applications in neurodegenerative and neuropsychiatric disorders. This review explores oxytocin's neuroprotective properties, including anti-inflammatory, antioxidant and anti-apoptotic effects, which counteract pathological mechanisms underlying diseases like Alzheimer's, Parkinson's and Epilepsy. Oxytocin's ability to modulate key neurotransmitter systems GABAergic, dopaminergic, and serotonergic pathways enhances synaptic plasticity, neurogenesis, and emotional regulation. These mechanisms have positioned oxytocin as a promising intervention for neuropsychiatric conditions such as autism, schizophrenia, depression, and anxiety. Preclinical and clinical studies have shown that intranasal administration of oxytocin improves social cognition, reduces symptom severity, and is well-tolerated, though challenges remain in standardizing dosages and measuring oxytocin levels due to individual variability. Emerging technologies, such as nanoparticle-based drug delivery systems, offer solutions to enhance oxytocin's bioavailability and brain penetration, making targeted, patient-specific therapies feasible. Epigenetic modifications of", "source": "PubMed"}, {"chunk_id": "41759439_1", "pmid": "41759439", "title": "Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.", "authors": "Paul S, Verma J, Mehan S", "year": "2026", "journal": "Neuropeptides", "keywords": "Nanotechnology drug delivery, Neurodegenerative disorders, Neuroprotection, Oxytocin, Therapeutic potential, neuropsychiatric disorders", "chunk": "levels due to individual variability. Emerging technologies, such as nanoparticle-based drug delivery systems, offer solutions to enhance oxytocin's bioavailability and brain penetration, making targeted, patient-specific therapies feasible. Epigenetic modifications of the oxytocin receptor gene including DNA methylation have been associated with variability in social and stress-related behaviors. While these findings offer insight into inter-individual differences, their application to precision medicine remains speculative and will require rigorous clinical validation. Combination therapies, integrating oxytocin with agents targeting neuroinflammation and synaptic plasticity, hold potential for synergistic effects. Despite methodological and translational challenges, oxytocin represents a transformative therapeutic agent with broad applications across neurological, psychiatric, and systemic disorders. Future research focusing on nanotechnology, epigenetics, and long-term clinical trials will be pivotal in realizing the full potential of oxytocin-based interventions for complex, multifactorial diseases.", "source": "PubMed"}, {"chunk_id": "41759439_2", "pmid": "41759439", "title": "Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.", "authors": "Paul S, Verma J, Mehan S", "year": "2026", "journal": "Neuropeptides", "keywords": "Nanotechnology drug delivery, Neurodegenerative disorders, Neuroprotection, Oxytocin, Therapeutic potential, neuropsychiatric disorders", "chunk": "full potential of oxytocin-based interventions for complex, multifactorial diseases.", "source": "PubMed"}, {"chunk_id": "37682322_0", "pmid": "37682322", "title": "Commentaries: Lecanemab: pioneering the way as the first approved drug for Alzheimer's disease treatment.", "authors": "Zhang J", "year": "2023", "journal": "Inflammation research : official journal of the European Histamine Research Society ... [et al.]", "keywords": "Alzheimer\u2019s disease, Amyloid-beta, Clinical trials, FDA approval drug, Lecanemab", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and neuronal abnormalities. Current therapies address symptoms without altering disease progression. Lecanemab, an anti-amyloid antibody, binds to amyloid-beta (A\u03b2) protofibrils. Phase II trials revealed dose-dependent amyloid clearance and reduced clinical decline. Phase III trials demonstrated cognitive benefits with potential adverse events. Full FDA approval was granted for lecanemab due to its ability to eliminate toxic brain amyloids. However, longer trials are needed to assess its efficacy and safety. While lecanemab marks a significant advancement, further breakthroughs are essential for effective AD treatment.", "source": "PubMed"}, {"chunk_id": "41496364_0", "pmid": "41496364", "title": "Ultramicronized palmitoylethanolamide restores astrocyte-neuron metabolic coupling and Klotho/FGF21 signaling in a triple-transgenic mouse model of Alzheimer's disease.", "authors": "Facchinetti R, Valenza M, Ciarla C et al.", "year": "2026", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "3\u202f\u00d7Tg-AD mice, Alzheimer\u2019s disease, FGF21, Klotho, Palmitoylethanolamide, Taurine", "chunk": "Alzheimer's disease (AD), a multifactorial neurodegenerative disorder, is characterized by metabolic deficiency, neuroinflammation, and synaptic impairment. Astrocyte-neuron metabolic coupling regulates cerebral energy homeostasis through key metabolites such as lactate, glutamate, and taurine. We investigated the therapeutic potential of ultramicronized-palmitoylethanolamide (um-PEA) in restoring the homeostasis of these metabolites in the triple transgenic (3 \u00d7Tg-AD) mouse model of AD. Using in vivo magnetic resonance imaging and spectroscopy (MRI/MRS) combined with Western blot, we evaluated the effects of chronic um-PEA treatment on lactate-glutamate dynamics and taurine metabolism in the frontal cortex and hippocampus of 6- and 12 month-old mice. Our findings demonstrate that 3 \u00d7Tg-AD mice exhibit lactate accumulation, glutamine/glutamate imbalance, and taurine depletion, alongside reduced expression of metabolic processes regulators such as FGF21, Klotho, and insulin receptor. Treatment with um-PEA successfully restored these metabolic changes by: (i) rebalancing lactate-glutamate metabolism, (ii) increasing taurine synthesis and transport, (iii) upregulating FGF21, Klotho, and insulin", "source": "PubMed"}, {"chunk_id": "41496364_1", "pmid": "41496364", "title": "Ultramicronized palmitoylethanolamide restores astrocyte-neuron metabolic coupling and Klotho/FGF21 signaling in a triple-transgenic mouse model of Alzheimer's disease.", "authors": "Facchinetti R, Valenza M, Ciarla C et al.", "year": "2026", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "3\u202f\u00d7Tg-AD mice, Alzheimer\u2019s disease, FGF21, Klotho, Palmitoylethanolamide, Taurine", "chunk": "FGF21, Klotho, and insulin receptor. Treatment with um-PEA successfully restored these metabolic changes by: (i) rebalancing lactate-glutamate metabolism, (ii) increasing taurine synthesis and transport, (iii) upregulating FGF21, Klotho, and insulin receptor expression, and (iv) modulating the metalloproteases ADAM10 and ADAM17, which regulate Klotho processing. These results identify um-PEA as a promising metabolic modulator capable of mitigating AD-related neurodegenerative processes. By targeting astrocyte-neuron metabolism and enhancing both FGF21 and Klotho pathways, um-PEA holds significant potential as an adjunctive therapeutic strategy for AD.", "source": "PubMed"}, {"chunk_id": "41410235_0", "pmid": "41410235", "title": "Prodromal Peripheral Immune Cell Profile in Drug-Induced Parkinsonism Relative to Parkinson's Disease.", "authors": "Lien B, Kasibhatla V, Mawad M et al.", "year": "2025", "journal": "Movement disorders clinical practice", "keywords": "Parkinson's disease, drug\u2010induced parkinsonism, neutrophil\u2010to\u2010lymphocyte ratio, peripheral inflammation", "chunk": "Drug-induced Parkinsonism (DIP) is a predictor of future idiopathic Parkinson's disease (PD), yet the prodromal characteristics of DIP remain unexplored. To compare prodromal peripheral immune cell profiles in DIP and PD. We applied independent regression models to evaluate the peripheral immune cell profiles in individuals with incident DIP (n = 108) and PD (n = 1055) relative to 20,070 healthy controls from the UK Biobank. Approximately 9 years before diagnosis, both DIP and PD cases exhibited elevated neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). Only PD cases showed reduced lymphocyte counts. After adjusting for psychiatric comorbidities, DIP-associated peripheral immune alterations were no longer significant. The elevated neutrophil counts in DIP and PD suggest a shared innate immune system involvement. However, in DIP, the peripheral immune changes appear driven by psychiatric comorbidities, whereas lymphopenia may represent a distinctive prodromal biomarker of PD.", "source": "PubMed"}, {"chunk_id": "41410235_1", "pmid": "41410235", "title": "Prodromal Peripheral Immune Cell Profile in Drug-Induced Parkinsonism Relative to Parkinson's Disease.", "authors": "Lien B, Kasibhatla V, Mawad M et al.", "year": "2025", "journal": "Movement disorders clinical practice", "keywords": "Parkinson's disease, drug\u2010induced parkinsonism, neutrophil\u2010to\u2010lymphocyte ratio, peripheral inflammation", "chunk": "system involvement. However, in DIP, the peripheral immune changes appear driven by psychiatric comorbidities, whereas lymphopenia may represent a distinctive prodromal biomarker of PD.", "source": "PubMed"}, {"chunk_id": "41543103_0", "pmid": "41543103", "title": "Correlation of Plasma Neuropeptide Y with Specific Cognitive Domains in Patients with Parkinson's Disease Cognitive Impairment.", "authors": "Zhang AR, Wu ML, Pang WJ et al.", "year": "2026", "journal": "Clinical laboratory", "keywords": "None", "chunk": "We aimed to investigate the correlation of plasma neuropeptide Y (NPY) with specific cognitive domains in patients with Parkinson's disease (PD) cognitive impairment (CI). The study included thirty-six PD patients with normal cognitive function (PD-NC), 57 PD patients with mild cognitive impairment (PD-MCI), 30 PD patients with dementia (PDD), and 46 healthy individuals. Every patient underwent thorough clinical evaluations and neuropsychological examinations. Plasma NPY expression was assessed using ELISA. The effects of plasma NYP levels on PD-CI events or PDD were analyzed using univariate and multivariate logistic models. Multiple linear regression analyses were constructed to assess the independent associations of plasma NYP levels with z scores in 5 cognitive domains. Plasma NYP levels were reduced in patients with PD compared with healthy controls (p < 0.001). Plasma NYP levels were the highest in PD-NC patients and decreased with increasing CI, with the PDD group having the lowest plasma NYP levels.", "source": "PubMed"}, {"chunk_id": "41543103_1", "pmid": "41543103", "title": "Correlation of Plasma Neuropeptide Y with Specific Cognitive Domains in Patients with Parkinson's Disease Cognitive Impairment.", "authors": "Zhang AR, Wu ML, Pang WJ et al.", "year": "2026", "journal": "Clinical laboratory", "keywords": "None", "chunk": "with healthy controls (p < 0.001). Plasma NYP levels were the highest in PD-NC patients and decreased with increasing CI, with the PDD group having the lowest plasma NYP levels. Multivariate logistic regression adjusted for years of education and UPDRS-III subscores showed a significant correlation between NYP and CI (p = 0.005). Plasma NYP was significantly correlated with a linear model between each of the 5 cognitive domains, including attention, executive function, language, memory, and visuospatial function. Reduced plasma NPY levels are associated with CI in PD patients and are strongly correlated with 5 cognitive domains.", "source": "PubMed"}, {"chunk_id": "41075284_0", "pmid": "41075284", "title": "Plasma p-tau217 and A\u03b242/40 as markers of A\u03b2 pathology in the Lewy body continuum.", "authors": "Woo KA, Yoon EJ, Kim R et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "A\u03b242/40, Parkinson's disease, blood biomarkers, dementia with Lewy bodies, idiopathic/isolated REM sleep behavior disorder, p\u2010tau217", "chunk": "This study evaluated whether plasma phosphorylated tau-217 (p-tau217), amyloid beta (A\u03b2)42/40, and their combination could serve as biomarkers of A\u03b2 co-pathology across the Lewy body continuum, where A\u03b2 is frequently observed from prodromal to symptomatic stages. Individuals with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and their shared prodromal stage, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) underwent plasma sampling, A\u03b2-PET, and cognitive testing. Higher plasma p-tau217, lower A\u03b242/40, and their interaction were associated with greater A\u03b2-PET uptake. Individuals with higher-than-median p-tau217 and lower-than-median A\u03b242/40 showed the highest A\u03b2 burden. Both biomarkers predicted A\u03b2-PET positivity, but only p-tau217 correlated with cognition. Among 44 iRBD participants followed prospectively, elevated baseline p-tau217 predicted phenoconversion to overt Lewy body disease. Plasma p-tau217 and A\u03b242/40 may serve as accessible biomarkers of cerebral A\u03b2 pathology and help identify individuals across the Lewy body continuum who could benefit from A\u03b2-targeted therapy. Plasma phosphorylated", "source": "PubMed"}, {"chunk_id": "41075284_1", "pmid": "41075284", "title": "Plasma p-tau217 and A\u03b242/40 as markers of A\u03b2 pathology in the Lewy body continuum.", "authors": "Woo KA, Yoon EJ, Kim R et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "A\u03b242/40, Parkinson's disease, blood biomarkers, dementia with Lewy bodies, idiopathic/isolated REM sleep behavior disorder, p\u2010tau217", "chunk": "Plasma p-tau217 and A\u03b242/40 may serve as accessible biomarkers of cerebral A\u03b2 pathology and help identify individuals across the Lewy body continuum who could benefit from A\u03b2-targeted therapy. Plasma phosphorylated tau-217 (p-tau217) and amyloid beta (A\u03b2)42/40 predict cerebral A\u03b2 burden in the Lewy body continuum. Both biomarkers individually show high accuracy for identifying A\u03b2 positron emission tomography positivity. Plasma p-tau217, but not A\u03b242/40, is associated with cognitive performance. Elevated plasma p-tau217 predicts future phenoconversion in isolated rapid eye movement sleep behavior disorder.", "source": "PubMed"}, {"chunk_id": "41110663_0", "pmid": "41110663", "title": "Detection and rehabilitation of age-related motor skills impairment: Neurophysiological biomarkers and perspectives.", "authors": "Gordleeva S, Grigorev N, Pitsik E et al.", "year": "2026", "journal": "Ageing research reviews", "keywords": "Age-related motor skills impairment, Digital medicine, Earlier risk identification, Neurophysiological biomarkers, Rehabilitative interventions", "chunk": "Age-related decline in motor control, manifesting as impaired posture, gait, and slowed movement execution, significantly diminishes the quality of life in older adults. These functional deficits are associated with alterations in neurophysiological data, which are analyzed using advanced techniques including spectral analysis, complexity measures, and functional connectivity network analysis. These methodologies provide valuable insights into the neurobiological mechanisms underpinning age-related motor function impairments, linking physiological changes to non-invasively recorded electrophysiological and hemodynamic responses. Recent investigations have demonstrated an age-dependent impairment in access to working memory during motor tasks, evidenced by significant correlations between electroencephalographic biomarkers and neural response latencies. Furthermore, these functional biomarkers are associated with the degradation of motor learning abilities in older individuals. There is a broad consensus that non-invasive assessment of brain activity accurately reflects the processes underlying age-related motor decline, thereby opening avenues for targeted intervention strategies. A key area of investigation is the utilization of", "source": "PubMed"}, {"chunk_id": "41110663_1", "pmid": "41110663", "title": "Detection and rehabilitation of age-related motor skills impairment: Neurophysiological biomarkers and perspectives.", "authors": "Gordleeva S, Grigorev N, Pitsik E et al.", "year": "2026", "journal": "Ageing research reviews", "keywords": "Age-related motor skills impairment, Digital medicine, Earlier risk identification, Neurophysiological biomarkers, Rehabilitative interventions", "chunk": "that non-invasive assessment of brain activity accurately reflects the processes underlying age-related motor decline, thereby opening avenues for targeted intervention strategies. A key area of investigation is the utilization of motor system function for the early detection of neurodegenerative diseases. Seemingly, simple motor tasks engage cortical regions responsible for attention, vision, and memory through a process known as sensorimotor integration. Sensorimotor training implemented via brain-computer interfaces with neurofeedback demonstrates potential for ameliorating both cognitive and motor deficits in both healthy older adults and those with age-related conditions. This review synthesizes current research on age-related changes revealed through neuroimaging data analysis, highlighting how biomarkers derived from brain electrical and hemodynamic activity reflect both normative and pathological aging processes. Finally, we emphasize the considerable potential of neurophysiological data analysis for advancing the field of aging research. Digital medicine platforms, including brain-computer interfaces and a range of wearable monitoring devices, hold significant promise", "source": "PubMed"}, {"chunk_id": "41110663_2", "pmid": "41110663", "title": "Detection and rehabilitation of age-related motor skills impairment: Neurophysiological biomarkers and perspectives.", "authors": "Gordleeva S, Grigorev N, Pitsik E et al.", "year": "2026", "journal": "Ageing research reviews", "keywords": "Age-related motor skills impairment, Digital medicine, Earlier risk identification, Neurophysiological biomarkers, Rehabilitative interventions", "chunk": "the considerable potential of neurophysiological data analysis for advancing the field of aging research. Digital medicine platforms, including brain-computer interfaces and a range of wearable monitoring devices, hold significant promise for transforming the diagnosis of age-related diseases. These technologies empower continuous, objective monitoring of older adults, paving the way for personalized, precision-based medical interventions.", "source": "PubMed"}, {"chunk_id": "41290133_0", "pmid": "41290133", "title": "Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-\u03b1) in Parkinson's disease.", "authors": "Yang Y, Wang J, Gao L et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Entacapone, Inflammatory factors, Pain, Parkinson\u2019 s disease, Transcranial repetitive magnetic stimulation", "chunk": "To evaluate the efficacy of entacapone (EN) combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating pain in patients with Parkinson's disease (PD), with the primary outcome defined as the change in pain severity assessed by the Visual Analog Scale (VAS).Secondary outcomes included motor function (UPDRS), other pain dimensions (KPPS), depressive symptoms (HAMD), and levels of inflammatory markers (TNF-\u03b1 and IL-6). A total of 72 PD patients with pain were enrolled and randomly assigned to three groups: Group 1 (LD + sham stimulation), Group 2 (LD + EN + sham stimulation), and Group 3 (LD + EN + rTMS) and assessed via motor, pain, and depression scales (UPDRS/VAS/KPPS/HAMD) to evaluate the efficacy of the treatment, and also to observe the changes in the levels of interleukin (IL-6) and tumor necrosis factor (TNF-\u03b1), which are associated with pain in PD. After six months of combined pharmacotherapy and rTMS, the primary", "source": "PubMed"}, {"chunk_id": "41290133_1", "pmid": "41290133", "title": "Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-\u03b1) in Parkinson's disease.", "authors": "Yang Y, Wang J, Gao L et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Entacapone, Inflammatory factors, Pain, Parkinson\u2019 s disease, Transcranial repetitive magnetic stimulation", "chunk": "the changes in the levels of interleukin (IL-6) and tumor necrosis factor (TNF-\u03b1), which are associated with pain in PD. After six months of combined pharmacotherapy and rTMS, the primary outcome, VAS score, demonstrated a significantly greater reduction in Group 3 compared to Group 2 (2.86 \u00b1 1.25 vs. 8.22 \u00b1 1.31, P < 0.05).In addition, from the indexes of inflammatory factors, this study found that after six months of regular and systematic treatment, the reduction in serum IL-6 and TNF-\u03b1 levels was most pronounced in the combined therapy group (LD+EN+rTMS), with statistically significant differences compared to Group 2 (P = 0.003 for TNF-\u03b1). High-frequency rTMS, as a non-invasive neuromodulation technique combined with EN, improves muscle rigidity, alleviates depressive symptoms, reduces pain, and attenuates inflammatory factor secretion in PD patients, can improve muscle tension, regulate depression, relieve pain, and reduce the secretion of inflammatory factors in Parkinson's patients.This combined therapy", "source": "PubMed"}, {"chunk_id": "41290133_2", "pmid": "41290133", "title": "Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-\u03b1) in Parkinson's disease.", "authors": "Yang Y, Wang J, Gao L et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Entacapone, Inflammatory factors, Pain, Parkinson\u2019 s disease, Transcranial repetitive magnetic stimulation", "chunk": "reduces pain, and attenuates inflammatory factor secretion in PD patients, can improve muscle tension, regulate depression, relieve pain, and reduce the secretion of inflammatory factors in Parkinson's patients.This combined therapy was clinically effective and demonstrated a favorable safety profile, with no serious adverse events reported and only mild, transient side effects (e.g., scalp discomfort, headache) observed in the rTMS group. However, its long-term efficacy requires further investigation.", "source": "PubMed"}, {"chunk_id": "39885660_0", "pmid": "39885660", "title": "Adiponectin as a potential mediator of the pro-cognitive effects of physical exercise on Alzheimer's disease.", "authors": "Guo HH, Ou HN, Yu JS et al.", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Tau, adiponectin, adiponectin receptor agonists, amyloid-\u03b2, hippocampus, learning and memory, physical exercise", "chunk": "Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally. Physical exercise, as an effective strategy for improving general health, has been largely reported for its effectiveness in slowing neurodegeneration and increasing brain functional plasticity, particularly in aging brains. However, the underlying mechanisms of exercise in cognitive aging remain largely unclear. Adiponectin, a cell-secreted protein hormone, has recently been found to regulate synaptic plasticity and mediate the antidepressant effects of physical exercise. Studies on the neuroprotective effects of adiponectin have revealed potential innovative treatments for Alzheimer's disease. Here, we reviewed the functions of adiponectin and its receptor in the brains of human and animal models of cognitive impairment. We summarized the role of adiponectin in Alzheimer's disease, focusing on its impact on energy metabolism, insulin resistance, and inflammation. We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory. Finally,", "source": "PubMed"}, {"chunk_id": "39885660_1", "pmid": "39885660", "title": "Adiponectin as a potential mediator of the pro-cognitive effects of physical exercise on Alzheimer's disease.", "authors": "Guo HH, Ou HN, Yu JS et al.", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Tau, adiponectin, adiponectin receptor agonists, amyloid-\u03b2, hippocampus, learning and memory, physical exercise", "chunk": "Alzheimer's disease, focusing on its impact on energy metabolism, insulin resistance, and inflammation. We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory. Finally, we highlight the latest research on chemical compounds that mimic exercise-enhanced secretion of adiponectin and its receptor in Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41580946_0", "pmid": "41580946", "title": "Label-Free SERS Fingerprinting of Neuroprotein Conformational Dynamics in Human Saliva.", "authors": "Ja'farawy MSA, Yang JY, Mun C et al.", "year": "2026", "journal": "Advanced materials (Deerfield Beach, Fla.)", "keywords": "hotspot engineering, label\u2010free diagnosis, neurological disorders, neuroprotein, plasmonic materials, surface\u2010enhanced Raman scattering", "chunk": "Conformational transitions of neuroproteins are closely associated with neurological disorders and represent key biomarkers for diagnosis and disease monitoring. A reliable and label-free method for detecting and tracking these structural changes is critical for effective clinical application. In this work, a galvanic molecular entrapment (GME) strategy is presented to combine with surface-enhanced Raman scattering (SERS) for localization and label-free detection of neuroproteins. This approach integrates galvanic replacement with in situ Au surface growth to enable precise molecular entrapment and plasmonic hotspot formation directly around target analytes. Such spatial confinement optimizes analyte positioning within the electromagnetic field, thereby enhancing SERS signal intensity and overcoming geometric mismatches that typically limit sensitivity. The GME method successfully profiled neuroprotein conformational states and demonstrated strong potential for proteomic analysis. A logistic regression model applied to the spectral dataset enabled accurate classification of saliva samples from individuals with epilepsy, schizophrenia, Parkinson's disease, and healthy controls, achieving", "source": "PubMed"}, {"chunk_id": "41580946_1", "pmid": "41580946", "title": "Label-Free SERS Fingerprinting of Neuroprotein Conformational Dynamics in Human Saliva.", "authors": "Ja'farawy MSA, Yang JY, Mun C et al.", "year": "2026", "journal": "Advanced materials (Deerfield Beach, Fla.)", "keywords": "hotspot engineering, label\u2010free diagnosis, neurological disorders, neuroprotein, plasmonic materials, surface\u2010enhanced Raman scattering", "chunk": "potential for proteomic analysis. A logistic regression model applied to the spectral dataset enabled accurate classification of saliva samples from individuals with epilepsy, schizophrenia, Parkinson's disease, and healthy controls, achieving high sensitivity, specificity, and diagnostic accuracy. This integrated platform offers a non-invasive tool for neurological diagnostics and holds significant promise for advancing personalized healthcare in the management of neurological disorders.", "source": "PubMed"}, {"chunk_id": "39952449_0", "pmid": "39952449", "title": "Association between fibrinogen and cognitive impairment in patients with ischemic cerebrovascular disease.", "authors": "Wu K, Wang J, Li X et al.", "year": "2025", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "keywords": "Brain atrophy, Cognitive impairment, Fibrinogen, Ischemic cerebrovascular disease, White matter hyperintensities", "chunk": "Fibrinogen has been reported as a potential risk factor for vascular dementia (VaD). However, the association between fibrinogen and cognition in patients with ischemic cerebrovascular disease (ICVD) has not been studied adequately. We aimed to examine the association of fibrinogen with cognitive impairment among patients with ICVD and to test whether white matter hyperintensities (WMH) and brain atrophy play a role under the association. In this case-control study, ICVD patients were recruited from the Neurology Department. Cognitive function was assessed using the Montreal Cognitive Assessment. WMH and brain atrophy were quantified by brain magnetic resonance imaging (MRI). The associations of fibrinogen with cognition and MRI markers were investigated by conditional logistic regression models and generalized additive models. The risk of cognitive impairment increased with each unit increase in fibrinogen (AOR = 1.92, 95 % CI = 1.06 - 3.48). Individuals with fibrinogen levels > 4 g/L presented a substantially higher", "source": "PubMed"}, {"chunk_id": "39952449_1", "pmid": "39952449", "title": "Association between fibrinogen and cognitive impairment in patients with ischemic cerebrovascular disease.", "authors": "Wu K, Wang J, Li X et al.", "year": "2025", "journal": "Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association", "keywords": "Brain atrophy, Cognitive impairment, Fibrinogen, Ischemic cerebrovascular disease, White matter hyperintensities", "chunk": "cognitive impairment increased with each unit increase in fibrinogen (AOR = 1.92, 95 % CI = 1.06 - 3.48). Individuals with fibrinogen levels > 4 g/L presented a substantially higher risk of cognitive impairment than those with fibrinogen levels of 2-4 g/L (AOR = 5.72, 95 % CI = 1.22- 26.82). Fibrinogen was negatively correlated with global cognitive function (r<sub>s</sub> = -0.235) and visuospatial/executive function (r<sub>s</sub> = -0.251). A negative correlation between fibrinogen and normal-appearing white matter (NAWM) volume was observed (r<sub>s</sub> = -0.282). Fibrinogen is associated with cognitive impairment among patients with ICVD, and significantly negatively impacts global cognitive function and visuospatial/executive function. Furthermore, the negative correlation between fibrinogen and NAWM volume supports further exploration of potential mechanistic paths.", "source": "PubMed"}, {"chunk_id": "37875308_0", "pmid": "37875308", "title": "Metallic Nanocarriers for Therapeutic Peptides: Emerging Solutions Addressing the Delivery Challenges in Brain Ailments.", "authors": "Rathnam SS, Deepak T, Sahoo BN et al.", "year": "2024", "journal": "The Journal of pharmacology and experimental therapeutics", "keywords": "None", "chunk": "Peptides and proteins have recently emerged as efficient therapeutic alternatives to conventional therapies. Although they emerged a few decades back, extensive exploration of various ailments or disorders began recently. The drawbacks of current chemotherapies and irradiation treatments, such as drug resistance and damage to healthy tissues, have enabled the rise of peptides in the quest for better prospects. The chemical tunability and smaller size make them easy to design selectively for target tissues. Other remarkable properties include antifungal, antiviral, anti-inflammatory, protection from hemorrhage stroke, and as therapeutic agents for gastric disorders and Alzheimer and Parkinson diseases. Despite these unmatched properties, their practical applicability is often hindered due to their weak susceptibility to enzymatic digestion, serum degradation, liver metabolism, kidney clearance, and immunogenic reactions. Several methods are adapted to increase the half-life of peptides, such as chemical modifications, fusing with Fc fragment, change in amino acid composition, and carrier-based delivery. Among", "source": "PubMed"}, {"chunk_id": "37875308_1", "pmid": "37875308", "title": "Metallic Nanocarriers for Therapeutic Peptides: Emerging Solutions Addressing the Delivery Challenges in Brain Ailments.", "authors": "Rathnam SS, Deepak T, Sahoo BN et al.", "year": "2024", "journal": "The Journal of pharmacology and experimental therapeutics", "keywords": "None", "chunk": "and immunogenic reactions. Several methods are adapted to increase the half-life of peptides, such as chemical modifications, fusing with Fc fragment, change in amino acid composition, and carrier-based delivery. Among these, nanocarrier-mediated encapsulation not only increases the half-life of the peptides in vivo but also aids in the targeted delivery. Despite its structural complexity, they also efficiently deliver therapeutic molecules across the blood-brain barrier. Here, in this review, we tried to emphasize the possible potentiality of metallic nanoparticles to be used as an efficient peptide delivery system against brain tumors and neurodegenerative disorders. SIGNIFICANCE STATEMENT: In this review, we have emphasized the various therapeutic applications of peptides/proteins, including antimicrobial, anticancer, anti-inflammatory, and neurodegenerative diseases. We also focused on these peptides' challenges under physiological conditions after administration. We highlighted the importance and potentiality of metallic nanocarriers in the ability to cross the blood-brain barrier, increasing the stability and half-life of peptides,", "source": "PubMed"}, {"chunk_id": "37875308_2", "pmid": "37875308", "title": "Metallic Nanocarriers for Therapeutic Peptides: Emerging Solutions Addressing the Delivery Challenges in Brain Ailments.", "authors": "Rathnam SS, Deepak T, Sahoo BN et al.", "year": "2024", "journal": "The Journal of pharmacology and experimental therapeutics", "keywords": "None", "chunk": "challenges under physiological conditions after administration. We highlighted the importance and potentiality of metallic nanocarriers in the ability to cross the blood-brain barrier, increasing the stability and half-life of peptides, their efficiency in targeting the delivery, and their diagnostic applications.", "source": "PubMed"}, {"chunk_id": "41136919_0", "pmid": "41136919", "title": "Dual-task walking for early detection of Alzheimer's disease: comparative analysis of tasks using whole-body gait variables.", "authors": "Katagiri R, Yamada Y, Shinkawa K et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Alzheimer\u2019s disease, Dual task, Gait, Machine learning, Mild cognitive impairment", "chunk": "The worldwide rise in dementia creates an urgent need for screening methods that are both sensitive and easy to administer. Dual-task walking-requiring people to walk while performing a second cognitive or motor task-meets these criteria because it stresses gait and cognition simultaneously, revealing deficits that emerge early in Alzheimer's disease and Mild Cognitive Impairment (MCI). Although recent studies have explored integrating various gait variables from dual-task assessment with classification models, there remains uncertainty regarding the effective gait variables for inclusion in these models and the selection of the most effective tasks. This study aims to investigate whether incorporating gait variables derived from whole-body movement characteristics improves the performance of classification models and to identify the most effective tasks for inclusion in these models. We analyzed data from 36 participants, including 18 cognitively normal individuals and 18 with MCI. Using motion capture technology, gait variables encompassing whole-body movements, including upper body", "source": "PubMed"}, {"chunk_id": "41136919_1", "pmid": "41136919", "title": "Dual-task walking for early detection of Alzheimer's disease: comparative analysis of tasks using whole-body gait variables.", "authors": "Katagiri R, Yamada Y, Shinkawa K et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Alzheimer\u2019s disease, Dual task, Gait, Machine learning, Mild cognitive impairment", "chunk": "in these models. We analyzed data from 36 participants, including 18 cognitively normal individuals and 18 with MCI. Using motion capture technology, gait variables encompassing whole-body movements, including upper body dynamics, were recorded under both normal walking conditions and during dual-task performance. The dual tasks included: (1) Subtracting threes from a given number, (2) Carrying a cup on a tray without moving it, (3) Holding a cup filled with water without spilling it, and (4) Answering verbal questions. Classification models utilized were k-nearest neighbors, random forest, and support vector machines, with performance evaluated by the area under the curve (AUC). First, we observed that variables related to upper-body motion (i.e., Anterior-Posterior and Medial-Lateral sway) while walking played an important role in the classification models for detecting MCI, particularly during cognitively demanding tasks (subtracting numbers and answering verbal questions) while walking. Second, the tasks carrying a cup on a tray and", "source": "PubMed"}, {"chunk_id": "41136919_2", "pmid": "41136919", "title": "Dual-task walking for early detection of Alzheimer's disease: comparative analysis of tasks using whole-body gait variables.", "authors": "Katagiri R, Yamada Y, Shinkawa K et al.", "year": "2025", "journal": "BMC geriatrics", "keywords": "Alzheimer\u2019s disease, Dual task, Gait, Machine learning, Mild cognitive impairment", "chunk": "in the classification models for detecting MCI, particularly during cognitively demanding tasks (subtracting numbers and answering verbal questions) while walking. Second, the tasks carrying a cup on a tray and holding a cup filled with water while walking yielded superior classification model performance to other tasks especially in considering multiple features (AUC = 0.79). This study underscores the benefits of incorporating gait variables of the upper body to enhance the performance of classification models for MCI detection. These insights could contribute to the development of more precise and practical screening tools for MCI.", "source": "PubMed"}, {"chunk_id": "40297425_0", "pmid": "40297425", "title": "Independent validation of the PrecivityAD2<sup>\u2122</sup> blood test to identify presence or absence of brain amyloid pathology in individuals with cognitive impairment.", "authors": "Coppinger J, West T, Kirmess KM et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, amyloid beta, amyloid probability score 2, blood biomarkers, diagnostic performance, p-tau217", "chunk": "The diagnostic performance of the Amyloid Probability Score 2 (APS2) - the algorithmic result of the PrecivityAD2<sup>\u2122</sup> blood test - was originally trained and validated in two cohorts of cognitively impaired (CI) individuals. Using an independent cohort to evaluate blood test reliability, we conducted an external diagnostic accuracy assessment of the validated APS2 cut point as it is currently applied in clinical practice. Plasma biomarker ratios A\u03b242/40 and p-tau217/np-tau217 (expressed as %p-tau217) were quantified and incorporated into the APS2 algorithm in samples obtained from 192 Alzheimer's Disease Neuroimaging Initiative participants with CI (70% mild cognitive impairment / 30% dementia). APS2 diagnostic performance was determined using amyloid positron emission tomography (PET) as the reference standard. Plasma biomarkers were quantified in a CLIA-certified, CAP-accredited laboratory (C2N Diagnostics, St. Louis, MO) using liquid chromatography-tandem mass spectrometry. APS2 values were significantly higher in the 56% of CI participants with a positive amyloid PET scan.", "source": "PubMed"}, {"chunk_id": "40297425_1", "pmid": "40297425", "title": "Independent validation of the PrecivityAD2<sup>\u2122</sup> blood test to identify presence or absence of brain amyloid pathology in individuals with cognitive impairment.", "authors": "Coppinger J, West T, Kirmess KM et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, amyloid beta, amyloid probability score 2, blood biomarkers, diagnostic performance, p-tau217", "chunk": "CLIA-certified, CAP-accredited laboratory (C2N Diagnostics, St. Louis, MO) using liquid chromatography-tandem mass spectrometry. APS2 values were significantly higher in the 56% of CI participants with a positive amyloid PET scan. Concordance with amyloid PET was high (AUC-ROC 0.95 (95%CI): 0.93-0.98); 54% of participants had a positive APS2. The previously validated APS2 cut point yielded an overall accuracy of 91% (95%CI: 86-94%), sensitivity 90% (95%CI: 83-94%) and specificity 92% (95%CI: 84-96%). The PrecivityAD2 blood test's APS2 identified brain amyloid pathology with accuracy, sensitivity, and specificity \u2265 90% in this intended use population. This external validation reaffirms the diagnostic robustness of this blood biomarker test and supports its use as a confirmatory test, consistent with published expert recommendations, for assessment of presence or absence of brain amyloid pathology in symptomatic patients.", "source": "PubMed"}, {"chunk_id": "40297425_2", "pmid": "40297425", "title": "Independent validation of the PrecivityAD2<sup>\u2122</sup> blood test to identify presence or absence of brain amyloid pathology in individuals with cognitive impairment.", "authors": "Coppinger J, West T, Kirmess KM et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, amyloid beta, amyloid probability score 2, blood biomarkers, diagnostic performance, p-tau217", "chunk": "or absence of brain amyloid pathology in symptomatic patients.", "source": "PubMed"}, {"chunk_id": "40145364_0", "pmid": "40145364", "title": "Does white matter and vascular injury from repetitive head impacts lead to a novel pattern on T2 FLAIR MRI? A hypothesis proposal and call for research.", "authors": "Miner AE, Groh JR, Farris C et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "FLAIR MRI, RHI\u2010WMH, chronic traumatic encephalopathy, contact and collision sports, fluid attenuated inversion recovery neuroimaging biomarkers, head trauma, neurodegenerative disease, repetitive head impacts, repetitive head impact\u2010associated white matter hyperintensities, traumatic brain injury, traumatic encephalopathy syndrome, white matter hyperintensities", "chunk": "The goal of this paper is to introduce the hypothesis that white matter (WM) and vascular injury are long-term consequences of repetitive head impacts (RHI) that result in a novel T2 fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging pattern. A non-systematic literature review of autopsy and FLAIR studies of RHI-exposed adults was first conducted as a foundation for our hypothesis. A case series of RHI-exposed participants is presented to illustrate the unique FLAIR WM hyperintensities (WMH) pattern. Current literature shows a direct link between RHI and later-life WM/vascular neuropathologies, and that FLAIR WMH are associated with RHI, independent of modifiable vascular risk factors. Initial observations suggest a distinctive pattern of WMH in RHI-exposed participants, termed RHI-associated WMH (RHI-WMH). RHI-WMH defining features are as follows: (1) small, punctate, non-confluent, (2) spherical, and (3) proximal to the gray matter. Our hypothesis serves as a call for research to empirically validate RHI-WMH", "source": "PubMed"}, {"chunk_id": "40145364_1", "pmid": "40145364", "title": "Does white matter and vascular injury from repetitive head impacts lead to a novel pattern on T2 FLAIR MRI? A hypothesis proposal and call for research.", "authors": "Miner AE, Groh JR, Farris C et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "FLAIR MRI, RHI\u2010WMH, chronic traumatic encephalopathy, contact and collision sports, fluid attenuated inversion recovery neuroimaging biomarkers, head trauma, neurodegenerative disease, repetitive head impacts, repetitive head impact\u2010associated white matter hyperintensities, traumatic brain injury, traumatic encephalopathy syndrome, white matter hyperintensities", "chunk": "defining features are as follows: (1) small, punctate, non-confluent, (2) spherical, and (3) proximal to the gray matter. Our hypothesis serves as a call for research to empirically validate RHI-WMH and clarify their biological and clinical correlates. HIGHLIGHTS: Repetitive head impacts (RHI) have been associated with later-life white matter (WM) and vascular neuropathologies. T2 FLAIR MRI of RHI-exposed participants reveals a potentially unique WM hyperintensity (WMH) pattern that is termed RHI-associated WMH (RHI-WMH). RHI-WMH are characterized as (1) small, punctate, and non-confluent, (2) spherical, and (3) proximal to the gray matter at an area anatomically susceptible to impact injury, such as the depths of the cortical sulci.", "source": "PubMed"}, {"chunk_id": "40944318_0", "pmid": "40944318", "title": "The predictive role of olfactory identification on episodic memory and mild cognitive impairment: Results from the CIMA-Q cohort.", "authors": "Jobin B, Phillips NA, Frasnelli J et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, episodic memory, mild cognitive impairment, olfactory identification, subjective cognitive decline", "chunk": "BackgroundOlfactory identification decline is a known early marker of Alzheimer's disease and is already present at the mild cognitive impairment (MCI) stage. While being linked with episodic memory, its predictive value for cognitive performance and distinguishing between clinical stages remains unclear.ObjectiveThis study examined (1) the predictive value of olfactory identification for episodic memory performance and (2) its utility for discriminating individuals with MCI from those with subjective cognitive decline (SCD).MethodsParticipants included 45 individuals with MCI (mean age = 80.08, SD = 5.86) and 48 with SCD (mean age = 75.82, SD = 5.64) from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort. We evaluated olfactory identification with the University of Pennsylvania Smell Identification Test (UPSIT), and episodic memory with the Rey Auditory Verbal Learning Test (RAVLT). LASSO regression models were used to predict RAVLT total and delayed recall scores, using 80% of data for training and 20% for", "source": "PubMed"}, {"chunk_id": "40944318_1", "pmid": "40944318", "title": "The predictive role of olfactory identification on episodic memory and mild cognitive impairment: Results from the CIMA-Q cohort.", "authors": "Jobin B, Phillips NA, Frasnelli J et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, episodic memory, mild cognitive impairment, olfactory identification, subjective cognitive decline", "chunk": "with the Rey Auditory Verbal Learning Test (RAVLT). LASSO regression models were used to predict RAVLT total and delayed recall scores, using 80% of data for training and 20% for testing.ResultsUPSIT significantly predicted both RAVLT total (\u03b2 = 0.45, <i>p</i> = 0.03) and delayed recall (\u03b2 = 0.18, <i>p</i> = 0.02), independent of diagnostic group. Including UPSIT in the models increased explained variance from 9% to 19% for total recall, and from 8% to 20% for delayed recall. The MCI group had significantly lower UPSIT performance than the SCD group (<i>p</i> = 0.01). Linear discriminant analysis yielded 69% classification accuracy, with higher specificity (79%) than sensitivity (58%).ConclusionsOlfactory identification enhances prediction of episodic memory performance and may be used as a cost-effective, non-invasive early screening tool for MCI.", "source": "PubMed"}, {"chunk_id": "40944318_2", "pmid": "40944318", "title": "The predictive role of olfactory identification on episodic memory and mild cognitive impairment: Results from the CIMA-Q cohort.", "authors": "Jobin B, Phillips NA, Frasnelli J et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, episodic memory, mild cognitive impairment, olfactory identification, subjective cognitive decline", "chunk": "cost-effective, non-invasive early screening tool for MCI.", "source": "PubMed"}, {"chunk_id": "17277711_0", "pmid": "17277711", "title": "Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies.", "authors": "Christensen DD", "year": "2007", "journal": "CNS spectrums", "keywords": "None", "chunk": "The amyloid hypothesis--the leading mechanistic theory of Alzheimer's disease--states that an imbalance in production or clearance of amyloid beta (Abeta) results in accumulation of Abeta and triggers a cascade of events leading to neurodegeneration and dementia. The number of persons with Alzheimer's disease is expected to triple by mid-century. If steps are not taken to delay the onset or slow the progression of Alzheimer's disease, the economic and personal tolls will be immense. Different classes of potentially disease-modifying treatments that interrupt early pathological events (ie, decreasing production or aggregation of Abeta or increasing its clearance) and potentially prevent downstream events are in phase II or III clinical studies. These include immunotherapies; secretase inhibitors; selective Abeta42-lowering agents; statins; anti-Abeta aggregation agents; peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and gamma-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that", "source": "PubMed"}, {"chunk_id": "17277711_1", "pmid": "17277711", "title": "Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies.", "authors": "Christensen DD", "year": "2007", "journal": "CNS spectrums", "keywords": "None", "chunk": "peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and gamma-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that seem promising and have reached phase III clinical trials include those that selectively target Abeta42 production (eg, tarenflurbil), enhance the activity of alpha-secretase (eg, statins), and block Abeta aggregation (eg, transiposate).", "source": "PubMed"}, {"chunk_id": "18781290_0", "pmid": "18781290", "title": "[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus].", "authors": "Axer H, H\u00fcge S, Wilhelm C et al.", "year": "2009", "journal": "Der Nervenarzt", "keywords": "None", "chunk": "We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.", "source": "PubMed"}, {"chunk_id": "37857825_0", "pmid": "37857825", "title": "Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer's disease.", "authors": "Liu CC, Wang N, Chen Y et al.", "year": "2023", "journal": "Nature immunology", "keywords": "None", "chunk": "Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes by impairing lipid metabolism. Single-cell transcriptomic profiling reveals increased antigen presentation and interferon pathways upon apoE3 expression. In contrast, apoE4 expression downregulates complement and lysosomal pathways, and promotes stress-related responses. Moreover, in the presence of mouse endogenous apoE, microglial apoE4 exacerbates amyloid pathology. Finally, we observed a reduction in Lgals3-positive", "source": "PubMed"}, {"chunk_id": "37857825_1", "pmid": "37857825", "title": "Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer's disease.", "authors": "Liu CC, Wang N, Chen Y et al.", "year": "2023", "journal": "Nature immunology", "keywords": "None", "chunk": "expression downregulates complement and lysosomal pathways, and promotes stress-related responses. Moreover, in the presence of mouse endogenous apoE, microglial apoE4 exacerbates amyloid pathology. Finally, we observed a reduction in Lgals3-positive responsive microglia surrounding amyloid plaque and an increased accumulation of lipid droplets in APOE4 human brains and induced pluripotent stem cell-derived microglia. Our findings establish critical isoform-dependent effects of microglia/CAM-expressed apoE in brain function and the development of amyloid pathology, providing new insight into how apoE4 vastly increases AD risk.", "source": "PubMed"}, {"chunk_id": "36453167_0", "pmid": "36453167", "title": "Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis.", "authors": "Hegen H, Walde J, Berek K et al.", "year": "2023", "journal": "Multiple sclerosis (Houndmills, Basingstoke, England)", "keywords": "Cerebrospinal fluid, biomarker, clinically isolated syndrome, diagnosis, index, intrathecal fraction, kappa free light chains, meta-analysis, multiple sclerosis, systematic review", "chunk": "Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by \u03ba-free light chains (\u03ba-FLC) in cerebrospinal fluid. To perform a systematic review and meta-analysis to evaluate whether \u03ba-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine \u03ba-FLC index cut-off. PubMed was searched for studies that assessed diagnostic sensitivity and specificity of \u03ba-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models. A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of \u03ba-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for \u03ba-FLC", "source": "PubMed"}, {"chunk_id": "36453167_1", "pmid": "36453167", "title": "Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis.", "authors": "Hegen H, Walde J, Berek K et al.", "year": "2023", "journal": "Multiple sclerosis (Houndmills, Basingstoke, England)", "keywords": "Cerebrospinal fluid, biomarker, clinically isolated syndrome, diagnosis, index, intrathecal fraction, kappa free light chains, meta-analysis, multiple sclerosis, systematic review", "chunk": "were included in the meta-analysis to evaluate diagnostic value of \u03ba-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for \u03ba-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between \u03ba-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between \u03ba-FLC index and OCB. A discriminatory cut-off for \u03ba-FLC index was determined at 6.1. The findings indicate that \u03ba-FLC index has similar diagnostic accuracy in MS as OCB.", "source": "PubMed"}, {"chunk_id": "41264165_0", "pmid": "41264165", "title": "Breaking the Alzheimer's Treatment Stalemate: Synergistic Application Strategies of Nanomaterials and Pharmaceutical Agents.", "authors": "Gao H, Cheng F, Zhang Z et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2/A\u03b2, Nanomedicines, Neurodegeneration, Tau protein", "chunk": "Alzheimer's disease (AD), the leading cause of dementia, is characterized by amyloid beta accumulation and tau pathology propagation. Nanomedicine, a discipline enabling targeted drug delivery with precision, holds significant promise in the treatment of neurodegenerative diseases. This review explores the diagnostic and therapeutic applications of nanomaterials in neurodegenerative diseases, particularly AD, emphasizing their properties and their role in modulating pathogenic proteins. Advances in the development of novel anti-AD nanomedicines and their clinical progress are also highlighted. Despite the growing potential of nanotechnology in AD therapy, a definitive cure remains elusive. The review further addresses the current challenges in the field of AD nanomedicines and outlines future research directions to propel their development.", "source": "PubMed"}, {"chunk_id": "41168813_0", "pmid": "41168813", "title": "Sex differences in Alzheimer's disease CSF biomarkers and their association with A\u03b2 pathology on PET in cognitively unimpaired individuals.", "authors": "Mil\u00e0-Alom\u00e0 M, Van Hulle C, Brugulat-Serrat A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Preclinical, Sex", "chunk": "Alzheimer's disease (AD) exhibits sex differences in prevalence, symptoms and risk factors. Understanding the effect of sex in AD cerebrospinal fluid (CSF) biomarkers and their association with amyloid-beta (A\u03b2) pathology in preclinical stages have important implications for their use in prevention trials. The objective of this study was to examine sex differences in core AD CSF biomarkers used in early diagnosis and prevention trials, as well as in CSF biomarkers reflecting downstream pathophysiological mechanisms, and in their associations with A\u03b2 pathology as measured by Positron Emission Tomography (PET). Cognitively Unimpaired (CU) participants from the ALFA + (N = 400) and the WRAP/WADRC (N = 548) cohorts were included in the study. CSF biomarkers for core AD pathology (A\u03b242, A\u03b242/40, p-tau181/A\u03b242, p-tau181, p-tau217 and p-tau231), neurodegeneration (NfL, t-tau), synaptic dysfunction (neurogranin, GAP-43, SNAP25, synaptotagmin-1, \u03b1-synuclein), glial reactivity (GFAP, S100B, sTREM2, YKL-40), neuroinflammation (IL-6, MCP-1), and vascular dysregulation (sICAM-1, sVCAM-1) were measured.", "source": "PubMed"}, {"chunk_id": "41168813_1", "pmid": "41168813", "title": "Sex differences in Alzheimer's disease CSF biomarkers and their association with A\u03b2 pathology on PET in cognitively unimpaired individuals.", "authors": "Mil\u00e0-Alom\u00e0 M, Van Hulle C, Brugulat-Serrat A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Preclinical, Sex", "chunk": "p-tau181, p-tau217 and p-tau231), neurodegeneration (NfL, t-tau), synaptic dysfunction (neurogranin, GAP-43, SNAP25, synaptotagmin-1, \u03b1-synuclein), glial reactivity (GFAP, S100B, sTREM2, YKL-40), neuroinflammation (IL-6, MCP-1), and vascular dysregulation (sICAM-1, sVCAM-1) were measured. Participants underwent A\u03b2 PET at baseline and follow-up visit. We used Analyses of Covariance (ANCOVA) to evaluate sex differences in CSF biomarker levels and performed sex-stratified Receiver-Operating Characteristic (ROC) analyses to test their performance to identify A\u03b2 PET-positive individuals. Additionally, we run linear regression models to study the modifying effect of sex on the association of baseline CSF biomarkers with cross-sectional and longitudinal A\u03b2 PET uptake. Men had higher CSF NfL, glial reactivity and vascular dysregulation biomarkers (Cohen's d ranging from -0.22 to -0.44, P < 0.05), and lower synaptic biomarkers (Cohen's d ranging from 0.18 to 0.30, P < 0.05) compared to women at baseline. There were no sex differences in the core AD CSF biomarkers' performance to identify", "source": "PubMed"}, {"chunk_id": "41168813_2", "pmid": "41168813", "title": "Sex differences in Alzheimer's disease CSF biomarkers and their association with A\u03b2 pathology on PET in cognitively unimpaired individuals.", "authors": "Mil\u00e0-Alom\u00e0 M, Van Hulle C, Brugulat-Serrat A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Preclinical, Sex", "chunk": "biomarkers (Cohen's d ranging from 0.18 to 0.30, P < 0.05) compared to women at baseline. There were no sex differences in the core AD CSF biomarkers' performance to identify A\u03b2 PET-positive individuals (DeLong's test P values > 0.05), with CSF p-tau181/A\u03b242 and p-tau217 showing the highest performance in both sexes (Areas Under the Curve (AUCs) ranging from 87.1 to 96.3). However, sex modified the associations of baseline CSF biomarkers with A\u03b2 PET uptake, which were more pronounced in women than in men. Our results suggest that tailoring core AD CSF biomarkers by sex is not necessary for detecting A\u03b2 PET positivity in CU individuals. However, sex differences in their association with A\u03b2 deposition could influence their prognostic or monitoring applications.", "source": "PubMed"}, {"chunk_id": "41168813_3", "pmid": "41168813", "title": "Sex differences in Alzheimer's disease CSF biomarkers and their association with A\u03b2 pathology on PET in cognitively unimpaired individuals.", "authors": "Mil\u00e0-Alom\u00e0 M, Van Hulle C, Brugulat-Serrat A et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Preclinical, Sex", "chunk": "applications.", "source": "PubMed"}, {"chunk_id": "39835876_0", "pmid": "39835876", "title": "Association Between Oral Health Status and DMFT Index with Cognitive Dysfunction in Community-Dwelling Older Adults with Type 2 Diabetes: A Cross-Sectional Study.", "authors": "Khalili Z, Mozafarimanesh A, Najafi H et al.", "year": "2025", "journal": "Experimental aging research", "keywords": "None", "chunk": "Cognitive dysfunction is a significant issue in old age and can cause many problems in older adults, especially those with diabetes. This study aimed to investigate the association between oral health status and DMFT index with cognitive dysfunction in community-dwelling older adults with T2D (type 2 diabetes). This was a cross-sectional study that included 245 older people aged 60 years and older with T2D, visiting healthcare centers in north of Iran, using the cluster sampling method. Data collection tools included clinical-demographic questionnaire, the Geriatric Oral Health Assessment Index (GOHAI) and the Mini-Mental State Examination (MMSE) questionnaire. A P-value <.05 was considered significant. The mean age of older adults in this study was 64.86 \u00b1 3.99 years. The mean and standard deviation for the DMFT index, GOHAI index and MMSE scale were 9.39 \u00b1 3.83, 34.29 \u00b1 17.93 and 15.18 \u00b1 10.04 respectively. The results showed statistically significant relationship between poor", "source": "PubMed"}, {"chunk_id": "39835876_1", "pmid": "39835876", "title": "Association Between Oral Health Status and DMFT Index with Cognitive Dysfunction in Community-Dwelling Older Adults with Type 2 Diabetes: A Cross-Sectional Study.", "authors": "Khalili Z, Mozafarimanesh A, Najafi H et al.", "year": "2025", "journal": "Experimental aging research", "keywords": "None", "chunk": "deviation for the DMFT index, GOHAI index and MMSE scale were 9.39 \u00b1 3.83, 34.29 \u00b1 17.93 and 15.18 \u00b1 10.04 respectively. The results showed statistically significant relationship between poor oral health status and the cognitive status of older adults with T2D (<i>p</i> < .001). Additionally, the relationship between oral health index domains (physical function, psychosocial function and pain) and cognitive status in older adults was significant (<i>p</i> < .001). Another finding indicated an inverse and significant relationship between the DMFT index and cognitive dysfunction in older adults (<i>p</i> < .001). Poor oral health was associated with cognitive dysfunction among the community-dwelling older adults with T2D. Given the high prevalence of T2D in older adults and the critical importance of oral and dental health for cognition, it is necessary to develop interventions to improve oral health in older adults with T2D.", "source": "PubMed"}, {"chunk_id": "39835876_2", "pmid": "39835876", "title": "Association Between Oral Health Status and DMFT Index with Cognitive Dysfunction in Community-Dwelling Older Adults with Type 2 Diabetes: A Cross-Sectional Study.", "authors": "Khalili Z, Mozafarimanesh A, Najafi H et al.", "year": "2025", "journal": "Experimental aging research", "keywords": "None", "chunk": "oral and dental health for cognition, it is necessary to develop interventions to improve oral health in older adults with T2D.", "source": "PubMed"}, {"chunk_id": "35450525_0", "pmid": "35450525", "title": "The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.", "authors": "Tseng PT, Zeng BY, Chen YW et al.", "year": "2022", "journal": "Current neuropharmacology", "keywords": "Alzheimer\u2019s dementia, circadian rhythm, cognition, dementia, melatonin, network meta-analysis, psychiatry, quality of life", "chunk": "While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the", "source": "PubMed"}, {"chunk_id": "35450525_1", "pmid": "35450525", "title": "The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.", "authors": "Tseng PT, Zeng BY, Chen YW et al.", "year": "2022", "journal": "Current neuropharmacology", "keywords": "Alzheimer\u2019s dementia, circadian rhythm, cognition, dementia, melatonin, network meta-analysis, psychiatry, quality of life", "chunk": "of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.", "source": "PubMed"}, {"chunk_id": "35450525_2", "pmid": "35450525", "title": "The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.", "authors": "Tseng PT, Zeng BY, Chen YW et al.", "year": "2022", "journal": "Current neuropharmacology", "keywords": "Alzheimer\u2019s dementia, circadian rhythm, cognition, dementia, melatonin, network meta-analysis, psychiatry, quality of life", "chunk": "AD.", "source": "PubMed"}, {"chunk_id": "41192218_0", "pmid": "41192218", "title": "Sleep phenotypes of \u03b1-synucleinopathies and tauopathies with Parkinsonism.", "authors": "Briel N, Marti C, Werth E et al.", "year": "2025", "journal": "Parkinsonism & related disorders", "keywords": "Neurodegeneration, Parkinson, Polysomnography, RBD/REM sleep behavior disorder, Sleep, Tau, \u03b1-synuclein", "chunk": "In neurodegenerative Parkinsonism, biomarkers of \u03b1-synucleinopathy (Syn) or tauopathy (Tau) are an unmet need. Rapid eye movement (REM) sleep behavior disorder (RBD) strongly indicates Syn. However, it remains unknown if sleep features other than RBD could reflect underlying neuropathology. Here we assess sleep phenotypes of Syn or Tau in neurodegenerative Parkinsonism and explore their properties as potential biomarkers. We retrospectively analyzed polysomnography recordings from 198 patients with clinically diagnosed Parkinsonism (20 DLB, 100 PD, 45 MSA, 27 PSP, 6 CBS). We compared sleep features between clinical diagnoses and between Syn (DLB + PD + MSA) and Tau (PSP + CBS) patients. We established linear discriminant analysis-informed parsimonious logistic regression models for differentiating Syn and Tau proteinopathies. Sleep architecture was more disturbed in Tau compared to Syn patients, with less REM and non-REM stage 2 sleep, lower sleep efficiency, and more wake after sleep onset. Stridor was unique to MSA, with", "source": "PubMed"}, {"chunk_id": "41192218_1", "pmid": "41192218", "title": "Sleep phenotypes of \u03b1-synucleinopathies and tauopathies with Parkinsonism.", "authors": "Briel N, Marti C, Werth E et al.", "year": "2025", "journal": "Parkinsonism & related disorders", "keywords": "Neurodegeneration, Parkinson, Polysomnography, RBD/REM sleep behavior disorder, Sleep, Tau, \u03b1-synuclein", "chunk": "disturbed in Tau compared to Syn patients, with less REM and non-REM stage 2 sleep, lower sleep efficiency, and more wake after sleep onset. Stridor was unique to MSA, with a prevalence of 42 %. Parsimonious modeling identified sleep features sufficient to differentiate Tau from Syn patients; Diagnostic accuracy was robust with RBD (AUC = 0.78) but even higher after adding more polysomnography features (AUC = 0.83) and demographic variables to the model (AUC = 0.9). The best classification model of Syn vs. Tau is available online for exploration and custom data input at SynTauSleepTool. Distinct sleep phenotypes characterize neurodegenerative Parkinsonism with Syn or Tau. Pending pathological confirmation, our data suggests that neurodegeneration could affect sleep-wake regulatory brain systems in a proteinopathy-dependent manner. Sleep phenotypes hold promise as non-invasive biomarkers of Syn or Tau in Parkinsonism.", "source": "PubMed"}, {"chunk_id": "41192218_2", "pmid": "41192218", "title": "Sleep phenotypes of \u03b1-synucleinopathies and tauopathies with Parkinsonism.", "authors": "Briel N, Marti C, Werth E et al.", "year": "2025", "journal": "Parkinsonism & related disorders", "keywords": "Neurodegeneration, Parkinson, Polysomnography, RBD/REM sleep behavior disorder, Sleep, Tau, \u03b1-synuclein", "chunk": "a proteinopathy-dependent manner. Sleep phenotypes hold promise as non-invasive biomarkers of Syn or Tau in Parkinsonism.", "source": "PubMed"}, {"chunk_id": "38771688_0", "pmid": "38771688", "title": "Deep Geometric Learning With Monotonicity Constraints for Alzheimer's Disease Progression.", "authors": "Jeong S, Jung W, Sohn J et al.", "year": "2025", "journal": "IEEE transactions on neural networks and learning systems", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a devastating neurodegenerative condition that precedes progressive and irreversible dementia; thus, predicting its progression over time is vital for clinical diagnosis and treatment. For this, numerous studies have implemented structural magnetic resonance imaging (MRI) to model AD progression, focusing on three integral aspects: 1) temporal variability; 2) incomplete observations; and 3) temporal geometric characteristics. However, many pioneer deep learning-based approaches addressing data variability and sparsity have yet to consider inherent geometrical properties sufficiently. These properties are integral to modeling as they correlate with brain region size, thickness, volume, and shape in AD progression. The ordinary differential equation-based geometric modeling method (ODE-RGRU) has recently emerged as a promising strategy for modeling time-series data by intertwining a recurrent neural network (RNN) and an ODE in Riemannian space. Despite its achievements, ODE-RGRU encounters limitations when extrapolating positive definite symmetric matrices from incomplete samples, leading to feature reverse occurrences that", "source": "PubMed"}, {"chunk_id": "38771688_1", "pmid": "38771688", "title": "Deep Geometric Learning With Monotonicity Constraints for Alzheimer's Disease Progression.", "authors": "Jeong S, Jung W, Sohn J et al.", "year": "2025", "journal": "IEEE transactions on neural networks and learning systems", "keywords": "None", "chunk": "neural network (RNN) and an ODE in Riemannian space. Despite its achievements, ODE-RGRU encounters limitations when extrapolating positive definite symmetric matrices from incomplete samples, leading to feature reverse occurrences that are particularly problematic, especially within the clinical facet. Therefore, this study proposes a novel geometric learning approach that models longitudinal MRI biomarkers and cognitive scores by combining three modules: topological space shift, ODE-RGRU, and trajectory estimation. We have also developed a training algorithm that integrates the manifold mapping with monotonicity constraints to reflect measurement transition irreversibility. We verify our proposed method's efficacy by predicting clinical labels and cognitive scores over time in regular and irregular settings. Furthermore, we thoroughly analyze our proposed framework through an ablation study.", "source": "PubMed"}, {"chunk_id": "37852961_0", "pmid": "37852961", "title": "FSH and ApoE4 contribute to Alzheimer's disease-like pathogenesis via C/EBP\u03b2/\u03b4-secretase in female mice.", "authors": "Xiong J, Kang SS, Wang M et al.", "year": "2023", "journal": "Nature communications", "keywords": "None", "chunk": "Alzheimer's disease (AD) is the most common dementia. It is known that women with one ApoE4 allele display greater risk and earlier onset of AD compared with men. In mice, we previously showed that follicle-stimulating hormone (FSH), a gonadotropin that rises in post-menopausal females, activates its receptor FSHR in the hippocampus, to drive AD-like pathology and cognitive impairment. Here we show in mice that ApoE4 and FSH jointly trigger AD-like pathogenesis by activating C/EBP\u03b2/\u03b4-secretase signaling. ApoE4 and FSH additively activate C/EBP\u03b2/\u03b4-secretase pathway that mediates APP and Tau proteolytic fragmentation, stimulating A\u03b2 and neurofibrillary tangles. Ovariectomy-provoked AD-like pathologies and cognitive defects in female ApoE4-TR mice are ameliorated by anti-FSH antibody treatment. FSH administration facilitates AD-like pathologies in both young male and female ApoE4-TR mice. Furthermore, FSH stimulates AD-like pathologies and cognitive defects in ApoE4-TR mice, but not ApoE3-TR mice. Our findings suggest that in mice, augmented FSH in females with ApoE4", "source": "PubMed"}, {"chunk_id": "37852961_1", "pmid": "37852961", "title": "FSH and ApoE4 contribute to Alzheimer's disease-like pathogenesis via C/EBP\u03b2/\u03b4-secretase in female mice.", "authors": "Xiong J, Kang SS, Wang M et al.", "year": "2023", "journal": "Nature communications", "keywords": "None", "chunk": "female ApoE4-TR mice. Furthermore, FSH stimulates AD-like pathologies and cognitive defects in ApoE4-TR mice, but not ApoE3-TR mice. Our findings suggest that in mice, augmented FSH in females with ApoE4 but not ApoE3 genotype increases vulnerability to AD-like process by activating C/EBP\u03b2/\u03b4-secretase signalling.", "source": "PubMed"}, {"chunk_id": "36544184_0", "pmid": "36544184", "title": "Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study.", "authors": "McDade E, Cummings JL, Dhadda S et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "None", "chunk": "Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated A\u03b2 species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab. The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9 to 59 months (mean 24 months). At 12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of", "source": "PubMed"}, {"chunk_id": "36544184_1", "pmid": "36544184", "title": "Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study.", "authors": "McDade E, Cummings JL, Dhadda S et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "None", "chunk": "12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of cognitive decline. The rates of clinical progression during the gap were similar in lecanemab and placebo subjects, with clinical treatment differences maintained after discontinued dosing over an average of 24 months in the gap period. During the gap, plasma A\u03b242/40 ratio and p-tau181 levels began to return towards pre-randomization levels more quickly than amyloid PET. At OLE baseline, treatment differences vs placebo at 18 months in the randomized period were maintained across 3 clinical assessments. In the OLE, lecanemab 10 mg/kg biweekly treatment produced dose-dependent reductions in amyloid PET SUVr, improvements in plasma A\u03b242/40 ratio, and reductions in plasma p-tau181. Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and", "source": "PubMed"}, {"chunk_id": "36544184_2", "pmid": "36544184", "title": "Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study.", "authors": "McDade E, Cummings JL, Dhadda S et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "None", "chunk": "improvements in plasma A\u03b242/40 ratio, and reductions in plasma p-tau181. Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and pronounced amyloid reduction correlates with clinical benefit and potential disease-modifying effects, as well as the potential to use plasma biomarkers to monitor for lecanemab treatment effects. ClinicalTrials.gov NCT01767311 .", "source": "PubMed"}, {"chunk_id": "41667529_0", "pmid": "41667529", "title": "Alzheimer's disease prediction using deep learning and XAI based interpretable feature selection from blood gene expression data.", "authors": "Hariharan J, Jothi R", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer disease prediction, Blood gene biomarkers, Deep learning, Deep neural network, Explainable AI, Feature selection", "chunk": "Alzheimer's disease (AD), a type of neurodegenerative disorder, has seen an increase in cases over the past decade, necessitating the construction of a comprehensive early detection method. Existing methods are typically invasive and costly, so our research concentrates on blood gene expression as a possible biomarker for early diagnosis of AD. Many research directions using machine learning and deep learning techniques exist in the literature for AD diagnosis. However, most of them use MRI scans as the primary data, and very few studies have been carried out on the use of blood gene biomarkers. The analysis of blood gene expression data is complicated by its high dimensionality and limited sample size. In this paper, we attempt to address these issues by applying multiple feature selection methods to identify the critical genes that act as biomarkers for AD diagnosis. To select the genes linked to AD and identify AD patients, we", "source": "PubMed"}, {"chunk_id": "41667529_1", "pmid": "41667529", "title": "Alzheimer's disease prediction using deep learning and XAI based interpretable feature selection from blood gene expression data.", "authors": "Hariharan J, Jothi R", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer disease prediction, Blood gene biomarkers, Deep learning, Deep neural network, Explainable AI, Feature selection", "chunk": "by applying multiple feature selection methods to identify the critical genes that act as biomarkers for AD diagnosis. To select the genes linked to AD and identify AD patients, we employ four feature selection approaches, including Chi-square, ANOVA, Recursive Feature Elimination (RFE), and ElasticNet, and build two deep learning models for AD classification. The selected genes are assessed with nested five-fold cross-validation to avoid overfitting. Further, we employ SHapley Additive exPlanations (SHAP), an Explainable AI (XAI) model, for ranking the selected genes and explaining why the feature selection algorithms predict a subset of genes as probable biomarkers. Generative Adversarial Network (GAN)-based data augmentation is used to address the issue of small sample size and improve model generalization. We demonstrate the results of feature selection and AD classification on three blood gene expression datasets, namely GSE63060, GSE63061, and ADNI, and their integrated version. Experimental results indicate that the deep neural network", "source": "PubMed"}, {"chunk_id": "41667529_2", "pmid": "41667529", "title": "Alzheimer's disease prediction using deep learning and XAI based interpretable feature selection from blood gene expression data.", "authors": "Hariharan J, Jothi R", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer disease prediction, Blood gene biomarkers, Deep learning, Deep neural network, Explainable AI, Feature selection", "chunk": "results of feature selection and AD classification on three blood gene expression datasets, namely GSE63060, GSE63061, and ADNI, and their integrated version. Experimental results indicate that the deep neural network classifier achieved an accuracy of 91% and a precision of 95% in identifying AD samples. Feature selection along with data augmentation has significantly enhanced the precision and interpretability of early detection of AD using blood gene expression.", "source": "PubMed"}, {"chunk_id": "41816611_0", "pmid": "41816611", "title": "APP E590D mutation increases generation of A\u03b2 and A\u03b7 peptides and exacerbates tauopathy.", "authors": "Liu T, Wetzel L, Roy D et al.", "year": "2026", "journal": "NPJ dementia", "keywords": "Diseases, Neurology, Neuroscience", "chunk": "Accumulation of Amyloid \u03b2 (A\u03b2), a peptide derived from endocytic processing of the amyloid precursor protein (APP), is a critical initial step in the development of Alzheimer's disease (AD). While the APP695<sup>E590D</sup> mutation was previously discovered in 2 pathologically confirmed AD patients, the pathogenicity of this mutation has remained uncertain due to its exceptional rarity. Here, we characterize the APP695<sup>E590D</sup> mutation by evaluating multiple APP metabolites and determining its effects on tauopathy in cellular and animal models. We show that APP695<sup>E590D</sup> not only increases A\u03b2 through endocytic \u03b2-secretase processing but also increases A\u03b7, an alternative APP-derived synaptotoxic peptide. We further demonstrate that APP695<sup>E590D</sup> promotes tauopathy by increasing tau seeding and aggregation in cellular models and exacerbating phospho-tau pathology and neuroinflammation in tau<sup>P301S</sup> mice. These results reveal a unique modality by which APP695<sup>E590D</sup> impinges on AD pathology by enhancing both A\u03b2 and A\u03b7 generation and accelerating tauopathy.", "source": "PubMed"}, {"chunk_id": "41816611_1", "pmid": "41816611", "title": "APP E590D mutation increases generation of A\u03b2 and A\u03b7 peptides and exacerbates tauopathy.", "authors": "Liu T, Wetzel L, Roy D et al.", "year": "2026", "journal": "NPJ dementia", "keywords": "Diseases, Neurology, Neuroscience", "chunk": "in tau<sup>P301S</sup> mice. These results reveal a unique modality by which APP695<sup>E590D</sup> impinges on AD pathology by enhancing both A\u03b2 and A\u03b7 generation and accelerating tauopathy.", "source": "PubMed"}, {"chunk_id": "38053285_0", "pmid": "38053285", "title": "Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer's disease.", "authors": "Shukla AK, Misra S", "year": "2024", "journal": "Journal of basic and clinical physiology and pharmacology", "keywords": "Alzheimer\u2019s disease (AD), donanemab, neurodegenerative disease", "chunk": "The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer's disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer's disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-\u03b2) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab's accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional", "source": "PubMed"}, {"chunk_id": "38053285_1", "pmid": "38053285", "title": "Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer's disease.", "authors": "Shukla AK, Misra S", "year": "2024", "journal": "Journal of basic and clinical physiology and pharmacology", "keywords": "Alzheimer\u2019s disease (AD), donanemab, neurodegenerative disease", "chunk": "the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-\u03b2 plaque reduction and toxic tau levels.", "source": "PubMed"}, {"chunk_id": "41220873_0", "pmid": "41220873", "title": "Mendelian Randomization Reveals Unidirectional Links Between Amyloid-\u03b2 and Tau in Alzheimer's Disease.", "authors": "Kim JP, Lee H, Kim BH et al.", "year": "2025", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer's Disease, Amyloid Beta-Peptides, Cerebrospinal Fluid, Genome-Wide Association Study, Positron-Emission Tomography, Tau Proteins", "chunk": "Prior research has indicated that changes in the amyloid-beta (A\u03b2) biomarker precede tau biomarker alterations in Alzheimer's disease (AD). However, establishing causality through temporal correlations remains contentious. This study aimed to explore the causal relationship between A\u03b2 and tau using Mendelian randomization (MR) analysis. We conducted two-sample MR analyses employing genome-wide association studies (GWASs) summary statistics for A\u03b2 positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau (CSF pTau). Additionally, to reinforce and validate the results of the two-sample MR, we performed two-sample MR using tau PET GWAS summary statistics and one-sample MR analysis using autopsy data. In the one-sample MR analysis, the exposure and outcome variables were neuritic plaque burden and neurofibrillary tangle burden, respectively, determined through neuropathological examination. The two-sample MR analysis unveiled a causal association between A\u03b2 accumulation and CSF pTau level (BETA [standard error]=0.30 [0.10], <i>p</i>=0.004). The absence of heterogeneity and horizontal pleiotropy was confirmed. In", "source": "PubMed"}, {"chunk_id": "41220873_1", "pmid": "41220873", "title": "Mendelian Randomization Reveals Unidirectional Links Between Amyloid-\u03b2 and Tau in Alzheimer's Disease.", "authors": "Kim JP, Lee H, Kim BH et al.", "year": "2025", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer's Disease, Amyloid Beta-Peptides, Cerebrospinal Fluid, Genome-Wide Association Study, Positron-Emission Tomography, Tau Proteins", "chunk": "The two-sample MR analysis unveiled a causal association between A\u03b2 accumulation and CSF pTau level (BETA [standard error]=0.30 [0.10], <i>p</i>=0.004). The absence of heterogeneity and horizontal pleiotropy was confirmed. In contrast, there was no evidence causally relating CSF pTau level to A\u03b2 accumulation (<i>p</i>=0.56). Our results were reinforced by consistently directional effects observed in the two-sample MR using tau PET GWAS and one-sample MR analysis, indicating a causal direction from A\u03b2 burdens (measured by neuritic plaques) to tau burdens (measured by neurofibrillary tangles) (<i>p</i>=1.24\u00d710<sup>-13</sup>). Our findings suggest a causal relationship between A\u03b2 burdens and tau burdens in AD, reinforcing the notion of A\u03b2 as a pivotal upstream factor in AD pathogenesis.", "source": "PubMed"}, {"chunk_id": "40667488_0", "pmid": "40667488", "title": "Immunoassay for pyruvate kinase M1/2 as an Alzheimer's biomarker in CSF.", "authors": "de Geus MB, Kivis\u00e4kk P, Trombetta BA et al.", "year": "2025", "journal": "Open life sciences", "keywords": "Alzheimer\u2019s disease, biomarker, glucose metabolism, immunoassay, pyruvate kinase", "chunk": "Alzheimer's disease (AD) is characterized by amyloid-beta plaques and tau tangles in the brain, but these markers alone do not predict disease progression. The intersection of these pathologies with other processes including metabolic changes may contribute to disease progression. Brain glucose metabolism changes are among the earliest detectable events in AD. Pyruvate kinase (PKM) has been implicated as a potential biomarker to track these metabolic changes. We have developed an enzyme-linked immunosorbent assay (ELISA) to assess PKM levels in cerebrospinal fluid (CSF). First, we verified the relationship of CSF PKM levels with cognitive decline, revealing a correlation between elevated CSF PKM levels and accelerated cognitive decline in preclinical AD patients in a tau-dependent manner. We developed the ELISA using two PKM-specific antibodies and validated it through quality control steps, indicating robust quantification of PKM. We showed that ELISA measurements of PKM correlate with mass spectrometry values in matching samples. When", "source": "PubMed"}, {"chunk_id": "40667488_1", "pmid": "40667488", "title": "Immunoassay for pyruvate kinase M1/2 as an Alzheimer's biomarker in CSF.", "authors": "de Geus MB, Kivis\u00e4kk P, Trombetta BA et al.", "year": "2025", "journal": "Open life sciences", "keywords": "Alzheimer\u2019s disease, biomarker, glucose metabolism, immunoassay, pyruvate kinase", "chunk": "PKM-specific antibodies and validated it through quality control steps, indicating robust quantification of PKM. We showed that ELISA measurements of PKM correlate with mass spectrometry values in matching samples. When tested on an independent cohort, the assay confirmed elevation of PKM in AD. These findings support the use of PKM as a potential biomarker for tracking early metabolic changes in AD, offering a novel tool for investigating metabolic alterations and their intersection with other underlying pathologies in AD progression.", "source": "PubMed"}, {"chunk_id": "34897092_0", "pmid": "34897092", "title": "Multimodal Classification of Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Integrated 18F-FDG PET and DTI Study.", "authors": "Li W, Zhao Z, Liu M et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "18F-FDG PET, Alzheimer\u2019s disease, diffusion tensor imaging, mild cognitive impairment", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory impairment. Amnestic mild cognitive impairment (aMCI) is the intermediate stage between normal cognitive aging and early dementia caused by AD. It can be challenging to differentiate aMCI patients from healthy controls (HC) and mild AD patients. To validate whether the combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and diffusion tensor imaging (DTI) will improve classification performance compared with that based on a single modality. A total of thirty patients with AD, sixty patients with aMCI, and fifty healthy controls were included. AD was diagnosed according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable. aMCI diagnosis was based on Petersen's criteria. The 18F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI,", "source": "PubMed"}, {"chunk_id": "34897092_1", "pmid": "34897092", "title": "Multimodal Classification of Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Integrated 18F-FDG PET and DTI Study.", "authors": "Li W, Zhao Z, Liu M et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "18F-FDG PET, Alzheimer\u2019s disease, diffusion tensor imaging, mild cognitive impairment", "chunk": "aMCI diagnosis was based on Petersen's criteria. The 18F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI, and AD using receiver operating characteristic analysis together with binary logistic regression. The rate of accuracy was based on the area under the curve (AUC). For classifying AD from HC, we achieve an AUC of 0.96 when combining two modalities of biomarkers and 0.93 when using 18F-FDG PET individually. For classifying aMCI from HC, we achieve an AUC of 0.79 and 0.76 using the best individual modality of biomarkers. Our results show that the combination of two modalities improves classification performance, compared with that using any individual modality.", "source": "PubMed"}, {"chunk_id": "34548476_0", "pmid": "34548476", "title": "Transferrin-Pep63-liposomes accelerate the clearance of A\u03b2 and rescue impaired synaptic plasticity in early Alzheimer's disease models.", "authors": "Yang X, Li X, Liu L et al.", "year": "2021", "journal": "Cell death discovery", "keywords": "None", "chunk": "Alzheimer's disease (AD) is characterized by aberrant accumulation of extracellular \u03b2-amyloid (A\u03b2) peptides in the brain. Soluble A\u03b2 oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both A\u03b2 oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the A\u03b2 burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture A\u03b2 oligomers or", "source": "PubMed"}, {"chunk_id": "34548476_1", "pmid": "34548476", "title": "Transferrin-Pep63-liposomes accelerate the clearance of A\u03b2 and rescue impaired synaptic plasticity in early Alzheimer's disease models.", "authors": "Yang X, Li X, Liu L et al.", "year": "2021", "journal": "Cell death discovery", "keywords": "None", "chunk": "and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture A\u03b2 oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered A\u03b21-42 aggregation and disaggregated A\u03b21-42 assembly due to multivalent PA-A\u03b2. Pep63 effectively inhibited the binding between EphB2 and A\u03b2 oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.", "source": "PubMed"}, {"chunk_id": "35603771_0", "pmid": "35603771", "title": "Prenatal development of the human entorhinal cortex.", "authors": "\u0160imi\u0107 G, Krsnik \u017d, Knezovi\u0107 V et al.", "year": "2022", "journal": "The Journal of comparative neurology", "keywords": "Alzheimer's disease, acetylcholinesterase, consciousness, cytoarchitecture, entorhinal cortex, lamina dissecans, perforant path, periallocortex, schizophrenia, temporal lobe epilepsy", "chunk": "Little is known about the development of the human entorhinal cortex (EC), a major hub in a widespread network for learning and memory, spatial navigation, high-order processing of object information, multimodal integration, attention and awareness, emotion, motivation, and perception of time. We analyzed a series of 20 fetal and two adult human brains using Nissl stain, acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for myelin basic protein (MBP), neuronal nuclei antigen (NeuN), a pan-axonal neurofilament marker, and synaptophysin, as well as postmortem 3T MRI. In comparison with other parts of the cerebral cortex, the cytoarchitectural differentiation of the EC begins remarkably early, in the 10th week of gestation (w.g.). The differentiation occurs in a superficial magnocellular layer in the deep part of the marginal zone, accompanied by cortical plate (CP) condensation and multilayering of the deep part of CP. These processes last until the 13-14th w.g. At 14 w.g., the superficial lamina", "source": "PubMed"}, {"chunk_id": "35603771_1", "pmid": "35603771", "title": "Prenatal development of the human entorhinal cortex.", "authors": "\u0160imi\u0107 G, Krsnik \u017d, Knezovi\u0107 V et al.", "year": "2022", "journal": "The Journal of comparative neurology", "keywords": "Alzheimer's disease, acetylcholinesterase, consciousness, cytoarchitecture, entorhinal cortex, lamina dissecans, perforant path, periallocortex, schizophrenia, temporal lobe epilepsy", "chunk": "the marginal zone, accompanied by cortical plate (CP) condensation and multilayering of the deep part of CP. These processes last until the 13-14th w.g. At 14 w.g., the superficial lamina dissecans (LD) is visible, which divides the CP into the lamina principalis externa (LPE) and interna (LPI). Simultaneously, the rostral LPE separates into vertical cell-dense islands, whereas in the LPI, the deep LD emerges as a clear acellular layer. In the 16th w.g., the LPE remodels into vertical cell-dense and cell-sparse zones with a caudorostral gradient. At 20 w.g., NeuN immunoreactivity is most pronounced in the islands of layer II cells, whereas migration and differentiation inside-out gradients are seen simultaneously in both the upper (LPE) and the lower (LPI) pyramidal layers. At this stage, the EC adopts for the first time an adult-like cytoarchitectural organization, the superficial LD becomes discernible by 3T MRI, MBP-expressing oligodendrocytes first appear in the fimbria", "source": "PubMed"}, {"chunk_id": "35603771_2", "pmid": "35603771", "title": "Prenatal development of the human entorhinal cortex.", "authors": "\u0160imi\u0107 G, Krsnik \u017d, Knezovi\u0107 V et al.", "year": "2022", "journal": "The Journal of comparative neurology", "keywords": "Alzheimer's disease, acetylcholinesterase, consciousness, cytoarchitecture, entorhinal cortex, lamina dissecans, perforant path, periallocortex, schizophrenia, temporal lobe epilepsy", "chunk": "layers. At this stage, the EC adopts for the first time an adult-like cytoarchitectural organization, the superficial LD becomes discernible by 3T MRI, MBP-expressing oligodendrocytes first appear in the fimbria and the perforant path (PP) penetrates the subiculum to reach its molecular layer and travels along through the Cornu Ammonis fields to reach the suprapyramidal blade of the dentate gyrus, whereas the entorhinal-dentate branch perforates the hippocampal sulcus about 2-3 weeks later. The first AChE reactivity appears as longitudinal stripes at 23 w.g. in layers I and II of the rostrolateral EC and then also as AChE-positive in-growing fibers in islands of superficial layer III and layer II neurons. At 40 w.g., myelination of the PP starts as patchy MBP-immunoreactive oligodendrocytes and their processes. Our results refute the possibility of an inside-out pattern of the EC development and support the key role of layer II prospective stellate cells in the", "source": "PubMed"}, {"chunk_id": "35603771_3", "pmid": "35603771", "title": "Prenatal development of the human entorhinal cortex.", "authors": "\u0160imi\u0107 G, Krsnik \u017d, Knezovi\u0107 V et al.", "year": "2022", "journal": "The Journal of comparative neurology", "keywords": "Alzheimer's disease, acetylcholinesterase, consciousness, cytoarchitecture, entorhinal cortex, lamina dissecans, perforant path, periallocortex, schizophrenia, temporal lobe epilepsy", "chunk": "oligodendrocytes and their processes. Our results refute the possibility of an inside-out pattern of the EC development and support the key role of layer II prospective stellate cells in the EC lamination. As the early cytoarchitectural differentiation of the EC is paralleled by the neurochemical development, these developmental milestones in EC structure and connectivity have implications for understanding its normal function, including its puzzling modular organization and potential contribution to consciousness content (awareness), as well as for its insufficiently explored deficits in developmental, psychiatric, and degenerative brain disorders.", "source": "PubMed"}, {"chunk_id": "35779670_0", "pmid": "35779670", "title": "The cardiometabolic depression subtype and its association with clinical characteristics: The Maastricht Study.", "authors": "Geraets AFJ, Schram MT, Jansen JFA et al.", "year": "2022", "journal": "Journal of affective disorders", "keywords": "Cardiometabolic abnormalities, Depression, Epidemiology, Latent class analysis, Major depressive disorder, Metabolic syndrome", "chunk": "Individuals with depression often show an adverse cardiometabolic risk profile and might represent a distinct depression subtype. The aim of this study was to investigate whether a cardiometabolic depression subtype could be identified and to investigate its association with demographics and clinical characteristics (severity, symptomatology, anti-depressant use, persistence and cognitive functioning). We used data from The Maastricht Study, a population-based cohort in the southern part of The Netherlands. A total of 248 participants with major depressive disorder were included (mean [SD] age, 58.8 \u00b1 8.5 years; 121 [48.8 %] were men). Major depressive disorder was assessed at baseline by the Mini-International Neuropsychiatric Interview. Cardiometabolic risk factors were defined as indicators of the metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. We measured severity and persistence of depressive symptoms by use of the 9-item Patient Health Questionnaire. Latent class analysis resulted in two subtypes, one", "source": "PubMed"}, {"chunk_id": "35779670_1", "pmid": "35779670", "title": "The cardiometabolic depression subtype and its association with clinical characteristics: The Maastricht Study.", "authors": "Geraets AFJ, Schram MT, Jansen JFA et al.", "year": "2022", "journal": "Journal of affective disorders", "keywords": "Cardiometabolic abnormalities, Depression, Epidemiology, Latent class analysis, Major depressive disorder, Metabolic syndrome", "chunk": "Program Adult Treatment Panel III guidelines. We measured severity and persistence of depressive symptoms by use of the 9-item Patient Health Questionnaire. Latent class analysis resulted in two subtypes, one with cardiometabolic depression (n = 145) and another with non-cardiometabolic depression (n = 103). The cardiometabolic depression subtype was characterized by being male, low education, more severe depressive symptoms, less symptoms of depressed mood and more symptoms of loss of energy, more use of antidepressant medication and lower cognitive functioning. No conclusions can be made about causality. Latent class analysis suggested a distinct cardiometabolic depression subtype. Participants with cardiometabolic depression differed from participants with non-cardiometabolic depression in terms of demographics and clinical characteristics. The existence of a cardiometabolic depression subtype may indicate the need for prevention and treatment targeting cardiometabolic risk management.", "source": "PubMed"}, {"chunk_id": "35779670_2", "pmid": "35779670", "title": "The cardiometabolic depression subtype and its association with clinical characteristics: The Maastricht Study.", "authors": "Geraets AFJ, Schram MT, Jansen JFA et al.", "year": "2022", "journal": "Journal of affective disorders", "keywords": "Cardiometabolic abnormalities, Depression, Epidemiology, Latent class analysis, Major depressive disorder, Metabolic syndrome", "chunk": "may indicate the need for prevention and treatment targeting cardiometabolic risk management.", "source": "PubMed"}, {"chunk_id": "33725354_0", "pmid": "33725354", "title": "Therapeutic Strategies and Nano-Drug Delivery Applications in Management of Aging Alzheimer's Disease.", "authors": "Nguyen TT, Vo TK, Vo GV", "year": "2021", "journal": "Advances in experimental medicine and biology", "keywords": "Alzheimer\u2019s disease, CNS, Molecular targets, Nanotherapeutic, Oxidative stress", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline. Existing drugs only suppress symptoms or delay further deterioration but do not address the cause of the disease. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates, such as acetylcholinesterase inhibitors, are currently utilized as an effective clinical therapy. Currently, nano-based therapies can make a difference, providing new therapeutic options by helping drugs to cross the blood-brain barrier and enter the brain more effectively. The main aim of this review was to highlight advances in research on the development of nano-based therapeutics for improved treatment of AD.", "source": "PubMed"}, {"chunk_id": "40000575_0", "pmid": "40000575", "title": "Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.", "authors": "Qiao M, Ni J, Qing H et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Cognitive impairments, Dementia, NLRP3 inflammasome, Peripheral inflammation", "chunk": "Cognitive impairments are common clinical manifestation of Alzheimer's disease, vascular dementia, type 2 diabetes mellitus, and autoimmune diseases. Emerging evidence has suggested a strong correlation between peripheral chronic inflammation and cognitive impairments. For example, nearly 40% of individuals with inflammatory bowel disease also suffer from cognitive impairments. In this condition, NLRP3 inflammasome (NLRP3-I) generating pro-inflammatory cytokines like IL-1\u03b2 serves as a significant effector, and its persistence exerts adverse effects to both periphery and the brain. Moreover, investigations on serum biomarkers of mild cognitive impairments have shown NLRP3-I components' upregulation, suggesting the involvement of peripheral inflammasome pathway in this disorder. Here, we systematically reviewed the current knowledge of NLRP3-I in inflammatory disease to uncover its potential role in bridging peripheral chronic inflammation and cognitive impairments. This review summarizes the molecular features and ignition process of NLRP3-I in inflammatory response. Meanwhile, various effects of NLRP3-I involved in peripheral inflammation-associated disease are also", "source": "PubMed"}, {"chunk_id": "40000575_1", "pmid": "40000575", "title": "Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.", "authors": "Qiao M, Ni J, Qing H et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Cognitive impairments, Dementia, NLRP3 inflammasome, Peripheral inflammation", "chunk": "inflammation and cognitive impairments. This review summarizes the molecular features and ignition process of NLRP3-I in inflammatory response. Meanwhile, various effects of NLRP3-I involved in peripheral inflammation-associated disease are also reviewed, especially its chronic disturbances to brain homeostasis and cognitive function through routes including gut-brain, liver-brain, and kidney-brain axes. In addition, current promising compounds and their targets relative to NLRP3-I are discussed in the context of cognitive impairments. Through the detailed investigation, this review highlights the critical role of peripheral NLRP3-I in the pathogenesis of cognitive disorders, and offers novel perspectives for developing effective therapeutic interventions for diseases associated with cognitive impairments. The present review outlines the current knowledge on the ignition of NLRP3-I in inflammatory disease and more importantly, emphasizes the role of peripheral NLRP3-I as a causal pathway in the development of cognitive disorders. Although major efforts to restrain cognitive decline are mainly focused on the central nervous", "source": "PubMed"}, {"chunk_id": "40000575_2", "pmid": "40000575", "title": "Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.", "authors": "Qiao M, Ni J, Qing H et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "Cognitive impairments, Dementia, NLRP3 inflammasome, Peripheral inflammation", "chunk": "emphasizes the role of peripheral NLRP3-I as a causal pathway in the development of cognitive disorders. Although major efforts to restrain cognitive decline are mainly focused on the central nervous system, it has become clear that disturbances from peripheral immune are closely associated with the dysfunctional brain. Therefore, attenuation of these inflammatory changes through inhibiting the NLRP3-I pathway in early inflammatory disease may reduce future risk of cognitive impairments, and in the meantime, considerations on such pathogenesis for combined drug therapy will be required in the clinical evaluation of cognitive disorders.", "source": "PubMed"}, {"chunk_id": "38642715_0", "pmid": "38642715", "title": "Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.", "authors": "Tong B, Ba Y, Li Z et al.", "year": "2024", "journal": "Neurobiology of disease", "keywords": "Alzheimer's disease, ApoE, Lipid metabolism, Mitochondria, PPARs, Parkinson's disease", "chunk": "Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating A\u03b2 deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of \u03b1-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism", "source": "PubMed"}, {"chunk_id": "38642715_1", "pmid": "38642715", "title": "Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.", "authors": "Tong B, Ba Y, Li Z et al.", "year": "2024", "journal": "Neurobiology of disease", "keywords": "Alzheimer's disease, ApoE, Lipid metabolism, Mitochondria, PPARs, Parkinson's disease", "chunk": "and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "40948708_0", "pmid": "40948708", "title": "Emerging exosomal biomarkers for essential hypertension: a systematic review.", "authors": "Zhong D, Chen Y, Zhang Y et al.", "year": "2025", "journal": "Cardiovascular diagnosis and therapy", "keywords": "Exosome, essential hypertension (EH), exosomal microRNA (exosomal miRNA), exosomal protein, systematic review", "chunk": "Exosomes show promise as biomarkers for essential hypertension (EH) progression and complications. However, existing studies on dysregulation of exosomal biomarkers in hypertension lack consistency. Thus, we conducted a comprehensive systematic review to synthesize evidence on exosomal biomarkers associated with EH. We performed an exhaustive search across PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and Chinese Clinical Trial Registry. Our search encompassed all available Chinese and English records from their inception through August 14<sup>th</sup>, 2025, without any restrictions on study design. The primary outcome focused on exosomal microRNA (miRNA) alterations, with secondary analyses of other cargo types (e.g., proteins). We employed the Joanna Briggs Institute (JBI) critical appraisal tool and the risk of bias in non-randomized studies of interventions (ROBINS-I) tool to assess the risk of bias. Due to the limitations of the data in the included studies, we conducted a qualitative narrative synthesis", "source": "PubMed"}, {"chunk_id": "40948708_1", "pmid": "40948708", "title": "Emerging exosomal biomarkers for essential hypertension: a systematic review.", "authors": "Zhong D, Chen Y, Zhang Y et al.", "year": "2025", "journal": "Cardiovascular diagnosis and therapy", "keywords": "Exosome, essential hypertension (EH), exosomal microRNA (exosomal miRNA), exosomal protein, systematic review", "chunk": "in non-randomized studies of interventions (ROBINS-I) tool to assess the risk of bias. Due to the limitations of the data in the included studies, we conducted a qualitative narrative synthesis to summarize key study characteristics and synthesize their principal findings. The protocol was prospectively registered on PROSPERO (CRD42023470885). The qualitative analysis included 11 identified studies, which revealed moderate-to-high methodological quality (JBI: 6 moderate, 4 high), with one study exhibiting a moderate risk of bias (ROBINS-I). This systematic review revealed that exosomal biomarkers in blood and urine had diagnostic potential for hypertension and its complications. Evidence suggested that exosomal biomarkers were associated with hypertensive vascular dysfunction (e.g., increased miR-320d/423-5p) and may provide a molecular basis for precise typing of hypertension (platelet-derived extracellular vesicles). Notably, exosomal biomarkers may serve as indicators of target organ damage, reflecting early renal injury (decreased miR-26a-5p) and cognitive dysfunction (decreased miR-330-3p) in hypertension. This systematic review highlights", "source": "PubMed"}, {"chunk_id": "40948708_2", "pmid": "40948708", "title": "Emerging exosomal biomarkers for essential hypertension: a systematic review.", "authors": "Zhong D, Chen Y, Zhang Y et al.", "year": "2025", "journal": "Cardiovascular diagnosis and therapy", "keywords": "Exosome, essential hypertension (EH), exosomal microRNA (exosomal miRNA), exosomal protein, systematic review", "chunk": "extracellular vesicles). Notably, exosomal biomarkers may serve as indicators of target organ damage, reflecting early renal injury (decreased miR-26a-5p) and cognitive dysfunction (decreased miR-330-3p) in hypertension. This systematic review highlights the value of blood and urine exosomal biomarkers in the early diagnosis, precise typing, and monitoring of target organ damage in hypertension and its complications. Future studies should systematically compare exosomal biomarkers with conventional markers using standardized protocols. Methodological improvements should focus on expanding larger sample sizes, enhancing reporting completeness and transparency, and standardizing data-sharing practices.", "source": "PubMed"}, {"chunk_id": "38379519_0", "pmid": "38379519", "title": "BrainAGE: Revisited and reframed machine learning workflow.", "authors": "Kalc P, Dahnke R, Hoffstaedter F et al.", "year": "2024", "journal": "Human brain mapping", "keywords": "Alzheimer's disease, Gaussian process regression, UK Biobank, brain age, machine learning, mean absolute error, pre-processing, schizophrenia, structural MRI", "chunk": "Since the introduction of the BrainAGE method, novel machine learning methods for brain age prediction have continued to emerge. The idea of estimating the chronological age from magnetic resonance images proved to be an interesting field of research due to the relative simplicity of its interpretation and its potential use as a biomarker of brain health. We revised our previous BrainAGE approach, originally utilising relevance vector regression (RVR), and substituted it with Gaussian process regression (GPR), which enables more stable processing of larger datasets, such as the UK Biobank (UKB). In addition, we extended the global BrainAGE approach to regional BrainAGE, providing spatially specific scores for five brain lobes per hemisphere. We tested the performance of the new algorithms under several different conditions and investigated their validity on the ADNI and schizophrenia samples, as well as on a synthetic dataset of neocortical thinning. The results show an improved performance of", "source": "PubMed"}, {"chunk_id": "38379519_1", "pmid": "38379519", "title": "BrainAGE: Revisited and reframed machine learning workflow.", "authors": "Kalc P, Dahnke R, Hoffstaedter F et al.", "year": "2024", "journal": "Human brain mapping", "keywords": "Alzheimer's disease, Gaussian process regression, UK Biobank, brain age, machine learning, mean absolute error, pre-processing, schizophrenia, structural MRI", "chunk": "several different conditions and investigated their validity on the ADNI and schizophrenia samples, as well as on a synthetic dataset of neocortical thinning. The results show an improved performance of the reframed global model on the UKB sample with a mean absolute error (MAE) of less than 2 years and a significant difference in BrainAGE between healthy participants and patients with Alzheimer's disease and schizophrenia. Moreover, the workings of the algorithm show meaningful effects for a simulated neocortical atrophy dataset. The regional BrainAGE model performed well on two clinical samples, showing disease-specific patterns for different levels of impairment. The results demonstrate that the new improved algorithms provide reliable and valid brain age estimations.", "source": "PubMed"}, {"chunk_id": "40482347_0", "pmid": "40482347", "title": "Silicon-enriched meat consumption mitigates brain cortex damage associated with diabetic dyslipidemia in a late-stage type 2 diabetes mellitus rat model.", "authors": "Redondo-Castillejo R, Ticona LA, Macho-Gonz\u00e1lez A et al.", "year": "2025", "journal": "Redox biology", "keywords": "Antioxidant defense, Brain insulin resistance, Cholinergic transmission, Neuroinflammation, Nutritional adjuvant, Oxysterol", "chunk": "Neuroprotective properties of silicon have been reported, particularly in mitigating dementia and Alzheimer's disease due to its ability to reduce aluminum bioavailability. However, its potential as a nutritional adjuvant in reducing brain damage associated with hypercholesterolemia and central insulin resistance (IR) in late-stage type 2 diabetes mellitus (T2DM) remains unexplored. This study aimed to evaluate the effects of silicon-enriched meat (Si-RM) on the brain cortex of T2DM rats. Rat models of early-stage-T2DM (ED) (n = 8) and late-stage-T2DM (LD) (n = 16) were induced by high-saturated fat diet and high-saturated fat high-cholesterol diet plus streptozotocin/nicotinamide injection, respectively. A control meat (C-RM) was included in the diet of both ED and LD groups. Finally, after confirming hyperglycemia in LD rats, the C-RM was replaced by Si-RM in half of the animals for the last five weeks of the study, obtaining the LD-Si group (n = 8), while the other half continued", "source": "PubMed"}, {"chunk_id": "40482347_1", "pmid": "40482347", "title": "Silicon-enriched meat consumption mitigates brain cortex damage associated with diabetic dyslipidemia in a late-stage type 2 diabetes mellitus rat model.", "authors": "Redondo-Castillejo R, Ticona LA, Macho-Gonz\u00e1lez A et al.", "year": "2025", "journal": "Redox biology", "keywords": "Antioxidant defense, Brain insulin resistance, Cholinergic transmission, Neuroinflammation, Nutritional adjuvant, Oxysterol", "chunk": "C-RM was replaced by Si-RM in half of the animals for the last five weeks of the study, obtaining the LD-Si group (n = 8), while the other half continued eating C-RM. In LD rats pathological outcomes included: harmful oxysterol profile, decreased antioxidant defenses, neuroinflammation, brain IR, augmented glucose uptake and impaired cholinergic transmission. Si-RM consumption ameliorates these key outcomes by reducing brain levels of pro-oxidant oxysterols (25-OHC and 27-OHC) to levels of ED rats. Antioxidant defenses, including SOD and arylesterase activity, were enhanced, and inflammatory markers, such as GFAP, IL6, and TNF\u03b1, were reduced compared to LD and ED counterparts. Notably, silicon restored brain insulin signaling, normalized glucose uptake via GLUT3, and shifted to an acetylcholine-preserving profile, significantly mitigating neurodegenerative risks. This study demonstrates for the first time that silicon, provided as a functional dietary ingredient of meat-products, exhibited a capacity to partially counteract brain cortex metabolic damage caused", "source": "PubMed"}, {"chunk_id": "40482347_2", "pmid": "40482347", "title": "Silicon-enriched meat consumption mitigates brain cortex damage associated with diabetic dyslipidemia in a late-stage type 2 diabetes mellitus rat model.", "authors": "Redondo-Castillejo R, Ticona LA, Macho-Gonz\u00e1lez A et al.", "year": "2025", "journal": "Redox biology", "keywords": "Antioxidant defense, Brain insulin resistance, Cholinergic transmission, Neuroinflammation, Nutritional adjuvant, Oxysterol", "chunk": "neurodegenerative risks. This study demonstrates for the first time that silicon, provided as a functional dietary ingredient of meat-products, exhibited a capacity to partially counteract brain cortex metabolic damage caused by T2DM.", "source": "PubMed"}, {"chunk_id": "35739484_0", "pmid": "35739484", "title": "Association of \u03b2-cell function and cognitive impairment in patients with abnormal glucose metabolism.", "authors": "Guo M, Jia J, Zhang J et al.", "year": "2022", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease (AD), Cognitive impairment, Diabetes, HOMA-\u03b2, \u03b2-Cell function", "chunk": "Insulin has been demonstrated to play an important role in the occurrence and development of Alzheimer's disease, especially in those with diabetes. \u03b2 cells are important insulin-producing cells in human pancreas. This study aimed to investigate the association between \u03b2-cell dysfunction and cognitive impairment among patients over 40-year-old with abnormal glucose metabolism in Chinese rural communities. A sample of 592 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Abnormal glucose metabolism was defined when hemoglobin Alc \u2265 5.7%. Cognitive function was assessed by the Beijing edition of the Montreal Cognitive Assessment scale. Homeostasis assessment of \u03b2-cell function was performed and classified into 4 groups according to the quartiles. A lower value of HOMA-\u03b2 indicated a worse condition of \u03b2-cell function. Multivariate logistic regression was used to analyze the association between \u03b2-cell function and cognitive impairment.", "source": "PubMed"}, {"chunk_id": "35739484_1", "pmid": "35739484", "title": "Association of \u03b2-cell function and cognitive impairment in patients with abnormal glucose metabolism.", "authors": "Guo M, Jia J, Zhang J et al.", "year": "2022", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease (AD), Cognitive impairment, Diabetes, HOMA-\u03b2, \u03b2-Cell function", "chunk": "to the quartiles. A lower value of HOMA-\u03b2 indicated a worse condition of \u03b2-cell function. Multivariate logistic regression was used to analyze the association between \u03b2-cell function and cognitive impairment. In a total of 592 patients with abnormal glucose metabolism, the average age was 60.20 \u00b1 7.63 years and 60.1% patients had cognitive impairment. After adjusting for all potential risk factors, we found the first quartile of \u03b2-cell function was significantly associated with cognitive impairment (OR: 2.27, 95%CI: 1.32-3.92), especially at the domains of language (OR: 1.64, 95%CI: 1.01-2.65) and abstraction (OR: 2.29, 95%CI: 1.46-3.58). Our study showed that worse \u03b2-cell function is associated with cognitive impairment of people over 40-year-old with abnormal glucose metabolism in Chinese rural communities, especially in the cognitive domains of abstraction and language.", "source": "PubMed"}, {"chunk_id": "35739484_2", "pmid": "35739484", "title": "Association of \u03b2-cell function and cognitive impairment in patients with abnormal glucose metabolism.", "authors": "Guo M, Jia J, Zhang J et al.", "year": "2022", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease (AD), Cognitive impairment, Diabetes, HOMA-\u03b2, \u03b2-Cell function", "chunk": "in the cognitive domains of abstraction and language.", "source": "PubMed"}, {"chunk_id": "41511697_0", "pmid": "41511697", "title": "When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in \u03b1-Synuclein Pathophysiology and RT-QuIC Detection.", "authors": "Labajov\u00e1 N, Pol\u00e1k A, Cehl\u00e1r O et al.", "year": "2026", "journal": "Molecular neurobiology", "keywords": "Aggregation, Neurodegeneration, Parkinson\u2019s disease, RT-QuIC, Synucleinopathies, \u03b1-Synuclein", "chunk": "\u0391-Synuclein (\u03b1-Syn) aggregation and fibrillation are pathological hallmarks of several neurodegenerative disorders, collectively termed synucleinopathies. The misfolded \u03b1-Syn protein exhibits a prion-like seeding behavior, promoting misfolding, intracellular spread, and progressive neurodegeneration. Recent advances in structural biology have revealed critical insights into the conformational heterogeneity of \u03b1-Syn aggregates and their strain-specific properties across distinct synucleinopathies. In parallel, significant progress has been made in biomarker development, particularly with the arrival of seed amplification assays. Among these, Real-Time Quaking-Induced Conversion (RT-QuIC) has emerged as a highly sensitive, specific, and scalable method for detecting pathogenic \u03b1-Syn species in cerebrospinal fluid and other tissues. This review summarizes the latest findings from structural studies on \u03b1-Syn oligomers and aggregates, their relevance to disease mechanisms, and highlights RT-QuIC as the most clinically advanced and rapidly evolving assay. We discuss its potential for early, biomarker-driven diagnostics, patient stratification, and clinical implementation.", "source": "PubMed"}, {"chunk_id": "41511697_1", "pmid": "41511697", "title": "When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in \u03b1-Synuclein Pathophysiology and RT-QuIC Detection.", "authors": "Labajov\u00e1 N, Pol\u00e1k A, Cehl\u00e1r O et al.", "year": "2026", "journal": "Molecular neurobiology", "keywords": "Aggregation, Neurodegeneration, Parkinson\u2019s disease, RT-QuIC, Synucleinopathies, \u03b1-Synuclein", "chunk": "RT-QuIC as the most clinically advanced and rapidly evolving assay. We discuss its potential for early, biomarker-driven diagnostics, patient stratification, and clinical implementation.", "source": "PubMed"}, {"chunk_id": "41207452_0", "pmid": "41207452", "title": "Imaging characteristics correlated with outcomes of cranial MRgFUS - a systematic review.", "authors": "Wang F, Ye K, Paerhati H et al.", "year": "2025", "journal": "NeuroImage", "keywords": "Biomarkers, Essential tremor, Magnetic resonance-guided focused ultrasound, Neuroimaging, Parkinson\u2019s disease", "chunk": "While research on imaging correlates of magnetic resonance guided focused ultrasound (MRgFUS) outcomes accumulates, a comprehensive synthesis across different disease populations remains absent. This systematic review aims to identify, technique-specific imaging biomarkers linked to treatment outcomes across distinct clinical conditions, including essential tremor (53 studies), Parkinson's disease (8 studies), and psychiatric disorders (2 studies). Key findings demonstrate that in ET, larger ventral intermediate nucleus (Vim) lesions intersecting the dentatorubrothalamic tract (DRTT) correlate with greater tremor reduction but increased adverse event risks. Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) revealed post-treatment white matter remodeling and functional restoration within sensorimotor, cerebellar, and visual networks. For PD, symptom improvement depended on ablation specificity within subthalamic nucleus (STN) or Vim subregions, with pre-treatment connectivity to motor cortices serving as predictive markers. Limited psychiatric studies implicated anatomical targeting and lesion-related functional connectivity in treatment response. The review concludes that lesion characteristics and brain", "source": "PubMed"}, {"chunk_id": "41207452_1", "pmid": "41207452", "title": "Imaging characteristics correlated with outcomes of cranial MRgFUS - a systematic review.", "authors": "Wang F, Ye K, Paerhati H et al.", "year": "2025", "journal": "NeuroImage", "keywords": "Biomarkers, Essential tremor, Magnetic resonance-guided focused ultrasound, Neuroimaging, Parkinson\u2019s disease", "chunk": "pre-treatment connectivity to motor cortices serving as predictive markers. Limited psychiatric studies implicated anatomical targeting and lesion-related functional connectivity in treatment response. The review concludes that lesion characteristics and brain connectivity are pivotal for optimizing MRgFUS strategies and outcomes across diseases.", "source": "PubMed"}, {"chunk_id": "36415625_0", "pmid": "36415625", "title": "Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.", "authors": "Golubnitschaja O, Potuznik P, Polivka J et al.", "year": "2022", "journal": "The EPMA journal", "keywords": "Blood pressure, Blood\u2013brain barrier breakdown, Body mass index, COVID-19, Cancer, Coagulation, Connective tissue impairments, Diabetes comorbidities, Endothelial dysfunction, Endothelin-1, Flammer Syndrome phenotype, Health policy, Health risk assessment, Health-to-disease transition, Hypoxia-reperfusion, Individualised protection, Ischemic stroke, Lacunar stroke, Mental health, Metastasis, Normal-tension glaucoma, Optic nerve degeneration, Paradigm change, Pre-pregnancy check-up, Predictive preventive personalised medicine (PPPM\u00a0/\u00a03PM), Primary care, Pro-inflammation, Retinal microvascular abnormalities, Screening, Secondary care, Silent brain infarct, Small vessel disease, Stress, Sub-optimal health, Systemic effects, Thromboembolism, Vascular stiffness, Vasospasm, Young populations", "chunk": "Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years", "source": "PubMed"}, {"chunk_id": "36415625_1", "pmid": "36415625", "title": "Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.", "authors": "Golubnitschaja O, Potuznik P, Polivka J et al.", "year": "2022", "journal": "The EPMA journal", "keywords": "Blood pressure, Blood\u2013brain barrier breakdown, Body mass index, COVID-19, Cancer, Coagulation, Connective tissue impairments, Diabetes comorbidities, Endothelial dysfunction, Endothelin-1, Flammer Syndrome phenotype, Health policy, Health risk assessment, Health-to-disease transition, Hypoxia-reperfusion, Individualised protection, Ischemic stroke, Lacunar stroke, Mental health, Metastasis, Normal-tension glaucoma, Optic nerve degeneration, Paradigm change, Pre-pregnancy check-up, Predictive preventive personalised medicine (PPPM\u00a0/\u00a03PM), Primary care, Pro-inflammation, Retinal microvascular abnormalities, Screening, Secondary care, Silent brain infarct, Small vessel disease, Stress, Sub-optimal health, Systemic effects, Thromboembolism, Vascular stiffness, Vasospasm, Young populations", "chunk": "of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the \"tip of the iceberg\": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence", "source": "PubMed"}, {"chunk_id": "36415625_2", "pmid": "36415625", "title": "Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.", "authors": "Golubnitschaja O, Potuznik P, Polivka J et al.", "year": "2022", "journal": "The EPMA journal", "keywords": "Blood pressure, Blood\u2013brain barrier breakdown, Body mass index, COVID-19, Cancer, Coagulation, Connective tissue impairments, Diabetes comorbidities, Endothelial dysfunction, Endothelin-1, Flammer Syndrome phenotype, Health policy, Health risk assessment, Health-to-disease transition, Hypoxia-reperfusion, Individualised protection, Ischemic stroke, Lacunar stroke, Mental health, Metastasis, Normal-tension glaucoma, Optic nerve degeneration, Paradigm change, Pre-pregnancy check-up, Predictive preventive personalised medicine (PPPM\u00a0/\u00a03PM), Primary care, Pro-inflammation, Retinal microvascular abnormalities, Screening, Secondary care, Silent brain infarct, Small vessel disease, Stress, Sub-optimal health, Systemic effects, Thromboembolism, Vascular stiffness, Vasospasm, Young populations", "chunk": "infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further<b>,</b> small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative", "source": "PubMed"}, {"chunk_id": "36415625_3", "pmid": "36415625", "title": "Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.", "authors": "Golubnitschaja O, Potuznik P, Polivka J et al.", "year": "2022", "journal": "The EPMA journal", "keywords": "Blood pressure, Blood\u2013brain barrier breakdown, Body mass index, COVID-19, Cancer, Coagulation, Connective tissue impairments, Diabetes comorbidities, Endothelial dysfunction, Endothelin-1, Flammer Syndrome phenotype, Health policy, Health risk assessment, Health-to-disease transition, Hypoxia-reperfusion, Individualised protection, Ischemic stroke, Lacunar stroke, Mental health, Metastasis, Normal-tension glaucoma, Optic nerve degeneration, Paradigm change, Pre-pregnancy check-up, Predictive preventive personalised medicine (PPPM\u00a0/\u00a03PM), Primary care, Pro-inflammation, Retinal microvascular abnormalities, Screening, Secondary care, Silent brain infarct, Small vessel disease, Stress, Sub-optimal health, Systemic effects, Thromboembolism, Vascular stiffness, Vasospasm, Young populations", "chunk": "is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarctionApplication of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transitionApplication of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.", "source": "PubMed"}, {"chunk_id": "36415625_4", "pmid": "36415625", "title": "Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.", "authors": "Golubnitschaja O, Potuznik P, Polivka J et al.", "year": "2022", "journal": "The EPMA journal", "keywords": "Blood pressure, Blood\u2013brain barrier breakdown, Body mass index, COVID-19, Cancer, Coagulation, Connective tissue impairments, Diabetes comorbidities, Endothelial dysfunction, Endothelin-1, Flammer Syndrome phenotype, Health policy, Health risk assessment, Health-to-disease transition, Hypoxia-reperfusion, Individualised protection, Ischemic stroke, Lacunar stroke, Mental health, Metastasis, Normal-tension glaucoma, Optic nerve degeneration, Paradigm change, Pre-pregnancy check-up, Predictive preventive personalised medicine (PPPM\u00a0/\u00a03PM), Primary care, Pro-inflammation, Retinal microvascular abnormalities, Screening, Secondary care, Silent brain infarct, Small vessel disease, Stress, Sub-optimal health, Systemic effects, Thromboembolism, Vascular stiffness, Vasospasm, Young populations", "chunk": "in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.", "source": "PubMed"}, {"chunk_id": "41518423_0", "pmid": "41518423", "title": "HDAC3 Mediates Hippocampal Microglial Pyroptosis Via the STING/NLRP3 Pathway and Contributes To Cognitive Impairment in Sepsis-Associated Encephalopathy.", "authors": "Cai M, Shao H, Xu S et al.", "year": "2026", "journal": "Inflammation", "keywords": "Cognitive impairment, Histone deacetylase 3, Microglial pyroptosis, STING/NLRP3 pathway, Sepsis-associated encephalopathy", "chunk": "Microglial pyroptosis-mediated neuroinflammation emerges as a critical pathogenic mechanism underlying sepsis-associated encephalopathy (SAE). Epigenetic modifications, especially histone acetylation states, exert fundamental regulatory effects on microglial pyroptosis. Among these, histone deacetylase 3 (HDAC3) has been identified as a central epigenetic regulator orchestrating these processes. This study investigates the functional role of HDAC3 in microglial pyroptosis and its underlying mechanisms contributing to SAE-related cognitive impairment. To explore this, male C57BL/6 mice subjected to cecal ligation and puncture (CLP) served as the SAE model. We employed RGFP966, a selective HDAC3 inhibitor, administered at 20 mg/kg/day via daily subcutaneous injections for 14 days starting 2 h prior to CLP surgery. To specifically examine HDAC3's role in microglia, we bilaterally injected recombinant adeno-associated virus (rAAV)-expressing rEGFP under the control of a DIO promoter into the hippocampus of Cx3cr1-Cre mice to achieve selective overexpression. Our data demonstrate that HDAC3 in microglia activates pyroptosis through the STING/NLRP3", "source": "PubMed"}, {"chunk_id": "41518423_1", "pmid": "41518423", "title": "HDAC3 Mediates Hippocampal Microglial Pyroptosis Via the STING/NLRP3 Pathway and Contributes To Cognitive Impairment in Sepsis-Associated Encephalopathy.", "authors": "Cai M, Shao H, Xu S et al.", "year": "2026", "journal": "Inflammation", "keywords": "Cognitive impairment, Histone deacetylase 3, Microglial pyroptosis, STING/NLRP3 pathway, Sepsis-associated encephalopathy", "chunk": "rEGFP under the control of a DIO promoter into the hippocampus of Cx3cr1-Cre mice to achieve selective overexpression. Our data demonstrate that HDAC3 in microglia activates pyroptosis through the STING/NLRP3 pathway, exacerbating oxidative stress responses and impairing neural activity, ultimately leading to cognitive deficits in SAE. Furthermore, HDAC3 overexpression in microglia recapitulates these pathological changes, underscoring its central role in driving disease progression. Conversely, RGFP966 treatment effectively attenuates these abnormalities by suppressing HDAC3 expression and downstream inflammatory pathways. These findings highlight the therapeutic potential of targeting microglial HDAC3 to mitigate neuroinflammation and cognitive dysfunction in SAE, offering a novel direction for future clinical applications.", "source": "PubMed"}, {"chunk_id": "40432717_0", "pmid": "40432717", "title": "Artificial intelligence based advancements in nanomedicine for brain disorder management: an updated narrative review.", "authors": "Dipankar P, Salazar D, Dennard E et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "artificial intelligence, brain disorders, deep learning, machine learning, nanomaterial, nanomedicine", "chunk": "Nanomedicines are nanoscale, biocompatible materials that offer promising alternatives to conventional treatment options for brain disorders. The recent technological developments in artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), are transforming the nanomedicine field by improving disease diagnosis, biomarker identification, prognostic assessment and disease monitoring, targeted drug delivery, and therapeutic intervention as well as contributing to computational and methodological developments. These advancements can be achieved by analysis of large clinical datasets and facilitating the design and optimization of nanomaterials for <i>in vivo</i> testing. Such advancement offers exciting possibilities for the improvement in the management of brain disorders, including brain cancer, Alzheimer's disease, Parkinson's disease, and multiple sclerosis, where early diagnosis, targeted delivery, and effective treatment strategies remain a great challenge. This review article provides an overview of recent advances in AI-based nanomedicine development to accelerate effective and quick diagnosis, biomarker identification, prognosis, drug delivery, methodological advancement and", "source": "PubMed"}, {"chunk_id": "40432717_1", "pmid": "40432717", "title": "Artificial intelligence based advancements in nanomedicine for brain disorder management: an updated narrative review.", "authors": "Dipankar P, Salazar D, Dennard E et al.", "year": "2025", "journal": "Frontiers in medicine", "keywords": "artificial intelligence, brain disorders, deep learning, machine learning, nanomaterial, nanomedicine", "chunk": "a great challenge. This review article provides an overview of recent advances in AI-based nanomedicine development to accelerate effective and quick diagnosis, biomarker identification, prognosis, drug delivery, methodological advancement and patient-specific therapies for managing brain disorders.", "source": "PubMed"}, {"chunk_id": "41093090_0", "pmid": "41093090", "title": "Intracranial Neural Biomarkers of Psychiatric Symptoms and Their Utility for Guiding Neuromodulation Therapy: A Systematic Review.", "authors": "Kabotyanski KE, Provenza NR, Sheth SA", "year": "2025", "journal": "Biological psychiatry", "keywords": "Biomarkers, Closed-loop, Electrophysiology, Intracranial, Neuromodulation, Psychiatry", "chunk": "The quest to develop and improve neuromodulatory therapies for treatment-resistant psychiatric disorders has been fueled by the discovery of intracranial neural biomarkers of symptom dimensions. These neural correlates shed light on the underlying neurophysiology of the disorder and may even be useful in guiding therapy delivery. This systematic review summarizes recent efforts in this field relating neural activity to behavior and symptomatology. For years, most of these neurobehavioral relationships were studied in the hospital or clinic environment. Recent technological advances in implanted neuromodulation devices that permit not only stimulation but also intracranial neural recording have enabled this research to move into natural settings and record for longer periods of time in the real world. We review this combined literature to identify neurobehavioral relationships that show commonalities across these different recording strategies and environments. We also discuss potential ways to use this information for guiding neuromodulation therapy. The success of closed-loop", "source": "PubMed"}, {"chunk_id": "41093090_1", "pmid": "41093090", "title": "Intracranial Neural Biomarkers of Psychiatric Symptoms and Their Utility for Guiding Neuromodulation Therapy: A Systematic Review.", "authors": "Kabotyanski KE, Provenza NR, Sheth SA", "year": "2025", "journal": "Biological psychiatry", "keywords": "Biomarkers, Closed-loop, Electrophysiology, Intracranial, Neuromodulation, Psychiatry", "chunk": "identify neurobehavioral relationships that show commonalities across these different recording strategies and environments. We also discuss potential ways to use this information for guiding neuromodulation therapy. The success of closed-loop stimulation strategies for movement disorders and epilepsy has led to interest in exploring similar approaches for psychiatric disorders. However, such efforts need to consider the disorder-specific time constant relating changes in a neural biomarker to changes in symptoms and behavior. This relationship likely differs between Parkinson's disease and depression, obsessive-compulsive disorder, or addiction. We interpret the results of our systematic review in this light to offer suggestions for future closed-loop or clinician-in-the-loop implementations to inform the next generation of neuromodulatory therapies.", "source": "PubMed"}, {"chunk_id": "38073389_0", "pmid": "38073389", "title": "Exercise-Related Physical Activity Relates to Brain Volumes in 10,125 Individuals.", "authors": "Raji CA, Meysami S, Hashemi S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, brain volumes, deep learning, magnetic resonance imaging, physical activity", "chunk": "The potential neuroprotective effects of regular physical activity on brain structure are unclear, despite links between activity and reduced dementia risk. To investigate the relationships between regular moderate to vigorous physical activity and quantified brain volumes on magnetic resonance neuroimaging. A total of 10,125 healthy participants underwent whole-body MRI scans, with brain sequences including isotropic MP-RAGE. Three deep learning models analyzed axial, sagittal, and coronal views from the scans. Moderate to vigorous physical activity, defined by activities increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes via partial correlations. Analyses adjusted for age, sex, and total intracranial volume, and a 5% Benjamini-Hochberg False Discovery Rate addressed multiple comparisons. Participant average age was 52.98\u00b113.04 years (range 18-97) and 52.3% were biologically male. Of these, 7,606 (75.1%) reported engaging in moderate or vigorous physical activity approximately 4.05\u00b13.43 days per week. Those with vigorous activity were", "source": "PubMed"}, {"chunk_id": "38073389_1", "pmid": "38073389", "title": "Exercise-Related Physical Activity Relates to Brain Volumes in 10,125 Individuals.", "authors": "Raji CA, Meysami S, Hashemi S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, brain volumes, deep learning, magnetic resonance imaging, physical activity", "chunk": "years (range 18-97) and 52.3% were biologically male. Of these, 7,606 (75.1%) reported engaging in moderate or vigorous physical activity approximately 4.05\u00b13.43 days per week. Those with vigorous activity were slightly younger (p < 0.00001), and fewer women compared to men engaged in such activities (p = 3.76e-15). Adjusting for age, sex, body mass index, and multiple comparisons, increased days of moderate to vigorous activity correlated with larger normalized brain volumes in multiple regions including: total gray matter (Partial R = 0.05, p = 1.22e-7), white matter (Partial R = 0.06, p = 9.34e-11), hippocampus (Partial R = 0.05, p = 5.96e-7), and frontal, parietal, and occipital lobes (Partial R = 0.04, p\u22641.06e-5). Exercise-related physical activity is associated with increased brain volumes, indicating potential neuroprotective effects.", "source": "PubMed"}, {"chunk_id": "38073389_2", "pmid": "38073389", "title": "Exercise-Related Physical Activity Relates to Brain Volumes in 10,125 Individuals.", "authors": "Raji CA, Meysami S, Hashemi S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, brain volumes, deep learning, magnetic resonance imaging, physical activity", "chunk": "brain volumes, indicating potential neuroprotective effects.", "source": "PubMed"}, {"chunk_id": "33965026_0", "pmid": "33965026", "title": "An electrochemical aptasensor based on AuPt alloy nanoparticles for ultrasensitive detection of amyloid-\u03b2 oligomers.", "authors": "Liu Y, Xu Q, Zhang Y et al.", "year": "2021", "journal": "Talanta", "keywords": "Alzheimer's disease (AD), Amyloid-\u03b2 oligomer, AuPt alloy Nanoparticles, Electrochemical aptasensor, Resisting nonspecific adsorption", "chunk": "Amyloid-\u03b2 oligomer is an important biomarker and a potential therapeutic target of Alzheimer's disease in its early stage. Here, we combined superhydrophobic carbon fiber paper (CFP) with AuPt alloy nanoparticles to prepare a CFP/AuPt nanocomposite with larger specific surface area and hydrophobic surface. On this basis, we constructed an electrochemical aptasensor based on CFP/AuPt for the ultrasensitive detection of amyloid-\u03b2 oligomers. The surface-coated AuPt nanoparticles greatly enhanced the electroactive area, and the hydrophobic surface increased the resisting nonspecific adsorption performance of sensor. A combination of these two features significantly improved the sensitivity and specificity of the sensor. This electrochemical aptasensor based on CFP/AuPt displayed a low detection limit of 0.16 pg/mL. This work shows a promising future in clinical diagnosis of Alzheimer's disease and provides a possible solution to electrochemical biosensors that are susceptible to interference in biological fluids.", "source": "PubMed"}, {"chunk_id": "33965026_1", "pmid": "33965026", "title": "An electrochemical aptasensor based on AuPt alloy nanoparticles for ultrasensitive detection of amyloid-\u03b2 oligomers.", "authors": "Liu Y, Xu Q, Zhang Y et al.", "year": "2021", "journal": "Talanta", "keywords": "Alzheimer's disease (AD), Amyloid-\u03b2 oligomer, AuPt alloy Nanoparticles, Electrochemical aptasensor, Resisting nonspecific adsorption", "chunk": "of Alzheimer's disease and provides a possible solution to electrochemical biosensors that are susceptible to interference in biological fluids.", "source": "PubMed"}, {"chunk_id": "39665408_0", "pmid": "39665408", "title": "Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 <i>In Vitro</i> and <i>In Vivo</i> in Mice.", "authors": "Muolokwu CE, Gothwal A, Kanekiyo T et al.", "year": "2025", "journal": "Molecular pharmaceutics", "keywords": "Alzheimer\u2019s disease, ApoE2, cell-penetrating peptides, gene therapy, liposomes, targeting ligand", "chunk": "Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by the aggregation of amyloid-\u03b2 plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and neuronal degeneration. Recently, new treatment approaches involving drugs such as donanemab and lecanemab have been introduced for AD. However, these drug regimens have been associated with adverse effects, leading to the exploration of gene therapy as a potential treatment option. The apolipoprotein E (ApoE) isoforms (ApoE2, ApoE3, and ApoE4) play pivotal roles in AD pathology, with ApoE2 known for its protective effects against AD, making it a promising candidate for gene therapy interventions. However, delivering therapeutics across the blood-brain barrier (BBB) remains a crucial challenge in treating neurological disorders. Liposomes, lipid-based vesicles, are effective nanocarriers due to their ability to shield therapeutics from degradation, though they often lack specificity for brain delivery. To address this issue, liposomes were functionalized with cell-penetrating peptides such as", "source": "PubMed"}, {"chunk_id": "39665408_1", "pmid": "39665408", "title": "Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 <i>In Vitro</i> and <i>In Vivo</i> in Mice.", "authors": "Muolokwu CE, Gothwal A, Kanekiyo T et al.", "year": "2025", "journal": "Molecular pharmaceutics", "keywords": "Alzheimer\u2019s disease, ApoE2, cell-penetrating peptides, gene therapy, liposomes, targeting ligand", "chunk": "nanocarriers due to their ability to shield therapeutics from degradation, though they often lack specificity for brain delivery. To address this issue, liposomes were functionalized with cell-penetrating peptides such as penetratin (Pen), cingulin (Cgn), and a targeting ligand transferrin (T<sub>f</sub>). This modification strategy aimed to enhance the delivery of therapeutic ApoE2 plasmids across the BBB to neurons, thereby increasing the level of ApoE2 protein expression. Experimental findings demonstrated that dual-functionalized liposomes (CgnT<sub>f</sub> and PenT<sub>f</sub>) exhibited higher cellular uptake, biodistribution, and transfection efficiency than single-functionalized (Pen, Cgn, or T<sub>f</sub>) and nonfunctionalized liposomes. <i>In vitro</i> studies using primary neuronal cells, bEnd.3 cells, and primary astrocytes consistently supported these findings. Following a single dose treatment via tail vein administration in C57BL6/J mice, <i>in vivo</i> biodistribution results showed significantly higher biodistribution levels in the brain (\u223c12% ID/gram of tissue) for dual-functionalized liposomes. Notably, treatment with dual-functionalized liposomes resulted in a 2-fold increase in ApoE2", "source": "PubMed"}, {"chunk_id": "39665408_2", "pmid": "39665408", "title": "Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 <i>In Vitro</i> and <i>In Vivo</i> in Mice.", "authors": "Muolokwu CE, Gothwal A, Kanekiyo T et al.", "year": "2025", "journal": "Molecular pharmaceutics", "keywords": "Alzheimer\u2019s disease, ApoE2, cell-penetrating peptides, gene therapy, liposomes, targeting ligand", "chunk": "vivo</i> biodistribution results showed significantly higher biodistribution levels in the brain (\u223c12% ID/gram of tissue) for dual-functionalized liposomes. Notably, treatment with dual-functionalized liposomes resulted in a 2-fold increase in ApoE2 expression levels compared to baseline levels. These findings highlight the potential of dual-functionalized liposomes as an efficacious delivery system for ApoE2 gene therapy in AD, highlighting a promising strategy to address the disease's underlying mechanisms.", "source": "PubMed"}, {"chunk_id": "31156174_0", "pmid": "31156174", "title": "Epigenetic Control of CDK5 Promoter Regulates Diabetes-Associated Development of Alzheimer's Disease.", "authors": "Cai HB, Fan ZZ, Tian T et al.", "year": "2019", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cyclin-dependent kinase-5, diabetes, methylation, promoter acetylation, tau", "chunk": "Cyclin-dependent kinase-5 (CDK5) is activated by p35 and then binds to both p35 and its truncated form p25 to promote hyperphosphorylation of tau protein, thereby facilitating the pathological progression of Alzheimer's disease (AD). However, it is unknown whether a patient's diabetic status promotes the later onset of AD in a CDK5-dependent manner. Here, we induced pro-diabetic insulin resistance and glucose intolerance in rats using a combined high fat and high glucose diet. Compared to normal diet-fed rats, these pro-diabetic rats exhibited poorer behavioral performance in the Morris water maze test and the novel object recognition test. Increased phosphorylation of tau protein was detected in the hippocampal CA1 region of the rat brain, suggesting neurodegeneration. Moreover, CDK5 transcriptional activity was significantly increased in the HFGD-rat brain, likely resulting from an increase in acetylation and a decrease in methylation of the CDK5 promoter. Together, these data suggest that epigenetic control of the", "source": "PubMed"}, {"chunk_id": "31156174_1", "pmid": "31156174", "title": "Epigenetic Control of CDK5 Promoter Regulates Diabetes-Associated Development of Alzheimer's Disease.", "authors": "Cai HB, Fan ZZ, Tian T et al.", "year": "2019", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cyclin-dependent kinase-5, diabetes, methylation, promoter acetylation, tau", "chunk": "increased in the HFGD-rat brain, likely resulting from an increase in acetylation and a decrease in methylation of the CDK5 promoter. Together, these data suggest that epigenetic control of the CDK5 promoter by acetylation and methylation may regulate the diabetes-associated development of AD.", "source": "PubMed"}, {"chunk_id": "40820409_0", "pmid": "40820409", "title": "Plasma IL-6 Levels as a Biomarker for Behavioral Changes in Alzheimer's Disease.", "authors": "Yasuno F, Watanabe A, Kimura Y et al.", "year": "2025", "journal": "Neuroimmunomodulation", "keywords": "None", "chunk": "Behavioral and psychological symptoms of dementia (BPSD) significantly affect the quality of life for patients with Alzheimer's disease (AD) and contribute to caregiver burden. Although systemic inflammation is implicated in AD pathophysiology, the specific role of peripheral immune activity-particularly interleukin-6 (IL-6)-in relation to BPSD remains unclear, especially regarding its independent effects from central neuroinflammation. We conducted a cross-sectional study of 23 biomarker-confirmed patients diagnosed with AD or prodromal AD. Plasma and cerebrospinal fluid (CSF) levels of IL-6, IL-1\u03b2, TNF-\u03b1, and C-reactive protein (CRP) were measured. BPSD was assessed using the Dementia Behavior Disturbance (DBD) scale. Central neuroinflammation was quantified via 11C-DPA-713 translocator protein positron emission tomography (TSPO-PET). Stepwise multiple linear regression and Bayesian analyses were used to identify predictors of BPSD severity. Plasma IL-6 emerged as the only significant predictor of DBD scores in frequentist and Bayesian regression models. Other demographic, cognitive, and inflammatory variables, including CSF IL-6 and TSPO-PET", "source": "PubMed"}, {"chunk_id": "40820409_1", "pmid": "40820409", "title": "Plasma IL-6 Levels as a Biomarker for Behavioral Changes in Alzheimer's Disease.", "authors": "Yasuno F, Watanabe A, Kimura Y et al.", "year": "2025", "journal": "Neuroimmunomodulation", "keywords": "None", "chunk": "BPSD severity. Plasma IL-6 emerged as the only significant predictor of DBD scores in frequentist and Bayesian regression models. Other demographic, cognitive, and inflammatory variables, including CSF IL-6 and TSPO-PET binding, showed no significant association with behavioral symptoms. No correlation was observed between plasma and CSF IL-6 levels, nor between plasma IL-6 and TSPO-PET measures. Peripheral IL-6 is significantly associated with BPSD severity in AD, independently of central inflammatory markers. This finding suggests a distinct peripheral immune mechanism underlying neuropsychiatric symptoms, potentially mediated through systemic pathways such as vagus nerve signaling or gut-brain-immune interactions. Peripheral IL-6 may serve as a clinically relevant biomarker and therapeutic target for behavioral disturbances in AD.", "source": "PubMed"}, {"chunk_id": "22258512_0", "pmid": "22258512", "title": "Why have we failed to cure Alzheimer's disease?", "authors": "Korczyn AD", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "There is widespread recognition in the urgency to understand the causes and mechanisms of senile dementia. Attempts to find cures for Alzheimer's disease (AD) have, however, failed so far, in spite of enormous investments, intellectual and financial. We therefore have to reconsider the problem from new angles. AD is regarded as a disease because of its clinical manifestations and underlying pathology. However, this combination does not define a disease but rather a syndrome, just like hepatic cirrhosis in which liver pathology causes metabolic changes, but which can result from many different etiologies. It is unlikely that attacking a downstream phenomenon, like apoptosis or amyloid-\u03b2 accumulation, can cure AD, or prevent the progression of the disease. It is probable that senile dementia is the result of a combination of several processes, working differently in each person. Epidemiological studies have identified many risk factors for \"senile dementia of the Alzheimer type\", some", "source": "PubMed"}, {"chunk_id": "22258512_1", "pmid": "22258512", "title": "Why have we failed to cure Alzheimer's disease?", "authors": "Korczyn AD", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "dementia is the result of a combination of several processes, working differently in each person. Epidemiological studies have identified many risk factors for \"senile dementia of the Alzheimer type\", some genetic but most environmental and therefore modifiable. Thus, a concerted action to fight the dementia epidemic must be made by aggressive action against its risk factors, and this battle must begin in midlife, not in old age.", "source": "PubMed"}, {"chunk_id": "38769578_0", "pmid": "38769578", "title": "Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.", "authors": "Yaqub A, Vojinovic D, Vernooij MW et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Dementia, Gut-microbiome, Metabolites, Neuroimaging, Population-based", "chunk": "The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine - have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain. In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function. Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition", "source": "PubMed"}, {"chunk_id": "38769578_1", "pmid": "38769578", "title": "Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.", "authors": "Yaqub A, Vojinovic D, Vernooij MW et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Dementia, Gut-microbiome, Metabolites, Neuroimaging, Population-based", "chunk": "analysis for individuals with impaired renal function. Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses. Plasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.", "source": "PubMed"}, {"chunk_id": "38769578_2", "pmid": "38769578", "title": "Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.", "authors": "Yaqub A, Vojinovic D, Vernooij MW et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Cognition, Dementia, Gut-microbiome, Metabolites, Neuroimaging, Population-based", "chunk": "markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.", "source": "PubMed"}, {"chunk_id": "37019342_0", "pmid": "37019342", "title": "African walnut (Tetracarpidium conophorum) extract upregulates glucocerebrosidase activity and circumvents Parkinsonian changes in the Hippocampus via the activation of heatshock proteins.", "authors": "Tokunbo OS, Arogundade TT, Abayomi TA et al.", "year": "2023", "journal": "Journal of chemical neuroanatomy", "keywords": "African Walnut, Glucocerebrosidase, Heat shock proteins, Molecular chaperon, Parkinson Disease", "chunk": "Neurodegenerative illnesses like Parkinson's and Alzheimer's are largely caused by the accumulation of aggregated proteins. Heat shock proteins (HSPs), which are molecular chaperons, have been linked with the modulation of \u03b2-glucocerebrosidase (GCase) function encoded by GBA1 and Synucleinopathies. Herein, the chaperonic properties of African walnut ethanolic extract (WNE) in manganese-induced Parkinsonian neuropathology in the hippocampus was examined. 48 adult male rats weighing 185 g \u00b1 10 g were randomly assigned into 6 (A - F) groups (n = 8) and treated orally as follows: A-PBS (1 ml daily for 28 days), B-WNE (200 mg/kg daily for 28 days), C- WNE (400 mg/kg daily for 28 days), D-Mn (100 mg/kg daily for 28 days), E-Mn plus WNE (100 mg/kg Mn + 200 mg/kg WNE daily concomitantly for 28 days), F-Mn plus WNE (100 mg/kg Mn + 400 mg/kg WNE daily concomitantly for 28 days). Rats treated with WNE showed increased levels", "source": "PubMed"}, {"chunk_id": "37019342_1", "pmid": "37019342", "title": "African walnut (Tetracarpidium conophorum) extract upregulates glucocerebrosidase activity and circumvents Parkinsonian changes in the Hippocampus via the activation of heatshock proteins.", "authors": "Tokunbo OS, Arogundade TT, Abayomi TA et al.", "year": "2023", "journal": "Journal of chemical neuroanatomy", "keywords": "African Walnut, Glucocerebrosidase, Heat shock proteins, Molecular chaperon, Parkinson Disease", "chunk": "200 mg/kg WNE daily concomitantly for 28 days), F-Mn plus WNE (100 mg/kg Mn + 400 mg/kg WNE daily concomitantly for 28 days). Rats treated with WNE showed increased levels of HSP70 and HSP90 in comparison with the Mn-intoxicated group. GCase activity also increased significantly in animals treated with WNE. Our results further revealed the therapeutic tendencies of WNE against Mn toxicity by modulating oligomeric \u03b1-synuclein levels, redox activity, and glucose bioenergetics. Furthermore, immunohistochemical evaluation revealed reduced expression of neurofibrillary tangles, and reactive astrogliosis following WNE treatment. The ethanolic extract of African Walnut induced the activation of HSPs and increased the expression of GBA1 gene in the hippocampus. Activated heat shock proteins suppressed neurodegenerative changes due to Manganese toxicity. WNE was also shown to modulate neuroinflammatory, bioenergetics and neural redox balance in Parkinson-like neuropathology. This study was limited to the use of crude walnut extract and the evaluation of non-motor", "source": "PubMed"}, {"chunk_id": "37019342_2", "pmid": "37019342", "title": "African walnut (Tetracarpidium conophorum) extract upregulates glucocerebrosidase activity and circumvents Parkinsonian changes in the Hippocampus via the activation of heatshock proteins.", "authors": "Tokunbo OS, Arogundade TT, Abayomi TA et al.", "year": "2023", "journal": "Journal of chemical neuroanatomy", "keywords": "African Walnut, Glucocerebrosidase, Heat shock proteins, Molecular chaperon, Parkinson Disease", "chunk": "was also shown to modulate neuroinflammatory, bioenergetics and neural redox balance in Parkinson-like neuropathology. This study was limited to the use of crude walnut extract and the evaluation of non-motor cascades of Parkinson's disease.", "source": "PubMed"}, {"chunk_id": "34211388_0", "pmid": "34211388", "title": "Alix: A Candidate Serum Biomarker of Alzheimer's Disease.", "authors": "Sun Y, Hua J, Chen G et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "ROC analysis, diagnosis, sensitivity, specificity, vascular dementia", "chunk": "Alzheimer's disease (AD) is the most common fatal neurodegenerative disease of the elderly worldwide. The identification of AD biomarkers will allow for earlier diagnosis and thus earlier intervention. The aim of this study was to find such biomarkers. It was observed that the expression of Alix was significantly decreased in brain tissues and serum samples from AD patients compared to the controls. A significant correlation between Alix levels and cognitive decline was observed (<i>r</i> = 0.80; <i>p</i> < 0.001) as well as a significant negative correlation between Alix and A\u03b2<sub>40</sub> in serum levels (<i>r</i> =-0.60, <i>p</i> < 0.001). The receiver operating characteristic curve (ROC) analysis showed the area under the curve (AUC) of Alix was 0.80, and the optimal cut-off point of 199.5 pg/ml was selected with the highest sum of sensitivity and specificity. The diagnostic accuracy for serum Alix was 74%, with 76% sensitivity and 71% specificity respectively, which", "source": "PubMed"}, {"chunk_id": "34211388_1", "pmid": "34211388", "title": "Alix: A Candidate Serum Biomarker of Alzheimer's Disease.", "authors": "Sun Y, Hua J, Chen G et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "ROC analysis, diagnosis, sensitivity, specificity, vascular dementia", "chunk": "point of 199.5 pg/ml was selected with the highest sum of sensitivity and specificity. The diagnostic accuracy for serum Alix was 74%, with 76% sensitivity and 71% specificity respectively, which could differentiate AD from controls. In addition, the expression of Alix was found to be significantly decreased in AD compared to vascular dementia (VaD). ROC analysis between AD and VaD showed that the AUC was 0.777, which could be indicative of the role of serum Alix as a biomarker in the differential diagnosis between AD and VaD. Most surprisingly, the decreased expression of Alix was attenuated after the treatment of Memantine in different AD animal models. In conclusion, our results indicate the possibility of serum Alix as a novel and non-invasive biomarker for AD for the first time.", "source": "PubMed"}, {"chunk_id": "34211388_2", "pmid": "34211388", "title": "Alix: A Candidate Serum Biomarker of Alzheimer's Disease.", "authors": "Sun Y, Hua J, Chen G et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "ROC analysis, diagnosis, sensitivity, specificity, vascular dementia", "chunk": "non-invasive biomarker for AD for the first time.", "source": "PubMed"}, {"chunk_id": "39492095_0", "pmid": "39492095", "title": "Sleep-related regions in neurodegenerative diseases by central nervous system localization using magnetic resonance imaging.", "authors": "Mohammadi S, Mohammadi M, Ghaderi S", "year": "2023", "journal": "Psychiatry research. Neuroimaging", "keywords": "Biomarker, MRI, Neurodegenerative disease, Neuroimaging, Sleep disorder", "chunk": "Sleep disruptions associated with neurodegenerative diseases (NDDs) damage the brain's sleep-regulating regions. Advanced magnetic resonance imaging (MRI) techniques can characterize the signature of each neurodegenerative pathology. We performed an evaluation of sleep-related regions in NDDs using MRI to localize the central nervous system (CNS). In the initial search, 61 related papers were discovered using predetermined inclusion and exclusion criteria. Finally, 30 articles were included in this study. The study included patients with Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), rapid eye movement (REM) sleep behavior disorder (RBD), idiopathic RBD (iRBD), amyotrophic lateral sclerosis (ALS), and mild cognitive impairment (MCI). Sleep-related regions recognized by CNS localization in NDDs can be linked to important regions. MRI also revealed cortical thinning, GM atrophy, WM, and tract loss, changes in diffusion tensor imaging (DTI) biomarkers (fractional anisotropy (FA), axial diffusivity (Da), and radial diffusivity (Dr)), a decrease in DMN connectivity, a reduction", "source": "PubMed"}, {"chunk_id": "39492095_1", "pmid": "39492095", "title": "Sleep-related regions in neurodegenerative diseases by central nervous system localization using magnetic resonance imaging.", "authors": "Mohammadi S, Mohammadi M, Ghaderi S", "year": "2023", "journal": "Psychiatry research. Neuroimaging", "keywords": "Biomarker, MRI, Neurodegenerative disease, Neuroimaging, Sleep disorder", "chunk": "GM atrophy, WM, and tract loss, changes in diffusion tensor imaging (DTI) biomarkers (fractional anisotropy (FA), axial diffusivity (Da), and radial diffusivity (Dr)), a decrease in DMN connectivity, a reduction in functional connectivity (FC), and amplitude of low-frequency fluctuation (ALFF) alterations. Sleep plays an important role in predicting future risks for the development of NDDs. Other neuroimaging, cognitive-behavioral, and clinical research can use the information found in this research about the brain regions, MRI biomarker changes, and their relationships.", "source": "PubMed"}, {"chunk_id": "40681225_0", "pmid": "40681225", "title": "Cardiovascular influence on cognitive decline: The heart's role in neurodegenerative disorders.", "authors": "Gautam G, Moradikor N", "year": "2025", "journal": "Progress in brain research", "keywords": "Cognitive decline, Heart-brain connection, Neurodegeneration, Neurovascular integrity, Vascular health", "chunk": "Cognitive performance is greatly influenced by cardiovascular health, as vascular integrity and brain perfusion are directly related to diseases including Parkinson's disease, Alzheimer's disease, and vascular dementia. Examining the intricate relationship between the heart and brain, this chapter highlights how atrial fibrillation, diabetes, hypertension, and dyslipidemia affect neurovascular coupling (NVC). Chronic inflammation, oxidative stress, and endothelial dysfunction are some of the risk factors that lead to neurodegeneration. The cerebral microvasculature is further compromised by atherosclerosis and heart failure, which exacerbates neuronal damage and increases the risk of dementia. Supported by clinical and epidemiological data, the discussion delves into the mechanisms behind vascular dementia and the vascular contributions to Alzheimer's disease. Slowing cognitive deterioration requires early intervention through lipid management, blood pressure control, and anticoagulant medication. Additionally, developments in precision medicine and neurovascular-targeted therapies present encouraging paths toward management and prevention. Through the discussion of modifiable cardiovascular risks, this chapter emphasizes", "source": "PubMed"}, {"chunk_id": "40681225_1", "pmid": "40681225", "title": "Cardiovascular influence on cognitive decline: The heart's role in neurodegenerative disorders.", "authors": "Gautam G, Moradikor N", "year": "2025", "journal": "Progress in brain research", "keywords": "Cognitive decline, Heart-brain connection, Neurodegeneration, Neurovascular integrity, Vascular health", "chunk": "pressure control, and anticoagulant medication. Additionally, developments in precision medicine and neurovascular-targeted therapies present encouraging paths toward management and prevention. Through the discussion of modifiable cardiovascular risks, this chapter emphasizes how vital vascular health is to maintaining cognitive function and slowing the progression of neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "35516416_0", "pmid": "35516416", "title": "Alzheimer's disease drug development pipeline: 2022.", "authors": "Cummings J, Lee G, Nahed P et al.", "year": "2022", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, Common Alzheimer's Disease Research Ontology (CADRO), aducanumab, amyloid, biomarkers, clinical trials, donanemab, drug development, inflammation, lecanemab, pharmaceutical companies, repurposed drugs, tau", "chunk": "Alzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow the progression, improve cognition, and reduce behavioral disturbances of AD. We review the current clinical trials and drugs in development for the treatment of AD. We searched the governmental website clinicaltrials.gov where are all clinical trials conducted in the United States must be registered. We used artificial intelligence (AI) and machine learning (ML) approaches to ensure comprehensive detection and characterization of trials and drugs in development. We use the Common Alzheimer's Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline. As of January 25, 2022 (index date for this study) there were 143 agents in 172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials", "source": "PubMed"}, {"chunk_id": "35516416_1", "pmid": "35516416", "title": "Alzheimer's disease drug development pipeline: 2022.", "authors": "Cummings J, Lee G, Nahed P et al.", "year": "2022", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, Common Alzheimer's Disease Research Ontology (CADRO), aducanumab, amyloid, biomarkers, clinical trials, donanemab, drug development, inflammation, lecanemab, pharmaceutical companies, repurposed drugs, tau", "chunk": "172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials in Phase 1. Disease-modifying therapies represent 83.2% of the total number of agents in trials; symptomatic cognitive enhancing treatments represent 9.8% of agents in trials; and drugs for the treatment of neuropsychiatric symptoms comprise 6.9%. There is a diverse array of drug targets represented by agents in trials including nearly all CADRO categories. Thirty-seven percent of the candidate agents in the pipeline are repurposed drugs approved for other indications. A total of 50,575 participants are needed to fulfill recruitment requirements for all currently active clinical trials. The AD drug development pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of", "source": "PubMed"}, {"chunk_id": "35516416_2", "pmid": "35516416", "title": "Alzheimer's disease drug development pipeline: 2022.", "authors": "Cummings J, Lee G, Nahed P et al.", "year": "2022", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, Common Alzheimer's Disease Research Ontology (CADRO), aducanumab, amyloid, biomarkers, clinical trials, donanemab, drug development, inflammation, lecanemab, pharmaceutical companies, repurposed drugs, tau", "chunk": "pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of new and better treatments for patients with AD. There are 143 drugs in the current Alzheimer's disease (AD) drug development pipeline.Disease-modifying therapies represent 83.2% of the candidate treatments.Current trials require 50,575 participants who will donate 3,878,843 participant-weeks to clinical trials.The biopharmaceutical industry sponsors 50% of all clinical trials including 68% of Phase 3 trials.Sixty-three percent of Phase 3 trials and 46% of Phase 2 trials include non-North American clinical trial site locations indicating the global ecosystem required for AD drug development.", "source": "PubMed"}, {"chunk_id": "41367783_0", "pmid": "41367783", "title": "Cerebral microstructural alteration patterns in motor subtypes of Parkinson's disease: a neurite orientation dispersion and density imaging study.", "authors": "Zhu N, He S, Huang Z et al.", "year": "2025", "journal": "Quantitative imaging in medicine and surgery", "keywords": "Parkinson\u2019s disease motor subtypes (PD motor subtypes), diffusion magnetic resonance imaging (diffusion MRI), gray matter-based spatial statistics (GBSS), tract-based spatial statistics (TBSS)", "chunk": "Tremor-dominant (TD) and postural instability and gait difficulty (PIGD) are motor subtypes of Parkinson's disease (PD) characterized by distinct clinical and disease progression. For these subtypes, the microstructural alterations in white matter (WM) and gray matter (GM), such as axonal density or dispersion, remain unclear. We aimed to ascertain distinct microstructural alterations in WM and GM between TD and PIGD, explicating neuroanatomical differences underlying these diverse clinical presentations. This study analyzed WM and GM microstructures using neurite orientation dispersion and density imaging (NODDI). Totals of 74 patients with PD and 47 age- and sex-matched healthy controls (HCs) were included. Tract-based spatial statistics (TBSS) and GM-based spatial statistics (GBSS) were applied to evaluate NODDI-derived metrics across groups. A total of 24 TD patients (40.0%) and 36 PIGD patients (60.0%) were included for TBSS. In WM, PIGD showed a higher orientation dispersion index (ODI) in corona radiata compared to TD, and a", "source": "PubMed"}, {"chunk_id": "41367783_1", "pmid": "41367783", "title": "Cerebral microstructural alteration patterns in motor subtypes of Parkinson's disease: a neurite orientation dispersion and density imaging study.", "authors": "Zhu N, He S, Huang Z et al.", "year": "2025", "journal": "Quantitative imaging in medicine and surgery", "keywords": "Parkinson\u2019s disease motor subtypes (PD motor subtypes), diffusion magnetic resonance imaging (diffusion MRI), gray matter-based spatial statistics (GBSS), tract-based spatial statistics (TBSS)", "chunk": "TD patients (40.0%) and 36 PIGD patients (60.0%) were included for TBSS. In WM, PIGD showed a higher orientation dispersion index (ODI) in corona radiata compared to TD, and a lower neurite density index (NDI) in multiple WM tracts than HCs [P<sub>family-wise error (FWE)</sub><0.05]. Totals of 22 TD patients (39.3%) and 34 PIGD patients (60.7%) were included for GBSS. In GM, both subtypes exhibited widespread reductions in NDI, particularly in temporal lobes, with PIGD showing a greater reduction range (P<sub>FWE</sub><0.05). The microstructure of WM (PIGD: r=-0.66, P<sub>FWE</sub><0.001; TD: r=0.71, P<sub>FWE</sub><0.001) and putamen (TD: r=0.71, P<sub>FWE</sub>=0.001) were significantly correlated with cognition in subtypes. PIGD exhibited more extensive cerebral microstructural alterations than TD, and the microstructures showed significant cognitive correlations. NODDI-derived metrics may serve as potential biomarkers for cognitive and motor symptom assessment in PD.", "source": "PubMed"}, {"chunk_id": "41367783_2", "pmid": "41367783", "title": "Cerebral microstructural alteration patterns in motor subtypes of Parkinson's disease: a neurite orientation dispersion and density imaging study.", "authors": "Zhu N, He S, Huang Z et al.", "year": "2025", "journal": "Quantitative imaging in medicine and surgery", "keywords": "Parkinson\u2019s disease motor subtypes (PD motor subtypes), diffusion magnetic resonance imaging (diffusion MRI), gray matter-based spatial statistics (GBSS), tract-based spatial statistics (TBSS)", "chunk": "may serve as potential biomarkers for cognitive and motor symptom assessment in PD.", "source": "PubMed"}, {"chunk_id": "33516914_0", "pmid": "33516914", "title": "Insulin resistance, oxidative stress and mitochondrial defects in Ts65dn mice brain: A harmful synergistic path in down syndrome.", "authors": "Lanzillotta C, Tramutola A, Di Giacomo G et al.", "year": "2021", "journal": "Free radical biology & medicine", "keywords": "Alzheimer disease, Brain development, Brain insulin resistance, Down syndrome, Intellectual disability, Mitochondria, Oxidative stress, Trisomy 21", "chunk": "Dysregulation of brain insulin signaling with reduced downstream neuronal survival and plasticity mechanisms are fundamental abnormalities observed in Alzheimer disease (AD). This phenomenon, known as brain insulin resistance, is associated with poor cognitive performance and is driven by the inhibition of IRS1. Since Down syndrome (DS) and AD neuropathology share many common features, we investigated metabolic aspects of neurodegeneration in DS and whether they contribute to early onset AD in DS. We evaluated levels and activation of proteins belonging to the insulin signaling pathway (IR, IRS1, BVR-A, MAPK, PTEN, Akt, GSK3\u03b2, PKC\u03b6, AS160, GLUT4) in the frontal cortex of Ts65dn (DS model) (n = 5-6/group) and euploid mice (n = 6/group) at different ages (1, 3, 9 and 18 months). Furthermore, we analyzed whether changes of brain insulin signaling were associated with alterations of: (i) proteins regulating brain energy metabolism (mitochondrial complexes, hexokinase-II, Sirt1); (ii) oxidative stress (OS) markers (iii)", "source": "PubMed"}, {"chunk_id": "33516914_1", "pmid": "33516914", "title": "Insulin resistance, oxidative stress and mitochondrial defects in Ts65dn mice brain: A harmful synergistic path in down syndrome.", "authors": "Lanzillotta C, Tramutola A, Di Giacomo G et al.", "year": "2021", "journal": "Free radical biology & medicine", "keywords": "Alzheimer disease, Brain development, Brain insulin resistance, Down syndrome, Intellectual disability, Mitochondria, Oxidative stress, Trisomy 21", "chunk": "Furthermore, we analyzed whether changes of brain insulin signaling were associated with alterations of: (i) proteins regulating brain energy metabolism (mitochondrial complexes, hexokinase-II, Sirt1); (ii) oxidative stress (OS) markers (iii) APP cleavage; and (iv) proteins mediating synaptic plasticity mechanisms (PSD95, syntaxin-1 and BDNF). Ts65dn mice showed an overall impairment of the above-mentioned pathways, mainly characterized by defects of proteins activation state. Such alterations start early in life (at 1 month, during brain maturation). In particular, accumulation of inhibited IRS1, together with the uncoupling among the proteins downstream from IRS1 (brain insulin resistance), characterize Ts65dn mice. Furthermore, reduced levels of mitochondrial complexes and Sirt1, as well as increased indices of OS also were observed. These alterations precede the accumulation of APP-C99 in Ts65dn mice. Tellingly, oxidative stress levels were negatively associated with IR, IRS1 and AS160 activation as well as mitochondrial complexes levels in Ts65dn mice, suggesting a role for oxidative", "source": "PubMed"}, {"chunk_id": "33516914_2", "pmid": "33516914", "title": "Insulin resistance, oxidative stress and mitochondrial defects in Ts65dn mice brain: A harmful synergistic path in down syndrome.", "authors": "Lanzillotta C, Tramutola A, Di Giacomo G et al.", "year": "2021", "journal": "Free radical biology & medicine", "keywords": "Alzheimer disease, Brain development, Brain insulin resistance, Down syndrome, Intellectual disability, Mitochondria, Oxidative stress, Trisomy 21", "chunk": "in Ts65dn mice. Tellingly, oxidative stress levels were negatively associated with IR, IRS1 and AS160 activation as well as mitochondrial complexes levels in Ts65dn mice, suggesting a role for oxidative stress in the observed alterations. We propose that a close link exists among brain insulin resistance, mitochondrial defects and OS that contributes to brain dysfunctions observed in DS, likely favoring the development of AD in DS.", "source": "PubMed"}, {"chunk_id": "41766410_0", "pmid": "41766410", "title": "Chronic Starch-Based Microplastic Exposure Enhances the Risk of Alzheimer's Disease in Mice by Perturbing the Gut-Brain Axis.", "authors": "Liu J, Xia P, Zhang X et al.", "year": "2026", "journal": "Environmental science & technology", "keywords": "Alzheimer\u2019s disease, gut\u2212brain axis, neuroinflammation, neurotoxicity, short-chain fatty acids, starch-based microplastics", "chunk": "The potential neurotoxicity of biomicroplastics has attracted increasing attention with the global expansion of bioplastics. Our recent findings revealed that starch-based microplastics (SB-MPs) can disrupt fatty acid metabolism, a perturbation strongly linked to neurotoxicity disorders. However, systematic investigations into the neurotoxic potential of chronic SB-MP exposure and its underlying mechanisms remain scarce, limiting comprehensive risk assessment. Here, we exposed mice to food-relevant concentrations of SB-MPs for 180 days and evaluated the risk of Alzheimer's disease (AD). SB-nanoparticles (SB-NPs) were found in the brain, accompanied by significantly impaired locomotor activity, learning, and memory, while increasing cerebral A\u03b2-42 protein levels, indicating a strong potential to promote AD-like pathology. Multiomics integration further revealed that SB-MPs are driving the expansion of bacterial taxa and metabolic pathways associated with short-chain fatty acid (SCFA) production. The resulting SCFAs overload and SB-NPs entered circulation and accumulated in brain tissue, where they disturbed fatty acid homeostasis and provoked", "source": "PubMed"}, {"chunk_id": "41766410_1", "pmid": "41766410", "title": "Chronic Starch-Based Microplastic Exposure Enhances the Risk of Alzheimer's Disease in Mice by Perturbing the Gut-Brain Axis.", "authors": "Liu J, Xia P, Zhang X et al.", "year": "2026", "journal": "Environmental science & technology", "keywords": "Alzheimer\u2019s disease, gut\u2212brain axis, neuroinflammation, neurotoxicity, short-chain fatty acids, starch-based microplastics", "chunk": "metabolic pathways associated with short-chain fatty acid (SCFA) production. The resulting SCFAs overload and SB-NPs entered circulation and accumulated in brain tissue, where they disturbed fatty acid homeostasis and provoked neuroinflammation, ultimately increasing AD risk. Collectively, these findings demonstrate that chronic exposure to SB-MPs can elevate AD risk by perturbing the gut-brain axis. Continued research is needed to clarify the neurotoxicity of SB-MPs and to inform the design of greener bioplastics with reduced health impacts.", "source": "PubMed"}, {"chunk_id": "41338025_0", "pmid": "41338025", "title": "Neurobiotech innovative strategies targeting Alzheimer's disease through therapeutic micro and macroalgae potentials.", "authors": "Wagdy M, Ibrahim AA, Yahia AM et al.", "year": "2026", "journal": "Journal of neuroimmunology", "keywords": "Algae, Alzheimer's disease, CRISPR-Cas9, Gene editing, Natural compounds, Neurodegenerative disorders", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder identified by cognitive decline, memory loss, and behavioral changes, affecting approximately 50 million people worldwide. Genetic predisposition, environmental variables, and aging all play a role in the development of AD. Current therapeutic approaches primarily focus on alleviating symptoms through drugs such as donepezil and memantine. However, these treatments offer limited efficacy and may be accompanied by adverse effects. In contrast, natural therapies derived from algae present a promising alternative. Microalgae, including Chlorella and Spirulina, and macroalgae such as Fucus vesiculosus, Ecklonia cava, Sargassum, Laminaria japonica, and Fucus species, are rich in bioactive molecules having antioxidant and anti-inflammatory characteristics. These substances demonstrated potential in addressing the pathological features of AD, such as oxidative stress and neuroinflammation. Furthermore, advances in biotechnological tools like CRISPR-Cas9 gene editing are poised to enhance the efficacy of these natural therapies by targeting and modifying disease-associated genes. This review", "source": "PubMed"}, {"chunk_id": "41338025_1", "pmid": "41338025", "title": "Neurobiotech innovative strategies targeting Alzheimer's disease through therapeutic micro and macroalgae potentials.", "authors": "Wagdy M, Ibrahim AA, Yahia AM et al.", "year": "2026", "journal": "Journal of neuroimmunology", "keywords": "Algae, Alzheimer's disease, CRISPR-Cas9, Gene editing, Natural compounds, Neurodegenerative disorders", "chunk": "stress and neuroinflammation. Furthermore, advances in biotechnological tools like CRISPR-Cas9 gene editing are poised to enhance the efficacy of these natural therapies by targeting and modifying disease-associated genes. This review aims to bridge the fields of neurobiotechnology and marine bioresources by examining the synergistic potential of algal compounds and gene-editing strategies in combating Alzheimer's disease. Algal-derived compounds are utilized in pharmaceuticals, nutraceuticals, and dietary supplements, and may offer neuroprotective benefits that could aid in the prevention or treatment of AD.By integrating insights from molecular biology, pharmacology, and genomics, we seek to illuminate a novel, multidisciplinary framework for future therapeutic innovation.", "source": "PubMed"}, {"chunk_id": "39276712_0", "pmid": "39276712", "title": "Individual analysis of fMRI data reveals incongruency in a potential CADASIL biomarker.", "authors": "Boido D, Huneau C, Lebenberg J et al.", "year": "2024", "journal": "Journal of the neurological sciences", "keywords": "CADASIL, Single-subject analysis, fMRI biomarkers", "chunk": "fMRI-based studies on neurodegenerative diseases rarely report single-subject information, which is useful for assessing potential biomarkers. In a previous fMRI study, CADASIL patients showed, at the group level, a significant reduction of the long-lasting visually stimulated hyperaemic response. Here, we used data interpolation and computed a hemodynamic response function from the 20-s visual response to achieve a 40-s response prediction at the individual level. The comparison between the expected and recorded 40-s responses confirmed the occurrence of a late and frequent response reduction among patients. However, this feature was inversely related to age and was also detected in control subjects, which suggests that this potential biomarker cannot be retained for monitoring vascular dysfunction in CADASIL. We showcase an open-source analytical pipeline for single-subject analysis to quickly assess potential biomarkers in fMRI studies.", "source": "PubMed"}, {"chunk_id": "39276712_1", "pmid": "39276712", "title": "Individual analysis of fMRI data reveals incongruency in a potential CADASIL biomarker.", "authors": "Boido D, Huneau C, Lebenberg J et al.", "year": "2024", "journal": "Journal of the neurological sciences", "keywords": "CADASIL, Single-subject analysis, fMRI biomarkers", "chunk": "pipeline for single-subject analysis to quickly assess potential biomarkers in fMRI studies.", "source": "PubMed"}, {"chunk_id": "38925590_0", "pmid": "38925590", "title": "Type 2 diabetes, glycaemic traits, structural brain capacity and cognitive function: A Mendelian randomization analysis.", "authors": "Luo M, Sun M, Wang T et al.", "year": "2024", "journal": "Diabetes, obesity & metabolism", "keywords": "cognitive function, fasting proinsulin, mendelian randomization, structural brain capacity, type 2 diabetes", "chunk": "To estimate the causal associations of type 2 diabetes and glycaemic traits with cognitive function, and to determine the potential mediating role of various brain imaging-derived phenotypes (IDPs) using Mendelian randomization (MR) analysis. Using publicly available summary data, we performed a series of univariable and multivariable MR analysis to infer causality. Two-step MR analysis was then conducted in turn to evaluate the potential mediating role of each brain IDP. There was no evidence of causal associations between type 2 diabetes and cognitive function outcomes. Each 1-SD unit higher genetically predicted fasting proinsulin was associated with worse cognitive performance, as evidenced by both univariable (beta: -0.022; 95% confidence interval [CI] -0.038, -0.007) and multivariable MR analysis (beta: -0.027; 95% CI -0.048, -0.005). In addition, the univariable MR analysis identified several causal associations between fasting proinsulin and brain IDPs, and between brain IDPs and cognitive performance. The inverse association of genetically predicted", "source": "PubMed"}, {"chunk_id": "38925590_1", "pmid": "38925590", "title": "Type 2 diabetes, glycaemic traits, structural brain capacity and cognitive function: A Mendelian randomization analysis.", "authors": "Luo M, Sun M, Wang T et al.", "year": "2024", "journal": "Diabetes, obesity & metabolism", "keywords": "cognitive function, fasting proinsulin, mendelian randomization, structural brain capacity, type 2 diabetes", "chunk": "-0.005). In addition, the univariable MR analysis identified several causal associations between fasting proinsulin and brain IDPs, and between brain IDPs and cognitive performance. The inverse association of genetically predicted fasting proinsulin with cognitive performance did not attenuate after adjusting for each of the brain IDPs in multivariable MR analysis. The present MR study provided credible evidence for the causal association between genetically predicted fasting proinsulin and cognitive function, informing a potential diagnosis and intervention target for patients with cognitive impairment. No significant brain IDP included in this study was identified as lying on the causal pathway from fasting proinsulin to cognitive performance. Future research involving more specific and granular brain IDP or other brain process is warranted to explore the potential biological mechanism underlying the association.", "source": "PubMed"}, {"chunk_id": "38925590_2", "pmid": "38925590", "title": "Type 2 diabetes, glycaemic traits, structural brain capacity and cognitive function: A Mendelian randomization analysis.", "authors": "Luo M, Sun M, Wang T et al.", "year": "2024", "journal": "Diabetes, obesity & metabolism", "keywords": "cognitive function, fasting proinsulin, mendelian randomization, structural brain capacity, type 2 diabetes", "chunk": "the potential biological mechanism underlying the association.", "source": "PubMed"}, {"chunk_id": "41252291_0", "pmid": "41252291", "title": "Alzheimer's Disease Biomarker-Nigeria (ADIBIO-N): Cohort description and baseline data report.", "authors": "Ucheagwu VA, Morgan D, Rose S et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "ADIBIO-N, Alzheimer's disease, Nigeria, amyloid-\u03b2, blood biomarkers, glial fibrillary acidic protein, neurofilament light chain, phosphorylated tau 181", "chunk": "BackgroundThere is knowledge gap between the West and sub-Saharan Africa on dementia biomarkers. To bridge this, the Alzheimer's Disease Biomarker-Nigeria (ADIBIO-N) cohort was established.ObjectiveThis study reported baseline data for Alzheimer's disease (AD) blood-based biomarkers in ADIBIO-N and the association of these biomarkers with measures of cognition. We also reported demographic differences in plasma biomarkers.MethodsThree hundred older adults were recruited. At baseline, blood samples were analyzed for amyloid-\u03b2 42/40 (A\u03b2<sub>42/40</sub>), phosphorylated tau 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Cognition was measured at baseline and two follow-up visits.ResultsResults showed significant sex differences for NfL. Significant relationships were found between GFAP, education, and composite cognition. The same is true for NfL and composite cognition. Significant negative associations were found between GFAP, memory, and language. A significant negative relationship was found between NfL and visuospatial cognition. Equally, significant positive associations were found for GFAP and age (0.26), and", "source": "PubMed"}, {"chunk_id": "41252291_1", "pmid": "41252291", "title": "Alzheimer's Disease Biomarker-Nigeria (ADIBIO-N): Cohort description and baseline data report.", "authors": "Ucheagwu VA, Morgan D, Rose S et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "ADIBIO-N, Alzheimer's disease, Nigeria, amyloid-\u03b2, blood biomarkers, glial fibrillary acidic protein, neurofilament light chain, phosphorylated tau 181", "chunk": "were found between GFAP, memory, and language. A significant negative relationship was found between NfL and visuospatial cognition. Equally, significant positive associations were found for GFAP and age (0.26), and A\u03b2<sub>42/40</sub> ratio and age (0.17) while adjusting for sex and education. Using the area under the curve for receiver operating characteristics, GFAP demonstrated good discriminative ability (0.70) for classifying cognitively unimpaired from non-amnestic mild cognitive impairment. Finally, a reference value was established for all the biomarkers across three diagnostic categories.ConclusionsWe found a baseline significant association of GFAP and NfL with composite and domain-specific cognitions, respectively, but not on amyloid and p-tau, contrary to findings from outside Africa that have repeatedly shown an association of amyloid and p-tau with cognition.", "source": "PubMed"}, {"chunk_id": "39626664_0", "pmid": "39626664", "title": "\u03b2-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.", "authors": "Madhavan SS, Roa Diaz S, Peralta S et al.", "year": "2025", "journal": "Cell chemical biology", "keywords": "Alzheimer disease, aging, ketone body, neurodegenerative disease, proteostasis", "chunk": "Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify \u03b2-hydroxybutyrate (\u03b2HB), a ketone body, as a regulator of protein solubility. \u03b2HB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate \u03b2HB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. This mechanism is selective for pathological proteins such as amyloid-\u03b2, and exogenous \u03b2HB ameliorates pathology in nematode models of amyloid-\u03b2 aggregation toxicity. We generate libraries of the \u03b2HB-induced protein insolublome using mass spectrometry proteomics, and identify common protein domains and upstream regulators. We show enrichment of neurodegeneration-related proteins among \u03b2HB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.", "source": "PubMed"}, {"chunk_id": "39626664_1", "pmid": "39626664", "title": "\u03b2-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.", "authors": "Madhavan SS, Roa Diaz S, Peralta S et al.", "year": "2025", "journal": "Cell chemical biology", "keywords": "Alzheimer disease, aging, ketone body, neurodegenerative disease, proteostasis", "chunk": "neurodegeneration-related proteins among \u03b2HB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.", "source": "PubMed"}, {"chunk_id": "40812585_0", "pmid": "40812585", "title": "Verapamil modulates astrocytic glycolytic dysfunction via TXNIP inhibition in the hippocampus of 3\u00a0\u00d7\u00a0Tg-AD mice.", "authors": "Zhou W, Yin X, Huang J et al.", "year": "2025", "journal": "Biochemical pharmacology", "keywords": "Alzheimer\u2019s disease, Astrocytic glycolysis, GLUT1, TXNIP, Verapamil", "chunk": "Alzheimer's disease (AD) is a gradually worsening neurodegenerative condition marked by the accumulation of amyloid-\u03b2 plaques and a decline in cognitive abilities. Emerging research emphasizes astrocytic metabolic disturbances as contributors to AD development. This study investigates the therapeutic effects of Verapamil (VPM), a clinically approved calcium channel blocker, on astrocytic glycolysis in 3 \u00d7 Tg-AD mice, focusing on the involvement of the thioredoxin-interacting protein (TXNIP)/glucose transporter 1 (GLUT1) pathway. VPM treatment significantly enhanced glycolytic activity in astrocytes, as evidenced by increased lactate production and improved metabolic function. Western blot and PCR analyses revealed a reduction in TXNIP levels and an upregulation of GLUT1 expression, particularly in the plasma membrane fraction, suggesting enhanced glucose uptake and glycolysis. Additionally, VPM treatment decreased soluble \u03b2-amyloid (A\u03b2) levels and alleviated cognitive impairments in the 3 \u00d7 Tg-AD mice. These findings indicate that VPM restores glycolytic function in astrocytes through the TXNIP/GLUT1 pathway, offering a", "source": "PubMed"}, {"chunk_id": "40812585_1", "pmid": "40812585", "title": "Verapamil modulates astrocytic glycolytic dysfunction via TXNIP inhibition in the hippocampus of 3\u00a0\u00d7\u00a0Tg-AD mice.", "authors": "Zhou W, Yin X, Huang J et al.", "year": "2025", "journal": "Biochemical pharmacology", "keywords": "Alzheimer\u2019s disease, Astrocytic glycolysis, GLUT1, TXNIP, Verapamil", "chunk": "soluble \u03b2-amyloid (A\u03b2) levels and alleviated cognitive impairments in the 3 \u00d7 Tg-AD mice. These findings indicate that VPM restores glycolytic function in astrocytes through the TXNIP/GLUT1 pathway, offering a promising intervention targeting metabolic disruption and cognitive decline in AD. This study underscores the critical role of glycolysis in glial cells and highlights VPM's therapeutic potential in AD by targeting metabolic dysfunction.", "source": "PubMed"}, {"chunk_id": "41370824_0", "pmid": "41370824", "title": "Smartphone-Based Physical Activity Program to Reduce \"Chemo-Brain\" Symptoms and Improve Health in Cancer Survivors With and Without Type 2 Diabetes: Protocol for a Single-Arm Pre-Post Pilot Trial.", "authors": "Pope ZC, Yabluchanskiy A, Mukli P et al.", "year": "2025", "journal": "JMIR research protocols", "keywords": "aerobic physical activity, resistance training, smartphone applications, social cognitive theory, wearable technology", "chunk": "The US cancer survivor population is projected to hit 26M by 2040. Chemotherapy is an effective cancer treatment, but can diminish cancer survivors' quality of life-particularly cognitive function-through select pathophysiological processes, including immune system and antioxidant dysregulation. The resulting cytokine release can impair cerebrovascular function-likely contributing to chemotherapy-induced cognitive impairment (CICI; \"chemo-brain\"). Type 2 diabetes mellitus (T2DM)-a common cancer survivor comorbidity-shares underlying pathophysiology with CICI. Cancer survivors with T2DM might thus have a higher CICI risk than those without T2DM. Physical activity (PA) counteracts CICI's and T2DM's pathophysiology, but little to no research has been conducted assessing the impact of PA on this joint pathophysiology. To compare cerebrovascular and cognitive function as well as proinflammatory, cardiometabolic, epigenetic, and psychosocial outcomes between ancer survivors with and without T2DM pre- to postengagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory. We hypothesize that cancer survivors with and without", "source": "PubMed"}, {"chunk_id": "41370824_1", "pmid": "41370824", "title": "Smartphone-Based Physical Activity Program to Reduce \"Chemo-Brain\" Symptoms and Improve Health in Cancer Survivors With and Without Type 2 Diabetes: Protocol for a Single-Arm Pre-Post Pilot Trial.", "authors": "Pope ZC, Yabluchanskiy A, Mukli P et al.", "year": "2025", "journal": "JMIR research protocols", "keywords": "aerobic physical activity, resistance training, smartphone applications, social cognitive theory, wearable technology", "chunk": "between ancer survivors with and without T2DM pre- to postengagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory. We hypothesize that cancer survivors with and without T2DM will demonstrate similar pre to poststudy improvements in psychosocial outcomes, but that changes in cerebrovascular and cardiometabolic outcomes, as well as PA engagement, will be greater for cancer survivors with T2DM. We also believe that each group will have distinct epigenetic profiles that will change pre to poststudy. We are conducting a 30-participant pilot study in cancer survivors with (n=15) and without (n=15) T2DM-all of whom report currently experiencing \"chemo-brain.\" To account for attrition, we are recruiting 38 cancer survivors from Oklahoma City, OK, and the surrounding area. Among the most important eligibility criteria are the self-report of cognitive difficulties following primary cancer treatment, being \u226518 years old, being within 3 years of primary cancer treatment, and not meeting", "source": "PubMed"}, {"chunk_id": "41370824_2", "pmid": "41370824", "title": "Smartphone-Based Physical Activity Program to Reduce \"Chemo-Brain\" Symptoms and Improve Health in Cancer Survivors With and Without Type 2 Diabetes: Protocol for a Single-Arm Pre-Post Pilot Trial.", "authors": "Pope ZC, Yabluchanskiy A, Mukli P et al.", "year": "2025", "journal": "JMIR research protocols", "keywords": "aerobic physical activity, resistance training, smartphone applications, social cognitive theory, wearable technology", "chunk": "the most important eligibility criteria are the self-report of cognitive difficulties following primary cancer treatment, being \u226518 years old, being within 3 years of primary cancer treatment, and not meeting nationally recommended PA guidelines. Participants receive 2 smartphone apps. One smartphone app provides health education and the ability to set goals and journal about their wellness journey. The other provides a workout program continually tailored to each participant via their communication with the study exercise physiologist, with resistance bands and a wearable device provided to support the program. At Baseline and Poststudy, we assess cerebrovascular function (transcranial doppler [TCD]), cognition (National Institutes of Health Toolbox), cardiometabolic outcomes (venipuncture), and epigenetics (saliva collection). Participants also wear accelerometers at Baseline and Poststudy to objectively assess PA, with Baseline, Midpoint, and Poststudy surveys assessing psychosocial outcomes. We will use t tests and chi-square tests to assess baseline differences and repeated-measures ANCOVA to assess", "source": "PubMed"}, {"chunk_id": "41370824_3", "pmid": "41370824", "title": "Smartphone-Based Physical Activity Program to Reduce \"Chemo-Brain\" Symptoms and Improve Health in Cancer Survivors With and Without Type 2 Diabetes: Protocol for a Single-Arm Pre-Post Pilot Trial.", "authors": "Pope ZC, Yabluchanskiy A, Mukli P et al.", "year": "2025", "journal": "JMIR research protocols", "keywords": "aerobic physical activity, resistance training, smartphone applications, social cognitive theory, wearable technology", "chunk": "to objectively assess PA, with Baseline, Midpoint, and Poststudy surveys assessing psychosocial outcomes. We will use t tests and chi-square tests to assess baseline differences and repeated-measures ANCOVA to assess changes over time. Participant recruitment started in March 2025, and we expect to recruit until late 2026. We will begin analyzing baseline data in 2026. Successful study completion will provide valuable insights into the remote delivery of PA-oriented supportive care for cancer survivors experiencing chemo-brain, as well as how T2DM and PA contribute to the mechanistic underpinnings of chemo-brain. ClinicalTrials.gov NCT06725953; https://clinicaltrials.gov/study/NCT06725953. DERR1-10.2196/79739.", "source": "PubMed"}, {"chunk_id": "41486993_0", "pmid": "41486993", "title": "miRNAs: Promising Biomarkers for Alzheimer's Diagnosis and Treatment.", "authors": "Cai M, Yan S, Sun Y et al.", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease (AD), amyloid-beta (A\u03b2), biomarkers, exosomal miRNAs, microRNAs (miRNAs), neuroinflammation, tau phosphorylation, therapeutic targets.", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (A\u03b2) plaque deposition, neurofibrillary tangles of hyperphosphorylated tau protein, and chronic neuroinflammation, leading to synaptic dysfunction and cognitive decline. Current diagnostic methods rely on clinical symptoms and limited biomarkers, while available treatments only provide symptomatic relief without halting disease progression. MicroRNAs (miRNAs), small non-coding RNAs of 19-22 nucleotides, have emerged as crucial regulators of gene expression through post-transcriptional mechanisms and show distinct dysregulation patterns in AD patients' blood, cerebrospinal fluid (CSF), and brain tissues. Key miRNAs such as miR-132, miR-146a, miR-34a, and miR-125b demonstrate consistent alterations in expression levels, correlating with disease progression and offering potential as non-invasive diagnostic tools. This review comprehensively examines the dual role of miRNAs as diagnostic biomarkers and therapeutic targets for AD. We also provide an analysis of specific miRNA signatures in different biofluids (plasma, serum, CSF) and brain regions that correlate with disease", "source": "PubMed"}, {"chunk_id": "41486993_1", "pmid": "41486993", "title": "miRNAs: Promising Biomarkers for Alzheimer's Diagnosis and Treatment.", "authors": "Cai M, Yan S, Sun Y et al.", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease (AD), amyloid-beta (A\u03b2), biomarkers, exosomal miRNAs, microRNAs (miRNAs), neuroinflammation, tau phosphorylation, therapeutic targets.", "chunk": "as diagnostic biomarkers and therapeutic targets for AD. We also provide an analysis of specific miRNA signatures in different biofluids (plasma, serum, CSF) and brain regions that correlate with disease stages, highlighting their potential for early and non-invasive diagnosis. Therapeutically, miRNAs modulate multiple AD-related pathways, including neuroinflammation via NF-\u03baB signaling, A\u03b2 production through BACE1 inhibition, and tau phosphorylation via GSK3\u03b2 regulation. miRNAs also influence synaptic plasticity, mitochondrial function, and autophagy, presenting multifaceted opportunities for intervention. However, challenges, including miRNA heterogeneity, stability, and targeted delivery, remain critical impediments. Advances in nanocarriers, exosomal miRNAs, and viral vectors show promise in overcoming these obstacles, enabling precise miRNA modulation. In addition, we underscore the need for standardized protocols, further validation in clinical cohorts, and the development of cost-effective detection methods to translate miRNA-based approaches into practical diagnostics and therapies. By integrating miRNA biomarkers with existing diagnostic tools and exploring combinatorial therapeutic strategies, researchers can", "source": "PubMed"}, {"chunk_id": "41486993_2", "pmid": "41486993", "title": "miRNAs: Promising Biomarkers for Alzheimer's Diagnosis and Treatment.", "authors": "Cai M, Yan S, Sun Y et al.", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease (AD), amyloid-beta (A\u03b2), biomarkers, exosomal miRNAs, microRNAs (miRNAs), neuroinflammation, tau phosphorylation, therapeutic targets.", "chunk": "the development of cost-effective detection methods to translate miRNA-based approaches into practical diagnostics and therapies. By integrating miRNA biomarkers with existing diagnostic tools and exploring combinatorial therapeutic strategies, researchers can harness the potential of miRNAs to revolutionize AD intervention, paving the way for early detection and effective treatment of this devastating disease.", "source": "PubMed"}, {"chunk_id": "32321529_0", "pmid": "32321529", "title": "Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL.", "authors": "Chen CH, Cheng YW, Chen YF et al.", "year": "2020", "journal": "Journal of neuroinflammation", "keywords": "Biomarkers, CADASIL, Glial fibrillary acidic protein, Intracerebral hemorrhage, Neurofilament light chain, Stroke", "chunk": "Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Sixty-three CADASIL patients (mean age 58.9 \u00b1 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the", "source": "PubMed"}, {"chunk_id": "32321529_1", "pmid": "32321529", "title": "Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL.", "authors": "Chen CH, Cheng YW, Chen YF et al.", "year": "2020", "journal": "Journal of neuroinflammation", "keywords": "Biomarkers, CADASIL, Glial fibrillary acidic protein, Intracerebral hemorrhage, Neurofilament light chain, Stroke", "chunk": "of plasma biomarkers at baseline for predicting incident stroke during follow-up. Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06-3.87) and ICH (odds ratio 2.06, 95% CI 1.26-3.35) at baseline, respectively. Within a mean follow-up period of 3.1 \u00b1 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19-3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH. In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may", "source": "PubMed"}, {"chunk_id": "32321529_2", "pmid": "32321529", "title": "Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL.", "authors": "Chen CH, Cheng YW, Chen YF et al.", "year": "2020", "journal": "Journal of neuroinflammation", "keywords": "Biomarkers, CADASIL, Glial fibrillary acidic protein, Intracerebral hemorrhage, Neurofilament light chain, Stroke", "chunk": "incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH. In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.", "source": "PubMed"}, {"chunk_id": "37095270_0", "pmid": "37095270", "title": "Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin.", "authors": "Lin HC, Chung CH, Chen LC et al.", "year": "2023", "journal": "Scientific reports", "keywords": "None", "chunk": "Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203-1.967, p < 0.05) higher than that in the non-pioglitazone controls. Compared to patients without both insulin and pioglitazone, higher cumulative risk of developing AD was found in patients receiving both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702-2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398-1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125-1.572),", "source": "PubMed"}, {"chunk_id": "37095270_1", "pmid": "37095270", "title": "Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin.", "authors": "Lin HC, Chung CH, Chen LC et al.", "year": "2023", "journal": "Scientific reports", "keywords": "None", "chunk": "both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702-2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398-1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125-1.572), respectively (all p < 0.05). A similar observation also found in the evaluation the use of diabetic drugs with a cumulative defined daily dose (cDDD). No interaction between pioglitazone and major risk factors (comorbidities) of AD was observed. In conclusion, alternative drug therapies may be an effective strategy for reducing risk of developing AD in T2DM patients.", "source": "PubMed"}, {"chunk_id": "41687112_0", "pmid": "41687112", "title": "[Prevalence of Dementia and Cognitive Decline in Portuguese Residential Care Homes: A Cross-Sectional Study].", "authors": "Padeiro M, Borges-Machado F, Ribeiro O et al.", "year": "2026", "journal": "Acta medica portuguesa", "keywords": "Alzheimer Disease/epidemiology, Cognitive Dysfunction/epidemiology, Dementia/epidemiology, Geriatric Assessment, Homes for the Aged, Portugal, Residential Facilities", "chunk": "Dementia is one of the leading causes of dependency among older people and poses a critical challenge for long-term care systems. Despite the importance of the issue, national data on the prevalence of dementia in residential care homes remain limited. A cross-sectional, observational, and institution-based study was conducted within the framework of the SINDIA project. The study was based on an online survey addressed to the technical directors of residential care homes for older people in Portugal, carried out between January and July 2024. The questionnaire collected information on institutional characteristics (sector, territorial location, base monthly fee, dementia specialization, and total number of residents) and on the prevalence of formally diagnosed dementia cases and of cognitive decline without a recorded diagnosis. Data were analyzed using the R software (version 4.1.2). Mean percentages and 95% confidence intervals (Student's t-method), weighted by NUTS-2 region, were calculated. A hierarchical cluster analysis (Ward's method)", "source": "PubMed"}, {"chunk_id": "41687112_1", "pmid": "41687112", "title": "[Prevalence of Dementia and Cognitive Decline in Portuguese Residential Care Homes: A Cross-Sectional Study].", "authors": "Padeiro M, Borges-Machado F, Ribeiro O et al.", "year": "2026", "journal": "Acta medica portuguesa", "keywords": "Alzheimer Disease/epidemiology, Cognitive Dysfunction/epidemiology, Dementia/epidemiology, Geriatric Assessment, Homes for the Aged, Portugal, Residential Facilities", "chunk": "diagnosis. Data were analyzed using the R software (version 4.1.2). Mean percentages and 95% confidence intervals (Student's t-method), weighted by NUTS-2 region, were calculated. A hierarchical cluster analysis (Ward's method) was also performed to identify distinct institutional profiles. On average, 31.7% of residents had a formal dementia diagnosis and 22.3% showed signs of undiagnosed cognitive decline, resulting in 50.2% of the resident population presenting some degree of cognitive impairment, after data cleaning. The proportion varied across territories, institutional sectors, monthly fees and self-reported specialization. A cluster analysis identified three distinct institutional profiles, with a majority group of facilities characterized by lower diagnostic formalization, especially in the non-profit sector and among lower-cost institutions. The findings are suggestive of a very high prevalence of cognitive impairment in Portuguese residential care homes. These results highlight the need for public policies aimed at improving early diagnosis, enhancing staff training, and reducing territorial and institutional", "source": "PubMed"}, {"chunk_id": "41687112_2", "pmid": "41687112", "title": "[Prevalence of Dementia and Cognitive Decline in Portuguese Residential Care Homes: A Cross-Sectional Study].", "authors": "Padeiro M, Borges-Machado F, Ribeiro O et al.", "year": "2026", "journal": "Acta medica portuguesa", "keywords": "Alzheimer Disease/epidemiology, Cognitive Dysfunction/epidemiology, Dementia/epidemiology, Geriatric Assessment, Homes for the Aged, Portugal, Residential Facilities", "chunk": "prevalence of cognitive impairment in Portuguese residential care homes. These results highlight the need for public policies aimed at improving early diagnosis, enhancing staff training, and reducing territorial and institutional inequalities in the response to dementia.", "source": "PubMed"}, {"chunk_id": "37234274_0", "pmid": "37234274", "title": "Using Clinical Decision Intelligence Applications to Improve Pathways For Earlier Detection Of Underrecognized Cognitive Disorders.", "authors": "Khachaturian AS, Cassin B, Finney GR", "year": "2023", "journal": "JAR life", "keywords": "Alzheimer, Dementia, artificial intelligence, clinical decision applications, healthcare system preparedness, healthcare systems, machine learning, technology adoption", "chunk": "Cost estimates for care for those with dementia and other cognitive impairments are rising globally, estimated to reach US $1 trillion by 2025. Lack of specialized personnel, infrastructure, diagnostic capabilities, and healthcare access impedes the timely identification of patients progressing to dementia, particularly in underserved populations. International healthcare infrastructure may be unable to handle existing cases in addition to a sudden increase due to undiagnosed cognitive impairment and dementia. Healthcare bioinformatics offers a potential route for quicker access to healthcare services; however, a better preparedness plan must be implemented now if expected demands are to be met. The most critical consideration for implementing artificial intelligence/machine learning (AI/ML) -driven clinical decision intelligence applications (CDIA) is ensuring patients and practitioners take action on the information provided.", "source": "PubMed"}, {"chunk_id": "37234274_1", "pmid": "37234274", "title": "Using Clinical Decision Intelligence Applications to Improve Pathways For Earlier Detection Of Underrecognized Cognitive Disorders.", "authors": "Khachaturian AS, Cassin B, Finney GR", "year": "2023", "journal": "JAR life", "keywords": "Alzheimer, Dementia, artificial intelligence, clinical decision applications, healthcare system preparedness, healthcare systems, machine learning, technology adoption", "chunk": "on the information provided.", "source": "PubMed"}, {"chunk_id": "41740214_0", "pmid": "41740214", "title": "Test-retest reliability of resting-state functional magnetic resonance imaging during deep brain stimulation for Parkinson's disease.", "authors": "Deutsch S, Mehta J, Reid LB et al.", "year": "2026", "journal": "NeuroImage. Clinical", "keywords": "Deep brain stimulation, Functional magnetic resonance imaging, Metal artifact, Open-source, Parkinson's disease, Test-retest reliability", "chunk": "Patients implanted with modern deep brain stimulation (DBS) hardware can now undergo functional magnetic resonance imaging (fMRI), leading to its increased used to study DBS' mechanisms and predict optimal therapy settings. To accurately interpret fMRI data and realize its clinical potential for DBS, a better understanding of reliability is needed. Sixteen patients with Parkinson's disease (PD) and DBS targeting the subthalamic nucleus or pallidum underwent 3T test-retest resting-state fMRI with and without concurrent stimulation. Effects of stimulation and device-metal artifacts on reliability of fMRI brain connectivity and moment-to-moment brain variability were explored, plus factors influencing between-subject variations in reliability such as motion. The brain variability fMRI metric yielded higher intra-class correlation coefficients than the connectivity metric (range across whole brain, motor, limbic, and cognitive networks: 0.36-0.85 and 0.68-0.99, respectively). Average network connectivity appeared less reproducible when DBS was ON versus OFF during fMRI, and fMRI metric reliability for brain areas", "source": "PubMed"}, {"chunk_id": "41740214_1", "pmid": "41740214", "title": "Test-retest reliability of resting-state functional magnetic resonance imaging during deep brain stimulation for Parkinson's disease.", "authors": "Deutsch S, Mehta J, Reid LB et al.", "year": "2026", "journal": "NeuroImage. Clinical", "keywords": "Deep brain stimulation, Functional magnetic resonance imaging, Metal artifact, Open-source, Parkinson's disease, Test-retest reliability", "chunk": "motor, limbic, and cognitive networks: 0.36-0.85 and 0.68-0.99, respectively). Average network connectivity appeared less reproducible when DBS was ON versus OFF during fMRI, and fMRI metric reliability for brain areas affected by metal artifacts was significantly higher (brain variability) or lower (connectivity) than unaffected areas (p<sub>uncorrected</sub> < 0.05). Motion and DBS target best explained between-subject variations. DBS hardware and active stimulation may alter fMRI reliability. To develop clinically useful fMRI biomarkers for DBS and aid assessments of reproducibility across studies, the reliability of single study results need reporting.", "source": "PubMed"}, {"chunk_id": "34603323_0", "pmid": "34603323", "title": "PET Imaging of Neuroinflammation in Alzheimer's Disease.", "authors": "Zhou R, Ji B, Kong Y et al.", "year": "2021", "journal": "Frontiers in immunology", "keywords": "Alzheimer\u2019s disease, TSPO (18 kDa translocator protein), amyloid (A) 42, astrocyte, microglia, neuroinflammation, positron emission tomography (PET), tau", "chunk": "Neuroinflammation play an important role in Alzheimer's disease pathogenesis. Advances in molecular imaging using positron emission tomography have provided insights into the time course of neuroinflammation and its relation with Alzheimer's disease central pathologies in patients and in animal disease models. Recent single-cell sequencing and transcriptomics indicate dynamic disease-associated microglia and astrocyte profiles in Alzheimer's disease. Mitochondrial 18-kDa translocator protein is the most widely investigated target for neuroinflammation imaging. New generation of translocator protein tracers with improved performance have been developed and evaluated along with tau and amyloid imaging for assessing the disease progression in Alzheimer's disease continuum. Given that translocator protein is not exclusively expressed in glia, alternative targets are under rapid development, such as monoamine oxidase B, matrix metalloproteinases, colony-stimulating factor 1 receptor, imidazoline-2 binding sites, cyclooxygenase, cannabinoid-2 receptor, purinergic P2X7 receptor, P2Y12 receptor, the fractalkine receptor, triggering receptor expressed on myeloid cells 2, and receptor for advanced", "source": "PubMed"}, {"chunk_id": "34603323_1", "pmid": "34603323", "title": "PET Imaging of Neuroinflammation in Alzheimer's Disease.", "authors": "Zhou R, Ji B, Kong Y et al.", "year": "2021", "journal": "Frontiers in immunology", "keywords": "Alzheimer\u2019s disease, TSPO (18 kDa translocator protein), amyloid (A) 42, astrocyte, microglia, neuroinflammation, positron emission tomography (PET), tau", "chunk": "metalloproteinases, colony-stimulating factor 1 receptor, imidazoline-2 binding sites, cyclooxygenase, cannabinoid-2 receptor, purinergic P2X7 receptor, P2Y12 receptor, the fractalkine receptor, triggering receptor expressed on myeloid cells 2, and receptor for advanced glycation end products. Promising targets should demonstrate a higher specificity for cellular locations with exclusive expression in microglia or astrocyte and activation status (pro- or anti-inflammatory) with highly specific ligand to enable <i>in vivo</i> brain imaging. In this review, we summarised recent advances in the development of neuroinflammation imaging tracers and provided an outlook for promising targets in the future.", "source": "PubMed"}, {"chunk_id": "34904299_0", "pmid": "34904299", "title": "Breakdown of the blood-brain barrier: A mediator of increased Alzheimer's risk in patients with metabolic disorders?", "authors": "Frank CJ, McNay EC", "year": "2022", "journal": "Journal of neuroendocrinology", "keywords": "cytokines, insulin, nitric oxide", "chunk": "Metabolic disorders (MDs), including type 1 and 2 diabetes and chronic obesity, are among the faster growing diseases globally and are a primary risk factor for Alzheimer's disease (AD). The term \"type-3 diabetes\" has been proposed for AD due to the interrelated cellular, metabolic, and immune features shared by diabetes, insulin resistance (IR), and the cognitive impairment and neurodegeneration found in AD. Patients with MDs and/or AD commonly exhibit altered glucose homeostasis and IR; systemic chronic inflammation encompassing all of the periphery, blood-brain barrier (BBB), and central nervous system; pathological vascular remodeling; and increased BBB permeability that allows transfusion of neurotoxic molecules from the blood to the brain. This review summarizes the components of the BBB, mechanisms through which MDs alter BBB permeability via immune and metabolic pathways, the contribution of BBB dysfunction to the manifestation and progression of AD, and current avenues of therapeutic research that address BBB permeability.", "source": "PubMed"}, {"chunk_id": "34904299_1", "pmid": "34904299", "title": "Breakdown of the blood-brain barrier: A mediator of increased Alzheimer's risk in patients with metabolic disorders?", "authors": "Frank CJ, McNay EC", "year": "2022", "journal": "Journal of neuroendocrinology", "keywords": "cytokines, insulin, nitric oxide", "chunk": "alter BBB permeability via immune and metabolic pathways, the contribution of BBB dysfunction to the manifestation and progression of AD, and current avenues of therapeutic research that address BBB permeability. In addition, issues with the translational applicability of current animal models of AD regarding BBB dysfunction and proposals for future directions of research that address the relationship between MDs, BBB dysfunction, and AD are discussed.", "source": "PubMed"}, {"chunk_id": "36539127_0", "pmid": "36539127", "title": "PREVALENCE OF COGNITIVE IMPAIRMENT AND ITS ASSOCIATED FACTORS AMONG TYPE 2DIABETIC PATIENTS: FINDING FROM A CROSS SECTIONAL STUDY IN IRAQ.", "authors": "Salih I, Al-Qazaz H", "year": "2022", "journal": "Georgian medical news", "keywords": "None", "chunk": "Diabetes mellitus is a metabolic condition characterized by chronic hyperglycemia and disturbance in body metabolic state. It is estimated that nearly half of patients with diabetes will suffer from cognitive impairment and impairment in the performance of daily functions. The aim was to determine the prevalence of cognitive impairment and its predictors among diabetics. A cross-sectional study was conducted on type 2 diabetic patients attending the AL-Wafaa clinic in Mosul. A validated questionnaire Saint Louis University Mental Status Examination (SLUMS) was used to evaluate cognitive function. The recent value of FBS or RBS and HbA1c were attained from the patient's records. The result demonstrated that 90% had impaired cognitive function. No significant correlation between cognitive function and age, BMI, HbA1c, duration of diabetes, and duration of co-morbid disease. Significant correlation between cognitive function and RBS level. Significant differences were found between cognitive function and gender, smoking, educational level, employment, and", "source": "PubMed"}, {"chunk_id": "36539127_1", "pmid": "36539127", "title": "PREVALENCE OF COGNITIVE IMPAIRMENT AND ITS ASSOCIATED FACTORS AMONG TYPE 2DIABETIC PATIENTS: FINDING FROM A CROSS SECTIONAL STUDY IN IRAQ.", "authors": "Salih I, Al-Qazaz H", "year": "2022", "journal": "Georgian medical news", "keywords": "None", "chunk": "duration of diabetes, and duration of co-morbid disease. Significant correlation between cognitive function and RBS level. Significant differences were found between cognitive function and gender, smoking, educational level, employment, and monthly income. While no significant differences were found with the marital state. The differences between SLUMS scores and the type of medications used for diabetes also were examined and no significant differences were found. Decline cognitive performance is common among diabetic patients, more than half had a cognitive function. It is associated with gender, smoking, educational level, employment, and monthly income. No association was reported with age, HbA1c, duration of diabetes, and medication used for diabetes.", "source": "PubMed"}, {"chunk_id": "40549285_0", "pmid": "40549285", "title": "Identification of Associations Between Peripheral Blood Gene Expression and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease Using an Improved Joint Multi-Task Sparse Canonical Correlation Analysis Algorithm.", "authors": "Wu Q, Ma Z, Wang F", "year": "2025", "journal": "Applied biochemistry and biotechnology", "keywords": "Alzheimer's disease, Biomarker discovery, Genetic biomarkers, Multi-task sparse canonical correlation analysis, Peripheral blood", "chunk": "Alzheimer's disease (AD) is an irreversible neurodegenerative disorder, and early diagnosis is crucial for effective clinical intervention. Traditional diagnostic methods involve detecting living brain tissue across the blood-brain barrier, but these invasive procedures cause unavoidable damage to patients. Genetic biomarkers in peripheral blood may provide valuable insights into brain lesions, potentially offering a non-invasive method for early AD diagnosis. The aim of this study is to propose an improved joint multi-task sparse canonical correlation analysis (MTSCCA) algorithm to identify significant genetic biomarkers in peripheral blood that correlate with brain markers of AD, such as cerebrospinal fluid (CSF) markers. This approach aims to accurately predict AD and assess disease progression. The study employs a multi-task sparse canonical correlation analysis (MTSCCA) approach with separate analyses for AD and healthy controls. Both tasks are constrained with class-consistent and class-specific conditions to identify significant features for each diagnostic group. To enhance robustness, the Laplacian", "source": "PubMed"}, {"chunk_id": "40549285_1", "pmid": "40549285", "title": "Identification of Associations Between Peripheral Blood Gene Expression and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease Using an Improved Joint Multi-Task Sparse Canonical Correlation Analysis Algorithm.", "authors": "Wu Q, Ma Z, Wang F", "year": "2025", "journal": "Applied biochemistry and biotechnology", "keywords": "Alzheimer's disease, Biomarker discovery, Genetic biomarkers, Multi-task sparse canonical correlation analysis, Peripheral blood", "chunk": "with separate analyses for AD and healthy controls. Both tasks are constrained with class-consistent and class-specific conditions to identify significant features for each diagnostic group. To enhance robustness, the Laplacian matrix constraints were incorporated into the MTSCCA-LR algorithm to reduce noise in genetic data. The proposed algorithm identifies key differentially expressed genes (DEGs) that are involved in pathways closely linked to AD pathogenesis. These genes have specific diagnostic significance. Validation of these genes for predicting CSF markers was conducted using two regression models, showing good predictive accuracy. Furthermore, a Support Vector Machine (SVM) classifier was used to classify the two diagnostic groups, demonstrating high classification accuracy. The Top 20 genes identified using the proposed algorithm were used to construct an AD diagnostic model, which exhibited strong potential for non-invasive AD diagnosis, with significant implications for clinical practice. The code and example data of the proposed algorithm have been made publicly", "source": "PubMed"}, {"chunk_id": "40549285_2", "pmid": "40549285", "title": "Identification of Associations Between Peripheral Blood Gene Expression and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease Using an Improved Joint Multi-Task Sparse Canonical Correlation Analysis Algorithm.", "authors": "Wu Q, Ma Z, Wang F", "year": "2025", "journal": "Applied biochemistry and biotechnology", "keywords": "Alzheimer's disease, Biomarker discovery, Genetic biomarkers, Multi-task sparse canonical correlation analysis, Peripheral blood", "chunk": "AD diagnostic model, which exhibited strong potential for non-invasive AD diagnosis, with significant implications for clinical practice. The code and example data of the proposed algorithm have been made publicly available on GitHub ( https://github.com/Zoe491/Improved-MTSCCA1 ).", "source": "PubMed"}, {"chunk_id": "36913908_0", "pmid": "36913908", "title": "Automatic segmentation of the choroid plexuses: Method and validation in controls and patients with multiple sclerosis.", "authors": "Yazdan-Panah A, Schmidt-Mengin M, Ricigliano VAG et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Choroid plexus, Deep learning, Multiple sclerosis, Radiologically isolated syndrome, Segmentation", "chunk": "Choroid Plexuses (ChP) are structures located in the ventricles that produce the cerebrospinal fluid (CSF) in the central nervous system. They are also a key component of the blood-CSF barrier. Recent studies have described clinically relevant ChP volumetric changes in several neurological diseases including Alzheimer's, Parkinson's disease, and multiple sclerosis (MS). Therefore, a reliable and automated tool for ChP segmentation on images derived from magnetic resonance imaging (MRI) is a crucial need for large studies attempting to elucidate their role in neurological disorders. Here, we propose a novel automatic method for ChP segmentation in large imaging datasets. The approach is based on a 2-step 3D U-Net to keep preprocessing steps to a minimum for ease of use and to lower memory requirements. The models are trained and validated on a first research cohort including people with MS and healthy subjects. A second validation is also performed on a cohort of", "source": "PubMed"}, {"chunk_id": "36913908_1", "pmid": "36913908", "title": "Automatic segmentation of the choroid plexuses: Method and validation in controls and patients with multiple sclerosis.", "authors": "Yazdan-Panah A, Schmidt-Mengin M, Ricigliano VAG et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Choroid plexus, Deep learning, Multiple sclerosis, Radiologically isolated syndrome, Segmentation", "chunk": "memory requirements. The models are trained and validated on a first research cohort including people with MS and healthy subjects. A second validation is also performed on a cohort of pre-symptomatic MS patients having acquired MRIs in routine clinical practice. Our method reaches an average Dice coefficient of 0.72 \u00b1 0.01 with the ground truth and a volume correlation of 0.86 on the first cohort while outperforming FreeSurfer and FastSurfer-based ChP segmentations. On the dataset originating from clinical practice, the method reaches a Dice coefficient of 0.67 \u00b1 0.01 (being close to the inter-rater agreement of 0.64 \u00b1 0.02) and a volume correlation of 0.84. These results demonstrate that this is a suitable and robust method for the segmentation of the ChP both on research and clinical datasets.", "source": "PubMed"}, {"chunk_id": "36913908_2", "pmid": "36913908", "title": "Automatic segmentation of the choroid plexuses: Method and validation in controls and patients with multiple sclerosis.", "authors": "Yazdan-Panah A, Schmidt-Mengin M, Ricigliano VAG et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Choroid plexus, Deep learning, Multiple sclerosis, Radiologically isolated syndrome, Segmentation", "chunk": "the ChP both on research and clinical datasets.", "source": "PubMed"}, {"chunk_id": "41241266_0", "pmid": "41241266", "title": "Next-generation neurotherapeutics: mechanistic insights on monoclonal antibodies in Alzheimer's disease.", "authors": "Sharma A, Singh TG", "year": "2026", "journal": "Brain research", "keywords": "Alzheimer\u2019s disease (AD), Amyloid beta (A\u03b2), Blood-brain-barrier (BBB), Monoclonal antibodies (mAbs), Neuroinflammation, Tau phosphorylation", "chunk": "Monoclonal antibodies (mAbs) for Alzheimer's disease (AD) present a fundamental translational challenge, as demonstrated by amyloid-beta (A\u03b2)-targeting mAbs that successfully employed Fragment crystallizable gamma receptor (Fc\u03b3R)/Immunoreceptor tyrosine-based activation motif (ITAM)-mediated microglial phagocytosis yet achieved only modest cognitive improvements while introducing significant Amyloid-related imaging abnormalities (ARIA) risk, thereby highlighting inherent single-therapy limitations. Building on these findings, tau-directed antibodies show preclinical promise by targeting pathological seeding and propagation, but face translational challenges including limited extracellular accessibility and variable efficacy across disease stages, necessitating expansion beyond single-target approaches. Consequently, the translational field is advancing toward innovative multi-mechanistic strategies, including synaptic restoration through anti-PrP and neurotrophic receptor agonists that provide functional benefits independent of plaque reduction, neuroinflammation modulation via anti-CD33 and complement inhibitors requiring careful patient selection due to variable outcomes, and emerging anti-TREM2 and anti-APOE4 mAbs enabling precision medicine tailored to individual genetic profiles. Importantly, comparative studies also reveal that combination therapies-especially dual", "source": "PubMed"}, {"chunk_id": "41241266_1", "pmid": "41241266", "title": "Next-generation neurotherapeutics: mechanistic insights on monoclonal antibodies in Alzheimer's disease.", "authors": "Sharma A, Singh TG", "year": "2026", "journal": "Brain research", "keywords": "Alzheimer\u2019s disease (AD), Amyloid beta (A\u03b2), Blood-brain-barrier (BBB), Monoclonal antibodies (mAbs), Neuroinflammation, Tau phosphorylation", "chunk": "careful patient selection due to variable outcomes, and emerging anti-TREM2 and anti-APOE4 mAbs enabling precision medicine tailored to individual genetic profiles. Importantly, comparative studies also reveal that combination therapies-especially dual A\u03b2/tau targeting-demonstrate superior synergistic effectiveness, driving next-generation engineering advances including Fc modifications that reduce ARIA risk, nanobodies/single-chain variable fragments (scFvs) with enhanced blood-brain barrier (BBB) penetration, cell-penetrating formats for intracellular tau access, and pH-sensitive glycoengineering for optimized tissue-specific binding. Ultimately, successful clinical translation depends on integrating biomarker-guided patient selection, optimized dosing strategies, and disease-stage-appropriate timing, with future progress anticipated through bispecific/multispecific antibodies targeting complementary pathways alongside personalized biomarker approaches, collectively providing realistic potential for achieving genuine neuroprotection and meaningful disease modification beyond symptomatic treatment in AD patients.", "source": "PubMed"}, {"chunk_id": "37389302_0", "pmid": "37389302", "title": "Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease.", "authors": "Liu KY, Villain N, Ayton S et al.", "year": "2023", "journal": "Brain communications", "keywords": "Alzheimer, MCI, amyloid immunotherapy, dementia, disease-modifying", "chunk": "The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer's disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a", "source": "PubMed"}, {"chunk_id": "37389302_1", "pmid": "37389302", "title": "Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease.", "authors": "Liu KY, Villain N, Ayton S et al.", "year": "2023", "journal": "Brain communications", "keywords": "Alzheimer, MCI, amyloid immunotherapy, dementia, disease-modifying", "chunk": "These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer's disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer's disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer's disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based", "source": "PubMed"}, {"chunk_id": "37389302_2", "pmid": "37389302", "title": "Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease.", "authors": "Liu KY, Villain N, Ayton S et al.", "year": "2023", "journal": "Brain communications", "keywords": "Alzheimer, MCI, amyloid immunotherapy, dementia, disease-modifying", "chunk": "and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.", "source": "PubMed"}, {"chunk_id": "37828595_0", "pmid": "37828595", "title": "Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts.", "authors": "Bernick C, Shan G, Ritter A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Biomarkers, Chronic traumatic encephalopathy, Neurodegeneration, Traumatic brain injury", "chunk": "It is unknown if fluid biomarkers reflective of brain pathologies are useful in detecting and following a neurodegenerative process in individuals exposed to repetitive head impacts. This study explores the relationship between blood biomarkers and longitudinal change in cognitive function and regional brain volumes in a cohort of professional fighters. Participants are drawn from a convenience sample of active and retired professional boxers and Mixed Martial Arts fighters and a control group with no prior exposure to head impacts. 3 T MRI brain imaging, plasma samples, and computerized cognitive testing were obtained at baseline and, for a subset, annually. MRI regional volumes were extracted, along with plasma levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), p-tau231, and N-terminal tau (NTA). Statistical analyses were performed to assess the relationship between plasma levels and regional brain volumes and cognitive performance at baseline and longitudinally. One hundred forty active boxers", "source": "PubMed"}, {"chunk_id": "37828595_1", "pmid": "37828595", "title": "Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts.", "authors": "Bernick C, Shan G, Ritter A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Biomarkers, Chronic traumatic encephalopathy, Neurodegeneration, Traumatic brain injury", "chunk": "N-terminal tau (NTA). Statistical analyses were performed to assess the relationship between plasma levels and regional brain volumes and cognitive performance at baseline and longitudinally. One hundred forty active boxers (mean age: 31 with standard deviation (SD) of 8), 211 active MMA (mean age of 30 with SD of 5), 69 retired boxers (mean age 49 with SD of 9), and 52 control participants (mean age 36 with SD of 12) were included in the analyses. Baseline GFAP levels were highest in the retired boxers (retired boxers v. active MMA: p = 0.0191), whereas active boxers had higher levels of NfL (active boxers v. MMA: p = 0.047). GFAP showed an increase longitudinally in retired boxers that was associated with decreasing volumes of multiple cortical and subcortical structures (e.g., hippocampus: B = - 1.25, 95% CI, - 1.65 to - 0.85) and increase in lateral ventricle size (B = 1.75,", "source": "PubMed"}, {"chunk_id": "37828595_2", "pmid": "37828595", "title": "Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts.", "authors": "Bernick C, Shan G, Ritter A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Biomarkers, Chronic traumatic encephalopathy, Neurodegeneration, Traumatic brain injury", "chunk": "decreasing volumes of multiple cortical and subcortical structures (e.g., hippocampus: B = - 1.25, 95% CI, - 1.65 to - 0.85) and increase in lateral ventricle size (B = 1.75, 95% CI, 1.46 to 2.04). Furthermore, performance on cognitive domains including memory, processing speed, psychomotor speed, and reaction time declined over time with increasing GFAP (e.g., processing speed: B = - 0.04, 95% CI, - 0.07 to - 0.02; reaction time: B = 0.52, 95% CI, 0.28 to 0.76). Among active fighters, increasing levels of GFAP were correlated with lower thalamic (B = - 1.42, 95% CI, - 2.34 to -0.49) and corpus callosum volumes, along with worsening scores on psychomotor speed (B = 0.14, 95% CI, 0.01 to 0.27). Longitudinal plasma GFAP levels may have a role in identifying individuals exposed to repetitive head impacts who are at risk of showing progressive regional atrophy and cognitive decline.", "source": "PubMed"}, {"chunk_id": "37828595_3", "pmid": "37828595", "title": "Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts.", "authors": "Bernick C, Shan G, Ritter A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Biomarkers, Chronic traumatic encephalopathy, Neurodegeneration, Traumatic brain injury", "chunk": "Longitudinal plasma GFAP levels may have a role in identifying individuals exposed to repetitive head impacts who are at risk of showing progressive regional atrophy and cognitive decline.", "source": "PubMed"}, {"chunk_id": "40522516_0", "pmid": "40522516", "title": "Human placental extract rescues hippocampal damage associated with cognitive impairment in diabetic male rats through antioxidative, anti-inflammatory, and neuromodulatory activities.", "authors": "Matar S, Gomaa RA, El Wakil A et al.", "year": "2025", "journal": "Metabolic brain disease", "keywords": "Hippocampus, Natural therapeutic products, Neuroinflammation, Neurotransmitters, Oxidative stress, Type 2 diabetes mellitus", "chunk": "Memory and cognitive impairment have emerged as significant comorbidities associated with diabetes, yet effective treatment remains elusive. Various studies have shown that human placental extract (HPE) is rich in bioactive molecules that exhibit anti-inflammatory, antioxidant, anti-apoptotic, and immunomodulatory properties. However, the impact of HPE on memory and cognitive decline is not well understood. This study aimed to investigate the therapeutic effects of HPE on memory and cognitive dysfunction induced by streptozotocin (STZ) in rats, while also exploring the underlying mechanisms. To induce type 2 diabetes mellitus (T2DM), rats were first fed a high-fat diet for two weeks, followed by a single intraperitoneal injection of STZ (40 mg/kg body weight) and subsequently treated with HPE (20 mg/kg body weight per day) for 14 days. The results of our behavioral tests demonstrated that HPE significantly enhanced learning, memory, and cognitive function in rats subjected to STZ administration. Specifically, HPE increased the discrimination", "source": "PubMed"}, {"chunk_id": "40522516_1", "pmid": "40522516", "title": "Human placental extract rescues hippocampal damage associated with cognitive impairment in diabetic male rats through antioxidative, anti-inflammatory, and neuromodulatory activities.", "authors": "Matar S, Gomaa RA, El Wakil A et al.", "year": "2025", "journal": "Metabolic brain disease", "keywords": "Hippocampus, Natural therapeutic products, Neuroinflammation, Neurotransmitters, Oxidative stress, Type 2 diabetes mellitus", "chunk": "for 14 days. The results of our behavioral tests demonstrated that HPE significantly enhanced learning, memory, and cognitive function in rats subjected to STZ administration. Specifically, HPE increased the discrimination index in the novel object recognition test from a negative value in STZ rats to a positive value in treated rats and improved spontaneous alternation in the T-maze from 41.25 \u00b1 8.25% to 74.50 \u00b1 8.50%. Additionally, HPE notably improved serum levels of insulin, glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and lipid profiles compared to untreated diabetic rats. It also modulated oxidative stress markers, antioxidants, as well as pro-inflammatory cytokines and neurochemicals levels in hippocampal tissue, underscoring its antioxidant and anti-inflammatory properties. Notably, HPE treatment improved the neurological morphology of the hippocampus and reduced DNA damage. The percentage of tailed cells dropped from 25.67 \u00b1 0.33 in diabetic rats to 13.67 \u00b1 0.88 with HPE treatment. In", "source": "PubMed"}, {"chunk_id": "40522516_2", "pmid": "40522516", "title": "Human placental extract rescues hippocampal damage associated with cognitive impairment in diabetic male rats through antioxidative, anti-inflammatory, and neuromodulatory activities.", "authors": "Matar S, Gomaa RA, El Wakil A et al.", "year": "2025", "journal": "Metabolic brain disease", "keywords": "Hippocampus, Natural therapeutic products, Neuroinflammation, Neurotransmitters, Oxidative stress, Type 2 diabetes mellitus", "chunk": "neurological morphology of the hippocampus and reduced DNA damage. The percentage of tailed cells dropped from 25.67 \u00b1 0.33 in diabetic rats to 13.67 \u00b1 0.88 with HPE treatment. In summary, HPE exhibits neuroprotective effects and could serve as a promising therapeutic strategy for addressing neurodegenerative symptoms associated with T2DM in a rat model.", "source": "PubMed"}, {"chunk_id": "40480904_0", "pmid": "40480904", "title": "Restoring glucose metabolism in Alzheimer's disease by targeting integrated stress response.", "authors": "Sun H, Guo S, Jin H et al.", "year": "2025", "journal": "Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics", "keywords": "Alzheimer's disease, Glucose hypometabolism, Glucose transporters, ISRIB, Integrated stress response", "chunk": "Cerebral glucose hypometabolism has been consistently associated with Alzheimer's disease (AD). With extensive efforts to eliminate AD pathologies, including the removal of amyloid-\u03b2 \u200b(A\u03b2) plaques and hyperphosphorylated Tau, strategies aimed at restoring glucose metabolism in the brain regions most affected by AD are believed to have significant clinical implications. In this study, we demonstrated that glucose hypometabolism preceded neuronal death in triple-transgenic AD (3xTg-AD) mice, likely attributable to reduced expression of glucose transporter type 1 (GLUT1) or glucose transporter type 3 (GLUT3). Furthermore, we observed aberrant activation of the integrated stress response (ISR) pathway in AD models, with A\u03b2 and Tau phosphorylation contributing to the activation of the ISR and subsequent reduction in GLUT1/3 expression. Inhibiting ISR activation by utilizing the ISR inhibitor ISRIB can effectively restore GLUT1/3 expression in both in vitro and in vivo models. Importantly, ISRIB treatment improved cognitive function and brain glucose metabolism in 3xTg-AD mice.", "source": "PubMed"}, {"chunk_id": "40480904_1", "pmid": "40480904", "title": "Restoring glucose metabolism in Alzheimer's disease by targeting integrated stress response.", "authors": "Sun H, Guo S, Jin H et al.", "year": "2025", "journal": "Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics", "keywords": "Alzheimer's disease, Glucose hypometabolism, Glucose transporters, ISRIB, Integrated stress response", "chunk": "the ISR inhibitor ISRIB can effectively restore GLUT1/3 expression in both in vitro and in vivo models. Importantly, ISRIB treatment improved cognitive function and brain glucose metabolism in 3xTg-AD mice. Our findings suggest that targeting the ISR pathway to restore GLUTs expression may be a potential therapeutic strategy for AD.", "source": "PubMed"}, {"chunk_id": "20351074_0", "pmid": "20351074", "title": "Caregiving, metabolic syndrome indicators, and 1-year decline in walking speed: results of Caregiver-SOF.", "authors": "Fredman L, Doros G, Cauley JA et al.", "year": "2010", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "None", "chunk": "Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers. The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term ((3)4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index (3)30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews. Walking speed declined for the total sample (adjusted mean = -0.005 m/second, +/-0.16) over an average of 1.04 years (+/-0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk", "source": "PubMed"}, {"chunk_id": "20351074_1", "pmid": "20351074", "title": "Caregiving, metabolic syndrome indicators, and 1-year decline in walking speed: results of Caregiver-SOF.", "authors": "Fredman L, Doros G, Cauley JA et al.", "year": "2010", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "None", "chunk": "Walking speed declined for the total sample (adjusted mean = -0.005 m/second, +/-0.16) over an average of 1.04 years (+/-0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3-4 metabolic indicators (-0.10 m/second and -0.155 m/second, respectively). Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline.", "source": "PubMed"}, {"chunk_id": "20351074_2", "pmid": "20351074", "title": "Caregiving, metabolic syndrome indicators, and 1-year decline in walking speed: results of Caregiver-SOF.", "authors": "Fredman L, Doros G, Cauley JA et al.", "year": "2010", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "None", "chunk": "suggesting these caregiver subgroups may have increased risk of health decline.", "source": "PubMed"}, {"chunk_id": "41000752_0", "pmid": "41000752", "title": "Distribution of big tau isoforms in the human central and peripheral nervous system.", "authors": "Koppisetti RK, Barth\u00e9lemy NR, Horie K et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, CNS, MAPT, PNS, cerebrospinal fluid, mass spectrometry, proteomics, tau isoforms", "chunk": "To characterize the distribution of \"big tau,\" a longer tau isoform expressed in the peripheral nervous system (PNS) and select central nervous system (CNS) regions, and to examine its relationship with aging and neurodegeneration. We performed mass spectrometric sequencing of big tau sequence and mapped its distribution across the human nervous system. Postmortem samples included brains from Alzheimer's disease (AD), disease controls, and amyotrophic lateral sclerosis (ALS); spinal cord from young controls, disease controls and ALS; and peripheral nerves. Big and small tau levels were also quantified in the cerebrospinal fluid (CSF) from young normal controls, amyloid positive and amyloid negative participants. Human 'big tau' results from the insertion of 355 amino acids in the tau protein, encoded by the exon 4a-long and not exon 4a-short. Alternative splicing of exons 2, 3, and 10 generates multiple big tau isoforms, expanding the known human tau repertoire. Total tau concentration is ~", "source": "PubMed"}, {"chunk_id": "41000752_1", "pmid": "41000752", "title": "Distribution of big tau isoforms in the human central and peripheral nervous system.", "authors": "Koppisetti RK, Barth\u00e9lemy NR, Horie K et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, CNS, MAPT, PNS, cerebrospinal fluid, mass spectrometry, proteomics, tau isoforms", "chunk": "exon 4a-long and not exon 4a-short. Alternative splicing of exons 2, 3, and 10 generates multiple big tau isoforms, expanding the known human tau repertoire. Total tau concentration is ~ 1000-fold higher in the brain than in PNS, where big tau rises sharply along a central-to-peripheral gradient, comprising ~ 50 % of total tau in peripheral nerves compared to only ~ 1 % in brain. CSF big tau levels remain unaltered with CSF A\u03b2 abnormalities in AD, unlike the small tau isoform, which increases significantly with concomitant A\u03b2 and cognitive abnormalities. Big tau exhibits a distinct distribution in the human nervous system, decoupled from the changes associated with brain-derived small tau in AD. These findings open opportunities for developing specific blood-based biomarkers to differentiate CNS versus PNS disorders.", "source": "PubMed"}, {"chunk_id": "41000752_2", "pmid": "41000752", "title": "Distribution of big tau isoforms in the human central and peripheral nervous system.", "authors": "Koppisetti RK, Barth\u00e9lemy NR, Horie K et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, CNS, MAPT, PNS, cerebrospinal fluid, mass spectrometry, proteomics, tau isoforms", "chunk": "blood-based biomarkers to differentiate CNS versus PNS disorders.", "source": "PubMed"}, {"chunk_id": "38160359_0", "pmid": "38160359", "title": "Type 2 Diabetes Moderates the Association Between Amyloid and 1-Year Change in Everyday Functioning in Older Veterans.", "authors": "Alshaheri Durazo A, Weigand AJ, Bangen KJ et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Veterans, amyloid PET, everyday functioning, type 2 diabetes", "chunk": "Type 2 diabetes mellitus (T2DM) affects \u223c25% of Veterans, a prevalence rate double that of the general population. T2DM is associated with greater dementia risk and has been shown to exacerbate the impact of Alzheimer's disease (AD) risk factors on declines in daily functioning; however, there are few studies that investigate these patterns in older Veterans. This study sought to determine whether T2DM moderates the association between amyloid-\u03b2 (A\u03b2) positron emission tomography (PET) and 1-year change in everyday functioning in older Veterans. One-hundred-ninety-eight predominately male Vietnam-Era Veterans without dementia from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) with (n = 74) and without (n = 124) T2DM completed A\u03b2 PET imaging and everyday functioning measures, including the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and Everyday Cognition (ECog). Linear mixed effects models tested the moderating role of T2DM on the association between A\u03b2 PET and 1-year change in everyday functioning.", "source": "PubMed"}, {"chunk_id": "38160359_1", "pmid": "38160359", "title": "Type 2 Diabetes Moderates the Association Between Amyloid and 1-Year Change in Everyday Functioning in Older Veterans.", "authors": "Alshaheri Durazo A, Weigand AJ, Bangen KJ et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Veterans, amyloid PET, everyday functioning, type 2 diabetes", "chunk": "Rating-Sum of Boxes (CDR-SB) and Everyday Cognition (ECog). Linear mixed effects models tested the moderating role of T2DM on the association between A\u03b2 PET and 1-year change in everyday functioning. The 3-way T2DM\u00d7A\u03b2 PET\u00d7time interaction was significant for CDR-SB (p < 0.001) as well as the Memory (p = 0.007) and Language (p = 0.011) subscales from the ECog. Greater amyloid burden was associated with greater increases in functional difficulties, but only in Veterans with T2DM. Higher A\u03b2 was only associated with declines in everyday functioning over 1 year in Veterans with T2DM. Given that people with T2DM are more likely to have co-occurring cerebrovascular disease, the combination of multiple neuropathologies may result in faster declines. Future studies should examine how diabetes duration, severity, and medications impact these associations.", "source": "PubMed"}, {"chunk_id": "38160359_2", "pmid": "38160359", "title": "Type 2 Diabetes Moderates the Association Between Amyloid and 1-Year Change in Everyday Functioning in Older Veterans.", "authors": "Alshaheri Durazo A, Weigand AJ, Bangen KJ et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Veterans, amyloid PET, everyday functioning, type 2 diabetes", "chunk": "how diabetes duration, severity, and medications impact these associations.", "source": "PubMed"}, {"chunk_id": "36802420_0", "pmid": "36802420", "title": "Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets.", "authors": "Billot B, Magdamo C, Cheng Y et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "clinical brain MRI, deep learning, domain-agnostic, segmentation", "chunk": "Every year, millions of brain MRI scans are acquired in hospitals, which is a figure considerably larger than the size of any research dataset. Therefore, the ability to analyze such scans could transform neuroimaging research. Yet, their potential remains untapped since no automated algorithm is robust enough to cope with the high variability in clinical acquisitions (MR contrasts, resolutions, orientations, artifacts, and subject populations). Here, we present <i>SynthSeg</i><sup>+</sup>, an AI segmentation suite that enables robust analysis of heterogeneous clinical datasets. In addition to whole-brain segmentation, <i>SynthSeg</i><sup>+</sup> also performs cortical parcellation, intracranial volume estimation, and automated detection of faulty segmentations (mainly caused by scans of very low quality). We demonstrate <i>SynthSeg</i><sup>+</sup> in seven experiments, including an aging study on 14,000 scans, where it accurately replicates atrophy patterns observed on data of much higher quality. <i>SynthSeg</i><sup>+</sup> is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry.", "source": "PubMed"}, {"chunk_id": "36802420_1", "pmid": "36802420", "title": "Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets.", "authors": "Billot B, Magdamo C, Cheng Y et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "clinical brain MRI, deep learning, domain-agnostic, segmentation", "chunk": "where it accurately replicates atrophy patterns observed on data of much higher quality. <i>SynthSeg</i><sup>+</sup> is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry.", "source": "PubMed"}, {"chunk_id": "40826256_0", "pmid": "40826256", "title": "Twenty years of therapeutic development in tauopathy mouse models: a scoping review.", "authors": "Langness VF, Simmons DA, McHugh TLM et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease (AD), MAPT mouse models, frontotemporal lobar degeneration (FTLD), scoping review, synapse, tauopathy, therapeutic strategies, treatment", "chunk": "Tauopathies are neurodegenerative diseases characterized by pathological tau protein inclusions and dementia. Tauopathy mouse models with MAPT mutations replicate tau-related pathologies and are widely used for therapeutic research. This scoping review examines 409 treatment evaluations in MAPT mouse models. We identify trends in therapeutic strategies and frequently used mouse models, treatment routes, and endpoints. We also document treatment effects and when treatment is initiated relative to tau pathology emergence. Many treatments produced positive effects in multiple MAPT mouse models across many endpoints but showed limited success in clinical trials. Potential barriers to mouse-to-human translation include differences between mouse and human studies in the timing of treatment initiation relative to tau pathology onset, predominant testing of a limited number of endpoints, lack of translatable treatment response biomarkers, and the limited ability of individual mouse models to represent the diversity of tauopathies. Addressing these obstacles could improve mouse-to-human translation for tauopathy therapeutics.", "source": "PubMed"}, {"chunk_id": "40826256_1", "pmid": "40826256", "title": "Twenty years of therapeutic development in tauopathy mouse models: a scoping review.", "authors": "Langness VF, Simmons DA, McHugh TLM et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease (AD), MAPT mouse models, frontotemporal lobar degeneration (FTLD), scoping review, synapse, tauopathy, therapeutic strategies, treatment", "chunk": "lack of translatable treatment response biomarkers, and the limited ability of individual mouse models to represent the diversity of tauopathies. Addressing these obstacles could improve mouse-to-human translation for tauopathy therapeutics. HIGHLIGHTS: Two decades of therapeutic research in tauopathy mouse models were reviewed. Treatments often began before or at tau pathology onset in tauopathy mouse models. Key endpoints (e.g., cognition and synaptic degeneration) were underassessed. Well-characterized preclinical treatments often had limited success in humans. Single-sex mouse studies and a lack of biomarkers hinder clinical translation.", "source": "PubMed"}, {"chunk_id": "41278633_0", "pmid": "41278633", "title": "Bridging Language Markers and Pathology: Correlations Between Digital Speech Measures and Surrogate CSF Biomarkers in Alzheimer's Disease.", "authors": "Pang Y, Chen L, Dodge HH et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, Cerebrospinal fluid biomarkers, Digital biomarkers, Mild cognitive impairment, Natural language processing", "chunk": "Digital language markers show promise in detecting early cognitive impairment related to Alzheimer's disease (AD), yet their relationship with cerebrospinal fluid (CSF) biomarkers of AD pathology remains unclear mainly due to the lack of data with both CSF and language markers. This study aims to build links between digital language markers and fluid biomarkers through surrogate CSF biomarkers. Using NACC clinical data as anchor variables, language makers in the I-CONECT study were linked to NACC CSF data. Surrogate CSF biomarkers were created for I-CONECT subjects using machine learning models from common NACC clinical variables. Correlations assessed associations between CSF and language markers. Lower predicted amyloid-\u03b2 correlated significantly with reduced syntactic complexity and shorter speech responses. Higher predicted total tau and phosphorylated tau correlated with reduced syntactic complexity. This study demonstrates novel links between language markers and fluid biomarkers, highlighting conversational language as a potential accessible, non-invasive approach for early detection", "source": "PubMed"}, {"chunk_id": "41278633_1", "pmid": "41278633", "title": "Bridging Language Markers and Pathology: Correlations Between Digital Speech Measures and Surrogate CSF Biomarkers in Alzheimer's Disease.", "authors": "Pang Y, Chen L, Dodge HH et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, Cerebrospinal fluid biomarkers, Digital biomarkers, Mild cognitive impairment, Natural language processing", "chunk": "phosphorylated tau correlated with reduced syntactic complexity. This study demonstrates novel links between language markers and fluid biomarkers, highlighting conversational language as a potential accessible, non-invasive approach for early detection and monitoring of Alzheimer's pathology.", "source": "PubMed"}, {"chunk_id": "40789853_0", "pmid": "40789853", "title": "AI-driven fusion of multimodal data for Alzheimer's disease biomarker assessment.", "authors": "Jasodanand VH, Kowshik SS, Puducheri S et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "Alzheimer's disease (AD) diagnosis hinges on detecting amyloid beta (A\u03b2) plaques and neurofibrillary tau (\u03c4) tangles, typically assessed using PET imaging. While accurate, these modalities are expensive and not widely accessible, limiting their utility in routine clinical practice. Here, we present a multimodal computational framework that integrates data from seven distinct cohorts comprising 12, 185 participants to estimate individual PET profiles using more readily available neurological assessments. Our approach achieved an AUROC of 0.79 and 0.84 in classifying A\u03b2 and \u03c4 status, respectively. Predicted PET status was consistent with various biomarker profiles and postmortem pathology, and model-identified regional brain volumes aligned with known spatial patterns of tau deposition. This approach can support scalable pre-screening of candidates for anti-amyloid therapies and clinical trials targeting A\u03b2 and \u03c4, offering a practical alternative to direct PET imaging.", "source": "PubMed"}, {"chunk_id": "40789853_1", "pmid": "40789853", "title": "AI-driven fusion of multimodal data for Alzheimer's disease biomarker assessment.", "authors": "Jasodanand VH, Kowshik SS, Puducheri S et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "clinical trials targeting A\u03b2 and \u03c4, offering a practical alternative to direct PET imaging.", "source": "PubMed"}, {"chunk_id": "40964139_0", "pmid": "40964139", "title": "An Update of the Treatment Landscape for Alzheimer's Disease: From Symptomatic Treatments to the Emergence of Amyloid-Targeting Therapies.", "authors": "Kovacik A, Vandergriff K, Jarrett B et al.", "year": "2025", "journal": "Sage open aging", "keywords": "Alzheimer\u2019s disease, amyloid-related imaging abnormalities, donanemab, lecanemab, treatment landscape", "chunk": "Several approved Alzheimer's disease (AD) treatments help manage its associated cognitive symptoms (e.g., donepezil and memantine) or non-cognitive symptoms. However, disease-modifying AD therapies have recently emerged. These treatments aim to slow disease progression by targeting the pathology associated with progressive neurodegeneration. Specifically, two amyloid-targeting therapies (ATTs) are currently approved and available for use in the United States: the monoclonal antibodies donanemab (Kisunla\u2122) and lecanemab (Leqembi<sup>\u00ae</sup>). Both treatments can slow disease progression and cognitive and functional decline in patients with mild cognitive impairment/mild dementia due to AD, but they are associated with class-based safety concerns, notably amyloid-related imaging abnormalities (ARIA). Because advanced practice providers (APPs) such as physician assistants and advanced practice nurses are key to AD patient care, they should be familiar with the biological continuum of AD and with ATTs and understand how to monitor and manage patients receiving these treatments. Therefore, this review aims to educate APPs about", "source": "PubMed"}, {"chunk_id": "40964139_1", "pmid": "40964139", "title": "An Update of the Treatment Landscape for Alzheimer's Disease: From Symptomatic Treatments to the Emergence of Amyloid-Targeting Therapies.", "authors": "Kovacik A, Vandergriff K, Jarrett B et al.", "year": "2025", "journal": "Sage open aging", "keywords": "Alzheimer\u2019s disease, amyloid-related imaging abnormalities, donanemab, lecanemab, treatment landscape", "chunk": "be familiar with the biological continuum of AD and with ATTs and understand how to monitor and manage patients receiving these treatments. Therefore, this review aims to educate APPs about these new therapies. Specifically, it summarizes the approved indications and dosing for donanemab and lecanemab, as well as key clinical evidence of efficacy and safety. It also outlines practical considerations around the monitoring and management of patients treated with ATTs, including recommendations about treatment duration, adverse reaction management, and patient counseling.", "source": "PubMed"}, {"chunk_id": "38468308_0", "pmid": "38468308", "title": "APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward A\u03b2, through P2RY12.", "authors": "Sepulveda J, Kim JY, Binder J et al.", "year": "2024", "journal": "Molecular neurodegeneration", "keywords": "Ex-vivo imaging, APOE4, Aging, Alzheimer\u2019s disease, Microglia, P2RY12", "chunk": "Microglia are highly dynamic cells that play a critical role in tissue homeostasis through the surveillance of brain parenchyma and response to cues associated with damage. Aging and APOE4 genotype are the strongest risk factors for Alzheimer's disease (AD), but how they affect microglial dynamics remains unclear. Using ex vivo confocal microscopy, we analyzed microglial dynamic behaviors in the entorhinal cortex (EC) and hippocampus CA1 of 6-, 12-, and 21-month-old mice APOE3 or APOE4 knock-in mice expressing GFP under the CX3CR1 promoter. To study microglia surveillance, we imaged microglia baseline motility for 20 min and measured the extension and retraction of processes. We found that APOE4 microglia exhibited significantly less brain surveillance (27%) compared to APOE3 microglia in 6-month-old mice; aging exacerbated this deficit. To measure microglia response to damage, we imaged process motility in response to ATP, an injury-associated signal, for 30 min. We found APOE4 microglia extended their", "source": "PubMed"}, {"chunk_id": "38468308_1", "pmid": "38468308", "title": "APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward A\u03b2, through P2RY12.", "authors": "Sepulveda J, Kim JY, Binder J et al.", "year": "2024", "journal": "Molecular neurodegeneration", "keywords": "Ex-vivo imaging, APOE4, Aging, Alzheimer\u2019s disease, Microglia, P2RY12", "chunk": "aging exacerbated this deficit. To measure microglia response to damage, we imaged process motility in response to ATP, an injury-associated signal, for 30 min. We found APOE4 microglia extended their processes significantly slower (0.9 \u00b5m/min, p < 0.005) than APOE3 microglia (1.1 \u03bcm/min) in 6-month-old animals. APOE-associated alterations in microglia motility were observed in 12- and 21-month-old animals, and this effect was exacerbated with aging in APOE4 microglia. We measured protein and mRNA levels of P2RY12, a core microglial receptor required for process movement in response to damage. We found that APOE4 microglia express significantly less P2RY12 receptors compared to APOE3 microglia despite no changes in P2RY12 transcripts. To examine if the effect of APOE4 on the microglial response to ATP also applied to amyloid \u03b2 (A\u03b2), we infused locally Hi-Lyte Fluor 555-labeled A\u03b2 in acute brain slices of 6-month-old mice and imaged microglia movement for 2 h. APOE4 microglia", "source": "PubMed"}, {"chunk_id": "38468308_2", "pmid": "38468308", "title": "APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward A\u03b2, through P2RY12.", "authors": "Sepulveda J, Kim JY, Binder J et al.", "year": "2024", "journal": "Molecular neurodegeneration", "keywords": "Ex-vivo imaging, APOE4, Aging, Alzheimer\u2019s disease, Microglia, P2RY12", "chunk": "ATP also applied to amyloid \u03b2 (A\u03b2), we infused locally Hi-Lyte Fluor 555-labeled A\u03b2 in acute brain slices of 6-month-old mice and imaged microglia movement for 2 h. APOE4 microglia showed a significantly slower (p < 0.0001) process movement toward the A\u03b2, and less A\u03b2 coverage at early time points after A\u03b2 injection. To test whether P2RY12 is involved in process movement in response to A\u03b2, we treated acute brain slices with a P2RY12 antagonist before A\u03b2 injection; microglial processes no longer migrated towards A\u03b2. These results provide mechanistic insights into the impact of APOE4 genotype and aging in dynamic microglial behaviors prior to gross A\u03b2 pathology and could help explain how APOE4 brains are more susceptible to AD pathogenesis.", "source": "PubMed"}, {"chunk_id": "41320758_0", "pmid": "41320758", "title": "Beyond Parkinson's Disease: A Narrative Review of Neuromelanin MRI in Neurodegenerative Diseases.", "authors": "Burade A, Lakhani DA, Dagher R et al.", "year": "2025", "journal": "Journal of neuroimaging : official journal of the American Society of Neuroimaging", "keywords": "Alzheimer's disease, Parkinson's disease, atypical parkinsonism, neurodegenerative diseases, neuromelanin MRI", "chunk": "Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is an emerging noninvasive biomarker of catecholaminergic neurons. It assesses neuromelanin-rich regions such as the substantia nigra pars compacta (SNc) and locus coeruleus (LC). Although initially developed for Parkinson's disease (PD), evidence supports broader utility. This narrative review highlights the diagnostic and prognostic applications of NM-MRI in PD, atypical parkinsonian syndromes, spinocerebellar ataxias (SCA), and Alzheimer's disease (AD), while evaluating methodological heterogeneity, diagnostic performance across diseases, and directions for clinical implementation. In PD, reduced SNc volume and contrast-to-noise ratio (CNR) correlate with motor symptom severity. Early-stage PD shows lateral SNc signal attenuation progressing ventromedially with disease advancement. NM-MRI sensitivity and specificity range from 70%-92% to 65%-89%, respectively, with higher accuracy at 7T. In progressive supranuclear palsy (PSP), SNc degeneration is more pronounced medially; LC contrast ratio (CR) is elevated compared to PD. In multiple system atrophy (MSA), LC signal attenuation is particularly marked in the", "source": "PubMed"}, {"chunk_id": "41320758_1", "pmid": "41320758", "title": "Beyond Parkinson's Disease: A Narrative Review of Neuromelanin MRI in Neurodegenerative Diseases.", "authors": "Burade A, Lakhani DA, Dagher R et al.", "year": "2025", "journal": "Journal of neuroimaging : official journal of the American Society of Neuroimaging", "keywords": "Alzheimer's disease, Parkinson's disease, atypical parkinsonism, neurodegenerative diseases, neuromelanin MRI", "chunk": "palsy (PSP), SNc degeneration is more pronounced medially; LC contrast ratio (CR) is elevated compared to PD. In multiple system atrophy (MSA), LC signal attenuation is particularly marked in the parkinsonian subtype (MSA-P). NM-MRI findings in SCA (notably SCA2 and SCA7) vary by genotype; AD is characterized by reduction in the middle and caudal segments of LC, reflecting early tau pathology. NM-MRI LC signal reduction variably correlates with cognitive scores and Braak staging, suggesting potential as a preclinical biomarker. NM-MRI holds promise for early diagnosis and monitoring of neurodegenerative diseases. While its role in PD is well established, emerging data in PSP, MSA, SCA, and AD suggest wider applicability. Standardization, multimodal imaging integration, and machine learning are critical for clinical translation.", "source": "PubMed"}, {"chunk_id": "41320758_2", "pmid": "41320758", "title": "Beyond Parkinson's Disease: A Narrative Review of Neuromelanin MRI in Neurodegenerative Diseases.", "authors": "Burade A, Lakhani DA, Dagher R et al.", "year": "2025", "journal": "Journal of neuroimaging : official journal of the American Society of Neuroimaging", "keywords": "Alzheimer's disease, Parkinson's disease, atypical parkinsonism, neurodegenerative diseases, neuromelanin MRI", "chunk": "translation.", "source": "PubMed"}, {"chunk_id": "41314753_0", "pmid": "41314753", "title": "Global case studies and collaborative frameworks.", "authors": "Jana MK, Mukherjee P, Chatla SS et al.", "year": "2025", "journal": "Progress in brain research", "keywords": "Artificial intelligence, Biomarker discovery, Data sharing, Global collaboration, Neurodegenerative diseases, Precision medicine", "chunk": "As neurodegenerative diseases (NDDs) like Alzheimer's and Parkinson's continue to rise globally, the need for cross-border collaboration in research and treatment has never been more critical. This chapter explores prominent global case studies and collaborative frameworks that exemplify how united efforts are transforming the landscape of NDD research. By pooling expertise, data, and resources, international initiatives are accelerating discoveries in early diagnosis, biomarker identification, and personalized therapies. Highlighting landmark consortia such as the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n.d.), Parkinson's Progression Markers Initiative (PPMI), and emerging multi-omics collaborations, the chapter illustrates how these partnerships overcome the complexity and heterogeneity of NDDs. It delves into technological innovations like artificial intelligence, blockchain data sharing, and real-time patient monitoring, which empower researchers and clinicians to connect genetic, environmental, and lifestyle factors in a holistic manner. Ethical considerations and data privacy frameworks are underscored as pivotal to fostering trust among participants and bridging disparities", "source": "PubMed"}, {"chunk_id": "41314753_1", "pmid": "41314753", "title": "Global case studies and collaborative frameworks.", "authors": "Jana MK, Mukherjee P, Chatla SS et al.", "year": "2025", "journal": "Progress in brain research", "keywords": "Artificial intelligence, Biomarker discovery, Data sharing, Global collaboration, Neurodegenerative diseases, Precision medicine", "chunk": "clinicians to connect genetic, environmental, and lifestyle factors in a holistic manner. Ethical considerations and data privacy frameworks are underscored as pivotal to fostering trust among participants and bridging disparities between regions with varying access to precision medicine. The chapter also sheds light on successful public-private partnerships and patient-focused global networks that place individuals at the center of discovery and care. Challenges such as standardizing protocols across countries, navigating legal frameworks, and securing sustainable funding are discussed alongside future directions for expanding collaborative reach. Ultimately, this comprehensive overview conveys the unprecedented promise held by global cooperation in combating neurodegenerative diseases-offering hope for improved diagnostics, innovative treatments, and enhanced quality of life for millions worldwide.", "source": "PubMed"}, {"chunk_id": "39638080_0", "pmid": "39638080", "title": "Exploring the impact of APOE \u025b4 on functional connectivity in Alzheimer's disease across cognitive impairment levels.", "authors": "Dong K, Liang W, Hou T et al.", "year": "2025", "journal": "NeuroImage", "keywords": "APOE \u025b4, Alzheimer, Functional connectivity, Graph neural network, fMRI", "chunk": "The apolipoprotein E (APOE) \u025b4 allele is a recognized genetic risk factor for Alzheimer's Disease (AD). Studies have shown that APOE \u025b4 mediates the modulation of intrinsic functional brain networks in cognitively normal individuals and significantly disrupts the whole-brain topological structure in AD patients. However, how APOE \u025b4 regulates brain functional connectivity (FC) and consequently affects the levels of cognitive impairment in AD patients remains unknown. In this study, we systematically analyzed functional magnetic resonance imaging (fMRI) data from two distinct cohorts: an In-house dataset includes 59 AD patients (73.37 \u00b1 6.42 years), and the ADNI dataset includes 117 AD patients (74.91 \u00b1 7.91 years). Experimental comparisons were conducted by grouping AD patients based on both APOE \u025b4 status and cognitive impairment levels of AD. Network-Based Statistic (NBS) method and the Graph Neural Network Explainer (GNN-Explainer) were combined to identify significant FC changes across different comparisons. Importantly, the GNN-Explainer method", "source": "PubMed"}, {"chunk_id": "39638080_1", "pmid": "39638080", "title": "Exploring the impact of APOE \u025b4 on functional connectivity in Alzheimer's disease across cognitive impairment levels.", "authors": "Dong K, Liang W, Hou T et al.", "year": "2025", "journal": "NeuroImage", "keywords": "APOE \u025b4, Alzheimer, Functional connectivity, Graph neural network, fMRI", "chunk": "cognitive impairment levels of AD. Network-Based Statistic (NBS) method and the Graph Neural Network Explainer (GNN-Explainer) were combined to identify significant FC changes across different comparisons. Importantly, the GNN-Explainer method was introduced as an enhancement over the NBS method to better model complex high-order nonlinear characteristics for discovering FC features that significantly contribute to classification tasks. The results showed that APOE \u025b4 primarily influenced temporal lobe FCs, while it influenced different cognitive impairment levels of AD by adjusting prefrontal-parietal FCs. These findings were validated by p-values < 0.05 from NBS method, and 5-fold cross-validation along with ablation studies from the GNN-Explainer method. In conclusion, our findings provide new insights into the role of APOE \u025b4 in altering FC dynamics during the progression of AD, highlighting potential targets for early intervention.", "source": "PubMed"}, {"chunk_id": "39638080_2", "pmid": "39638080", "title": "Exploring the impact of APOE \u025b4 on functional connectivity in Alzheimer's disease across cognitive impairment levels.", "authors": "Dong K, Liang W, Hou T et al.", "year": "2025", "journal": "NeuroImage", "keywords": "APOE \u025b4, Alzheimer, Functional connectivity, Graph neural network, fMRI", "chunk": "the progression of AD, highlighting potential targets for early intervention.", "source": "PubMed"}, {"chunk_id": "40528282_0", "pmid": "40528282", "title": "The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery.", "authors": "Videla L, Benejam B, Barroeta I et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, DABNI, Down syndrome, autosomal dominant Alzheimer's disease, biomarkers, clinical trials, cognition, health", "chunk": "Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) that offers crucial insights into AD pathogenesis. The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) is a population-based multimodal biomarker cohort studying AD's natural history and clinical trials in DS. DABNI included 1135 participants (mean age 42.82, 46.3% female). At baseline, 673 participants were cognitively stable, 113 had prodromal AD, 239 had AD dementia, and 110 were uncertain due to non-AD conditions. Over 10 years, > 10000 clinical visits were conducted; follow-up showed that progression to symptomatic AD before age 40 was rare, but rates increased after age 50 (> 50% within 5 years). Neuropsychological and biomarker assessments demonstrated excellent diagnostic performance and a predictable sequence of changes, similar to autosomal dominant AD. DABNI participates in AD clinical trials and produced approximately 100 publications. The 10-year DABNI study provided critical insights into DS-associated AD (DSAD) and serves as a key", "source": "PubMed"}, {"chunk_id": "40528282_1", "pmid": "40528282", "title": "The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery.", "authors": "Videla L, Benejam B, Barroeta I et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, DABNI, Down syndrome, autosomal dominant Alzheimer's disease, biomarkers, clinical trials, cognition, health", "chunk": "autosomal dominant AD. DABNI participates in AD clinical trials and produced approximately 100 publications. The 10-year DABNI study provided critical insights into DS-associated AD (DSAD) and serves as a key platform for DS clinical trials. HIGHLIGHTS: Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) is a population-based multimodal cohort studying Alzheimer's disease in Down syndrome. Over 10 years, 1135 participants contributed to more than 10000 clinical visits and extensive biomarker studies. DABNI findings have transformed the understanding of Alzheimer's disease in Down syndrome, reinforcing its classification as a genetic form of the disease. The cohort integrates clinical care and research, enhancing early detection and patient management. DABNI supports clinical trials and has produced over 100 publications advancing Down syndrome-related Alzheimer's research.", "source": "PubMed"}, {"chunk_id": "41407852_0", "pmid": "41407852", "title": "Prevalence of Alzheimer's disease pathology in the community.", "authors": "Aarsland D, Sunde AL, Tovar-Rios DA et al.", "year": "2026", "journal": "Nature", "keywords": "None", "chunk": "The prevalence of Alzheimer's disease neuropathological changes (ADNCs), the leading cause of cognitive impairment, remains uncertain. Recent blood-based biomarkers enable scalable assessment of ADNCs<sup>1</sup>. Here we measured phosphorylated tau at threonine 217 in 11,486 plasma samples from a Norwegian population-based cohort of individuals over 57 years of age as a surrogate marker for ADNCs. The estimated prevalence of ADNCs increased with age, from less than 8% in people 58-69.9 years of age to 65.2% in those over 90 years of age. Among participants aged 70 years or older, 10% had preclinical Alzheimer's disease, 10.4% had prodromal Alzheimer's disease and 9.8% had Alzheimer's disease dementia. Furthermore, among those 70 years of age or older, ADNCs were present in 60% of people with dementia, in 32.6% of those with mild cognitive impairment and in 23.5% of the cognitively unimpaired group. Our findings suggest a higher prevalence of Alzheimer's disease dementia in older", "source": "PubMed"}, {"chunk_id": "41407852_1", "pmid": "41407852", "title": "Prevalence of Alzheimer's disease pathology in the community.", "authors": "Aarsland D, Sunde AL, Tovar-Rios DA et al.", "year": "2026", "journal": "Nature", "keywords": "None", "chunk": "with dementia, in 32.6% of those with mild cognitive impairment and in 23.5% of the cognitively unimpaired group. Our findings suggest a higher prevalence of Alzheimer's disease dementia in older individuals and a lower prevalence of preclinical Alzheimer's disease in younger groups than previously estimated<sup>2</sup>.", "source": "PubMed"}, {"chunk_id": "41445192_0", "pmid": "41445192", "title": "First-in-class SAM-competitive G9a inhibitor FLAV-27 as a disease-modifying therapy for Alzheimer disease.", "authors": "Bellver-Sanchis A, Valle-Garcia D, Barbaraci C et al.", "year": "2025", "journal": "Molecular therapy : the journal of the American Society of Gene Therapy", "keywords": "Alzheimer's disease, G9a, SAM-competitive inhibitor, SMOC1, cognition, epigenetics, neuroprotection, translational", "chunk": "Alzheimer's disease (AD) is characterized by a progressive cognitive decline involving a multifactorial pathophysiology, including epigenetic dysregulation. Here, we report the discovery and preclinical validation of FLAV-27, a first-in-class, S-adenosyl-l-methionine (SAM)-competitive, brain-penetrant, and selective inhibitor of the histone methyltransferase G9a. Unlike prior G9a/GLP inhibitors, FLAV-27 exhibits subnanomolar potency, over 30-fold selectivity, and robust central nervous system bioavailability. Structural studies confirm a unique SAM-binding mode that confers superior specificity and avoids off-target effects. FLAV-27 reduces amyloid beta (A\u03b2) and p-tau aggregation and restores neuritic complexity in vitro. In Caenorhabditis elegans, it improves mobility, lifespan, and mitochondrial respiration. In mouse models of both late-onset AD (SAMP8) and early-onset AD (5xFAD), FLAV-27 rescues memory performance, social behavior, and synaptic structure. Multi-omics analyses reveal a global reprogramming of H3K9me2/H3K18me-mediated repression, reduced ferroptosis vulnerabilities, and normalization of AD-linked biomarkers, including SMOC1, H3K9me2, and p-Tau181, in the plasma and brain. Our findings position FLAV-27 as a", "source": "PubMed"}, {"chunk_id": "41445192_1", "pmid": "41445192", "title": "First-in-class SAM-competitive G9a inhibitor FLAV-27 as a disease-modifying therapy for Alzheimer disease.", "authors": "Bellver-Sanchis A, Valle-Garcia D, Barbaraci C et al.", "year": "2025", "journal": "Molecular therapy : the journal of the American Society of Gene Therapy", "keywords": "Alzheimer's disease, G9a, SAM-competitive inhibitor, SMOC1, cognition, epigenetics, neuroprotection, translational", "chunk": "a global reprogramming of H3K9me2/H3K18me-mediated repression, reduced ferroptosis vulnerabilities, and normalization of AD-linked biomarkers, including SMOC1, H3K9me2, and p-Tau181, in the plasma and brain. Our findings position FLAV-27 as a promising epigenetic therapeutic with disease-modifying potential and translational biomarker alignment in AD.", "source": "PubMed"}, {"chunk_id": "41377395_0", "pmid": "41377395", "title": "Multi-omics integration reveals hypoxia-driven mechanisms in vascular dementia: a machine learning and single-cell sequencing approach.", "authors": "Xuan Z, Yang H, Duan L et al.", "year": "2025", "journal": "Annals of medicine and surgery (2012)", "keywords": "bioinformatics, hypoxia, machine learning, single-cell sequencing analysis, vascular dementia", "chunk": "This study aimed to identify and analyze hub hypoxia-related genes in vascular dementia (VaD) and explore their roles in metabolism, immune response, and cell differentiation, thereby offering potential biomarkers and therapeutic targets. Using VaD datasets (GSE122063, GSE282111) from Gene Expression Omnibus (including high-throughput and single-cell sequencing data), analyses were performed via R preprocessing, WGCNA, and machine learning. A chronic cerebral hypoperfusion model was established by two-vessel occlusion (2VO), with verification through immunohistochemistry. WGCNA identified 7451 module genes and 36 overlapping hypoxia-related genes; machine learning pinpointed <i>DUSP1, MAFF</i>, and <i>TGFBI</i> as hub genes. ssGSEA linked these genes to metabolic pathways (e.g., cysteine-methionine metabolism, glycolysis) and cell death pathways (apoptosis, pyroptosis). They associated with immune cells like M2 macrophages and neutrophils. Single-cell analysis showed their expression in astrocytes, endothelial cells, and microglia, with endothelial cells exhibiting a hypoxic phenotype via pathways like PI3K-Akt. Immunohistochemistry revealed increased <i>DUSP1</i>, <i>MAFF</i> and <i>TGFBI</i> in models.", "source": "PubMed"}, {"chunk_id": "41377395_1", "pmid": "41377395", "title": "Multi-omics integration reveals hypoxia-driven mechanisms in vascular dementia: a machine learning and single-cell sequencing approach.", "authors": "Xuan Z, Yang H, Duan L et al.", "year": "2025", "journal": "Annals of medicine and surgery (2012)", "keywords": "bioinformatics, hypoxia, machine learning, single-cell sequencing analysis, vascular dementia", "chunk": "analysis showed their expression in astrocytes, endothelial cells, and microglia, with endothelial cells exhibiting a hypoxic phenotype via pathways like PI3K-Akt. Immunohistochemistry revealed increased <i>DUSP1</i>, <i>MAFF</i> and <i>TGFBI</i> in models. This study identified <i>DUSP1, MAFF</i>, and <i>TGFBI</i> as key players in hypoxia-related mechanisms in VaD, highlighting their pivotal roles in metabolic regulation, cell death pathways, immune microenvironment modulation, and neural differentiation. These insights enhance our understanding of VaD pathogenesis and suggest that these genes may be potential therapeutic targets for cognitive impairment.", "source": "PubMed"}, {"chunk_id": "36692249_0", "pmid": "36692249", "title": "Independent effect of cardiometabolic syndromes and depression on dementia in Parkinson's disease: A 12-year longitudinal follow-up study of a nationwide cohort.", "authors": "Kang SH, Choi Y, Chung SJ et al.", "year": "2023", "journal": "European journal of neurology", "keywords": "Parkinson's disease dementia, cardiometabolic syndromes, depression, incidence rate", "chunk": "We aimed to investigate the incidence rate of Parkinson's disease dementia (PDD) according to age and disease duration by sex. Furthermore, we explored the effect of each cardiometabolic syndrome and depression on the incidence of PDD. Using data from the Korean National Health Insurance Service, 79,622 patients with de novo Parkinson's disease (PD) aged \u226540 years between January 2002 and December 2010 were followed to December 2019. We analyzed the incidence of PDD according to age at PD diagnosis and disease duration. To determine cardiometabolic syndromes and depression that affected PDD, we used Fine and Gray competing regression after controlling for age and sex. During the 12.5-year follow-up period, the incidence of PDD increased with age at PD diagnosis (0.81-45.31 per 1000 person-years among those aged 40-44 and over 80 years, respectively) and longer disease duration (22.68 per 1000 person-years in 1-2 years to 34.16 per 1000 person-years in 15-16", "source": "PubMed"}, {"chunk_id": "36692249_1", "pmid": "36692249", "title": "Independent effect of cardiometabolic syndromes and depression on dementia in Parkinson's disease: A 12-year longitudinal follow-up study of a nationwide cohort.", "authors": "Kang SH, Choi Y, Chung SJ et al.", "year": "2023", "journal": "European journal of neurology", "keywords": "Parkinson's disease dementia, cardiometabolic syndromes, depression, incidence rate", "chunk": "per 1000 person-years among those aged 40-44 and over 80 years, respectively) and longer disease duration (22.68 per 1000 person-years in 1-2 years to 34.16 per 1000 person-years in 15-16 years). Hypertension (subdistribution hazard ratio [SHR] = 1.11; 95% confidence interval [CI] 1.07-1.16), diabetes (SHR = 1.09; 95% CI 1.05-1.14), dyslipidemia (SHR = 1.15; 95% CI 1.11-1.20), and depression (SHR = 1.36; 95% CI 1.30-1.41) independently increased the risk for PDD. Our findings provide insights into cardiometabolic syndromes as modifiable risk factors for incident PDD. Furthermore, our results will help in designing public health policies with respect to controlling cardiometabolic syndromes and depression to prevent incident PDD in patients with PD.", "source": "PubMed"}, {"chunk_id": "41391056_0", "pmid": "41391056", "title": "Retinal nerve fiber layer thinning in multiple sclerosis: clinical implications, cognitive associations, and effects of disease-modifying therapies.", "authors": "Tan H, Yin Z, Zhangbao J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Disease-modifying therapy, Multiple sclerosis, Optical coherence tomography, Paramagnetic rim lesions, Retinal nerve fiber layer, Symbol digit modalities test", "chunk": "Peripapillary retinal nerve fiber layer (pRNFL) thinning, detected by optical coherence tomography (OCT), is an early marker of neuroaxonal injury in multiple sclerosis (MS). Its prognostic value for long-term outcomes and responsiveness to disease-modifying therapies (DMTs) remains insufficiently explored, particularly in Asian populations. This study aimed to identify clinical and radiological correlates of pRNFL thickness, evaluate whether pRNFL thinning predicts disability and cognitive decline, and examine the effects of DMTs on retinal neurodegeneration in Chinese MS patients. We analyzed 354 Chinese MS patients who underwent OCT, neurological assessments, and brain MRI. Multivariate regression identified determinants of baseline pRNFL thickness. Among 159 patients with follow-up longer than 12 months, logistic regression was used to assess whether baseline pRNFL thickness and annualized pRNFL thinning predicted disability or cognitive decline. Linear mixed-effects models were applied to evaluate longitudinal effects of DMT classes on pRNFL thinning. Median pRNFL thickness was 105.0 \u03bcm (range: 65.0-136.5).", "source": "PubMed"}, {"chunk_id": "41391056_1", "pmid": "41391056", "title": "Retinal nerve fiber layer thinning in multiple sclerosis: clinical implications, cognitive associations, and effects of disease-modifying therapies.", "authors": "Tan H, Yin Z, Zhangbao J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Disease-modifying therapy, Multiple sclerosis, Optical coherence tomography, Paramagnetic rim lesions, Retinal nerve fiber layer, Symbol digit modalities test", "chunk": "pRNFL thinning predicted disability or cognitive decline. Linear mixed-effects models were applied to evaluate longitudinal effects of DMT classes on pRNFL thinning. Median pRNFL thickness was 105.0 \u03bcm (range: 65.0-136.5). Thinner pRNFL was associated with longer disease duration (p < 0.001), optic neuritis (p = 0.019), longer 9-Hole Peg Test completion time (p = 0.025), and increased paramagnetic rim lesions (p = 0.002). Baseline pRNFL thickness did not predict EDSS progression or Symbol Digit Modalities Test (SDMT) decline. In contrast, faster annualized pRNFL thinning predicted SDMT worsening (OR = 1.29, p = 0.018), alongside fewer years of education (OR = 0.84, p = 0.033) and a secondary progressive MS phenotype (OR = 7.67, p = 0.006). No significant differences in pRNFL preservation were observed among DMT classes. pRNFL thinning reflects disease severity and predicts cognitive decline in MS. Current DMTs provide limited retinal neuroprotection. These findings support the routine OCT-derived", "source": "PubMed"}, {"chunk_id": "41391056_2", "pmid": "41391056", "title": "Retinal nerve fiber layer thinning in multiple sclerosis: clinical implications, cognitive associations, and effects of disease-modifying therapies.", "authors": "Tan H, Yin Z, Zhangbao J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Disease-modifying therapy, Multiple sclerosis, Optical coherence tomography, Paramagnetic rim lesions, Retinal nerve fiber layer, Symbol digit modalities test", "chunk": "pRNFL preservation were observed among DMT classes. pRNFL thinning reflects disease severity and predicts cognitive decline in MS. Current DMTs provide limited retinal neuroprotection. These findings support the routine OCT-derived pRNFL monitoring and highlight the need for neuroprotective strategies in MS.", "source": "PubMed"}, {"chunk_id": "41289563_0", "pmid": "41289563", "title": "Evaluating the Effectiveness of Immersive Virtual Reality Rehabilitation Games With Enhanced Visual Training for Hand Motor Function Improvement Using Electromyography: Randomized Controlled Trial.", "authors": "Amin F, Waris A, Khan MJ et al.", "year": "2025", "journal": "JMIR serious games", "keywords": "electromyography, games, hand motor function, virtual reality, visual feedback", "chunk": "Hand motor dysfunction greatly reduces the performance of stroke survivors. This affects their ability to perform hand motor tasks effectively. Patients receive slow interventions due to interventional limitations in stroke rehabilitation, which can pose challenges for sustaining enduring improvements. We developed immersive virtual reality (VR) games that used an innovative approach to cognitive engagement within visual training feedback for achieving long-lasting improvements. This study aimed to evaluate the effectiveness of fully immersive VR-based hand games compared with conventional physical therapy and to assess the correlations between electromyographic data and clinical outcome measures for improving hand motor function in patients with subacute stroke. A randomized controlled study was conducted among 52 patients with subacute stroke who met the inclusion criteria. These patients were equally allocated to an experimental group (n=26) and a control group (n=26). The experimental group received both fully immersive VR-based hand game therapy and conventional physical therapy, whereas", "source": "PubMed"}, {"chunk_id": "41289563_1", "pmid": "41289563", "title": "Evaluating the Effectiveness of Immersive Virtual Reality Rehabilitation Games With Enhanced Visual Training for Hand Motor Function Improvement Using Electromyography: Randomized Controlled Trial.", "authors": "Amin F, Waris A, Khan MJ et al.", "year": "2025", "journal": "JMIR serious games", "keywords": "electromyography, games, hand motor function, virtual reality, visual feedback", "chunk": "patients were equally allocated to an experimental group (n=26) and a control group (n=26). The experimental group received both fully immersive VR-based hand game therapy and conventional physical therapy, whereas the control group received only conventional physical therapy. Owing to the nature of the intervention, the study was unblinded, and both therapists and patients were aware of the intervention. Both groups participated in intervention sessions 4 days a week for 6 weeks (24 sessions in total). Moreover, both groups underwent 2 weeks of follow-up. Clinical outcome measures, including the Fugl-Meyer Assessment-upper extremity (FMA-UE), Action Research Arm Test (ARAT), and Box and Block Test (BBT), were used to assess motor recovery and functional performance. The minimal clinically meaningful difference (MCID) was used for comparing clinical outcome measures to examine clinically meaningful improvements. Furthermore, the correlation between electromyography data and clinical outcome measures, and the weekly progression in movement performance were evaluated", "source": "PubMed"}, {"chunk_id": "41289563_2", "pmid": "41289563", "title": "Evaluating the Effectiveness of Immersive Virtual Reality Rehabilitation Games With Enhanced Visual Training for Hand Motor Function Improvement Using Electromyography: Randomized Controlled Trial.", "authors": "Amin F, Waris A, Khan MJ et al.", "year": "2025", "journal": "JMIR serious games", "keywords": "electromyography, games, hand motor function, virtual reality, visual feedback", "chunk": "used for comparing clinical outcome measures to examine clinically meaningful improvements. Furthermore, the correlation between electromyography data and clinical outcome measures, and the weekly progression in movement performance were evaluated to identify improvements in hand motor function. After the intervention, there were significant differences in FMA-UE, ARAT, and BBT scores (all P<.001) between the experimental and control groups. The MCID findings illustrated that the experimental group had clinically meaningful improvements compared to the control group. There were significant correlations between electromyography signal features and clinical outcome measures (all P<.05) in both groups after rehabilitation. However, the experimental group exhibited strong positive correlations, while the control group exhibited moderate positive correlations. At follow-up, the mean movement accuracy was notably higher in the experimental group than in the control group (mean 83.59%, SD 1.1% vs mean 79.20%, SD 0.8%), indicating that hand motor function was effectively sustained through the use of the", "source": "PubMed"}, {"chunk_id": "41289563_3", "pmid": "41289563", "title": "Evaluating the Effectiveness of Immersive Virtual Reality Rehabilitation Games With Enhanced Visual Training for Hand Motor Function Improvement Using Electromyography: Randomized Controlled Trial.", "authors": "Amin F, Waris A, Khan MJ et al.", "year": "2025", "journal": "JMIR serious games", "keywords": "electromyography, games, hand motor function, virtual reality, visual feedback", "chunk": "the experimental group than in the control group (mean 83.59%, SD 1.1% vs mean 79.20%, SD 0.8%), indicating that hand motor function was effectively sustained through the use of the VR-based intervention in the experimental group. The findings of this study revealed that VR-based hand games with enhanced visual training feedback substantially improved hand motor function in patients with subacute stroke.", "source": "PubMed"}, {"chunk_id": "34671708_0", "pmid": "34671708", "title": "Brain cerebrospinal fluid flow.", "authors": "Kelley DH", "year": "2021", "journal": "Physical review fluids", "keywords": "None", "chunk": "Cerebrospinal fluid flows around and into the brain, driven by intricate mechanisms, with profound implications for human health. According to the glymphatic hypothesis, in physiological conditions, cerebrospinal fluid flows primarily during sleep and serves to remove metabolic wastes like the amyloid-beta and tau proteins whose accumulation is believed to cause Alzheimer's disease. This paper reviews one research team's recent <i>in vivo</i> experiments and theoretical studies to better understand the fluid dynamics of brain cerebrospinal fluid flow. Driving mechanisms are considered, particularly arterial pulsation. Flow correlates closely with artery motion and changes when artery motion is manipulated. Though there are discrepancies between <i>in vivo</i> observations and predictions from simulations and theoretical studies of the mechanism, realistic boundary conditions bring closer agreement. Vessel shapes are considered, and have elongation that minimizes their hydraulic resistance, perhaps through evolutionary optimization. The pathological condition of stroke is considered. Much tissue damage after stroke is caused", "source": "PubMed"}, {"chunk_id": "34671708_1", "pmid": "34671708", "title": "Brain cerebrospinal fluid flow.", "authors": "Kelley DH", "year": "2021", "journal": "Physical review fluids", "keywords": "None", "chunk": "Vessel shapes are considered, and have elongation that minimizes their hydraulic resistance, perhaps through evolutionary optimization. The pathological condition of stroke is considered. Much tissue damage after stroke is caused by swelling, and there is now strong evidence that early swelling is caused not by fluid from blood, as is commonly thought, but by cerebrospinal fluid. Finally, drug delivery is considered, and demonstrations show the glymphatic system could quickly deliver drugs across the blood-brain barrier. The paper closes with a discussion of future opportunities in the fast-changing field of brain fluid dynamics.", "source": "PubMed"}, {"chunk_id": "32810755_0", "pmid": "32810755", "title": "Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease.", "authors": "Andersson E, Janelidze S, Lampinen B et al.", "year": "2020", "journal": "Neurobiology of aging", "keywords": "Alzheimer\u2019s disease, Biomarker, Blood, Cerebrospinal fluid, Imaging, Neurofilament light", "chunk": "Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer's disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to A\u03b2 pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of A\u03b2 pathology.", "source": "PubMed"}, {"chunk_id": "32810755_1", "pmid": "32810755", "title": "Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease.", "authors": "Andersson E, Janelidze S, Lampinen B et al.", "year": "2020", "journal": "Neurobiology of aging", "keywords": "Alzheimer\u2019s disease, Biomarker, Blood, Cerebrospinal fluid, Imaging, Neurofilament light", "chunk": "with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of A\u03b2 pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.", "source": "PubMed"}, {"chunk_id": "37884125_0", "pmid": "37884125", "title": "Effect of hypoglycemia on cognitive performance in older patients with diabetes: A meta-analysis.", "authors": "Mu Z, Sun M, Wen L et al.", "year": "2024", "journal": "Annales d'endocrinologie", "keywords": "Cognitive function, Hypoglycemia, Meta-analysis, Type-2 diabetes", "chunk": "The goal of this study was to use meta-analysis to compile information from various studies to investigate the existence and severity of cognitive impairment in elderly diabetes patients who have hypoglycemic episodes. For research studies on the relationship between hypoglycemia and cognitive decline or dementia in persons older than 45 years, we searched the PubMed, EMBASE, Cochrane Library, CNKI, WanFang, CBM and VIP databases for the period 1989 to 2022. We conducted random effects inverse variance on the meta-analysis and used the I<sup>2</sup> statistic to assess heterogeneity. We selected 44 of the 518 studies we retrieved, 7 being appropriate for meta-analysis. Six thousand and forty-five individuals were involved in total. Both types of older diabetic patients with hypoglycemia performed considerably worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized", "source": "PubMed"}, {"chunk_id": "37884125_1", "pmid": "37884125", "title": "Effect of hypoglycemia on cognitive performance in older patients with diabetes: A meta-analysis.", "authors": "Mu Z, Sun M, Wen L et al.", "year": "2024", "journal": "Annales d'endocrinologie", "keywords": "Cognitive function, Hypoglycemia, Meta-analysis, Type-2 diabetes", "chunk": "worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized mean difference, 0.19; 95% CI, 0.29-0.09). Additionally, we found that older type-2 diabetes patients with hypoglycemia had significantly poorer psychomotor function than those without hypoglycemia (standardized mean difference, 0.51; 95% CI, 0.38-0.63).", "source": "PubMed"}, {"chunk_id": "38623574_0", "pmid": "38623574", "title": "Trehalose improves the movement ability of A\u03b2<sub>arc</sub><i>Drosophila</i> by restoring the damaged mitochondria.", "authors": "Li L, Huang Z, Wu M et al.", "year": "2024", "journal": "Translational neuroscience", "keywords": "Alzheimer\u2019s disease, A\u03b2arcDrosophila, mitochondria, movement ability, trehalose", "chunk": "The deposition of A\u03b2<sub>42</sub> has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for A\u03b2<sub>42</sub> toxicity has been progressed slowly. Our aim was to introduce the effect and related mechanism of trehalose on an A\u03b2<sub>arc</sub> (arctic mutant A\u03b2<sub>42</sub>) <i>Drosophila</i> AD model. The human A\u03b2<sub>arc</sub> was expressed in <i>Drosophila</i> to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of A\u03b2<sub>arc</sub>, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function. Trehalose strongly improved the movement ability of A\u03b2<sub>arc</sub> <i>Drosophila</i> in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of A\u03b2<sub>arc</sub> and lactate both in the brain and thorax of", "source": "PubMed"}, {"chunk_id": "38623574_1", "pmid": "38623574", "title": "Trehalose improves the movement ability of A\u03b2<sub>arc</sub><i>Drosophila</i> by restoring the damaged mitochondria.", "authors": "Li L, Huang Z, Wu M et al.", "year": "2024", "journal": "Translational neuroscience", "keywords": "Alzheimer\u2019s disease, A\u03b2arcDrosophila, mitochondria, movement ability, trehalose", "chunk": "of A\u03b2<sub>arc</sub> <i>Drosophila</i> in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of A\u03b2<sub>arc</sub> and lactate both in the brain and thorax of A\u03b2<sub>arc</sub> <i>Drosophila</i>. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in A\u03b2<sub>arc</sub> <i>Drosophila</i>. Trehalose improves movement ability at least partly by reducing the A\u03b2<sub>arc</sub> level and restoring the mitochondrial structure and function in A\u03b2<sub>arc</sub> <i>Drosophila</i>.", "source": "PubMed"}, {"chunk_id": "38341444_0", "pmid": "38341444", "title": "Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-\u03b2 42/40 positivity.", "authors": "Pyun JM, Park YH, Youn YC et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "Various plasma biomarkers for amyloid-\u03b2 (A\u03b2) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma A\u03b242/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as A\u03b2 plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma A\u03b242/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET-/plasma-, PET-/plasma+, PET+/plasma-, PET+/plasma+) using Alzheimer's Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with", "source": "PubMed"}, {"chunk_id": "38341444_1", "pmid": "38341444", "title": "Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-\u03b2 42/40 positivity.", "authors": "Pyun JM, Park YH, Youn YC et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET-/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET-/plasma+ showed intermediate changes between PET-/plasma- and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma- represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma A\u03b242/40 than IA-Elc. IA-Elc showed more plasma A\u03b242/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be", "source": "PubMed"}, {"chunk_id": "38341444_2", "pmid": "38341444", "title": "Characteristics of discordance between amyloid positron emission tomography and plasma amyloid-\u03b2 42/40 positivity.", "authors": "Pyun JM, Park YH, Youn YC et al.", "year": "2024", "journal": "Translational psychiatry", "keywords": "None", "chunk": "A\u03b242/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET-/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.", "source": "PubMed"}, {"chunk_id": "30096758_0", "pmid": "30096758", "title": "Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?", "authors": "Bianchi M, Manco M", "year": "2018", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Pin1, Prolyl isomerases, brain glucose metabolism, neuronal degeneration, neuronal differentiation, type 2 diabetes, type 3 diabetes", "chunk": "Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze the isomerization between the <i>cis</i>/<i>trans</i> Pro conformations. Three subclasses belong to the class: FKBP (FK506 binding protein family), Cyclophilin and Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes such as mitosis, differentiation and metabolism: The enzyme is dysregulated in many diverse pathological conditions, i.e., cancer progression, neurodegenerative (i.e., Alzheimer's diseases, AD) and metabolic disorders (i.e., type 2 diabetes, T2D). Indeed, Pin1 KO mice develop a complex phenotype of premature aging, cognitive impairment in elderly mice and neuronal degeneration resembling that of the AD in humans. In addition, since the molecule modulates glucose homeostasis in the brain and peripherally, Pin1 KO mice are resistant to diet-induced obesity, insulin resistance, peripheral glucose intolerance and diabetic vascular dysfunction.", "source": "PubMed"}, {"chunk_id": "30096758_1", "pmid": "30096758", "title": "Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?", "authors": "Bianchi M, Manco M", "year": "2018", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Pin1, Prolyl isomerases, brain glucose metabolism, neuronal degeneration, neuronal differentiation, type 2 diabetes, type 3 diabetes", "chunk": "In addition, since the molecule modulates glucose homeostasis in the brain and peripherally, Pin1 KO mice are resistant to diet-induced obesity, insulin resistance, peripheral glucose intolerance and diabetic vascular dysfunction. In this review, we revise first critically the role of Pin1 in neuronal development and differentiation and then focus on the in vivo studies that demonstrate its pivotal role in neurodegenerative processes and glucose homeostasis. We discuss evidence that enables us to speculate about the role of Pin1 as molecular link in the pathogenesis of type 3 diabetes i.e., the clinical association of dementia/AD and T2D.", "source": "PubMed"}, {"chunk_id": "40483260_0", "pmid": "40483260", "title": "The patient pathway for mild cognitive impairment due to Alzheimer's disease in Asia: Current practices, barriers, and expert recommendations for optimization.", "authors": "Choi SH, Kim S, Ong PA et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Asia, Disease-modifying treatment, Mild cognitive impairment, Patient journey", "chunk": "The age-standardized prevalence of Alzheimer's disease in Asia has increased rapidly in recent years. Disease-modifying treatments that can slow disease progression are now becoming available for patients with early-stage Alzheimer's disease, including those with mild cognitive impairment. However, challenges in diagnosis and assessment for these patients remain. This study characterized the care pathway for mild cognitive impairment due to Alzheimer's disease in Asia, including barriers to care, and considered the future treatment landscape, with the aim of making recommendations for optimizing the care pathway in readiness for the availability of new disease-modifying treatments. Qualitative study based on semi-structured interviews. Interviews were conducted with physicians in general/tertiary hospitals in Hong Kong, India, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand. Physicians from mainland China and Japan were not included. Physicians managing patients with mild cognitive impairment. Number and/or proportion of participants providing a given response, and numerical estimates provided by", "source": "PubMed"}, {"chunk_id": "40483260_1", "pmid": "40483260", "title": "The patient pathway for mild cognitive impairment due to Alzheimer's disease in Asia: Current practices, barriers, and expert recommendations for optimization.", "authors": "Choi SH, Kim S, Ong PA et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Asia, Disease-modifying treatment, Mild cognitive impairment, Patient journey", "chunk": "Physicians from mainland China and Japan were not included. Physicians managing patients with mild cognitive impairment. Number and/or proportion of participants providing a given response, and numerical estimates provided by interview participants. Forty-four physicians, primarily neurologists (n = 31; 70.5 %), were interviewed. Participants managed a median of 67.5 patients with mild cognitive impairment per month, of whom 24.0-87.5 % had mild cognitive impairment due to Alzheimer's disease. Clinical investigations routinely comprised brief neuropsychological assessments, such as the Mini-Mental State Examination (n = 41), as well as neurological tests (n = 39) and magnetic resonance imaging (n = 40). Except in Korea, comprehensive neuropsychological test batteries and amyloid positron emission tomography were seldom conducted in Asia. Most patients with mild cognitive impairment due to Alzheimer's disease were treated with nootropics and/or acetylcholinesterase inhibitors (Korea, 96 %; all other regions, 69 %), and almost all were recommended a non-pharmacological treatment (Korea,", "source": "PubMed"}, {"chunk_id": "40483260_2", "pmid": "40483260", "title": "The patient pathway for mild cognitive impairment due to Alzheimer's disease in Asia: Current practices, barriers, and expert recommendations for optimization.", "authors": "Choi SH, Kim S, Ong PA et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Asia, Disease-modifying treatment, Mild cognitive impairment, Patient journey", "chunk": "cognitive impairment due to Alzheimer's disease were treated with nootropics and/or acetylcholinesterase inhibitors (Korea, 96 %; all other regions, 69 %), and almost all were recommended a non-pharmacological treatment (Korea, 93 %; all other regions, 100 %). Detection of mild cognitive impairment due to Alzheimer's disease was considered prompt in Korea but suboptimal in other regions (n = 16) owing to low disease awareness among patients. Barriers to assessment and diagnosis included delayed healthcare visits for initial assessment (n = 7), neuroimaging backlogs (n = 6), and insufficient neuropsychology resources (n = 13). Access to amyloid biomarker tests, including amyloid positron emission tomography, cerebrospinal fluid analysis, and blood tests, was limited in regions other than Korea. The survey findings showed that screening and diagnostic processes for mild cognitive impairment due to Alzheimer's disease in Asia require further optimization. Efforts should also be made to educate patients and caregivers, improve the", "source": "PubMed"}, {"chunk_id": "40483260_3", "pmid": "40483260", "title": "The patient pathway for mild cognitive impairment due to Alzheimer's disease in Asia: Current practices, barriers, and expert recommendations for optimization.", "authors": "Choi SH, Kim S, Ong PA et al.", "year": "2025", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Asia, Disease-modifying treatment, Mild cognitive impairment, Patient journey", "chunk": "that screening and diagnostic processes for mild cognitive impairment due to Alzheimer's disease in Asia require further optimization. Efforts should also be made to educate patients and caregivers, improve the diagnostic capabilities of primary and secondary healthcare providers, and reinforce cognitive screening services. The provision and reimbursement of confirmatory tests of amyloid burden should be expanded across the region to facilitate access to innovative disease-modifying therapies.", "source": "PubMed"}, {"chunk_id": "34776443_0", "pmid": "34776443", "title": "Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum.", "authors": "Nihashi T, Sakurai K, Kato T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "18F-THK5351, Alzheimer\u2019s disease, Braak stages, amyloid, positron emission tomography", "chunk": "Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351", "source": "PubMed"}, {"chunk_id": "34776443_1", "pmid": "34776443", "title": "Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer's Disease Continuum.", "authors": "Nihashi T, Sakurai K, Kato T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "18F-THK5351, Alzheimer\u2019s disease, Braak stages, amyloid, positron emission tomography", "chunk": "corresponding to Braak neurofibrillary tangle stage. On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.", "source": "PubMed"}, {"chunk_id": "38170841_0", "pmid": "38170841", "title": "Novel avenues of tau research.", "authors": "Sexton CE, Bitan G, Bowles KR et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "biomarkers, tau, tau-PET, tauopathies, therapeutics", "chunk": "The pace of innovation has accelerated in virtually every area of tau research in just the past few years. In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.", "source": "PubMed"}, {"chunk_id": "34418401_0", "pmid": "34418401", "title": "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.", "authors": "Thijssen EH, La Joie R, Strom A et al.", "year": "2021", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes. In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18-99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites", "source": "PubMed"}, {"chunk_id": "34418401_1", "pmid": "34418401", "title": "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.", "authors": "Thijssen EH, La Joie R, Strom A et al.", "year": "2021", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test. Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217", "source": "PubMed"}, {"chunk_id": "34418401_2", "pmid": "34418401", "title": "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.", "authors": "Thijssen EH, La Joie R, Strom A et al.", "year": "2021", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0\u00b790, p<0\u00b70001). Both p-tau217 and p-tau181 concentrations were increased in people with Alzheimer's disease syndromes (n=75, mean age 65 years [SD 10]) relative to cognitively unimpaired controls (n=118, mean age 61 years [SD 18]; AUC=0\u00b798 [95% CI 0\u00b795-1\u00b700] for p-tau217, AUC=0\u00b797 [0\u00b794-0\u00b799] for p-tau181; p<sub>diff</sub>=0\u00b731) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0\u00b796 [0\u00b792-1\u00b700] for p-tau217, AUC=0\u00b791 [0\u00b782-1\u00b700] for p-tau181; p<sub>diff</sub>=0\u00b722). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0\u00b793 [0\u00b791-0\u00b796] for p-tau217, AUC=0\u00b791 [0\u00b788-0\u00b794] for p-tau181; p<sub>diff</sub>=0\u00b701). P-tau217 was a stronger indicator of amyloid-PET", "source": "PubMed"}, {"chunk_id": "34418401_3", "pmid": "34418401", "title": "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.", "authors": "Thijssen EH, La Joie R, Strom A et al.", "year": "2021", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0\u00b793 [0\u00b791-0\u00b796] for p-tau217, AUC=0\u00b791 [0\u00b788-0\u00b794] for p-tau181; p<sub>diff</sub>=0\u00b701). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0\u00b791 [0\u00b788-0\u00b794]) than was p-tau181 (n=214, AUC=0\u00b789 [0\u00b786-0\u00b793]; p<sub>diff</sub>=0\u00b7049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0\u00b780 vs r=0\u00b772; p<sub>diff</sub><0\u00b70001, n=230). Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology. US National Institutes of Health, State of California Department of", "source": "PubMed"}, {"chunk_id": "34418401_4", "pmid": "34418401", "title": "Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.", "authors": "Thijssen EH, La Joie R, Strom A et al.", "year": "2021", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology. US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association.", "source": "PubMed"}, {"chunk_id": "37369531_0", "pmid": "37369531", "title": "Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes.", "authors": "She R, Al-Sari NH, Mattila IM et al.", "year": "2023", "journal": "BMJ open diabetes research & care", "keywords": "Diabetes complication, Energy metabolism, Hypoglycemia, Type 1 diabetes mellitus", "chunk": "Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes. Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. In total, 68 metabolites were studied.", "source": "PubMed"}, {"chunk_id": "37369531_1", "pmid": "37369531", "title": "Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes.", "authors": "She R, Al-Sari NH, Mattila IM et al.", "year": "2023", "journal": "BMJ open diabetes research & care", "keywords": "Diabetes complication, Energy metabolism, Hypoglycemia, Type 1 diabetes mellitus", "chunk": "and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8\u00d710<sup>-3</sup>) and isoleucine (p=2.2\u00d710<sup>-3</sup>), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days. In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a", "source": "PubMed"}, {"chunk_id": "37369531_2", "pmid": "37369531", "title": "Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes.", "authors": "She R, Al-Sari NH, Mattila IM et al.", "year": "2023", "journal": "BMJ open diabetes research & care", "keywords": "Diabetes complication, Energy metabolism, Hypoglycemia, Type 1 diabetes mellitus", "chunk": "and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations. NCT01337362.", "source": "PubMed"}, {"chunk_id": "41476597_0", "pmid": "41476597", "title": "Sex differences in depression in Parkinson's disease: cognitive dysfunction and female-specific associations.", "authors": "Zhao H, Sun Y, Wang Q et al.", "year": "2025", "journal": "Frontiers in neuroscience", "keywords": "Parkinson\u2019s disease, cognitions, depression, linear mixed model, sex differences", "chunk": "This study used a linear mixed model to explore the relationship between cognitive function and depression in Parkinson's disease (PD) patients. The study data were collected from 450 Parkinson's disease patients who participated in the Parkinson's Disease Progress Marker Project (PPMI) from 2010 to 2024, including 176 women and 274 men. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (Moca), and depression was measured using the Geriatric Depression Scale (GDS). The correlation between cognitive function and depression was determined using a linear mixed model. Anxiety, daily living ability, and autonomic nervous system function are significant factors affecting both men and women. Women experience a stronger impact of anxiety, daily activity limitations, and autonomic nervous system dysfunction on depression. The longer the duration of the illness, the more severe the depression in women. Moreover, cognitive abilities protect against depression only in women. Women exhibit higher individual heterogeneity in baseline", "source": "PubMed"}, {"chunk_id": "41476597_1", "pmid": "41476597", "title": "Sex differences in depression in Parkinson's disease: cognitive dysfunction and female-specific associations.", "authors": "Zhao H, Sun Y, Wang Q et al.", "year": "2025", "journal": "Frontiers in neuroscience", "keywords": "Parkinson\u2019s disease, cognitions, depression, linear mixed model, sex differences", "chunk": "The longer the duration of the illness, the more severe the depression in women. Moreover, cognitive abilities protect against depression only in women. Women exhibit higher individual heterogeneity in baseline depression and greater variability in the rate of change over time, with those who are more depressed showing a more gradual change. In female Parkinson's disease patients, there is a negative correlation between cognitive ability and depression, whereas this correlation is not observed in male patients. This study provides new evidence that sex differences influence the relationship between cognitive ability and depression in Parkinson's disease patients. Future research should consider the role of sex differences in the context of cognitive ability and depression.", "source": "PubMed"}, {"chunk_id": "41304884_0", "pmid": "41304884", "title": "Design, Synthesis and Evaluation of the First 2-Alkynyl(aza)indole <sup>18</sup>F Probe Targeting \u03b1-Synuclein Aggregates.", "authors": "Boiaryna L, Pieri L, Chalon S et al.", "year": "2025", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "PET, Parkinson\u2019s disease, alkynyl(aza)indoles, \u03b1-synuclein", "chunk": "<b>Background/Objectives</b>: The role of \u03b1-synuclein (\u03b1-syn) in the pathogenesis of Parkinson's disease (PD) or neurodegenerative diseases such as Lewy body dementia (LBD) and multiple system atrophy (MSA) is commonly accepted. Through different physiological dysfunctions, abnormal forms of \u03b1-syn are generated. These abnormal aggregates accumulate and alter pre- and postsynaptic transmission, in particular that of dopamine. Thus, the development of a diagnostic biomarker of synucleinopathies remains crucial and challenging. The development of an \u03b1-syn positron emission tomography (PET) radiopharmaceutical may be suitable to early diagnose and stratify patients, follow up disease progression, and evaluate future therapies. <b>Methods</b>: To develop a selective \u03b1-syn PET tracer, we synthesized an original series based on alkynyl(aza)indoles. Fifteen final ligands were synthesized bearing indoles or azaindoles from one side of the alkyne and a substituted phenyl ring for the opposite side of the alkyne. The final ligands were tested to determine Ki and/or Kd toward \u03b1-syn,", "source": "PubMed"}, {"chunk_id": "41304884_1", "pmid": "41304884", "title": "Design, Synthesis and Evaluation of the First 2-Alkynyl(aza)indole <sup>18</sup>F Probe Targeting \u03b1-Synuclein Aggregates.", "authors": "Boiaryna L, Pieri L, Chalon S et al.", "year": "2025", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "PET, Parkinson\u2019s disease, alkynyl(aza)indoles, \u03b1-synuclein", "chunk": "from one side of the alkyne and a substituted phenyl ring for the opposite side of the alkyne. The final ligands were tested to determine Ki and/or Kd toward \u03b1-syn, tau, and A\u03b2. <b>Results</b>: The SAR showed that the indole series exhibited moderate to low affinity for \u03b1-syn and, moreover, lower Ki toward A\u03b2 and tau (i.e., compound <b>39</b>, Ki<sub>(\u03b1syn)</sub> 21.7 nM, Ki<sub>(A\u03b2)</sub> 64.4 nM, Ki<sub>(Tau)</sub> 27.6 nM), highlighting the low potency of these series to afford an \u03b1-syn tracer. The introduction of a nitrogen on the different positions of the phenyl to obtain the corresponding azaindoles resulted for most of the compounds in better affinity for \u03b1-syn and selectivity towards A\u03b2 compared to the indole analogs (i.e., compound <b>43</b>, Ki<sub>(\u03b1syn)</sub> 4.7 nM, Ki<sub>(A\u03b2)</sub> 24.4 nM, and Ki<sub>(Tau)</sub> 4.61 nM). A fluorinated azaindole derivative was prepared with a view to obtaining a <sup>18</sup>F tracer and exhibited the highest affinity for", "source": "PubMed"}, {"chunk_id": "41304884_2", "pmid": "41304884", "title": "Design, Synthesis and Evaluation of the First 2-Alkynyl(aza)indole <sup>18</sup>F Probe Targeting \u03b1-Synuclein Aggregates.", "authors": "Boiaryna L, Pieri L, Chalon S et al.", "year": "2025", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "PET, Parkinson\u2019s disease, alkynyl(aza)indoles, \u03b1-synuclein", "chunk": "Ki<sub>(\u03b1syn)</sub> 4.7 nM, Ki<sub>(A\u03b2)</sub> 24.4 nM, and Ki<sub>(Tau)</sub> 4.61 nM). A fluorinated azaindole derivative was prepared with a view to obtaining a <sup>18</sup>F tracer and exhibited the highest affinity for \u03b1-syn but without selectivity against tau and A\u03b2. The radiosynthesis of [<sup>18</sup>F]<b>45</b> was performed in a two-step procedure starting from the tosylated and protected precursor. [<sup>18</sup>F]<b>45</b> was obtained in 85 \u00b1 5 min with a radiochemical yield of 32 \u00b1 3%. Molar activity, determined from a calibration with stable <b>45</b>, was around 130 GBq/\u00b5mole. The dynamic PET imaging showed that [<sup>18</sup>F]<b>45</b> was able to cross the blood-brain barrier, but non-specific uptake was observed, confirming the in vitro results. <b>Conclusions</b>: Although promising nanomolar affinity for the target, the new tracer showed mainly non-specific in vivo uptake in the rat brain, indicating that further pharmacomodulations on the azaindole series are required.", "source": "PubMed"}, {"chunk_id": "41304884_3", "pmid": "41304884", "title": "Design, Synthesis and Evaluation of the First 2-Alkynyl(aza)indole <sup>18</sup>F Probe Targeting \u03b1-Synuclein Aggregates.", "authors": "Boiaryna L, Pieri L, Chalon S et al.", "year": "2025", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "PET, Parkinson\u2019s disease, alkynyl(aza)indoles, \u03b1-synuclein", "chunk": "mainly non-specific in vivo uptake in the rat brain, indicating that further pharmacomodulations on the azaindole series are required.", "source": "PubMed"}, {"chunk_id": "41235134_0", "pmid": "41235134", "title": "Parkinson Disease <i>SNCA</i> Risk Variants Are Associated With Higher Asymmetric Putamen Dopaminergic Dysfunction.", "authors": "Alhusaini S, Dayanim G, Kandil M et al.", "year": "2025", "journal": "Neurology. Genetics", "keywords": "None", "chunk": "The aim of this study was to investigate the endophenotypic potential of striatal dopamine transporter (DAT) uptake in carriers of Parkinson disease (PD)-associated <i>SNCA</i> genetic risk variants. We analyzed 381 patients with de novo PD from the Parkinson's Progression Markers Initiative (PPMI). The genotype of previously identified PD-related <i>SNCA</i> risk variants was extracted and used to compute an individual PD<i>-</i>specific <i>SNCA</i> genetic risk score (GRS). Striatal DAT uptake was quantified using <sup>123</sup>I-FP-CIT SPECT and assessed at baseline and 24-month follow-up. Mixed models were applied to explore the relationship between striatal <sup>123</sup>I-FP-CIT SPECT specific binding ratios (SBRs) and PD <i>SNCA</i> risk variants. No significant associations were observed between <i>SNCA</i> risk variants and the mean putamen or caudate <sup>123</sup>I-FP-CIT SPECT SBRs. However, a higher <i>SNCA</i> GRS was significantly associated with increased baseline putamen <sup>123</sup>I-FP-CIT SPECT SBR asymmetry index (<i>p</i> < 0.001). This relationship appeared primarily driven by the 3' variant rs356182 and", "source": "PubMed"}, {"chunk_id": "41235134_1", "pmid": "41235134", "title": "Parkinson Disease <i>SNCA</i> Risk Variants Are Associated With Higher Asymmetric Putamen Dopaminergic Dysfunction.", "authors": "Alhusaini S, Dayanim G, Kandil M et al.", "year": "2025", "journal": "Neurology. Genetics", "keywords": "None", "chunk": "a higher <i>SNCA</i> GRS was significantly associated with increased baseline putamen <sup>123</sup>I-FP-CIT SPECT SBR asymmetry index (<i>p</i> < 0.001). This relationship appeared primarily driven by the 3' variant rs356182 and the 5' region variant rs763443 (<i>p</i> < 0.001) and was not observed at 24-month follow-up. Our findings suggest that a more lateralized putaminal dopaminergic degeneration in early PD may represent a viable endophenotype in carriers of <i>SNCA</i> risk variants, emphasizing the relevant role of neuroimaging in PD subtyping and biomarker identification.", "source": "PubMed"}, {"chunk_id": "39577322_0", "pmid": "39577322", "title": "Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders.", "authors": "Eratne D, Kang MJY, Lewis C et al.", "year": "2024", "journal": "Journal of the neurological sciences", "keywords": "Behavioural variant frontotemporal dementia, Biomarkers, Dementia, Diagnosis, Psychiatry", "chunk": "Timely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP. We investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD. Plasma GFAP levels were significantly (all p < 0.001) elevated in bvFTD (n = 22, mean (M) = 273 pg/mL) compared to BPAD (n = 121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/mL).", "source": "PubMed"}, {"chunk_id": "39577322_1", "pmid": "39577322", "title": "Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders.", "authors": "Eratne D, Kang MJY, Lewis C et al.", "year": "2024", "journal": "Journal of the neurological sciences", "keywords": "Behavioural variant frontotemporal dementia, Biomarkers, Dementia, Diagnosis, Psychiatry", "chunk": "121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95 % confidence interval [0.76, 0.95]. The optimal cut-off of 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (p = 0.02863) and combination of GFAP and NfL (p = 0.04726). This study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation", "source": "PubMed"}, {"chunk_id": "39577322_2", "pmid": "39577322", "title": "Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders.", "authors": "Eratne D, Kang MJY, Lewis C et al.", "year": "2024", "journal": "Journal of the neurological sciences", "keywords": "Behavioural variant frontotemporal dementia, Biomarkers, Dementia, Diagnosis, Psychiatry", "chunk": "in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.", "source": "PubMed"}, {"chunk_id": "40976838_0", "pmid": "40976838", "title": "Combining Lumipulse p-tau217 and A\u03b242/40 as confirmatory tests for A\u03b2 positivity prior to disease-modifying therapy.", "authors": "Doecke JD, Chenna A, Lo M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Centiloid, amyloid beta, cognitively unimpaired, plasma biomarker, prediction", "chunk": "For a blood-based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (A\u03b2) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests. In the current study we assessed the ability of phosphorylated tau (p-tau)217 and A\u03b242/40 from the Lumipulse G p-tau217 and \u03b2-amyloid ratio (1-42/1-40) tests, individually and combined, to predict A\u03b2 positron emission tomography status in two sub-cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Testing an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for the p-tau217/A\u03b242 ratio reached 0.961, 93%, 92%, and 93%, respectively. Validation in an intention-to-treat cohort demonstrated similar AUC (0.959), with increased sensitivity (99%), decreased specificity (87%), and increased accuracy (95%). Dual cut-offs generating balanced 95% sensitivity/specificity result in 93% accuracy. Combinations of plasma p-tau217 and A\u03b242 demonstrate recommended performance, confirming the presence of", "source": "PubMed"}, {"chunk_id": "40976838_1", "pmid": "40976838", "title": "Combining Lumipulse p-tau217 and A\u03b242/40 as confirmatory tests for A\u03b2 positivity prior to disease-modifying therapy.", "authors": "Doecke JD, Chenna A, Lo M et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Centiloid, amyloid beta, cognitively unimpaired, plasma biomarker, prediction", "chunk": "decreased specificity (87%), and increased accuracy (95%). Dual cut-offs generating balanced 95% sensitivity/specificity result in 93% accuracy. Combinations of plasma p-tau217 and A\u03b242 demonstrate recommended performance, confirming the presence of A\u03b2 positivity prior to selection for disease-modifying therapies. The phosphorylated tau (p-tau)217/amyloid beta (A\u03b2)42 ratio had high performance to detect A\u03b2 positron emission tomography (PET) status, with > 90% sensitivity, specificity, and accuracy. p-tau217/A\u03b242 ratio dual cut-offs set at 95% sensitivity and specificity found 10% to 15% of participants in the intermediate zone. Cut-offs derived for the intention-to-treat cohort meet confirmatory assay criteria for a disease-modifying therapy and can be used in clinical settings.", "source": "PubMed"}, {"chunk_id": "39318206_0", "pmid": "39318206", "title": "Stem Cells as a Novel Source for Regenerative Medicinal Applications in Alzheimer's Disease: An Update.", "authors": "Pandey K, Srivastava P, Pandey SK et al.", "year": "2025", "journal": "Current molecular medicine", "keywords": "Alzheimer\u2019s disease, clinical trial, dementia, neurodegenerative disease., pathogenesis, stem cells", "chunk": "Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded A\u03b2 and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.S. Food and Drug Administration (FDA) are not precisely efficient and curative. Stem cells possess great potential in aiding AD due to their self-renewal, proliferation, and differentiation properties. Stem cell therapy can aid by replacing the lost neurons, enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even", "source": "PubMed"}, {"chunk_id": "39318206_1", "pmid": "39318206", "title": "Stem Cells as a Novel Source for Regenerative Medicinal Applications in Alzheimer's Disease: An Update.", "authors": "Pandey K, Srivastava P, Pandey SK et al.", "year": "2025", "journal": "Current molecular medicine", "keywords": "Alzheimer\u2019s disease, clinical trial, dementia, neurodegenerative disease., pathogenesis, stem cells", "chunk": "enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even pre-clinical studies have shown rather positive results. Cell replacement therapies are potential curative means to treat AD, and there are a number of undergoing human clinical trials to make Stem Cell therapy accessible for AD patients. In this review, we aim to discuss the AD pathophysiology and varied stem cell types and their application.", "source": "PubMed"}, {"chunk_id": "36634906_0", "pmid": "36634906", "title": "Brain Functional Alterations and Association with Cognition in People with Preclinical Subjective Cognitive Decline and Objective Subtle Cognitive Difficulties.", "authors": "Ren S, Li J, Huang L et al.", "year": "2023", "journal": "Neuroscience", "keywords": "Amyloid deposition, Glucose metabolism, Objective subtle cognitive difficulties, Subjective cognitive decline", "chunk": "Subjective cognitive decline (SCD) and objective subtle cognitive difficulties (Obj-SCD) are considered the initial stages of aberrant cognition prior to mild cognitive impairment (MCI) due to Alzheimer's disease (AD). We aimed to determine the difference of brain function of SCD and Obj-SCD, furthermore, to figure out which one could be the marker of early AD. One hundred and eighty-five participants were enrolled in this study to determine the amyloid pathology and glucose metabolism changes in SCD and Obj-SCD. The association of amyloid deposition and glucose metabolism with cognitive domains were also investigated. Obj-SCD displayed significantly increased amyloid deposition in frontal and temporal lobes compared to SCD and normal cognitive control (NCC). No difference of amyloid deposition between SCD and NCC, and no difference of glucose metabolism among the three groups were observed. Amyloid deposition was associated with function of memory, language and executive domains, and glucose metabolism was only associated", "source": "PubMed"}, {"chunk_id": "36634906_1", "pmid": "36634906", "title": "Brain Functional Alterations and Association with Cognition in People with Preclinical Subjective Cognitive Decline and Objective Subtle Cognitive Difficulties.", "authors": "Ren S, Li J, Huang L et al.", "year": "2023", "journal": "Neuroscience", "keywords": "Amyloid deposition, Glucose metabolism, Objective subtle cognitive difficulties, Subjective cognitive decline", "chunk": "and no difference of glucose metabolism among the three groups were observed. Amyloid deposition was associated with function of memory, language and executive domains, and glucose metabolism was only associated with executive function in Obj-SCD. Amyloid deposition was only associated with executive function in SCD. Obj-SCD could be the early stage of AD, which displayed significant increased amyloid deposition, and the increased amyloid deposition was associated with cognitive function in different domains.", "source": "PubMed"}, {"chunk_id": "34036433_0", "pmid": "34036433", "title": "Cerebrospinal fluid \u03b1 synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms.", "authors": "Winkel I, Ermann N, \u017belwetro A et al.", "year": "2021", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "Alzheimer\u2019s disease, Biomarker, Cerebrospinal fluid, Extrapyramidal symptoms, \u03b1 Synuclein", "chunk": "Extrapyramidal symptoms (EP) are not uncommon in Alzheimer's Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies' pathology post mortem. Total \u03b1 Synuclein (\u03b1Syn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). \u03b1Syn CSF concentrations in AD patients with EP (EP+) have not been reported so far. \u03b1Syn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (A\u03b21-42, A\u03b242/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP-; n = 54), and in subjects with negative NDD results (NDD-; n = 34). Compared to the", "source": "PubMed"}, {"chunk_id": "34036433_1", "pmid": "34036433", "title": "Cerebrospinal fluid \u03b1 synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms.", "authors": "Winkel I, Ermann N, \u017belwetro A et al.", "year": "2021", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "Alzheimer\u2019s disease, Biomarker, Cerebrospinal fluid, Extrapyramidal symptoms, \u03b1 Synuclein", "chunk": "patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP-; n = 54), and in subjects with negative NDD results (NDD-; n = 34). Compared to the NDD- controls (379.8 \u00b1 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF \u03b1Syn (519 \u00b1 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP- subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of \u03b1Syn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower \u03b1Syn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. \u03b1Syn in AD", "source": "PubMed"}, {"chunk_id": "34036433_2", "pmid": "34036433", "title": "Cerebrospinal fluid \u03b1 synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms.", "authors": "Winkel I, Ermann N, \u017belwetro A et al.", "year": "2021", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "Alzheimer\u2019s disease, Biomarker, Cerebrospinal fluid, Extrapyramidal symptoms, \u03b1 Synuclein", "chunk": "AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. \u03b1Syn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF \u03b1Syn as a potential biomarker.", "source": "PubMed"}, {"chunk_id": "41800101_0", "pmid": "41800101", "title": "Therapeutic relevance of an EU-GMP certified <i>Cannabis sativa</i> L. strain in a dual <i>in vivo</i> model of cognitive impairment and chronic neuropathic pain.", "authors": "Costachescu I, Gogu RM, Stanciu GD et al.", "year": "2026", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Cannabis sativa L., EU-GMP certification, chronic intermittent therapy, comorbidities, shared neurobiological mechanisms", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and frequently co-occurs with chronic pain. Worldwide, over 55 million people are affected by AD, with nearly half experiencing persistent pain. Chronic pain has been linked to accelerated memory deterioration and an increased risk of dementia, but the interplay between these conditions remains poorly understood. Existing therapies for AD and chronic pain are limited in efficacy, highlighting the need for interventions targeting multiple pathological pathways. The endocannabinoid system, which is altered in both AD and chronic pain, represents a potential therapeutic target, though its role in AD patients with comorbid pain remains unexplored. The study evaluated the effects of an EU-GMP certified <i>Cannabis sativa</i> L. strain (5 mg/kg, Cannabixir\u00ae Medium Flos) on neurobiological alterations in a rat model designed to explore mechanistic interactions between scopolamine-induced transient cognitive impairment and chronic neuropathic pain induced by unilateral sciatic nerve ligation.", "source": "PubMed"}, {"chunk_id": "41800101_1", "pmid": "41800101", "title": "Therapeutic relevance of an EU-GMP certified <i>Cannabis sativa</i> L. strain in a dual <i>in vivo</i> model of cognitive impairment and chronic neuropathic pain.", "authors": "Costachescu I, Gogu RM, Stanciu GD et al.", "year": "2026", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Cannabis sativa L., EU-GMP certification, chronic intermittent therapy, comorbidities, shared neurobiological mechanisms", "chunk": "Cannabixir\u00ae Medium Flos) on neurobiological alterations in a rat model designed to explore mechanistic interactions between scopolamine-induced transient cognitive impairment and chronic neuropathic pain induced by unilateral sciatic nerve ligation. Treatment outcomes were assessed through nociceptive tests, clinical monitoring and tissue analyses to examine cognitive and pain-related effects. Cannabixir\u00ae Medium Flos induced robust, time-dependent analgesia in thermal nociceptive tests, with the combination of the <i>Cannabis sativa</i> L. strain, donepezil and tramadol producing significantly longer response latencies than tramadol alone. Mechanical sensitivity was minimally affected across treatments. Immunohistochemical analyses revealed that Cannabixir\u00ae Medium Flos, either alone or in combination with donepezil or tramadol, produced the most pronounced neuroprotective effects, reducing astrocytic (GFAP) and microglial (Iba1) activation, lowering Caspase-3 and IL-6 expression, and preserving both hippocampal neuronal integrity as well as peripheral nerve structure. These findings indicate that Cannabixir\u00ae Medium Flos, particularly when combined with donepezil and tramadol, provides superior analgesic and", "source": "PubMed"}, {"chunk_id": "41800101_2", "pmid": "41800101", "title": "Therapeutic relevance of an EU-GMP certified <i>Cannabis sativa</i> L. strain in a dual <i>in vivo</i> model of cognitive impairment and chronic neuropathic pain.", "authors": "Costachescu I, Gogu RM, Stanciu GD et al.", "year": "2026", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, Cannabis sativa L., EU-GMP certification, chronic intermittent therapy, comorbidities, shared neurobiological mechanisms", "chunk": "and preserving both hippocampal neuronal integrity as well as peripheral nerve structure. These findings indicate that Cannabixir\u00ae Medium Flos, particularly when combined with donepezil and tramadol, provides superior analgesic and neuroprotective effects compared to tramadol alone. Its multi-target action - alleviating thermal nociception, reducing neuroinflammation, limiting apoptosis and preserving neuronal and peripheral nerve integrity-supports its potential as an adjunct therapy in managing dementia with comorbid chronic neuropathic pain. Future studies should explore the molecular mechanisms underlying these effects and assess long-term safety and efficacy across diverse models of neurodegeneration and chronic pain.", "source": "PubMed"}, {"chunk_id": "41793476_0", "pmid": "41793476", "title": "miR-214-3p exacerbates mitochondrial dysfunction in parkinson's disease: a multi-omics and mechanistic study.", "authors": "Wang X, Wang D, Zhang C et al.", "year": "2026", "journal": "Experimental brain research", "keywords": "Dopaminergic, GFM1, Mitochondrial, Parkinson's disease, miR-214-3p", "chunk": "Parkinson\u2019s disease (PD) involves the loss of dopaminergic neurons, and prodromal PD exhibits elevated miR-214-3p, suggesting its role as a biomarker and pathogenic factor. This study investigated miR-214-3p\u2019s effects on mitochondrial function in dopaminergic SH-SY5Y cells and mouse primary cortical neurons. In SH-SY5Y cells, proteomic/transcriptomic analyses and target prediction confirmed GFM1 as a direct target of miR-214-3p. miR-214-3p upregulation downregulated GFM1, causing severe mitochondrial bioenergetic impairment: increased reactive oxygen species (ROS), reduced oxygen consumption, diminished ATP production, and decreased respiratory chain complexes (RCC) I/IV expression. Critically, restoring GFM1 reversed these mitochondrial deficits and neuronal dysfunction. In mouse primary cortical neurons, miR-214-3p overexpression also impaired RCC I/IV but did not affect GFM1, revealing a cell type-dependent regulatory mechanism. These findings demonstrate that elevated miR-214-3p impairs mitochondrial function in a cell-specific manner. In dopaminergic cells, this damage is mediated by GFM1 downregulation, highlighting the miR-214-3p/GFM1 axis as a potential cell-type specific therapeutic", "source": "PubMed"}, {"chunk_id": "41793476_1", "pmid": "41793476", "title": "miR-214-3p exacerbates mitochondrial dysfunction in parkinson's disease: a multi-omics and mechanistic study.", "authors": "Wang X, Wang D, Zhang C et al.", "year": "2026", "journal": "Experimental brain research", "keywords": "Dopaminergic, GFM1, Mitochondrial, Parkinson's disease, miR-214-3p", "chunk": "that elevated miR-214-3p impairs mitochondrial function in a cell-specific manner. In dopaminergic cells, this damage is mediated by GFM1 downregulation, highlighting the miR-214-3p/GFM1 axis as a potential cell-type specific therapeutic target for PD and related dopaminergic neuronopathies. The online version contains supplementary material available at 10.1007/s00221-026-07267-0.", "source": "PubMed"}, {"chunk_id": "36463452_0", "pmid": "36463452", "title": "Improved Prediction of Amyloid-\u03b2 and Tau Burden Using Hippocampal Surface Multivariate Morphometry Statistics and Sparse Coding.", "authors": "Wu J, Su Y, Zhu W et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Braak12 tau-SUVR, Braak34 tau-SUVR, Centiloid, amyloid deposition, dictionary and correntropy-induced sparse coding, hippocampal multivariate morphometry statistics, tau deposition", "chunk": "Amyloid-\u03b2 (A\u03b2) plaques and tau protein tangles in the brain are the defining 'A' and 'T' hallmarks of Alzheimer's disease (AD), and together with structural atrophy detectable on brain magnetic resonance imaging (MRI) scans as one of the neurodegenerative ('N') biomarkers comprise the \"ATN framework\" of AD. Current methods to detect A\u03b2/tau pathology include cerebrospinal fluid (invasive), positron emission tomography (PET; costly and not widely available), and blood-based biomarkers (promising but mainly still in development). To develop a non-invasive and widely available structural MRI-based framework to quantitatively predict the amyloid and tau measurements. With MRI-based hippocampal multivariate morphometry statistics (MMS) features, we apply our Patch Analysis-based Surface Correntropy-induced Sparse coding and max-pooling (PASCS-MP) method combined with the ridge regression model to individual amyloid/tau measure prediction. We evaluate our framework on amyloid PET/MRI and tau PET/MRI datasets from the Alzheimer's Disease Neuroimaging Initiative. Each subject has one pair consisting of a", "source": "PubMed"}, {"chunk_id": "36463452_1", "pmid": "36463452", "title": "Improved Prediction of Amyloid-\u03b2 and Tau Burden Using Hippocampal Surface Multivariate Morphometry Statistics and Sparse Coding.", "authors": "Wu J, Su Y, Zhu W et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Braak12 tau-SUVR, Braak34 tau-SUVR, Centiloid, amyloid deposition, dictionary and correntropy-induced sparse coding, hippocampal multivariate morphometry statistics, tau deposition", "chunk": "to individual amyloid/tau measure prediction. We evaluate our framework on amyloid PET/MRI and tau PET/MRI datasets from the Alzheimer's Disease Neuroimaging Initiative. Each subject has one pair consisting of a PET image and MRI scan, collected at about the same time. Experimental results suggest that amyloid/tau measurements predicted with our PASCP-MP representations are closer to the real values than the measures derived from other approaches, such as hippocampal surface area, volume, and shape morphometry features based on spherical harmonics. The MMS-based PASCP-MP is an efficient tool that can bridge hippocampal atrophy with amyloid and tau pathology and thus help assess disease burden, progression, and treatment effects.", "source": "PubMed"}, {"chunk_id": "40361247_0", "pmid": "40361247", "title": "Mouse models of Anti-A\u03b2 immunotherapies.", "authors": "Pikus P, Turner RS, Rebeck GW", "year": "2025", "journal": "Molecular neurodegeneration", "keywords": "ARIA, Alzheimer\u2019s disease, Amyloid-beta, Blood brain barrier, Cerebral amyloid angiopathy, Immunotherapy, Microglia, Mouse models, Neuronal dysfunction", "chunk": "The development of anti-amyloid-beta (A\u03b2) immunotherapies as the first disease modifying therapy for Alzheimer's Disease (AD) is a breakthrough of basic research and translational science. Genetically modified mouse models developed to study AD neuropathology and physiology were used for the discovery of A\u03b2 immunotherapies and helped ultimately propel therapies to FDA approval. Nonetheless, the combination of modest efficacy and significant rates of an adverse side effect (amyloid related imaging abnormalities, ARIA), has prompted reverse translational research in these same mouse models to better understand the mechanism of the therapies. This review considers the use of these mouse models in understanding the mechanisms of A\u03b2 clearance, cerebral amyloid angiopathy (CAA), blood brain barrier breakdown, neuroinflammation, and neuronal dysfunction in response to A\u03b2 immunotherapy.", "source": "PubMed"}, {"chunk_id": "40361247_1", "pmid": "40361247", "title": "Mouse models of Anti-A\u03b2 immunotherapies.", "authors": "Pikus P, Turner RS, Rebeck GW", "year": "2025", "journal": "Molecular neurodegeneration", "keywords": "ARIA, Alzheimer\u2019s disease, Amyloid-beta, Blood brain barrier, Cerebral amyloid angiopathy, Immunotherapy, Microglia, Mouse models, Neuronal dysfunction", "chunk": "A\u03b2 immunotherapy.", "source": "PubMed"}, {"chunk_id": "38747539_0", "pmid": "38747539", "title": "Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease.", "authors": "Brown C, Das S, Xie L et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, GFAP, PET, amyloid, diffusion MRI, medial temporal lobe, microstructure, neurodegeneration, neurofibrillary tangle, plasma biomarkers, tau", "chunk": "Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages. Participants had dMRI and either beta-amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D-map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages. There was higher isometric volume fraction in amyloid-positive compared to amyloid-negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and <sup>18</sup>F-flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages. Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration", "source": "PubMed"}, {"chunk_id": "38747539_1", "pmid": "38747539", "title": "Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease.", "authors": "Brown C, Das S, Xie L et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, GFAP, PET, amyloid, diffusion MRI, medial temporal lobe, microstructure, neurodegeneration, neurofibrillary tangle, plasma biomarkers, tau", "chunk": "were seen across disease stages. Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.", "source": "PubMed"}, {"chunk_id": "41234025_0", "pmid": "41234025", "title": "Associations of lifestyle factors with amyloid pathology in persons without dementia.", "authors": "Oomens JE, Vos SJ, Maserejian NN et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amyloid, amyloid biomarker study, cerebrospinal fluid, lifestyle, positron emission tomography", "chunk": "BackgroundThe association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood.ObjectiveThe aim of this study was to assess the association of alcohol consumption, smoking behavior, sleep quality and physical, cognitive, and social activity with cerebral amyloid pathology.MethodsFor this cross-sectional study, we selected participants from the Amyloid Biomarker Study data pooling initiative. We used generalized estimating equations to assess associations of dichotomized lifestyle measures with amyloid pathology.ResultsWe included 9171 participants with normal cognition (NC) and 2555 participants with mild cognitive impairment (MCI) from the Amyloid Biomarker Study. Of participants with NC, 58% were women, 34% were <i>APOE</i> \u03b54 carrier, and 27% had amyloid pathology. Of participants with MCI, 48% were women, 47% were <i>APOE</i> \u03b54 carrier, and 57% had amyloid pathology. In NC, cognitively active participants were less likely to have amyloid pathology (OR = 0.77, 95%CI 0.66-0.89, p < 0.001). In MCI, participants who had ever smoked or", "source": "PubMed"}, {"chunk_id": "41234025_1", "pmid": "41234025", "title": "Associations of lifestyle factors with amyloid pathology in persons without dementia.", "authors": "Oomens JE, Vos SJ, Maserejian NN et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amyloid, amyloid biomarker study, cerebrospinal fluid, lifestyle, positron emission tomography", "chunk": "amyloid pathology. In NC, cognitively active participants were less likely to have amyloid pathology (OR = 0.77, 95%CI 0.66-0.89, p < 0.001). In MCI, participants who had ever smoked or had sleep problems were less likely to have amyloid pathology (OR = 0.85, 95%CI 0.73-0.99, p = 0.029; OR = 0.62, 95%CI 0.45-0.86, p = 0.004).ConclusionsIn NC, cognitive activity was associated with a lower frequency of amyloid pathology. In MCI, favorable lifestyle behaviors were not associated with a lower frequency of amyloid pathology. The results of the current study contribute to the broader evidence base on lifestyle and AD by further characterizing the role of lifestyle behaviors in AD pathology across different clinical stages.", "source": "PubMed"}, {"chunk_id": "2563716_0", "pmid": "2563716", "title": "[Alzheimer's disease. Review of the current status of research].", "authors": "Wetterling T", "year": "1989", "journal": "Fortschritte der Neurologie-Psychiatrie", "keywords": "None", "chunk": "The enormous social problems and costs caused by patients suffering from dementia induce growing public interest and become a great challenge of medical science. This report attempts to give a review of recent investigations in neuropathology, genetics, neurotransmitter research, epidemiology, diagnostics and therapy of Alzheimer's dementia, the most common type of dementia. A lot of recent molecular genetic experiments and many neuropathological analogies of Alzheimer's dementia and Down's syndrome indicate a damage on the chromosome 21 as possible cause of Alzheimer's dementia. The neuropathological changes are not limited to the grey matter and cholinergic system, but the white matter and some neurotransmitter systems (noradrenaline, dopamine, serotonin and somatostatin) are affected too. Therapeutical trials to compensate these transmitter deficits show no or only poor clinical benefit. Metabolic studies show disturbances in glucose metabolism of Alzheimer brains suggesting an intraneural energy deficit may be the main damage in Alzheimer's dementia. In spite", "source": "PubMed"}, {"chunk_id": "2563716_1", "pmid": "2563716", "title": "[Alzheimer's disease. Review of the current status of research].", "authors": "Wetterling T", "year": "1989", "journal": "Fortschritte der Neurologie-Psychiatrie", "keywords": "None", "chunk": "or only poor clinical benefit. Metabolic studies show disturbances in glucose metabolism of Alzheimer brains suggesting an intraneural energy deficit may be the main damage in Alzheimer's dementia. In spite of extensive technical and psychopathometrical diagnostical attempts Alzheimer's dementia remains to be difficult to diagnose precisely clinically. Best information is given by PET.", "source": "PubMed"}, {"chunk_id": "37777962_0", "pmid": "37777962", "title": "ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes.", "authors": "Lee H, Cho S, Kim MJ et al.", "year": "2023", "journal": "Cell reports", "keywords": "ApoE4, CP: Cell biology, CP: Metabolism, glucose metabolism, human astrocytes, lysosomal cholesterol accumulation, mitophagy", "chunk": "Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer's disease (AD). Among them, genetic variant \u03b54 of the APOE gene (APOE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD. Using isogenic ApoE3 and ApoE4 astrocytes derived from human induced pluripotent stem cells, we find that ApoE4 increases glycolytic activity but impairs mitochondrial respiration in astrocytes. Ultrastructural and autophagy flux analyses show that ApoE4-induced cholesterol accumulation impairs lysosome-dependent removal of damaged mitochondria. Acute treatment with cholesterol-depleting agents restores autophagic activity, mitochondrial dynamics, and associated proteomes, and extended treatment rescues mitochondrial respiration in ApoE4 astrocytes. Taken together, our study provides a direct link between ApoE4-induced lysosomal cholesterol accumulation and abnormal oxidative phosphorylation.", "source": "PubMed"}, {"chunk_id": "37777962_1", "pmid": "37777962", "title": "ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes.", "authors": "Lee H, Cho S, Kim MJ et al.", "year": "2023", "journal": "Cell reports", "keywords": "ApoE4, CP: Cell biology, CP: Metabolism, glucose metabolism, human astrocytes, lysosomal cholesterol accumulation, mitophagy", "chunk": "and abnormal oxidative phosphorylation.", "source": "PubMed"}, {"chunk_id": "41372988_0", "pmid": "41372988", "title": "Acute neuroinflammation induces prolonged transcriptional reprogramming in microglia.", "authors": "Moon S, Kim CG, Kim YK et al.", "year": "2025", "journal": "Journal of neuroinflammation", "keywords": "Acute neuroinflammation, Microglia, Transcriptomic reprogramming", "chunk": "Acute neuroinflammation rapidly activates brain immune responses, but its lasting effects on microglia are unclear. Using systemic LPS administration and LCMV-Armstrong infection, we found that blood-brain barrier disruption and cytokine shifts resolved within 30 days, yet microglial recovery was incomplete-marked by persistent numerical loss and an IFN-\u03b3-low phenotype in the LPS model and reduced relative abundance in the LCMV model. Single-cell RNA sequencing revealed sustained transcriptional alterations, including disease-associated microglia (DAM) features and a distinct recovery-biased population. These acute signatures overlapped with profiles from Alzheimer's model mice and were enriched in human microglia from multiple sclerosis, Alzheimer's disease, and other neuroinflammatory conditions. Although our observation period was shorter than the chronic course of these diseases, the persistence of disease-like microglial states suggests that transient inflammation can prime the brain for long-term vulnerability. Targeting this primed state may offer new strategies to prevent or mitigate neurodegenerative pathology.", "source": "PubMed"}, {"chunk_id": "41372988_1", "pmid": "41372988", "title": "Acute neuroinflammation induces prolonged transcriptional reprogramming in microglia.", "authors": "Moon S, Kim CG, Kim YK et al.", "year": "2025", "journal": "Journal of neuroinflammation", "keywords": "Acute neuroinflammation, Microglia, Transcriptomic reprogramming", "chunk": "states suggests that transient inflammation can prime the brain for long-term vulnerability. Targeting this primed state may offer new strategies to prevent or mitigate neurodegenerative pathology.", "source": "PubMed"}, {"chunk_id": "38860393_0", "pmid": "38860393", "title": "Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.", "authors": "Adili A, Dilihumaer A, Zhu H et al.", "year": "2024", "journal": "Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences", "keywords": "Basic research, Central nervous system diseases, Clinical trial, Phosphodiesterase 4 inhibitors, Review", "chunk": "Phosphodiesterases (PDE) are involved in the regulation of cellular physiological processes and neurological functions, including neuronal plasticity, synapto-genesis, synaptic transmission, memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system (CNS) diseases by inhibiting cAMP hydrolysis, increasing cAMP content and enhancing its downstream effects. PDE4 inhibitors have long-term potentiation effect, which can enhance phosphorylation of cAMP response element binding protein (CREB) and upregulate expression of memory related Arc genes in hippocampal neurons, thereby improving cognitive impairment and Alzheimer's disease-like symptoms. They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by \u03b1-syn and increasing the effect of miR-124-3p on cell functions. Alteration of PDE4 activity is the molecular basis for psychosis and some", "source": "PubMed"}, {"chunk_id": "38860393_1", "pmid": "38860393", "title": "Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.", "authors": "Adili A, Dilihumaer A, Zhu H et al.", "year": "2024", "journal": "Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences", "keywords": "Basic research, Central nervous system diseases, Clinical trial, Phosphodiesterase 4 inhibitors, Review", "chunk": "Parkinson's disease by reducing the cytotoxicity induced by \u03b1-syn and increasing the effect of miR-124-3p on cell functions. Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders, therefore it is considered as a therapeutic target for schizophrenia. PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor (RAGE), TLR4 and NLRP3 pathways in the hippocampus, reducing the activation of microglia and the production of IL-1\u03b2, down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors. PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells, increasing nociceptive threshold, and improving mutual learning and memory deficits. PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein (FMRP). PDE4 inhibitors can also promote the differentiation of", "source": "PubMed"}, {"chunk_id": "38860393_2", "pmid": "38860393", "title": "Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.", "authors": "Adili A, Dilihumaer A, Zhu H et al.", "year": "2024", "journal": "Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences", "keywords": "Basic research, Central nervous system diseases, Clinical trial, Phosphodiesterase 4 inhibitors, Review", "chunk": "treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein (FMRP). PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination, which has potential in the treatment of multiple sclerosis. PDE4 is also related to bipolar disorder, which may be one of the therapeutic targets. At present, several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases. This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases, providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.", "source": "PubMed"}, {"chunk_id": "41256130_0", "pmid": "41256130", "title": "Lactoferrin levels in cerebrospinal fluid exhibits isoform-specific associations with Alzheimer's disease.", "authors": "Zhao F, Puerta R, Wang Y et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, Biomarkers, CSF, Lactoferrin, Plasma", "chunk": "Pathological changes in Alzheimer's disease (AD) begin years before the onset of clinical symptoms. Developing cost-effective and minimally invasive biomarkers for preclinical diagnosis remains a critical goal in the field. Lactoferrin, an iron-binding glycoprotein, has emerged as a promising candidate due to its multifunctional roles reported in previous studies. However, whether lactoferrin levels in biofluids are associated with established AD biomarkers, and whether it can serve as a reliable diagnostic indicator, remains controversial. We analyzed SOMAscan proteomic data from 1,367 paired plasma and cerebrospinal fluid (CSF) samples from the ACE Alzheimer's Center Barcelona cohort to evaluate lactoferrin levels. Associations between two lactoferrin-targeting SOMAmers and classical AD biomarkers, including total tau (t-tau), phosphorylated tau (p-tau181), and amyloid-beta 42 (A\u03b242), were assessed. The age, sex, proteomic principal components were considered as covariates for sensitive analysis. The prognostic value of lactoferrin in predicting dementia progression was further evaluated using survival analysis. Among the", "source": "PubMed"}, {"chunk_id": "41256130_1", "pmid": "41256130", "title": "Lactoferrin levels in cerebrospinal fluid exhibits isoform-specific associations with Alzheimer's disease.", "authors": "Zhao F, Puerta R, Wang Y et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, Biomarkers, CSF, Lactoferrin, Plasma", "chunk": "The age, sex, proteomic principal components were considered as covariates for sensitive analysis. The prognostic value of lactoferrin in predicting dementia progression was further evaluated using survival analysis. Among the two lactoferrin-targeting SOMAmers, Seq.2780.35 (LTF2) showed a weak and exclusive association with CSF A\u03b242 and syndromic status, whereas Seq.14755.4 (LTF1) was weakly associated with CSF p-tau and t-tau AD biomarker levels displayed expression-dependent stratification consistent with a ventricular-volume-related dilution effect rather than disease. Furthermore, lactoferrin levels were not significantly associated with the progression from mild cognitive impairment (MCI) to dementia. Isoform-specific lactoferrin expression changes in cerebrospinal fluid (CSF), but not plasma, appears to have biological relevance and diagnostic biomarker potential for AD.", "source": "PubMed"}, {"chunk_id": "40274681_0", "pmid": "40274681", "title": "Chronic inflammation in obesity and neurodegenerative diseases: exploring the link in disease onset and progression.", "authors": "Dhurandhar Y, Tomar S, Das A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Adipose tissue, Chronic inflammation, Gut microbiome, Insulin resistance, Neurodegenerative, Obesity, ROS", "chunk": "Obesity, a worldwide health emergency, is defined by excessive fat accumulation and significantly impacts metabolic health. In addition to its recognized association with cardiovascular disease, diabetes, and other metabolic illnesses, recent studies have revealed the connection between obesity and neurodegeneration. The main reason for this link is inflammation caused by the growth of fat tissue, which activates harmful processes that affect how the brain works. Fat tissue, particularly the fat around the organs, produces various substances that cause inflammation, such as cytokines (TNF-\u03b1, IL-6), adipokines (leptin, resistin), and free fatty acids. These chemicals cause low-grade, persistent systemic inflammation, which is becoming more widely acknowledged as a major factor in peripheral metabolic dysfunction and pathology of the central nervous system (CNS). Inflammatory signals in the brain cause neuroinflammatory reactions that harm neuronal structures, change neuroplasticity, and disrupt synaptic function. When obesity-related inflammation is present, the brain's resident immune cells, known as", "source": "PubMed"}, {"chunk_id": "40274681_1", "pmid": "40274681", "title": "Chronic inflammation in obesity and neurodegenerative diseases: exploring the link in disease onset and progression.", "authors": "Dhurandhar Y, Tomar S, Das A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Adipose tissue, Chronic inflammation, Gut microbiome, Insulin resistance, Neurodegenerative, Obesity, ROS", "chunk": "Inflammatory signals in the brain cause neuroinflammatory reactions that harm neuronal structures, change neuroplasticity, and disrupt synaptic function. When obesity-related inflammation is present, the brain's resident immune cells, known as microglia, become hyperactivated, which can lead to the production of neurotoxic chemicals, which can cause neuronal death. This neuroinflammation exacerbates the negative effects of obesity on brain health and is linked to cognitive decline, Alzheimer's disease, and other neurodegenerative disorders. Moreover, the blood-brain barrier (BBB) exhibits increased permeability during inflammatory states, facilitating the infiltration of peripheral immune cells and cytokines into the brain, hence exacerbating neurodegeneration. Adipose tissue is a source of chronic inflammatory mediators, which are examined in this review along with the molecular pathways that connect inflammation brought on by obesity to neurodegeneration. Additionally, it addresses various anti-inflammatory treatment approaches, including lifestyle modifications, anti-inflammatory medications, and gut microbiota modulation, to lessen the metabolic and neurological effects of obesity.", "source": "PubMed"}, {"chunk_id": "40274681_2", "pmid": "40274681", "title": "Chronic inflammation in obesity and neurodegenerative diseases: exploring the link in disease onset and progression.", "authors": "Dhurandhar Y, Tomar S, Das A et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Adipose tissue, Chronic inflammation, Gut microbiome, Insulin resistance, Neurodegenerative, Obesity, ROS", "chunk": "on by obesity to neurodegeneration. Additionally, it addresses various anti-inflammatory treatment approaches, including lifestyle modifications, anti-inflammatory medications, and gut microbiota modulation, to lessen the metabolic and neurological effects of obesity. Recognizing the link between obesity and inflammation opens up new opportunities for early intervention and the development of targeted treatments to prevent or alleviate neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "38144511_0", "pmid": "38144511", "title": "Current Anti-Amyloid-\u03b2 Therapy for Alzheimer's Disease Treatment: From Clinical Research to Nanomedicine.", "authors": "Zhao Z, Liu Y, Ruan S et al.", "year": "2023", "journal": "International journal of nanomedicine", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, anti-amyloid-\u03b2 monoclonal antibody, disease-modifying therapeutics, nanomedicine", "chunk": "Recent successive approval of anti-amyloid-\u03b2 (A\u03b2) monoclonal antibodies as disease-modifying therapies against Alzheimer's disease (AD) has raised great confidence in the development of anti-AD therapies; however, the current therapies still face the dilemma of significant adverse reactions and limited effects. In this review, we summarized the therapeutic characteristics of the approved anti-A\u03b2 immunotherapies and dialectically analyzed the gains and losses from clinical trials. The review further proposed the reasonable selection of animal models in preclinical studies from the perspective of different animal models of A\u03b2 deposition and deals in-depth with the recent advances of exploring preclinical nanomedical application in A\u03b2 targeted therapy, aiming to provide a reliable systematic summary for the development of novel anti-A\u03b2 therapies. Collectively, this review comprehensively dissects the pioneering work of A\u03b2-targeted therapies and proposed perspective insight into AD-modified therapies.", "source": "PubMed"}, {"chunk_id": "38144511_1", "pmid": "38144511", "title": "Current Anti-Amyloid-\u03b2 Therapy for Alzheimer's Disease Treatment: From Clinical Research to Nanomedicine.", "authors": "Zhao Z, Liu Y, Ruan S et al.", "year": "2023", "journal": "International journal of nanomedicine", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, anti-amyloid-\u03b2 monoclonal antibody, disease-modifying therapeutics, nanomedicine", "chunk": "dissects the pioneering work of A\u03b2-targeted therapies and proposed perspective insight into AD-modified therapies.", "source": "PubMed"}, {"chunk_id": "41656561_0", "pmid": "41656561", "title": "Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer's disease related areas.", "authors": "Hosseini SA, Servaes S, Macedo AC et al.", "year": "2026", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Alzheimer\u2019s disease, QSM, brain\u2019 susceptibility, immune biomarkers, neuroinflammation", "chunk": "Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer's disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain A\u03b2 and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers", "source": "PubMed"}, {"chunk_id": "41656561_1", "pmid": "41656561", "title": "Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer's disease related areas.", "authors": "Hosseini SA, Servaes S, Macedo AC et al.", "year": "2026", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Alzheimer\u2019s disease, QSM, brain\u2019 susceptibility, immune biomarkers, neuroinflammation", "chunk": "24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain A\u03b2 or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.", "source": "PubMed"}, {"chunk_id": "40960157_0", "pmid": "40960157", "title": "Protein aggregation in neurodegenerative diseases.", "authors": "Wang J, Dai L, Zhang Z", "year": "2025", "journal": "Chinese medical journal", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Amyotrophic lateral sclerosis, Biomarker, Huntington\u2019s disease, Parkinson\u2019s disease, Tau, \u03b1-synuclein", "chunk": "Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-\u03b2, tau, \u03b1-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.", "source": "PubMed"}, {"chunk_id": "40960157_1", "pmid": "40960157", "title": "Protein aggregation in neurodegenerative diseases.", "authors": "Wang J, Dai L, Zhang Z", "year": "2025", "journal": "Chinese medical journal", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Amyotrophic lateral sclerosis, Biomarker, Huntington\u2019s disease, Parkinson\u2019s disease, Tau, \u03b1-synuclein", "chunk": "also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.", "source": "PubMed"}, {"chunk_id": "37014414_0", "pmid": "37014414", "title": "Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?", "authors": "Le\u00dfmann V, Kartalou GI, Endres T et al.", "year": "2023", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "APP/PS1, Aducanumab, Alzheimer\u2019s disease, Astrogliosis, BDNF, Dementia, Drug repurposing, fingolimod, FTY720, Gantenerumab, Hippocampus, LTP, Learning and memory, Lecanemab, Microglia, Neurodegenerative disease, Neuroinflammation, Ozanimod, Siponimod, Spatial memory, Sphingosine-1-phosphate receptor, Spines", "chunk": "Therapeutic approaches providing effective medication for Alzheimer's disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models and in humans suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals or in elderly humans before onset of disease symptoms. However, a pharmacological treatment that can reverse memory deficits in AD patients was thus far not identified. Importantly, AD disease-related dysfunctions have increasingly been associated with neuro-inflammatory mechanisms and searching for anti-inflammatory medication to treat AD seems promising. Like for other diseases, repurposing of FDA-approved drugs for treatment of AD is an ideally suited strategy to reduce the time to bring such medication into clinical practice. Of note, the sphingosine-1-phosphate analogue fingolimod (FTY720) was FDA-approved in 2010 for treatment of multiple sclerosis patients. It binds to the five different isoforms of Sphingosine-1-phosphate receptors (S1PRs) that are", "source": "PubMed"}, {"chunk_id": "37014414_1", "pmid": "37014414", "title": "Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?", "authors": "Le\u00dfmann V, Kartalou GI, Endres T et al.", "year": "2023", "journal": "Journal of neural transmission (Vienna, Austria : 1996)", "keywords": "APP/PS1, Aducanumab, Alzheimer\u2019s disease, Astrogliosis, BDNF, Dementia, Drug repurposing, fingolimod, FTY720, Gantenerumab, Hippocampus, LTP, Learning and memory, Lecanemab, Microglia, Neurodegenerative disease, Neuroinflammation, Ozanimod, Siponimod, Spatial memory, Sphingosine-1-phosphate receptor, Spines", "chunk": "Of note, the sphingosine-1-phosphate analogue fingolimod (FTY720) was FDA-approved in 2010 for treatment of multiple sclerosis patients. It binds to the five different isoforms of Sphingosine-1-phosphate receptors (S1PRs) that are widely distributed across human organs. Interestingly, recent studies in five different mouse models of AD suggest that FTY720 treatment, even when starting after onset of AD symptoms, can reverse synaptic deficits and memory dysfunction in these AD mouse models. Furthermore, a very recent multi-omics study identified mutations in the sphingosine/ceramide pathway as a risk factor for sporadic AD, suggesting S1PRs as promising drug target in AD patients. Therefore, progressing with FDA-approved S1PR modulators into human clinical trials might pave the way for these potential disease modifying anti-AD drugs.", "source": "PubMed"}, {"chunk_id": "41817071_0", "pmid": "41817071", "title": "A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.", "authors": "Mallika AP, Mathuranath PS, Menon RN et al.", "year": "2026", "journal": "Neurology India", "keywords": "Alzheimer\u2019s disease, dementia, frontotemporal dementia, mutations, neuroinflammation", "chunk": "Triggering Receptor expressed on Myeloid cells 2 (TREM2) mutations can cause Nasu-Hakola disease, a rare form of dementia, and are also linked to an increased risk of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The TREM2 receptor plays a role in microglial cell function, including response to injury and amyloid beta pathology in the brain. Variants in TREM2, particularly in exon 2, can disrupt its function, contributing to AD pathology, such as accumulation of amyloid beta plaques and tau tangles. In this study, we conducted screening of exon 2 in TREM2 to identify mutations in a carefully characterized cohort comprising individuals with AD, FTD, and mild cognitive impairment (MCI) from South India. We report the identification of a homozygous p.R47C variant (rs753325601) in a case diagnosed with frontal variant AD. Our finding reinforces the correlation between TREM2 genetic variations and the manifestation of atypical AD phenotypes, highlighting the significance of", "source": "PubMed"}, {"chunk_id": "41817071_1", "pmid": "41817071", "title": "A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.", "authors": "Mallika AP, Mathuranath PS, Menon RN et al.", "year": "2026", "journal": "Neurology India", "keywords": "Alzheimer\u2019s disease, dementia, frontotemporal dementia, mutations, neuroinflammation", "chunk": "variant (rs753325601) in a case diagnosed with frontal variant AD. Our finding reinforces the correlation between TREM2 genetic variations and the manifestation of atypical AD phenotypes, highlighting the significance of TREM2 mediated pathogenic mechanisms in modulating disease presentation.", "source": "PubMed"}, {"chunk_id": "41373742_0", "pmid": "41373742", "title": "The Tetrapeptide HAEE Promotes Amyloid-Beta Clearance from the Brain.", "authors": "Mukhina KA, Varshavskaya KB, Rybak AD et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, A\u03b2 clearance, amyloid-beta, blood\u2013brain barrier, microglia, tetrapeptide HAEE", "chunk": "Alzheimer's disease is characterized by the accumulation of neurotoxic forms of amyloid-beta (A\u03b2) in the brain, leading to synaptic dysfunction, neuroinflammation, and neuronal death. The tetrapeptide HAEE crosses the blood-brain barrier (BBB), inhibits the formation of toxic A\u03b2 oligomers, and reduces amyloid burden <i>in vivo</i>. However, the mechanisms of HAEE's anti-amyloidogenic effect remained incompletely understood. In this study, we investigated the mechanism of HAEE-dependent A\u03b2 clearance both <i>in vitro and in vivo</i>. Using ELISA, we assessed the HAEE effect on the levels of A\u03b2, IL-6, and TNF\u03b1 in mouse brain tissue following intracerebroventricular administration. The mechanism of the anti-A\u03b2 effect of HAEE was studied using primary brain cell cultures and a BBB transwell model through ELISA, flow cytometry, and microscopy. We showed that HAEE reduced A\u03b2 level by 35% and IL-6 level by 40% in mouse brain tissue. HAEE enhanced A\u03b2 clearance via LRP1- and PgP-dependent A\u03b2 transport through the", "source": "PubMed"}, {"chunk_id": "41373742_1", "pmid": "41373742", "title": "The Tetrapeptide HAEE Promotes Amyloid-Beta Clearance from the Brain.", "authors": "Mukhina KA, Varshavskaya KB, Rybak AD et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, A\u03b2 clearance, amyloid-beta, blood\u2013brain barrier, microglia, tetrapeptide HAEE", "chunk": "We showed that HAEE reduced A\u03b2 level by 35% and IL-6 level by 40% in mouse brain tissue. HAEE enhanced A\u03b2 clearance via LRP1- and PgP-dependent A\u03b2 transport through the BBB and doubled the rate of A\u03b2 degradation by microglia. In addition to inhibition of A\u03b2 aggregation, HAEE dissolved already formed A\u03b2 oligomers. The HAEE-induced decrease in IL-6 levels in the mouse brain was associated with reduced pro-inflammatory activation of microglia. Thus, HAEE's effect against A\u03b2-related neuropathologies is realized through a decrease in the level of toxic A\u03b2 oligomer and inhibition of neuroinflammation.", "source": "PubMed"}, {"chunk_id": "31978603_0", "pmid": "31978603", "title": "ApoE and cerebral insulin: Trafficking, receptors, and resistance.", "authors": "Rhea EM, Raber J, Banks WA", "year": "2020", "journal": "Neurobiology of disease", "keywords": "Alzheimer's disease, Amyloid beta, Apolipoprotein E, Blood-brain barrier, Central nervous system insulin, Insulin receptor", "chunk": "Central nervous system (CNS) insulin resistance is associated with Alzheimer's disease (AD). In addition, the apolipoprotein E4 (apoE4) isoform is a risk factor for AD. The connection between these two factors in relation to AD is being actively explored. We summarize this literature with a focus on the transport of insulin and apoE across the blood-brain barrier (BBB) and into the CNS, the impact of apoE and insulin on the BBB, and the interactions between apoE, insulin, and the insulin receptor once present in the CNS. We highlight how CNS insulin resistance is apparent in AD and potential ways to overcome this resistance by repurposing currently approved drugs, with apoE genotype taken into consideration as the treatment response following most interventions is apoE isoform-dependent. This review is part of a special issue focusing on apoE in AD and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "31978603_1", "pmid": "31978603", "title": "ApoE and cerebral insulin: Trafficking, receptors, and resistance.", "authors": "Rhea EM, Raber J, Banks WA", "year": "2020", "journal": "Neurobiology of disease", "keywords": "Alzheimer's disease, Amyloid beta, Apolipoprotein E, Blood-brain barrier, Central nervous system insulin, Insulin receptor", "chunk": "interventions is apoE isoform-dependent. This review is part of a special issue focusing on apoE in AD and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "40195333_0", "pmid": "40195333", "title": "Clinical utility of cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic workup of complex patients with cognitive impairment.", "authors": "Wang MY, Chen KL, Huang YY et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "Cerebrospinal fluid (CSF) biomarkers have been widely adopted in Alzheimer's disease (AD) diagnosis. However, no studies focused on the application of CSF biomarkers in the clinical practice of complex and atypical patients with cognitive impairment in China. This study aimed to evaluate the added value of CSF AD biomarkers in cognitively impaired patients with complex conditions in a memory clinical setting. A total of 633 participants were included from the National Center for Neurological Disorders in Shanghai, China. The CSF AD biomarkers were measured with ELISA. Cutoff values were firstly identified using Youden's index. The neurologists proposed etiology diagnosis with a percentage estimate of their confidence and prescribed medication before and after CSF disclosure. Changes in etiological diagnosis, diagnostic confidence, and management plan were compared across the groups. Of the 633 patients (mean [SD] age, 61.1 [11.3] years; 295 males [46.6%]), 372 (58.8%) were diagnosed with dementia, 103 (16.3%) with", "source": "PubMed"}, {"chunk_id": "40195333_1", "pmid": "40195333", "title": "Clinical utility of cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic workup of complex patients with cognitive impairment.", "authors": "Wang MY, Chen KL, Huang YY et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "and management plan were compared across the groups. Of the 633 patients (mean [SD] age, 61.1 [11.3] years; 295 males [46.6%]), 372 (58.8%) were diagnosed with dementia, 103 (16.3%) with mild cognitive impairment, and 158 (24.9%) with subjective cognitive decline. Using those pre-defined cutoffs, we categorized patients into 3 groups: Alzheimer's continuum (68.1%), non-AD pathologic change (11.1%), and normal AD biomarkers (20.8%). After CSF disclosure, the proposed etiology changed in 158 (25.0%) participants and the prescribed medication changed in 200 (31.6%) patients. Mean diagnostic confidence increased from 69.5-83.0% (+13.5%; P < 0.001). In conclusion, CSF AD biomarkers significantly impacted the diagnosis, diagnostic confidence, and treatment plans for Chinese patients with complex cognitive impairment. CSF AD biomarkers are a useful tool for clinicians beyond routine clinical assessment.", "source": "PubMed"}, {"chunk_id": "40195333_2", "pmid": "40195333", "title": "Clinical utility of cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic workup of complex patients with cognitive impairment.", "authors": "Wang MY, Chen KL, Huang YY et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "for clinicians beyond routine clinical assessment.", "source": "PubMed"}, {"chunk_id": "37727082_0", "pmid": "37727082", "title": "Risk of cognitive decline progression is associated to increased blood-brain-barrier permeability: A longitudinal study in a memory unit clinical cohort.", "authors": "Puig-Pijoan A, Jimenez-Balado J, Fern\u00e1ndez-Lebrero A et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "blood-brain barrier, cerebrovascular disease, cognition, dementia, vascular dementia", "chunk": "This study examined the relationship between blood-brain-barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort. This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored. Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log-QAlb. Vascular cognitive impairment patients had the highest log-QAlb levels. Among the 273 participants with valid follow-up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log-QAlb. These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.", "source": "PubMed"}, {"chunk_id": "37727082_1", "pmid": "37727082", "title": "Risk of cognitive decline progression is associated to increased blood-brain-barrier permeability: A longitudinal study in a memory unit clinical cohort.", "authors": "Puig-Pijoan A, Jimenez-Balado J, Fern\u00e1ndez-Lebrero A et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "blood-brain barrier, cerebrovascular disease, cognition, dementia, vascular dementia", "chunk": "individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.", "source": "PubMed"}, {"chunk_id": "41724666_0", "pmid": "41724666", "title": "Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.", "authors": "Ariyath A, Mputhia Z, Dougherty C et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta protein, amyloid precursor protein, autophagy, calorie restriction, diet, exercise, fasting, lifestyle interventions, physical activity, sleep, sleep deprivation, sleep fragmentation", "chunk": "Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (A\u03b2) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and neurotrophic signaling; and adequate sleep supports autophagic processes, while sleep deprivation disrupts them. However, excessive autophagy may be detrimental. Understanding how lifestyle modulates autophagy is essential for developing non-pharmacological strategies to delay or prevent AD. This review explores the mechanistic links between autophagy and lifestyle interventions to support brain health", "source": "PubMed"}, {"chunk_id": "41724666_1", "pmid": "41724666", "title": "Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.", "authors": "Ariyath A, Mputhia Z, Dougherty C et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta protein, amyloid precursor protein, autophagy, calorie restriction, diet, exercise, fasting, lifestyle interventions, physical activity, sleep, sleep deprivation, sleep fragmentation", "chunk": "how lifestyle modulates autophagy is essential for developing non-pharmacological strategies to delay or prevent AD. This review explores the mechanistic links between autophagy and lifestyle interventions to support brain health in aging.", "source": "PubMed"}, {"chunk_id": "41568664_0", "pmid": "41568664", "title": "Engineering nanobodies for drug delivery systems in Alzheimer's disease.", "authors": "Jootar T, Hongeng S, Chiangjong W", "year": "2026", "journal": "Artificial cells, nanomedicine, and biotechnology", "keywords": "Alzheimer\u2019s disease, A\u03b2 plaques, Nanobodies, blood\u2013brain barrier, drug delivery, neurofibrillary tangles", "chunk": "Alzheimer's disease (AD) remains a major global health challenge, with current therapies offering only symptomatic relief. A significant constraint in the development of effective treatments is the blood-brain barrier (BBB), as it greatly limits the access of therapeutic drugs targeting amyloid-\u03b2 (A\u03b2) aggregation, tau hyperphosphorylation and neuroinflammation. Nanobodies, single-domain antibody fragments derived from camelids, have emerged as versatile tools with unique properties such as small size, high stability and the ability to penetrate the BBB. Engineered formats allow for specific targeting of A\u03b2 and tau, receptor-mediated transcytosis, and conjugation with therapeutic or diagnostic substances. Preclinical studies show that nanobody-based strategies can reduce pathological burden, attenuate neuroinflammation and improve cognitive outcomes in AD models. Manufacturing scale-up, long-term safety and regulatory validation are among the remaining challenges, yet nanobody engineering represents a viable path to disease-modifying medicines. Innovative approaches, including artificial intelligence-driven design, i.e. 4-1BB agonist nanobodies, and clustered regularly interspaced short", "source": "PubMed"}, {"chunk_id": "41568664_1", "pmid": "41568664", "title": "Engineering nanobodies for drug delivery systems in Alzheimer's disease.", "authors": "Jootar T, Hongeng S, Chiangjong W", "year": "2026", "journal": "Artificial cells, nanomedicine, and biotechnology", "keywords": "Alzheimer\u2019s disease, A\u03b2 plaques, Nanobodies, blood\u2013brain barrier, drug delivery, neurofibrillary tangles", "chunk": "are among the remaining challenges, yet nanobody engineering represents a viable path to disease-modifying medicines. Innovative approaches, including artificial intelligence-driven design, i.e. 4-1BB agonist nanobodies, and clustered regularly interspaced short palindromic repeat-facilitated diversification of nanobody libraries - such as targeted complementarity-determining region 3 mutagenesis followed by functional screening against disease-relevant tau or A\u03b2 conformers - alongside half-life extension strategies, are commencing to surmount these obstacles and enhance the potential of nanobody platforms to develop into clinically viable disease-modifying therapies.", "source": "PubMed"}, {"chunk_id": "36077227_0", "pmid": "36077227", "title": "Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Microglia from APOE Targeted Replacement Mice.", "authors": "Mhatre-Winters I, Eid A, Han Y et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "APOE, Alzheimer\u2019s disease, cytokine, microglia, neuroinflammation, sex", "chunk": "The sex and APOE4 genotype are significant risk factors for Alzheimer\u2019s disease (AD); however, the mechanism(s) responsible for this interaction are still a matter of debate. Here, we assess the responses of mixed-sex and sex-specific APOE3 and APOE4 primary microglia (PMG) to lipopolysaccharide and interferon-gamma. In our investigation, inflammatory cytokine profiles were assessed by qPCR and multiplex ELISA assays. Mixed-sex APOE4 PMG exhibited higher basal mRNA expression and secreted levels of TNFa and IL1b. In sex-specific cultures, basal expression and secreted levels of IL1b, TNFa, IL6, and NOS2 were 2\u22123 fold higher in APOE4 female PMG compared to APOE4 males, with both higher than APOE3 cells. Following an inflammatory stimulus, the expression of pro-inflammatory cytokines and the secreted cytokine level were upregulated in the order E4 female > E4 male > E3 female > E3 male in sex-specific cultures. These data indicate that the APOE4 genotype and female sex together", "source": "PubMed"}, {"chunk_id": "36077227_1", "pmid": "36077227", "title": "Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Microglia from APOE Targeted Replacement Mice.", "authors": "Mhatre-Winters I, Eid A, Han Y et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "APOE, Alzheimer\u2019s disease, cytokine, microglia, neuroinflammation, sex", "chunk": "were upregulated in the order E4 female > E4 male > E3 female > E3 male in sex-specific cultures. These data indicate that the APOE4 genotype and female sex together contribute to a greater inflammatory response in PMG isolated from targeted replacement humanized APOE mice. These data are consistent with clinical data and indicate that sex-specific PMG may provide a platform for exploring mechanisms of genotype and sex differences in AD related to neuroinflammation and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "34219721_0", "pmid": "34219721", "title": "A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.", "authors": "Tolea MI, Heo J, Chrisphonte S et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CAIDE, case discrimination, cognitive impairment, dementia risk scores, dementia screening", "chunk": "Although an efficacious dementia-risk score system, Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) was derived using midlife risk factors in a population with low educational attainment that does not reflect today's US population, and requires laboratory biomarkers, which are not always available. Develop and validate a modified CAIDE (mCAIDE) system and test its ability to predict presence, severity, and etiology of cognitive impairment in older adults. Population consisted of 449 participants in dementia research (N = 230; community sample; 67.9\u00b110.0 years old, 29.6%male, 13.7\u00b14.1 years education) or receiving dementia clinical services (N = 219; clinical sample; 74.3\u00b19.8 years old, 50.2%male, 15.5\u00b12.6 years education). The mCAIDE, which includes self-reported and performance-based rather than blood-derived measures, was developed in the community sample and tested in the independent clinical sample. Validity against Framingham, Hachinski, and CAIDE risk scores was assessed. Higher mCAIDE quartiles were associated with lower performance on global and domain-specific cognitive", "source": "PubMed"}, {"chunk_id": "34219721_1", "pmid": "34219721", "title": "A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.", "authors": "Tolea MI, Heo J, Chrisphonte S et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CAIDE, case discrimination, cognitive impairment, dementia risk scores, dementia screening", "chunk": "and tested in the independent clinical sample. Validity against Framingham, Hachinski, and CAIDE risk scores was assessed. Higher mCAIDE quartiles were associated with lower performance on global and domain-specific cognitive tests. Each one-point increase in mCAIDE increased the odds of mild cognitive impairment (MCI) by up to 65%, those of AD by 69%, and those for non-AD dementia by > 85%, with highest scores in cases with vascular etiologies. Being in the highest mCAIDE risk group improved ability to discriminate dementia from MCI and controls and MCI from controls, with a cut-off of \u22657 points offering the highest sensitivity, specificity, and positive and negative predictive values. mCAIDE is a robust indicator of cognitive impairment in community-dwelling seniors, which can discriminate well between dementia severity including MCI versus controls. The mCAIDE may be a valuable tool for case ascertainment in research studies, helping flag primary care patients for cognitive testing, and", "source": "PubMed"}, {"chunk_id": "34219721_2", "pmid": "34219721", "title": "A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.", "authors": "Tolea MI, Heo J, Chrisphonte S et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "CAIDE, case discrimination, cognitive impairment, dementia risk scores, dementia screening", "chunk": "well between dementia severity including MCI versus controls. The mCAIDE may be a valuable tool for case ascertainment in research studies, helping flag primary care patients for cognitive testing, and identify those in need of lifestyle interventions for symptomatic control.", "source": "PubMed"}, {"chunk_id": "40163151_0", "pmid": "40163151", "title": "Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature.", "authors": "Wadan AS, Shaaban AH, El-Sadek MZ et al.", "year": "2025", "journal": "Naunyn-Schmiedeberg's archives of pharmacology", "keywords": "Mitochondria-focused therapies, Mitochondrial dysfunction, Neurodegenerative diseases, Oxidative stress, Therapeutic strategies", "chunk": "Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor to the pathophysiology of various neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review paper examines the current literature highlighting the multifaceted functions of mitochondria, including energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, mitochondrial dynamics, axonal transport, endoplasmic reticulum-mitochondrial interactions, mitophagy, mitochondrial proteostasis, and their crucial involvement in neuronal health. The literature emphasizes the increasing recognition of mitochondrial dysfunction as a critical factor in the progression of neurodegenerative disorders, marking a shift from traditional symptom management to innovative mitochondrial-based therapies. By discussing mitochondrial mechanisms, including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity,", "source": "PubMed"}, {"chunk_id": "40163151_1", "pmid": "40163151", "title": "Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature.", "authors": "Wadan AS, Shaaban AH, El-Sadek MZ et al.", "year": "2025", "journal": "Naunyn-Schmiedeberg's archives of pharmacology", "keywords": "Mitochondria-focused therapies, Mitochondrial dysfunction, Neurodegenerative diseases, Oxidative stress, Therapeutic strategies", "chunk": "including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity, and slow disease progression. This comprehensive review aims to provide insights into potential interventions that could transform the treatment landscape for neurodegenerative diseases, addressing symptoms and underlying pathophysiological changes.", "source": "PubMed"}, {"chunk_id": "41300247_0", "pmid": "41300247", "title": "ERP Biomarkers of Auditory-Visual Distraction in Aging and Cognitive Impairment.", "authors": "Gumenyuk V, Korzyukov O, Parker SM et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, aging, and mild cognitive impairment, distraction, event-related potentials", "chunk": "<b>Background/Objectives</b>: Distraction is a form of impaired selective attention that becomes more pronounced with normal aging and in pathological conditions such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related potentials (ERPs) provide sensitive, time-resolved measures of neural mechanisms underlying distractibility. This study aimed to identify age- and disease-related ERP signatures of auditory-visual distraction as potential functional biomarkers for cognitive decline. <b>Methods</b>: Forty-six participants were enrolled, including young controls (Y), healthy older controls (O), individuals with MCI, and individuals with AD. Participants performed cross-modal interference tasks in which irrelevant auditory distracting sounds were paired with a relevant visual discriminating task. The distraction potential was quantified as the difference between ERP responses to novel distractors and standard stimuli, focusing on three core components: N1-enhancement, P3a, and reorienting negativity (RON). Behavioral measures (accuracy, reaction time, miss responses) were also assessed. <b>Results</b>: Compared to Y, O showed increased N1-enhancement and reduced P3a", "source": "PubMed"}, {"chunk_id": "41300247_1", "pmid": "41300247", "title": "ERP Biomarkers of Auditory-Visual Distraction in Aging and Cognitive Impairment.", "authors": "Gumenyuk V, Korzyukov O, Parker SM et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, aging, and mild cognitive impairment, distraction, event-related potentials", "chunk": "three core components: N1-enhancement, P3a, and reorienting negativity (RON). Behavioral measures (accuracy, reaction time, miss responses) were also assessed. <b>Results</b>: Compared to Y, O showed increased N1-enhancement and reduced P3a and RON amplitudes, consistent with age-related susceptibility to distraction. Patients with MCI and AD exhibited further abnormalities, including diminished P3a and altered RON responses, suggesting impaired orientation and reorientation of attention. Behavioral distraction effect was observed in all groups, with no significant difference between groups. ERP-cognition correlations indicated that reduced P3a amplitude and delayed RON were associated with executive dysfunction and memory deficits. <b>Conclusions</b>: ERP signatures of distraction, particularly altered P3a and RON components, differentiate normal aging from pathological decline and may serve as functional biomarkers for early detection of MCI and AD. These findings highlight the translational potential of distraction paradigms in clinical assessment of aging-related cognitive impairment.", "source": "PubMed"}, {"chunk_id": "41300247_2", "pmid": "41300247", "title": "ERP Biomarkers of Auditory-Visual Distraction in Aging and Cognitive Impairment.", "authors": "Gumenyuk V, Korzyukov O, Parker SM et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, aging, and mild cognitive impairment, distraction, event-related potentials", "chunk": "MCI and AD. These findings highlight the translational potential of distraction paradigms in clinical assessment of aging-related cognitive impairment.", "source": "PubMed"}, {"chunk_id": "34964149_0", "pmid": "34964149", "title": "Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.", "authors": "Baakman AC, Gavan C, van Doeselaar L et al.", "year": "2022", "journal": "British journal of clinical pharmacology", "keywords": "Alzheimer's disease, cholinergic challenge, galantamine, pharmacology", "chunk": "Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's disease (AD) patients, but are associated with multiple side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of administration of a single dose of galantamine on central nervous system (CNS) functioning in mild to moderate AD patients and its potential to predict long-term treatment response. This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine", "source": "PubMed"}, {"chunk_id": "34964149_1", "pmid": "34964149", "title": "Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.", "authors": "Baakman AC, Gavan C, van Doeselaar L et al.", "year": "2022", "journal": "British journal of clinical pharmacology", "keywords": "Alzheimer's disease, cholinergic challenge, galantamine, pharmacology", "chunk": "NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their minimental state examination (MMSE), neuropsychiatric inventory (NPI) and disability assessment in dementia (DAD) scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. A single dose of galantamine significantly reduced saccadic reaction time (-0.0099; 95% CI = -0.0195, -0.0003; P = .0430), absolute frontal EEG parameters in alpha (-14.9; 95% CI = -21.0, -8.3; P = .0002), beta (-12.6; 95% CI = -19.4, -5.3; P = .0019) and theta (-17.9; 95% CI = -25.0, -10.0; P = .0001) frequencies. Relative frontal (-1.669; 95% CI = -2.999, -0.339; P = .0156) and occipital (-1.856; 95%", "source": "PubMed"}, {"chunk_id": "34964149_2", "pmid": "34964149", "title": "Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.", "authors": "Baakman AC, Gavan C, van Doeselaar L et al.", "year": "2022", "journal": "British journal of clinical pharmacology", "keywords": "Alzheimer's disease, cholinergic challenge, galantamine, pharmacology", "chunk": "P = .0019) and theta (-17.9; 95% CI = -25.0, -10.0; P = .0001) frequencies. Relative frontal (-1.669; 95% CI = -2.999, -0.339; P = .0156) and occipital (-1.856; 95% CI = -3.339, -0.372; P = .0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95% CI = 0.158, 2.475; P = .0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (-20.4; 95% CI = -31.6, -7.47; P = .0046), beta (-15.7; 95% CI = -28.3, -0.93; P = .0390) and theta (-25.9; 95% CI = -38.4, -10.9; P = .0024) EEG parameters and of relative frontal theta power (-3.27%; 95% CI = -5.96, -0.58; P = .0187) on EEG significantly distinguished responders (n = 11) from non-responders (n = 32) after 6 months. This study demonstrates that acute PD effects after single dose of galantamine are correlated with", "source": "PubMed"}, {"chunk_id": "34964149_3", "pmid": "34964149", "title": "Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.", "authors": "Baakman AC, Gavan C, van Doeselaar L et al.", "year": "2022", "journal": "British journal of clinical pharmacology", "keywords": "Alzheimer's disease, cholinergic challenge, galantamine, pharmacology", "chunk": "EEG significantly distinguished responders (n = 11) from non-responders (n = 32) after 6 months. This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.", "source": "PubMed"}, {"chunk_id": "40562636_0", "pmid": "40562636", "title": "Clinical trials for neuropsychiatric syndromes in major and mild neurocognitive disorders: A CONSORT-based approach.", "authors": "Cummings JL, Zhong K, Ballard C et al.", "year": "2025", "journal": "International psychogeriatrics", "keywords": "Alzheimer's disease, Apathy, Bayesian design, Education, Neuropsychiatric syndromes, Outcome measures, Psychosis", "chunk": "Neuropsychiatric syndromes (NPS) such as agitation, psychosis, apathy, and irritability are among the most disabling features of major and mild neurocognitive disorders including Alzheimer's disease, other neurodegenerative disorders (NDD), and vascular cognitive impairment. Clinical trial methodologies for the treatment of these syndromes are evolving and the first agents to reduce NPS severity has been approved. Biomarkers are rapidly becoming available to guide clinical trial decision-making. Biomarkers can confirm the diagnosis of Alzheimer's disease and are playing a larger role in non-Alzheimer trials. The Consolidated Standards for Reporting Trials (CONSORT) specify the elements of clinical trials that must be reported when clinical trials are published. These criteria provide conventions for uniform reporting of all key aspects of a clinical trial and facilitate comparisons across trials. We describe best practices for clinical trials of NPS including research definitions of the NDD, use of biomarkers to support clinical diagnosis, research criteria for NPS,", "source": "PubMed"}, {"chunk_id": "40562636_1", "pmid": "40562636", "title": "Clinical trials for neuropsychiatric syndromes in major and mild neurocognitive disorders: A CONSORT-based approach.", "authors": "Cummings JL, Zhong K, Ballard C et al.", "year": "2025", "journal": "International psychogeriatrics", "keywords": "Alzheimer's disease, Apathy, Bayesian design, Education, Neuropsychiatric syndromes, Outcome measures, Psychosis", "chunk": "facilitate comparisons across trials. We describe best practices for clinical trials of NPS including research definitions of the NDD, use of biomarkers to support clinical diagnosis, research criteria for NPS, use of rating scales to define the severity of NPS at baseline and as endpoints for the clinical trial, and approaches to data analysis of specific interest in NPS trials. Standards for describing the limitations of trials and their generalizability are provided. The goal is to inform planning and reporting of NPS trials including the use of biomarkers based on CONSORT guidelines for best trial practices.", "source": "PubMed"}, {"chunk_id": "33918453_0", "pmid": "33918453", "title": "Diagnostic Classification and Biomarker Identification of Alzheimer's Disease with Random Forest Algorithm.", "authors": "Song M, Jung H, Lee S et al.", "year": "2021", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, Gini index, Random Forest, convolutional neural network, feature importance, machine learning, magnetic resonance imaging, mild-cognitive impairment", "chunk": "Random Forest (RF) is a bagging ensemble model and has many important advantages, such as robustness to noise, an effective structure for complex multimodal data and parallel computing, and also provides important features that help investigate biomarkers. Despite these benefits, RF is not used actively to predict Alzheimer's disease (AD) with brain MRIs. Recent studies have reported RF's effectiveness in predicting AD, but the test sample sizes were too small to draw any solid conclusions. Thus, it is timely to compare RF with other learning model methods, including deep learning, particularly with large amounts of data. In this study, we tested RF and various machine learning models with regional volumes from 2250 brain MRIs: 687 normal controls (NC), 1094 mild cognitive impairment (MCI), and 469 AD that ADNI (Alzheimer's Disease Neuroimaging Initiative database) provided. Three types of features sets (63, 29, and 22 features) were selected, and classification accuracies were", "source": "PubMed"}, {"chunk_id": "33918453_1", "pmid": "33918453", "title": "Diagnostic Classification and Biomarker Identification of Alzheimer's Disease with Random Forest Algorithm.", "authors": "Song M, Jung H, Lee S et al.", "year": "2021", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, Gini index, Random Forest, convolutional neural network, feature importance, machine learning, magnetic resonance imaging, mild-cognitive impairment", "chunk": "cognitive impairment (MCI), and 469 AD that ADNI (Alzheimer's Disease Neuroimaging Initiative database) provided. Three types of features sets (63, 29, and 22 features) were selected, and classification accuracies were computed with RF, Support vector machine (SVM), Multi-layer perceptron (MLP), and Convolutional neural network (CNN). As a result, RF, MLP, and CNN showed high performances of 90.2%, 89.6%, and 90.5% with 63 features. Interestingly, when 22 features were used, RF showed the smallest decrease in accuracy, -3.8%, and the standard deviation did not change significantly, while MLP and CNN yielded decreases in accuracy of -6.8% and -4.5% with changes in the standard deviation from 3.3% to 4.0% for MLP and 2.1% to 7.0% for CNN, indicating that RF predicts AD more reliably with fewer features. In addition, we investigated the importance of the features that RF provides, and identified the hippocampus, amygdala, and inferior lateral ventricle as the major contributors", "source": "PubMed"}, {"chunk_id": "33918453_2", "pmid": "33918453", "title": "Diagnostic Classification and Biomarker Identification of Alzheimer's Disease with Random Forest Algorithm.", "authors": "Song M, Jung H, Lee S et al.", "year": "2021", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, Gini index, Random Forest, convolutional neural network, feature importance, machine learning, magnetic resonance imaging, mild-cognitive impairment", "chunk": "more reliably with fewer features. In addition, we investigated the importance of the features that RF provides, and identified the hippocampus, amygdala, and inferior lateral ventricle as the major contributors in classifying NC, MCI, and AD. On average, AD showed smaller hippocampus and amygdala volumes and a larger volume of inferior lateral ventricle than those of MCI and NC.", "source": "PubMed"}, {"chunk_id": "40549317_0", "pmid": "40549317", "title": "Repurposing Saroglitazar for neurodegenerative disorders: insight into molecular signalling pathways and neuroprotective modulations.", "authors": "Kushawaha SK, Kumar H, Chauhan C et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Molecular signaling, Neurodegenerative disorders, Neuroinflammatory, Oxidative stress, Saroglitazar", "chunk": "Drug repurposing has emerged as a cost-efficient strategy for neurodegenerative disorders (NDDs), leveraging existing preclinical, safety, and tolerability data to identify therapeutic candidates. NDDs, including epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), and traumatic brain injury (TBI), are characterized by neuroinflammation, oxidative stress, and neuronal degeneration, with key signaling pathways such as HMGB1, TRPA1, NF-\u03baB, MAPK, and PI3K/Akt-GSK3\u03b2 playing pivotal roles in their pathogenesis. Given the established link between type 2 diabetes mellitus and neurodegeneration, Saroglitazar, a dual PPAR-\u03b1/\u03b3 agonist, holds promise in modulating insulin signaling, oxidative stress, neuroinflammation, and key pathways, including HMGB1, TRPA1, NF-\u03baB, MAPK, and PI3K/Akt-GSK3\u03b2. This is the first comprehensive review to examine the effects of Saroglitazar in modulating multiple pathways associated with NDDs, thereby addressing existing gaps in the literature. The review explores the mechanistic interplay among these pathways and emphasizes the potential of Saroglitazar as a neuroprotective agent, highlighting the need for further studies", "source": "PubMed"}, {"chunk_id": "40549317_1", "pmid": "40549317", "title": "Repurposing Saroglitazar for neurodegenerative disorders: insight into molecular signalling pathways and neuroprotective modulations.", "authors": "Kushawaha SK, Kumar H, Chauhan C et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Molecular signaling, Neurodegenerative disorders, Neuroinflammatory, Oxidative stress, Saroglitazar", "chunk": "existing gaps in the literature. The review explores the mechanistic interplay among these pathways and emphasizes the potential of Saroglitazar as a neuroprotective agent, highlighting the need for further studies to validate its clinical efficacy and disease-modifying capabilities in NDDs. All supporting data were obtained from peer-reviewed literature accessed via PubMed, Web of Science, and Scopus.", "source": "PubMed"}, {"chunk_id": "40000185_0", "pmid": "40000185", "title": "[Classification of Alzheimer's disease based on multi-example learning and multi-scale feature fusion].", "authors": "Zeng A, Shuai Z, Pan D et al.", "year": "2025", "journal": "Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi", "keywords": "Alzheimer\u2019s disease, Multi-example learning, Multi-scale, Positional coding, Voxel block", "chunk": "Alzheimer's disease (AD) classification models usually segment the entire brain image into voxel blocks and assign them labels consistent with the entire image, but not every voxel block is closely related to the disease. To this end, an AD auxiliary diagnosis framework based on weakly supervised multi-instance learning (MIL) and multi-scale feature fusion is proposed, and the framework is designed from three aspects: within the voxel block, between voxel blocks, and high-confidence voxel blocks. First, a three-dimensional convolutional neural network was used to extract deep features within the voxel block; then the spatial correlation information between voxel blocks was captured through position encoding and attention mechanism; finally, high-confidence voxel blocks were selected and combined with multi-scale information fusion strategy to integrate key features for classification decision. The performance of the model was evaluated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS) datasets. Experimental", "source": "PubMed"}, {"chunk_id": "40000185_1", "pmid": "40000185", "title": "[Classification of Alzheimer's disease based on multi-example learning and multi-scale feature fusion].", "authors": "Zeng A, Shuai Z, Pan D et al.", "year": "2025", "journal": "Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi", "keywords": "Alzheimer\u2019s disease, Multi-example learning, Multi-scale, Positional coding, Voxel block", "chunk": "integrate key features for classification decision. The performance of the model was evaluated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS) datasets. Experimental results showed that the proposed framework improved ACC and AUC by 3% and 4% on average compared with other mainstream frameworks in the two tasks of AD classification and mild cognitive impairment conversion classification, and could find the key voxel blocks that trigger the disease, providing an effective basis for AD auxiliary diagnosis.", "source": "PubMed"}, {"chunk_id": "41104612_0", "pmid": "41104612", "title": "Impact of regional white matter hyperintensity patterns on cognitive trajectories in NACC.", "authors": "Rotblatt LJ, Edwards L, Erani F et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, cognitive decline, neuropsychology, small vessel disease, white matter hyperintensities", "chunk": "White matter hyperintensities (WMHs) are a biomarker of small vessel cerebrovascular changes that can emerge early in Alzheimer's disease. While global WMHs correlate with cognitive decline, the impact of regional WMHs remains understudied. We examined associations of regional WMH distributions with longitudinal cognition. National Alzheimer's Coordinating Center cohort participants (n = 1047; cognitively normal, mild cognitive impairment, dementia) completed neuropsychological and neuroimaging assessments. Hierarchical cluster analysis identified baseline regional WMH patterns, and linear mixed-effects models assessed 2 year change in cognitive domain by cluster. Five WMH clusters emerged. Compared to those with low WMH burden, participants in the mild occipital and high parieto-occipital clusters had faster memory decline; mild fronto-parietal and high parieto-occipital clusters showed faster executive decline; and mild and high fronto-parietal and high parieto-occipital clusters had faster language decline. Regional WMH distributions showed distinct trajectories. Posterior WMHs were most associated with memory decline, while even mild WMHs accelerated", "source": "PubMed"}, {"chunk_id": "41104612_1", "pmid": "41104612", "title": "Impact of regional white matter hyperintensity patterns on cognitive trajectories in NACC.", "authors": "Rotblatt LJ, Edwards L, Erani F et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, cognitive decline, neuropsychology, small vessel disease, white matter hyperintensities", "chunk": "and high fronto-parietal and high parieto-occipital clusters had faster language decline. Regional WMH distributions showed distinct trajectories. Posterior WMHs were most associated with memory decline, while even mild WMHs accelerated decline in some domains. Hierarchical cluster analysis identified five white matter hyperintensity (WMH) patterns. Posterior WMHs were most related to memory decline. Mild frontal and elevated posterior patterns were associated with executive function decline. Multiple WMH patterns were associated with language decline.", "source": "PubMed"}, {"chunk_id": "41743329_0", "pmid": "41743329", "title": "Non-compacted, PET-insensitive amyloid states increase after systemic inflammation and predict neuritic damage across A\u03b2 pathology models and Alzheimer patients.", "authors": "Liu P, Wendeln AC, Wagner J et al.", "year": "2026", "journal": "Research square", "keywords": "None", "chunk": "Neuroinflammation is a key modulator of Alzheimer's disease (AD) risk, yet the impact of non-genetic inflammatory risk factors - such as systemic inflammation - remains poorly defined. Building on our previous work, here we show that 9 months after systemic lipopolysaccharide (LPS) challenge in APP23 mice, microglia-plaque interaction is disturbed and shifts A\u03b2 aggregates toward a less compacted state, as revealed by conformation-sensitive amyloid dyes. Importantly, these structural changes are associated with increased plaque-associated neuritic dystrophy, phenocopying the effects of microglial risk genes. Generalising these findings, we show that across aging in APP23 and APPPS1 mice, and in AD patient tissue, non-compacted amyloid and microgliosis - but not compacted amyloid - are consistent predictors of neuritic damage. Notably, both in mouse and human tissue, <i>ex vivo</i> amyloid-PET signal largely reflects compacted but not non-compacted amyloid load. Our findings suggest that genetic and environmental risk factors converge on shared mechanisms of", "source": "PubMed"}, {"chunk_id": "41743329_1", "pmid": "41743329", "title": "Non-compacted, PET-insensitive amyloid states increase after systemic inflammation and predict neuritic damage across A\u03b2 pathology models and Alzheimer patients.", "authors": "Liu P, Wendeln AC, Wagner J et al.", "year": "2026", "journal": "Research square", "keywords": "None", "chunk": "mouse and human tissue, <i>ex vivo</i> amyloid-PET signal largely reflects compacted but not non-compacted amyloid load. Our findings suggest that genetic and environmental risk factors converge on shared mechanisms of impaired microglial-plaque interaction and amyloid restructuring, and that commonly used amyloid-PET measures insufficiently capture amyloid states that define the severity of neuritic damage, with important implications for clinical trials in AD.", "source": "PubMed"}, {"chunk_id": "40392946_0", "pmid": "40392946", "title": "Intranasal insulin enhances resting-state functional connectivity in Type 2 Diabetes.", "authors": "Zhang Z, Novak V, Novak P et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "Type 2 diabetes mellitus (T2DM) affects cognition and resting-state functional connectivity (rsFC). Intranasal insulin (INI) has emerged as a potential treatment for T2DM-related cognitive decline. We aimed to evaluate the effect of INI treatment on rsFC with medio-prefrontal (mPFC) and left/right hippocampus (lHPC/rHPC), and their relationship with the cognition, hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and walking speed. An MRI sub-study of the MemAID trial was conducted, involving a 24-week treatment with either intranasal insulin or placebo. Blood oxygen level-dependent (BOLD) functional MRI (fMRI) images were acquired on eighteen DM subjects at baseline and eleven DM subjects (eight DM-INI patients and three DM-Placebo) at the end-of-treatment. Compared to DM-Placebo treated subjects, DM-INI patients showed increased mPFC-postcentral rsFC, lHPC-frontal rsFC, lHPC-postcentral rsFC, rHPC-frontal rsFC, and lHPC-mPFC rsFC (p < 0.05). The decreased HOMA-IR, which was observed in the MemAID trial, was associated with increased mPFC-basal ganglia", "source": "PubMed"}, {"chunk_id": "40392946_1", "pmid": "40392946", "title": "Intranasal insulin enhances resting-state functional connectivity in Type 2 Diabetes.", "authors": "Zhang Z, Novak V, Novak P et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "mPFC-postcentral rsFC, lHPC-frontal rsFC, lHPC-postcentral rsFC, rHPC-frontal rsFC, and lHPC-mPFC rsFC (p < 0.05). The decreased HOMA-IR, which was observed in the MemAID trial, was associated with increased mPFC-basal ganglia rsFC (p < 0.05). This sub-study provides insights into potential mechanisms of INI effects on rsFC that require validation in a larger trial.", "source": "PubMed"}, {"chunk_id": "39774202_0", "pmid": "39774202", "title": "Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).", "authors": "Devlin JW, Sieber F, Akeju O et al.", "year": "2025", "journal": "Critical care medicine", "keywords": "None", "chunk": "To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults. A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs). To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual", "source": "PubMed"}, {"chunk_id": "39774202_1", "pmid": "39774202", "title": "Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).", "authors": "Devlin JW, Sieber F, Akeju O et al.", "year": "2025", "journal": "Critical care medicine", "keywords": "None", "chunk": "conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews. We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance.", "source": "PubMed"}, {"chunk_id": "39774202_2", "pmid": "39774202", "title": "Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).", "authors": "Devlin JW, Sieber F, Akeju O et al.", "year": "2025", "journal": "Critical care medicine", "keywords": "None", "chunk": "duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key. By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.", "source": "PubMed"}, {"chunk_id": "26041981_0", "pmid": "26041981", "title": "Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration.", "authors": "van Dijk G, van Heijningen S, Reijne AC et al.", "year": "2015", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer's disease, TNF, aging, blood-brain barrier, metabolic syndrome, neuroinflammation, obesity, type-2 diabetes mellitus", "chunk": "Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid \u03b2 peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by \"systems biology\" approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses", "source": "PubMed"}, {"chunk_id": "26041981_1", "pmid": "26041981", "title": "Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration.", "authors": "van Dijk G, van Heijningen S, Reijne AC et al.", "year": "2015", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer's disease, TNF, aging, blood-brain barrier, metabolic syndrome, neuroinflammation, obesity, type-2 diabetes mellitus", "chunk": "these interact. Future research therefore might concentrate on integrating these by \"systems biology\" approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.", "source": "PubMed"}, {"chunk_id": "39331931_0", "pmid": "39331931", "title": "The role and mechanism of dapagliflozin in Alzheimer disease: A review.", "authors": "Chen P, Liang L, Dai Y et al.", "year": "2024", "journal": "Medicine", "keywords": "None", "chunk": "Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.", "source": "PubMed"}, {"chunk_id": "39331931_1", "pmid": "39331931", "title": "The role and mechanism of dapagliflozin in Alzheimer disease: A review.", "authors": "Chen P, Liang L, Dai Y et al.", "year": "2024", "journal": "Medicine", "keywords": "None", "chunk": "clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.", "source": "PubMed"}, {"chunk_id": "31397865_0", "pmid": "31397865", "title": "Longitudinal Association of Depression Symptoms With Cognition and Cortical Amyloid Among Community-Dwelling Older Adults.", "authors": "Gatchel JR, Rabin JS, Buckley RF et al.", "year": "2019", "journal": "JAMA network open", "keywords": "None", "chunk": "Depressive symptoms are prevalent among older adults and may be early manifestations of Alzheimer disease (AD) before onset of mild cognitive impairment. However, it remains unclear whether worsening depressive symptoms in the presence of AD pathology are associated with cognitive decline in older adults. To determine the longitudinal association between depressive symptoms, cognition, and cortical amyloid in community-dwelling older adults. Participants from the Harvard Aging Brain Study, a cohort study, underwent annual assessments of depression and cognition and baseline cortical amyloid measurement (mean, 4.42 years; range, 2-7 years). Data collection was from September 2010 to August 2017 in a convenience sample of community-dwelling adults (276 participants, all cognitively unimpaired) with at most mild depression at entry. Depression (Geriatric Depression Scale [GDS]), cognition (Preclinical Alzheimer Cognitive Composite [PACC]), and a continuous measure of cortical amyloid (Pittsburgh Compound-B positron emission tomography imaging). Change in GDS and baseline amyloid were examined as interactive", "source": "PubMed"}, {"chunk_id": "31397865_1", "pmid": "31397865", "title": "Longitudinal Association of Depression Symptoms With Cognition and Cortical Amyloid Among Community-Dwelling Older Adults.", "authors": "Gatchel JR, Rabin JS, Buckley RF et al.", "year": "2019", "journal": "JAMA network open", "keywords": "None", "chunk": "[GDS]), cognition (Preclinical Alzheimer Cognitive Composite [PACC]), and a continuous measure of cortical amyloid (Pittsburgh Compound-B positron emission tomography imaging). Change in GDS and baseline amyloid were examined as interactive predictors of PACC decline in a linear mixed model with backward elimination, adjusting for age, sex, and education. Participants were 164 women and 112 men (mean [SD] age, 73.5 [6.0] years). At baseline, the mean (SD) GDS score was 3.0 (2.8) (range, 0-12), the mean (SD) PACC score was -0.004 (0.67) (range, -2.32 to 1.88), and the mean (SD) amyloid positron emission tomography distribution volume ratio was 1.16 (0.20) (range, 0.92-1.94). At last follow-up, the mean (SD) GDS score was 3.9 (2.9) (range, 0-12), and the mean (SD) PACC score was -0.09 (1.27) (range, -5.66 to 1.67). The interaction between cortical amyloid and increasing GDS was associated with declining cognition (\u03b2 = -0.19; 95% CI, -0.27 to -0.12; P <", "source": "PubMed"}, {"chunk_id": "31397865_2", "pmid": "31397865", "title": "Longitudinal Association of Depression Symptoms With Cognition and Cortical Amyloid Among Community-Dwelling Older Adults.", "authors": "Gatchel JR, Rabin JS, Buckley RF et al.", "year": "2019", "journal": "JAMA network open", "keywords": "None", "chunk": "was -0.09 (1.27) (range, -5.66 to 1.67). The interaction between cortical amyloid and increasing GDS was associated with declining cognition (\u03b2 = -0.19; 95% CI, -0.27 to -0.12; P < .001). In this study, cortical amyloid moderated the association between worsening depressive symptoms and declining cognition in older adults. While future work is needed to better understand causal associations, these findings may enhance early detection and prevention of AD clinical symptoms.", "source": "PubMed"}, {"chunk_id": "40885031_0", "pmid": "40885031", "title": "Advanced intranasal peptide delivery systems for improved management of Alzheimer's disease.", "authors": "Majie A, Karmakar V, Ghosh A et al.", "year": "2026", "journal": "Biomaterials advances", "keywords": "Alzheimer's disease, Blood-brain-barrier, Intranasal drug delivery, Nanoparticles, Neuropeptide", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline, memory loss, and impairment in daily functioning, making up nearly 60 % of all dementia cases. Current treatments primarily manage symptoms rather than address the disease itself, underscoring the need for more effective solutions. Therapeutic peptides have emerged as promising candidates, targeting critical pathological processes in AD. Additionally, intranasal delivery offers significant advantages, including non-invasiveness, enhanced stability, rapid absorption, and the ability to bypass the blood-brain barrier. This review explores the potential of intranasal peptide delivery for AD treatment, beginning with an overview of the disease's mechanisms and existing therapies. We discuss the challenges of targeting the brain, examine nose-to-brain delivery pathways, and highlight recent advancements in delivery techniques, including the role of nanoparticles in improving efficacy. Our goal is to encourage further research into these innovative delivery strategies that could improve patient compliance and treatment outcomes.", "source": "PubMed"}, {"chunk_id": "40885031_1", "pmid": "40885031", "title": "Advanced intranasal peptide delivery systems for improved management of Alzheimer's disease.", "authors": "Majie A, Karmakar V, Ghosh A et al.", "year": "2026", "journal": "Biomaterials advances", "keywords": "Alzheimer's disease, Blood-brain-barrier, Intranasal drug delivery, Nanoparticles, Neuropeptide", "chunk": "delivery techniques, including the role of nanoparticles in improving efficacy. Our goal is to encourage further research into these innovative delivery strategies that could improve patient compliance and treatment outcomes. While preclinical studies indicate substantial promise, advancing these findings into clinical applications remains crucial to overcoming drug delivery challenges and ensuring long-term safety.", "source": "PubMed"}, {"chunk_id": "37012066_0", "pmid": "37012066", "title": "Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic.", "authors": "Altomare D, Stampacchia S, Ribaldi F et al.", "year": "2023", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "CSF, PET, alzheimer's disease, dementia, memory", "chunk": "The key Alzheimer's disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid A\u03b2<sub>42</sub> and p-tau<sub>181</sub>), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers. Participants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months. Overall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up to <i>r</i>=0.50 (p<0.001) among amyloid, <i>r</i>=0.43 (p=0.002) among tau, and <i>r</i>=-0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high", "source": "PubMed"}, {"chunk_id": "37012066_1", "pmid": "37012066", "title": "Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic.", "authors": "Altomare D, Stampacchia S, Ribaldi F et al.", "year": "2023", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "CSF, PET, alzheimer's disease, dementia, memory", "chunk": "biomarkers significantly correlated with biomarkers assessed through traditional techniques: up to <i>r</i>=0.50 (p<0.001) among amyloid, <i>r</i>=0.43 (p=0.002) among tau, and <i>r</i>=-0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers. The implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.", "source": "PubMed"}, {"chunk_id": "38476659_0", "pmid": "38476659", "title": "Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors.", "authors": "Ganesan K, Rentsch P, Langdon A et al.", "year": "2024", "journal": "Frontiers in aging neuroscience", "keywords": "Apolipoprotein E, dendritic spine density, lipopolysaccharide, neuroinflammation, sporadic and familial Alzheimer\u2019s disease", "chunk": "Developing effective treatment for Alzheimer's disease (AD) remains a challenge. This can be partially attributed to the fact that the mouse models used in preclinical research largely replicate familial form of AD, while majority of human cases are sporadic; both forms differ widely in the onset and origin of pathology, therefore requiring specific/targeted treatments. In this study, we aimed to model sporadic AD in mice by combining two of the many risk factors that are strongly implicated in AD: ApoE4, a major genetic risk factor, together with an inflammatory stimuli. Accordingly, we subjected ApoE4 knock in (KI) mice, expressing humanized ApoE4, to low doses of Lipopolysaccharide (LPS) injections (i.p, weekly, for 4 months). We assessed these animals for behavioral impairments at 6 months of age using Open Field, Y-maze, and Barnes Maze Test. LPS induced hypoactivity was observed in the Open Field and Y-maze test, whereas spatial learning and memory", "source": "PubMed"}, {"chunk_id": "38476659_1", "pmid": "38476659", "title": "Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors.", "authors": "Ganesan K, Rentsch P, Langdon A et al.", "year": "2024", "journal": "Frontiers in aging neuroscience", "keywords": "Apolipoprotein E, dendritic spine density, lipopolysaccharide, neuroinflammation, sporadic and familial Alzheimer\u2019s disease", "chunk": "at 6 months of age using Open Field, Y-maze, and Barnes Maze Test. LPS induced hypoactivity was observed in the Open Field and Y-maze test, whereas spatial learning and memory was intact. We then quantified differences in dendritic spine density, which is a strong correlate of AD. ApoE4KI mice showed a significant reduction in the number of spines after treatment with LPS, whereas there were no obvious differences in the total number of microglia and astrocytes. To conclude, in the current study the APoEe4 risk gene increases the vulnerability of hippocampal neurons to inflammation induced spine loss, laying a foundation for an early sporadic AD mouse model.", "source": "PubMed"}, {"chunk_id": "36958233_0", "pmid": "36958233", "title": "Multimodal cross enhanced fusion network for diagnosis of Alzheimer's disease and subjective memory complaints.", "authors": "Leng Y, Cui W, Peng Y et al.", "year": "2023", "journal": "Computers in biology and medicine", "keywords": "Alzheimer\u2019s disease (AD) diagnosis, Cross enhanced fusion, Multiscale long-range receptive field, Subjective memory complaints (SMC) diagnosis", "chunk": "Deep learning methods using multimodal imagings have been proposed for the diagnosis of Alzheimer's disease (AD) and its early stages (SMC, subjective memory complaints), which may help to slow the progression of the disease through early intervention. However, current fusion methods for multimodal imagings are generally coarse and may lead to suboptimal results through the use of shared extractors or simple downscaling stitching. Another issue with diagnosing brain diseases is that they often affect multiple areas of the brain, making it important to consider potential connections throughout the brain. However, traditional convolutional neural networks (CNNs) may struggle with this issue due to their limited local receptive fields. To address this, many researchers have turned to transformer networks, which can provide global information about the brain but can be computationally intensive and perform poorly on small datasets. In this work, we propose a novel lightweight network called MENet that adaptively recalibrates", "source": "PubMed"}, {"chunk_id": "36958233_1", "pmid": "36958233", "title": "Multimodal cross enhanced fusion network for diagnosis of Alzheimer's disease and subjective memory complaints.", "authors": "Leng Y, Cui W, Peng Y et al.", "year": "2023", "journal": "Computers in biology and medicine", "keywords": "Alzheimer\u2019s disease (AD) diagnosis, Cross enhanced fusion, Multiscale long-range receptive field, Subjective memory complaints (SMC) diagnosis", "chunk": "global information about the brain but can be computationally intensive and perform poorly on small datasets. In this work, we propose a novel lightweight network called MENet that adaptively recalibrates the multiscale long-range receptive field to localize discriminative brain regions in a computationally efficient manner. Based on this, the network extracts the intensity and location responses between structural magnetic resonance imagings (sMRI) and 18-Fluoro-Deoxy-Glucose Positron Emission computed Tomography (FDG-PET) as an enhancement fusion for AD and SMC diagnosis. Our method is evaluated on the publicly available ADNI datasets and achieves 97.67% accuracy in AD diagnosis tasks and 81.63% accuracy in SMC diagnosis tasks using sMRI and FDG-PET. These results achieve state-of-the-art (SOTA) performance in both tasks. To the best of our knowledge, this is one of the first deep learning research methods for SMC diagnosis with FDG-PET.", "source": "PubMed"}, {"chunk_id": "36958233_2", "pmid": "36958233", "title": "Multimodal cross enhanced fusion network for diagnosis of Alzheimer's disease and subjective memory complaints.", "authors": "Leng Y, Cui W, Peng Y et al.", "year": "2023", "journal": "Computers in biology and medicine", "keywords": "Alzheimer\u2019s disease (AD) diagnosis, Cross enhanced fusion, Multiscale long-range receptive field, Subjective memory complaints (SMC) diagnosis", "chunk": "our knowledge, this is one of the first deep learning research methods for SMC diagnosis with FDG-PET.", "source": "PubMed"}, {"chunk_id": "41072625_0", "pmid": "41072625", "title": "An in vivo PET/CT investigation of mitochondrial complex 1, sigma 1, and synaptic vesicle 2\u00a0A in patients with amyotrophic lateral sclerosis.", "authors": "de Natale ER, Verghese JP, Terry A et al.", "year": "2025", "journal": "Neurobiology of disease", "keywords": "Amyotrophic lateral sclerosis, Mitochondrial complex 1, Neurodegeneration, Positron emission tomography, SV2A, Sigma-1 receptors", "chunk": "Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder which pathology is still largely unclear. To perform an in vivo cross-sectional investigation of mitochondrial complex 1 (MC1), synaptic vesicle 2 A (SV2A), and sigma-1 receptor (S1R) expression in ALS patients using the PET radioligands [<sup>18</sup>F]BCPP-EF, [<sup>11</sup>C]UCB-J, and [<sup>11</sup>C]SA4503. Sixteen ALS patients (twelve males, mean age: 57.49 \u00b1 12.08 years) and sixteen healthy controls underwent clinical assessment, MRI, and PET imaging with [<sup>18</sup>F]BCPP-EF, [<sup>11</sup>C]UCB-J, and [<sup>11</sup>C]SA4503. Patients were stratified based on disease the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) progression rate into slow, and moderate/fast progressors. Volume of distribution (V<sub>T</sub>) of predefined regions of interest, corrected for partial volume effects, was the primary outcome. Across the ALS cohort, [<sup>18</sup>F]BCPP-EF binding was reduced in the amygdala (-13.9 %, F = 4.938 p = 0.034). Moderate/fast progression ALS patients exhibited [<sup>18</sup>F]BCPP-EF binding loss in the hippocampus (-20.0 %), amygdala (-21.4 %), cerebellum", "source": "PubMed"}, {"chunk_id": "41072625_1", "pmid": "41072625", "title": "An in vivo PET/CT investigation of mitochondrial complex 1, sigma 1, and synaptic vesicle 2\u00a0A in patients with amyotrophic lateral sclerosis.", "authors": "de Natale ER, Verghese JP, Terry A et al.", "year": "2025", "journal": "Neurobiology of disease", "keywords": "Amyotrophic lateral sclerosis, Mitochondrial complex 1, Neurodegeneration, Positron emission tomography, SV2A, Sigma-1 receptors", "chunk": "was reduced in the amygdala (-13.9 %, F = 4.938 p = 0.034). Moderate/fast progression ALS patients exhibited [<sup>18</sup>F]BCPP-EF binding loss in the hippocampus (-20.0 %), amygdala (-21.4 %), cerebellum (-19.5 %), insular cortex (-19.3 %), temporal lobe (-19.0 %), and anterior cingulate (-18.7 %) (all p < 0.05); and [<sup>11</sup>C]SA4503 binding loss in the caudate (-20.6 %), pallidus (-26.8 %), amygdala (-20.2 %), hippocampus (-17.4 %), insular cortex (-16.9 %), accumbens (-17.0 %), anterior cingulate (-16.4 %) and temporal lobe (-19.8 %) compared to controls (all p < 0.05). In moderate/fast progressors, [<sup>18</sup>F]BCPP-EF loss in the insular cortex, amygdala, anterior cingulate, and temporal lobe correlated with lower ALSFRS-R scores (p < 0.05). Our findings reveal loss of MC1 and S1R in ALS, suggesting mitochondrial dysfunction associated with disease progression. This work provides initial insights of mitochondrial and receptor pathology in ALS, potentially guiding future biomarker development and therapeutic interventions.", "source": "PubMed"}, {"chunk_id": "41072625_2", "pmid": "41072625", "title": "An in vivo PET/CT investigation of mitochondrial complex 1, sigma 1, and synaptic vesicle 2\u00a0A in patients with amyotrophic lateral sclerosis.", "authors": "de Natale ER, Verghese JP, Terry A et al.", "year": "2025", "journal": "Neurobiology of disease", "keywords": "Amyotrophic lateral sclerosis, Mitochondrial complex 1, Neurodegeneration, Positron emission tomography, SV2A, Sigma-1 receptors", "chunk": "S1R in ALS, suggesting mitochondrial dysfunction associated with disease progression. This work provides initial insights of mitochondrial and receptor pathology in ALS, potentially guiding future biomarker development and therapeutic interventions.", "source": "PubMed"}, {"chunk_id": "41232397_0", "pmid": "41232397", "title": "Critical nodes in precision diagnosis and treatment of Alzheimer's disease: exploration of multidimensional biomarkers and prospects for targeted intervention.", "authors": "Zuo Y, Ding X, Sun Y et al.", "year": "2025", "journal": "Journal of the neurological sciences", "keywords": "Alzheimer's disease (AD), Biomarkers, Neurodegeneration, Personalized treatment, Therapeutic targets", "chunk": "Alzheimer' s disease (AD), characterized by cognitive decline and progressive neurodegeneration, remains a major clinical and scientific challenge due to its complex pathophysiology and marked heterogeneity. Important signs of the disease, like the buildup of \u03b2-amyloid, changes in Tau proteins, inflammation in the brain, and problems with mitochondria, form the basis for developing targeted treatments. This review summarizes recent advances in the identification of therapeutic targets and multi-dimensional biomarkers, such as liquid, imaging, and multi-omics-based markers. These biomarkers hold potential for early diagnosis, disease subtyping, and therapeutic response monitoring. We suggest that combining biomarkers and treatment targets could be a key approach to improving personalized care for AD.", "source": "PubMed"}, {"chunk_id": "41748878_0", "pmid": "41748878", "title": "Predicting rates of cognitive and functional decline in Alzheimer's disease and mild cognitive impairment.", "authors": "Fogel A, Walsh C, Fletcher-Lloyd N et al.", "year": "2026", "journal": "Communications medicine", "keywords": "None", "chunk": "The global population of People Living with Dementia (PLWD) is expected to grow rapidly in the coming decades, increasing the need for personalised, generalisable, and scalable prognosis and care planning support. However, current prognostic guidance does not adequately capture the heterogeneity in dementia trajectories, and existing predictive models of dementia progression rely on costly and inaccessible data, limiting their scalability in resource-constrained settings. Using clinical assessments, demographic, and medical history data from 153 12-month clinical trajectories collected over three years, two machine learning algorithms were developed to predict 12-month cognitive and functional decline in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Models were externally validated on 741 trajectories from the ADNI cohort. Cognitive and functional decline were estimated using the Mini-Mental State Exam (MMSE) and Bristol Activities of Daily Living (BADL). The MMSE model achieves a mean absolute error (MAE) of 1.84 (95% CI: 1.64-2.04) internally and 2.19 in", "source": "PubMed"}, {"chunk_id": "41748878_1", "pmid": "41748878", "title": "Predicting rates of cognitive and functional decline in Alzheimer's disease and mild cognitive impairment.", "authors": "Fogel A, Walsh C, Fletcher-Lloyd N et al.", "year": "2026", "journal": "Communications medicine", "keywords": "None", "chunk": "the Mini-Mental State Exam (MMSE) and Bristol Activities of Daily Living (BADL). The MMSE model achieves a mean absolute error (MAE) of 1.84 (95% CI: 1.64-2.04) internally and 2.19 in external validation. The BADL model achieves an MAE of 3.88 (95% CI: 3.46-4.30). Baseline scores on ideational praxis, orientation, and word recall are among the strongest predictors of cognitive decline, while independence in food preparation, finances, and dressing are among the top predictors of functional decline. Our models use only routinely collected and easily accessible data, offering high translational potential. If implemented, our scalable, data-driven prognostic support tool could streamline clinical workflows, support personalised care planning, and provide PLWD and their families with greater clarity and reassurance.", "source": "PubMed"}, {"chunk_id": "39874294_0", "pmid": "39874294", "title": "Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.", "authors": "Jiang WI, Cao Y, Xue Y et al.", "year": "2025", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "APOE4, VHL\u2013HIF axis, mitochondrial dysfunction, neurodegeneration, oxidative stress", "chunk": "The \u03b54 variant of human apolipoprotein E (<i>APOE4</i>) is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of <i>APOE4</i> has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human <i>APOE4</i> in <i>Caenorhabditis elegans</i>. The protective effects of VHL-1 deletion are recapitulated by stabilized HIF-1 (hypoxia-inducible factor), a transcription factor degraded by VHL-1. HIF-1 activates a genetic program that safeguards against mitochondrial dysfunction, oxidative stress, proteostasis imbalance, and endolysosomal rupture-critical cellular events linked to neural pathologies and mortality. Furthermore, genetic inhibition of <i>Vhl</i> reduces cerebral vascular injury and synaptic lesions in <i>APOE4</i> mice, suggesting an evolutionarily conserved mechanism. Thus, we identify the VHL-HIF axis as a potent modulator of <i>APOE4</i>-induced neural pathologies and propose that targeting", "source": "PubMed"}, {"chunk_id": "39874294_1", "pmid": "39874294", "title": "Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.", "authors": "Jiang WI, Cao Y, Xue Y et al.", "year": "2025", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "APOE4, VHL\u2013HIF axis, mitochondrial dysfunction, neurodegeneration, oxidative stress", "chunk": "injury and synaptic lesions in <i>APOE4</i> mice, suggesting an evolutionarily conserved mechanism. Thus, we identify the VHL-HIF axis as a potent modulator of <i>APOE4</i>-induced neural pathologies and propose that targeting this pathway in nonproliferative tissues may curb cellular damage, protect against neurodegeneration, and reduce tissue injuries and mortality.", "source": "PubMed"}, {"chunk_id": "40161217_0", "pmid": "40161217", "title": "Unravelling pathological ageing with brain age gap estimation in Alzheimer's disease, diabetes and schizophrenia.", "authors": "Dias MF, Duarte JV, de Carvalho P et al.", "year": "2025", "journal": "Brain communications", "keywords": "brain age gap, deep learning, explainability, neuropsychiatric disorders", "chunk": "Brain age gap estimation (BrainAGE), the difference between predicted brain age and chronological age, might be a putative biomarker aiming to detect the transition from healthy to pathological brain ageing. The biomarker primarily models healthy ageing with machine learning models trained with structural magnetic resonance imaging (MRI) data. BrainAGE is expected to translate the deviations in neural ageing trajectory and has been shown to be increased in multiple pathologies, such as Alzheimer's disease (AD), schizophrenia and Type 2 diabetes (T2D). Thus, accelerated ageing seems to be a general feature of neuropathological processes. However, neurobiological constraints remain to be identified to provide specificity to this biomarker. Explainability might be the key to uncovering age predictions and understanding which brain regions lead to an elevated predicted age on a given pathology compared to healthy controls. This is highly relevant to understanding the similarities and differences in neurodegeneration in AD and T2D, which", "source": "PubMed"}, {"chunk_id": "40161217_1", "pmid": "40161217", "title": "Unravelling pathological ageing with brain age gap estimation in Alzheimer's disease, diabetes and schizophrenia.", "authors": "Dias MF, Duarte JV, de Carvalho P et al.", "year": "2025", "journal": "Brain communications", "keywords": "brain age gap, deep learning, explainability, neuropsychiatric disorders", "chunk": "to an elevated predicted age on a given pathology compared to healthy controls. This is highly relevant to understanding the similarities and differences in neurodegeneration in AD and T2D, which remains an outstanding biological question. Sensitivity maps explain models by computing the importance of each voxel on the final prediction, thereby contributing to the interpretability of deep learning approaches. This paper assesses whether sensitivity maps yield different results across three conditions related to pathological neural ageing: AD, schizophrenia and T2D. Five deep learning models were considered, each model trained with different MRI data types: minimally processed T<sub>1</sub>-weighted brain scans, and corresponding grey matter, white matter, cerebrospinal fluid tissue segmentation and deformation fields (after spatial normalization). Our results revealed an increased BrainAGE in all pathologies, with a different mean, which is the smallest in schizophrenia; this is in line with the observation that neural loss is secondary in this early-onset condition.", "source": "PubMed"}, {"chunk_id": "40161217_2", "pmid": "40161217", "title": "Unravelling pathological ageing with brain age gap estimation in Alzheimer's disease, diabetes and schizophrenia.", "authors": "Dias MF, Duarte JV, de Carvalho P et al.", "year": "2025", "journal": "Brain communications", "keywords": "brain age gap, deep learning, explainability, neuropsychiatric disorders", "chunk": "BrainAGE in all pathologies, with a different mean, which is the smallest in schizophrenia; this is in line with the observation that neural loss is secondary in this early-onset condition. Importantly, our findings suggest that the sensitivity, indexing regional weights, for all models varies with age. A set of regions were shown to yield statistical differences across conditions. These sensitivity results suggest that mechanisms of neurodegeneration are quite distinct in AD and T2D. For further validation, the sensitivity and the morphometric maps were compared. The findings outlined a high congruence between the sensitivity and morphometry maps for age and clinical group conditions. Our evidence outlines that the biological explanation of model predictions is vital in adding specificity to the BrainAGE and understanding the pathophysiology of chronic conditions affecting the brain.", "source": "PubMed"}, {"chunk_id": "40161217_3", "pmid": "40161217", "title": "Unravelling pathological ageing with brain age gap estimation in Alzheimer's disease, diabetes and schizophrenia.", "authors": "Dias MF, Duarte JV, de Carvalho P et al.", "year": "2025", "journal": "Brain communications", "keywords": "brain age gap, deep learning, explainability, neuropsychiatric disorders", "chunk": "and understanding the pathophysiology of chronic conditions affecting the brain.", "source": "PubMed"}, {"chunk_id": "41026459_0", "pmid": "41026459", "title": "Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.", "authors": "Nguyen HD", "year": "2025", "journal": "Acta neurologica Belgica", "keywords": "Biomarkers, GWAS, Molecular mechanisms, Parkinson\u2019s disease", "chunk": "Genetic variants can affect signaling pathways that are important in the pathophysiology of Parkinson's disease (PD). Comprehending their relationship is crucial for the development of diagnostic instruments and preventative drugs for PD. We thoroughly analyzed data from 68 genome-wide association studies to uncover significant genetic variations and clarify the molecular pathways underlying the etiology of Parkinson's disease (PD) resulting from genetic variants. Six common biomarkers linked to PD were found in all 68 investigations: SNCA, TMEM175, BST1, RIT2, LRRK2, and MCCC1. SNCA (\u2191rs5019538 and \u2191rs356182), LRRK2 (\u2191rs34637584 and \u2191rs76904798), and SH3GL2 (\u2191rs10756907 and \u2193rs13294100) were the main biomarkers associated with PD. The clinical traits of PD, such as age at onset, cognitive progression, motor progression, composite progression, tremor dominant, and postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13,", "source": "PubMed"}, {"chunk_id": "41026459_1", "pmid": "41026459", "title": "Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.", "authors": "Nguyen HD", "year": "2025", "journal": "Acta neurologica Belgica", "keywords": "Biomarkers, GWAS, Molecular mechanisms, Parkinson\u2019s disease", "chunk": "postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13, and FANCF. Significant evidence was found linking genetic variants linked to an increased risk of PD to reduced dopamine production, receptor recycling, oxidoreductase activity, and increased amyloid-beta accumulation. Considerable evidence links genetic variations with a lower risk of PD due to improved synaptic vesicle signaling, neuron projection development, controlled histone methylation, and excitatory postsynaptic potential. Additionally, we found MYT1L and hsa-miR-20a-5p, which are essential for understanding the genetic variations linked to PD. These findings provide a solid underpinning for future therapeutic approaches aimed at PD, with a focus on the genetic variants and processes connected to the illness.", "source": "PubMed"}, {"chunk_id": "41026459_2", "pmid": "41026459", "title": "Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.", "authors": "Nguyen HD", "year": "2025", "journal": "Acta neurologica Belgica", "keywords": "Biomarkers, GWAS, Molecular mechanisms, Parkinson\u2019s disease", "chunk": "genetic variants and processes connected to the illness.", "source": "PubMed"}, {"chunk_id": "41767157_0", "pmid": "41767157", "title": "Tears as a window to Alzheimer's disease: A systematic review of biomarkers for early detection.", "authors": "L\u00f3pez-Cuenca I, Masa-Castro R, Hoz-Ruiz Y et al.", "year": "2026", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "alzheimer's disease, biomarker, extracellular vesicles, microRNA, proteins, tears", "chunk": "Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid beta and tau proteins, leading to neuronal degeneration and brain atrophy. While cerebrospinal fluid and blood biomarkers have advanced early AD diagnosis, these methods are invasive and costly. This systematic review investigates tears as a non-invasive, accessible source of AD biomarkers. Using tears, directly linked to the central nervous system, we can effectively detect proteins, microRNA (miRNA), and extracellular vesicles (EVs), reflecting neurodegenerative processes. Tear collection is cost effective and minimally stressful, allowing continuous biomarker monitoring across disease stages. This review highlights recent findings on specific proteins, miRNA, and EVs in tears of patients with AD, and examines tear collection and analysis methods. The potential of these techniques for early, accessible disease detection is emphasized. Further research is needed to standardize methods and validate biomarkers in larger cohorts, positioning tears as a valuable tool for", "source": "PubMed"}, {"chunk_id": "41767157_1", "pmid": "41767157", "title": "Tears as a window to Alzheimer's disease: A systematic review of biomarkers for early detection.", "authors": "L\u00f3pez-Cuenca I, Masa-Castro R, Hoz-Ruiz Y et al.", "year": "2026", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "alzheimer's disease, biomarker, extracellular vesicles, microRNA, proteins, tears", "chunk": "of these techniques for early, accessible disease detection is emphasized. Further research is needed to standardize methods and validate biomarkers in larger cohorts, positioning tears as a valuable tool for early AD diagnosis and management.", "source": "PubMed"}, {"chunk_id": "37020050_0", "pmid": "37020050", "title": "Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau.", "authors": "Van Egroo M, Riphagen JM, Ashton NJ et al.", "year": "2023", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) imaging, we investigated whether imaging measures of the LC also reveal a specific anatomic correlation with tau using novel plasma biomarkers of different species of hyperphosphorylated tau, how early in adulthood these associations can be detected and if are associated with worse cognitive performance. To validate the anatomic correlations, we tested if a rostro-caudal gradient in tau pathology is also detected at autopsy in data from the Rush Memory and Aging Project (MAP). We found that higher plasma measures of phosphorylated tau, in particular ptau<sub>231</sub>, correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered", "source": "PubMed"}, {"chunk_id": "37020050_1", "pmid": "37020050", "title": "Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau.", "authors": "Van Egroo M, Riphagen JM, Ashton NJ et al.", "year": "2023", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "We found that higher plasma measures of phosphorylated tau, in particular ptau<sub>231</sub>, correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered throughout the LC including middle to caudal sections. In contrast, the plasma A\u03b2<sub>42/40</sub> ratio, associated with brain amyloidosis, did not correlate with LC integrity. These findings were specific to the rostral LC and not observed when using the entire LC or the hippocampus. Furthermore, in the MAP data, we observed higher rostral than caudal tangle density in the LC, independent of the disease stage. The in vivo LC-phosphorylated tau correlations became significant from midlife, with the earliest effect for ptau<sub>231</sub>, starting at about age 55. Finally, interactions between lower rostral LC integrity and higher ptau<sub>231</sub> concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic", "source": "PubMed"}, {"chunk_id": "37020050_2", "pmid": "37020050", "title": "Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau.", "authors": "Van Egroo M, Riphagen JM, Ashton NJ et al.", "year": "2023", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "LC integrity and higher ptau<sub>231</sub> concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic resonance imaging measures, highlighting the promise of LC imaging as an early marker of AD-related processes.", "source": "PubMed"}, {"chunk_id": "36705011_0", "pmid": "36705011", "title": "Recent research advances in young-onset dementia.", "authors": "Loi SM, Pijnenburg Y, Velakoulis D", "year": "2023", "journal": "Current opinion in psychiatry", "keywords": "None", "chunk": "Young-onset dementia (YOD) refers to a dementia for which symptom onset occurs below the age of 65. This review summarizes the recent literature in this area, focusing on updates in epidemiology, diagnosis and service provision. In the last year, internationally, the prevalence of YOD was reported as 119 per 100 000, but this may vary according to population types. Although the commonest causes of YOD are Alzheimer's disease (AD) and frontotemporal dementia (FTD), there is increasing recognition that YOD is diagnostically and phenotypically broader than AD and FTD. YOD may be due to many other diseases (e.g. Huntington's disease, vascular dementia) whereas accumulation of the same protein (e.g. amyloid protein) may lead to different phenotypes of Alzheimer's disease (such as posterior cortical atrophy and behavioural-variant/frontal-variant AD). This heterogeneity of phenotypic presentation is also seen in YOD due to known genetic mutations. Biomarkers such as plasma and cerebrospinal fluid proteins, neuroimaging", "source": "PubMed"}, {"chunk_id": "36705011_1", "pmid": "36705011", "title": "Recent research advances in young-onset dementia.", "authors": "Loi SM, Pijnenburg Y, Velakoulis D", "year": "2023", "journal": "Current opinion in psychiatry", "keywords": "None", "chunk": "posterior cortical atrophy and behavioural-variant/frontal-variant AD). This heterogeneity of phenotypic presentation is also seen in YOD due to known genetic mutations. Biomarkers such as plasma and cerebrospinal fluid proteins, neuroimaging and genetics have shown promise in the early identification of YOD as well as providing further understanding behind the overlap between psychiatric and neurodegenerative conditions occurring in younger people. The management of YOD needs to consider age-specific issues for younger people with dementia and their family networks together with better integration with other health services such as aged, disability and improved access to services and financial assistance. These findings emphasize the need for early identification and appropriate age-specific and person-centred management for people with young-onset dementia.", "source": "PubMed"}, {"chunk_id": "37090239_0", "pmid": "37090239", "title": "Regional Deep Atrophy: a Self-Supervised Learning Method to Automatically Identify Regions Associated With Alzheimer's Disease Progression From Longitudinal MRI.", "authors": "Dong M, Xie L, Das SR et al.", "year": "2023", "journal": "ArXiv", "keywords": "None", "chunk": "Longitudinal assessment of brain atrophy, particularly in the hippocampus, is a well-studied biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD). In clinical trials, estimation of brain progressive rates can be applied to track therapeutic efficacy of disease modifying treatments. However, most state-of-the-art measurements calculate changes directly by segmentation and/or deformable registration of MRI images, and may misreport head motion or MRI artifacts as neurodegeneration, impacting their accuracy. In our previous study, we developed a deep learning method DeepAtrophy that uses a convolutional neural network to quantify differences between longitudinal MRI scan pairs that are associated with time. DeepAtrophy has high accuracy in inferring temporal information from longitudinal MRI scans, such as temporal order or relative inter-scan interval. DeepAtrophy also provides an overall atrophy score that was shown to perform well as a potential biomarker of disease progression and treatment efficacy. However, DeepAtrophy is not interpretable, and it is unclear", "source": "PubMed"}, {"chunk_id": "37090239_1", "pmid": "37090239", "title": "Regional Deep Atrophy: a Self-Supervised Learning Method to Automatically Identify Regions Associated With Alzheimer's Disease Progression From Longitudinal MRI.", "authors": "Dong M, Xie L, Das SR et al.", "year": "2023", "journal": "ArXiv", "keywords": "None", "chunk": "provides an overall atrophy score that was shown to perform well as a potential biomarker of disease progression and treatment efficacy. However, DeepAtrophy is not interpretable, and it is unclear what changes in the MRI contribute to progression measurements. In this paper, we propose Regional Deep Atrophy (RDA), which combines the temporal inference approach from DeepAtrophy with a deformable registration neural network and attention mechanism that highlights regions in the MRI image where longitudinal changes are contributing to temporal inference. RDA has similar prediction accuracy as DeepAtrophy, but its additional interpretability makes it more acceptable for use in clinical settings, and may lead to more sensitive biomarkers for disease monitoring in clinical trials of early AD.", "source": "PubMed"}, {"chunk_id": "41314307_0", "pmid": "41314307", "title": "Association between metabolic profile and cognitive frailty in community-dwelling older adults: An eight-year cohort study.", "authors": "Huang TH, Chen YC, Lin CY et al.", "year": "2026", "journal": "Mechanisms of ageing and development", "keywords": "Cognition, Frailty, Metabolomics, Nuclear magnetic resonance, Older adults", "chunk": "Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated with cognitive frailty over time. This eight-year prospective cohort study (2011-2019) recruited 605 nondemented community-dwelling older adults at baseline. Cognitive frailty, assessed biennially, was defined as physical frailty and mild cognitive impairment. Baseline plasma metabolites were evaluated using <sup>1</sup>H nuclear magnetic resonance. Generalized linear mixed models assessed the longitudinal association between metabolites and cognitive frailty, further stratified by important covariates. We found that one unit increment of baseline fatty acyl chain (CH<sub>2</sub>CH<sub>2</sub>CC) Z-score was associated with worsening cognitive frailty at baseline [adjusted risk ratio (aRR)= 1.97], which attenuated over eight years (aRR=0.94). In contrast, one unit increment of baseline pyruvate Z-score was associated with attenuation in the progression to the next stage of cognitive frailty (aRR=0.94). These associations were more evident in men, individuals", "source": "PubMed"}, {"chunk_id": "41314307_1", "pmid": "41314307", "title": "Association between metabolic profile and cognitive frailty in community-dwelling older adults: An eight-year cohort study.", "authors": "Huang TH, Chen YC, Lin CY et al.", "year": "2026", "journal": "Mechanisms of ageing and development", "keywords": "Cognition, Frailty, Metabolomics, Nuclear magnetic resonance, Older adults", "chunk": "one unit increment of baseline pyruvate Z-score was associated with attenuation in the progression to the next stage of cognitive frailty (aRR=0.94). These associations were more evident in men, individuals with > 12 years of education, and apolipoprotein E (APOE) \u03b54 non-carriers (aRR=0.34-0.92). Significant interactions were found between APOE \u03b54 status and both fatty acyl chain (P<sub>interaction</sub>=0.004) and pyruvate (P<sub>interaction</sub>=0.03). Our findings suggest plasma metabolites may serve as markers for predicting cognitive frailty and APOE genotypes modifying this pathogenesis.", "source": "PubMed"}, {"chunk_id": "41395714_0", "pmid": "41395714", "title": "Intracranial stenosis and longitudinal progression of Alzheimer's disease pathologies.", "authors": "Kang KM, Park C, Nam H et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta, atherosclerosis, intracranial stenosis, magnetic resonance angiography, positron emission tomography imaging, tau", "chunk": "The relationship between intracranial stenosis (ICS) and Alzheimer's disease (AD) pathologies remains unclear. We investigated whether baseline ICS is associated with longitudinal changes in amyloid beta (A\u03b2) and tau deposition. We prospectively followed 180 older adults (mean age 70.06 \u00b1 7.40 years), including cognitively normal (CN) and cognitively impaired (CI) individuals. ICS was assessed with magnetic resonance angiography. A\u03b2 and tau deposition were measured using Pittsburgh compound B positron emission tomography (PET) and AV-1451 PET, respectively. Participants were classified into A\u03b2 and tau analysis groups, each including both CN and CI individuals, and separate models were constructed to evaluate associations between ICS and longitudinal changes in each biomarker. The presence of any ICS was significantly associated with greater A\u03b2 accumulation over 4 years, while ICS in two or more arteries predicted greater tau deposition over 2 years. ICS may accelerate both A\u03b2 and tau accumulation, supporting a vascular contribution to", "source": "PubMed"}, {"chunk_id": "41395714_1", "pmid": "41395714", "title": "Intracranial stenosis and longitudinal progression of Alzheimer's disease pathologies.", "authors": "Kang KM, Park C, Nam H et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid beta, atherosclerosis, intracranial stenosis, magnetic resonance angiography, positron emission tomography imaging, tau", "chunk": "over 4 years, while ICS in two or more arteries predicted greater tau deposition over 2 years. ICS may accelerate both A\u03b2 and tau accumulation, supporting a vascular contribution to AD pathogenesis. Intracranial stenosis at baseline predicts 4-year increase in amyloid beta deposition. Two or more stenotic intracranial arteries are linked to 2-year tau accumulation. Associations remain after adjusting for apolipoprotein E \u03b54 status and cognitive impairment. Intracranial atherosclerosis may accelerate both amyloid and tau accumulation.", "source": "PubMed"}, {"chunk_id": "39984543_0", "pmid": "39984543", "title": "Association of genetic risk of Alzheimer's disease and cognitive function in two European populations.", "authors": "Wang B, Chibnik LB, Choi SH et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive test, Cohort, Polygenic risk score", "chunk": "Although there is some evidence of an association between Alzheimer's disease polygenic risk score (AD PRS) and cognitive function, limited validations have been performed in large populations. We investigated the relationship between AD PRS and cognitive function in the UK Biobank in over 276,000 participants and further validated the association in the Alzheimer's Disease Neuroimaging Initiative (ADNI) sample. We developed the AD PRS (excluded the APOE variants) in the middle age UK Biobank participants (age ranged 39-72, mean age 57 years) of European ancestries by LDpred2. To validate the association of AD PRS and cognitive function internally in the UK Biobank, we linearly regressed standardized cognitive function on continuous standardized AD PRS with age at cognitive test, sex, genotyping array, first 10 principal components of genotyping, smoking, education in years, body mass index, and apolipoprotein E gene \u03b54 (APOE4) risk allele dosages. To validate the associations externally, we ran the", "source": "PubMed"}, {"chunk_id": "39984543_1", "pmid": "39984543", "title": "Association of genetic risk of Alzheimer's disease and cognitive function in two European populations.", "authors": "Wang B, Chibnik LB, Choi SH et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive test, Cohort, Polygenic risk score", "chunk": "first 10 principal components of genotyping, smoking, education in years, body mass index, and apolipoprotein E gene \u03b54 (APOE4) risk allele dosages. To validate the associations externally, we ran the linear mixed effects model in the ADNI sample free of dementia (age ranged 55-91, mean age 73), including similar covariates as fixed effects and participants' IDs as the random effect. Stratification by age, APOE4 carrier status, and cognitive status (cognitively normal or mild cognitive impairment) was also investigated. Our study validated the associations of AD PRS and cognitive function in both midlife and late-life observational cohorts. Although not all of the cognitive measures were significantly associated with AD PRS, non-verbal fluid reasoning (matrix pattern completion, \u03b2 = - 0.022, P = 0.003), processing speed (such as symbol digit substitution, \u03b2 = - 0.017, P = 1.08E-05), short-term memory and attention (such as pairs matching, \u03b2 = - 0.014, P =", "source": "PubMed"}, {"chunk_id": "39984543_2", "pmid": "39984543", "title": "Association of genetic risk of Alzheimer's disease and cognitive function in two European populations.", "authors": "Wang B, Chibnik LB, Choi SH et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Cognitive test, Cohort, Polygenic risk score", "chunk": "= 0.003), processing speed (such as symbol digit substitution, \u03b2 = - 0.017, P = 1.08E-05), short-term memory and attention (such as pairs matching, \u03b2 = - 0.014, P = 1.66E-10), and reaction time (\u03b2 = - 0.010, P = 1.19E-06) were inversely associated with increasing AD PRS in the UK Biobank. Higher likelihood of cognitive impairment was also associated with higher AD PRS in the ADNI cognitive normal individuals (AD assessment scale \u03b2 = 0.079, P = 0.02). In summary, we confirmed that poorer cognitive function was associated with a higher polygenic AD risk, and suggested the potential utility of the AD PRS in identifying those who may be at risk for further cognitive decline.", "source": "PubMed"}, {"chunk_id": "40498685_0", "pmid": "40498685", "title": "Machine learning driven biomarker selection for medical diagnosis.", "authors": "Bavikadi D, Agarwal A, Ganta S et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "Recent advances in experimental methods have enabled researchers to collect data on thousands of analytes simultaneously. This has led to correlational studies that associated molecular measurements with diseases such as Alzheimer's, Liver, and Gastric Cancer. However, the use of thousands of biomarkers selected from the analytes is not practical for real-world medical diagnosis and is likely undesirable due to potentially formed spurious correlations. In this study, we evaluate 4 different methods for biomarker selection and 5 different machine learning (ML) classifiers for identifying correlations-evaluating 20 approaches in all. We found that contemporary methods outperform previously reported logistic regression in cases where 3 and 10 biomarkers are permitted. When specificity is fixed at 0.9, ML approaches produced a sensitivity of 0.240 (3 biomarkers) and 0.520 (10 biomarkers), while standard logistic regression provided a sensitivity of 0.000 (3 biomarkers) and 0.040 (10 biomarkers). We also noted that causal-based methods for biomarker selection", "source": "PubMed"}, {"chunk_id": "40498685_1", "pmid": "40498685", "title": "Machine learning driven biomarker selection for medical diagnosis.", "authors": "Bavikadi D, Agarwal A, Ganta S et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "(3 biomarkers) and 0.520 (10 biomarkers), while standard logistic regression provided a sensitivity of 0.000 (3 biomarkers) and 0.040 (10 biomarkers). We also noted that causal-based methods for biomarker selection proved to be the most performant when fewer biomarkers were permitted, while univariate feature selection was the most performant when a greater number of biomarkers were permitted.", "source": "PubMed"}, {"chunk_id": "38108158_0", "pmid": "38108158", "title": "Cerebrovascular reactivity in Alzheimer's disease signature regions is associated with mild cognitive impairment in adults with hypertension.", "authors": "Aslanyan V, Mack WJ, Ortega NE et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "biomarkers, cerebrovascular reactivity, cognitive dysfunction, hypertension, mild cognitive impairment", "chunk": "Vascular risk factors contribute to cognitive decline suggesting that maintaining cerebrovascular health could reduce dementia risk. The objective of this study is to evaluate the association of cerebrovascular reactivity (CVR), a measure of brain blood vessel elasticity, with mild cognitive impairment (MCI) and dementia. Participants were enrolled in the Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT-MIND) magnetic resonance imaging substudy. Baseline CVR in Alzheimer's disease (AD) signature regions were primary variables of interest. The occipital pole and postcentral gyrus were included as control regions. Higher AD composite CVR was associated with lower MCI risk. No significant associations between inferior temporal gyrus, occipital pole, or postcentral gyrus CVR and MCI risk, or any regional CVR-combined risk associations were observed. CVR in AD signature regions is negatively associated with occurrence of MCI, implicating CVR in AD signature regions as a potential mechanism leading to cognitive impairment.", "source": "PubMed"}, {"chunk_id": "38108158_1", "pmid": "38108158", "title": "Cerebrovascular reactivity in Alzheimer's disease signature regions is associated with mild cognitive impairment in adults with hypertension.", "authors": "Aslanyan V, Mack WJ, Ortega NE et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "biomarkers, cerebrovascular reactivity, cognitive dysfunction, hypertension, mild cognitive impairment", "chunk": "associations were observed. CVR in AD signature regions is negatively associated with occurrence of MCI, implicating CVR in AD signature regions as a potential mechanism leading to cognitive impairment.", "source": "PubMed"}, {"chunk_id": "40615512_0", "pmid": "40615512", "title": "Aerobic exercise alleviates cognitive impairment in T2DM mice through gut microbiota.", "authors": "Ruan S, Liu J, Yuan X et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Cognitive, Exercise, Microbiota, Type 2 diabetes mellitus", "chunk": "The risk of cognitive impairment is markedly elevated in patients with type 2 diabetes mellitus (T2DM). While exercise has been shown to mitigate cognitive deficits associated with diabetes, the underlying mechanisms remain poorly understood. Recent studies suggest that exercise can modulate the composition of the gut microbiota, which, in turn, may influence the central nervous system via the microbiota-gut-brain axis. However, the specific role of gut microbiota in mediating exercise-induced improvements in cognitive function in T2DM remains unclear. In this study, we aimed to investigate whether exercise can alleviate cognitive impairment in T2DM mice by modulating the intestinal microbiota, and to elucidate the mechanisms underlying this effect. This study was conducted using male C57BL/6J mice. Mice fed a normal diet were assigned to the non-diabetic control group (NC), while those fed a high-fat diet were intraperitoneally injected with streptozotocin (STZ) and subsequently divided into the diabetic control group (DM), an", "source": "PubMed"}, {"chunk_id": "40615512_1", "pmid": "40615512", "title": "Aerobic exercise alleviates cognitive impairment in T2DM mice through gut microbiota.", "authors": "Ruan S, Liu J, Yuan X et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Cognitive, Exercise, Microbiota, Type 2 diabetes mellitus", "chunk": "were assigned to the non-diabetic control group (NC), while those fed a high-fat diet were intraperitoneally injected with streptozotocin (STZ) and subsequently divided into the diabetic control group (DM), an exercise group (DM-EXE), and a fecal microbiota transplantation group (DM-FMT). The DM-EXE group underwent treadmill exercise for 8 weeks. During this period, the DM-FMT group received fecal microbiota transplants from the DM-EXE group for 2 consecutive days per week. Following the 8-week intervention, stool samples were collected for 16S rDNA high-throughput sequencing. The fear conditioning test was performed to assess cognitive function. Intestinal mucosa samples were collected to evaluate the expression of intestinal tight junction proteins. Additionally, the expression levels of synaptic proteins, glucose transporters, neurotrophic factors, and inflammatory markers were measured in the hippocampus. Our findings demonstrate that T2DM mice exhibit impaired cognitive function and significant alterations in their gut microbiota compared to non-diabetic controls. Exercise partially reversed these", "source": "PubMed"}, {"chunk_id": "40615512_2", "pmid": "40615512", "title": "Aerobic exercise alleviates cognitive impairment in T2DM mice through gut microbiota.", "authors": "Ruan S, Liu J, Yuan X et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Cognitive, Exercise, Microbiota, Type 2 diabetes mellitus", "chunk": "were measured in the hippocampus. Our findings demonstrate that T2DM mice exhibit impaired cognitive function and significant alterations in their gut microbiota compared to non-diabetic controls. Exercise partially reversed these changes in the intestinal microbiota and alleviated cognitive impairment in T2DM mice. Additionally, transplantation of intestinal microbiota from exercised mice improved cognitive function in T2DM mice. Aerobic exercise may mitigate cognitive impairment in T2DM mice by modulating the gut microbiota. The underlying mechanisms appear to involve enhanced neural synaptic plasticity, reduced neuroinflammation, and improved neuronal glucose metabolism.", "source": "PubMed"}, {"chunk_id": "41515522_0", "pmid": "41515522", "title": "Multidimensional Characterization of Parkinson's Disease Subtypes Through Motor Neuron Excitability and Peripheral Immune Dynamics: Insights from F-Wave Modulation Metrics.", "authors": "Demir Unal E, Dagdelen YE", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "F-wave analysis, Parkinson\u2019s disease, hematoinflammatory indices, mean platelet volume, motor subtypes, nerve conduction studies, neurophysiology, platelet\u2013eosinophil index, proximal motor conduction, systemic inflammatory response index", "chunk": "<b>Background/Objective:</b> Central pathophysiological heterogeneity among Parkinson's disease (PD) motor subtypes has been increasingly recognized, yet subtype-specific peripheral disturbances are limited. We aimed to characterize demographic, biochemical, and neurophysiological differences among PD motor subtypes, evaluate hematoinflammatory effects on peripheral and proximal motor conduction, and identify prognostic phenotypic biomarkers. <b>Methods:</b> A total of 110 participants (60 idiopathic PD patients (30 akinetic-rigid (AR), 30 tremor-predominant (TD), and 50 age- and sex-matched healthy controls (HCs)) were enrolled. Demographic data, nerve conduction studies (NCS) including detailed F-wave analysis, and hematoinflammatory markers were collected. Kruskal-Wallis, linear mixed models, multivariable regression, and ROC analyses were applied. <b>Results:</b> Hematoinflammatory indices were elevated in both subtypes compared with HCs, with more pronounced changes in AR (mean platelet volume (MPV) H = 4.367, <i>p</i> = 0.003; systemic inflammatory response index (SIRI) H = 3.929, <i>p</i> = 0.004). AR showed severe upper-limb-predominant motor involvement (median motor onset latency H = 55.30,", "source": "PubMed"}, {"chunk_id": "41515522_1", "pmid": "41515522", "title": "Multidimensional Characterization of Parkinson's Disease Subtypes Through Motor Neuron Excitability and Peripheral Immune Dynamics: Insights from F-Wave Modulation Metrics.", "authors": "Demir Unal E, Dagdelen YE", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "F-wave analysis, Parkinson\u2019s disease, hematoinflammatory indices, mean platelet volume, motor subtypes, nerve conduction studies, neurophysiology, platelet\u2013eosinophil index, proximal motor conduction, systemic inflammatory response index", "chunk": "H = 4.367, <i>p</i> = 0.003; systemic inflammatory response index (SIRI) H = 3.929, <i>p</i> = 0.004). AR showed severe upper-limb-predominant motor involvement (median motor onset latency H = 55.30, <i>p</i> < 0.001; amplitude H = 50.52, <i>p</i> = 0.04; conduction velocity H = 49.15, <i>p</i> < 0.001), whereas TD showed milder, lower-limb-predominant changes (tibial motor onset latency H = 19.89, <i>p</i> < 0.001; amplitude H = 51.50, <i>p</i> = 0.02; velocity H = 15.39, <i>p</i> < 0.001). AR also demonstrated prolonged minimal (Fmin)/mean (Fmean) ulnar F-wave latencies versus TD (respectively, H = 10.51, <i>p</i> = 0.001; H = 8.79, <i>p</i> = 0.003), with both showing increased tibial Fmean/Fmax latencies. Platelet-eosinophil indices independently predicted ulnar F-latencies (B = 0.104-0.105; <i>p</i> = 0.001; model R<sup>2</sup> = 0.21-0.39). Select F-wave metrics yielded ROC AUCs \u2248 0.65-0.92 (ulnar Fmin AUC \u2248 0.92 vs. HCs); AR achieved sensitivity/specificity \u2248 70-74%. <b>Conclusions:</b> The AR subtype", "source": "PubMed"}, {"chunk_id": "41515522_2", "pmid": "41515522", "title": "Multidimensional Characterization of Parkinson's Disease Subtypes Through Motor Neuron Excitability and Peripheral Immune Dynamics: Insights from F-Wave Modulation Metrics.", "authors": "Demir Unal E, Dagdelen YE", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "F-wave analysis, Parkinson\u2019s disease, hematoinflammatory indices, mean platelet volume, motor subtypes, nerve conduction studies, neurophysiology, platelet\u2013eosinophil index, proximal motor conduction, systemic inflammatory response index", "chunk": "= 0.001; model R<sup>2</sup> = 0.21-0.39). Select F-wave metrics yielded ROC AUCs \u2248 0.65-0.92 (ulnar Fmin AUC \u2248 0.92 vs. HCs); AR achieved sensitivity/specificity \u2248 70-74%. <b>Conclusions:</b> The AR subtype showed increased hematoinflammatory changes, specifically in MPV and SIRI, as well as a tendency toward more pronounced proximal motor and peripheral nerve conduction impairment compared with TD. Platelet-eosinophil indices and F-wave metrics may represent potential candidate markers for diagnostic or stratification purposes in PD subtyping and could possibly aid in prognostic estimation.", "source": "PubMed"}, {"chunk_id": "37709055_0", "pmid": "37709055", "title": "Advancements in computer-assisted diagnosis of Alzheimer's disease: A comprehensive survey of neuroimaging methods and AI techniques for early detection.", "authors": "Shanmugavadivel K, Sathishkumar VE, Cho J et al.", "year": "2023", "journal": "Ageing research reviews", "keywords": "None", "chunk": "Alzheimer's Disease (AD) is a brain disorder that causes the brain to shrink and eventually causes brain cells to die. This neurological condition progressively hampers cognitive and memory functions, along with the ability to carry out fundamental tasks over time. From the symptoms it is very difficult to detect during its early stage. It has become necessary to develop a computer assisted diagnostic models for the early AD detection. This survey work, discussed about a review of 110 published AD detection methods and techniques from the year 2011 to till-date. This study lies in its comprehensive exploration of AD detection methods using a range of artificial intelligence (AI) techniques and neuroimaging modalities. By collecting and analysing 50 papers related to AD diagnosis datasets, the study provides a comprehensive understanding of the diversity of input types, subjects, and classes used in AD research. Summarizing 60 papers on methodologies gives researchers a", "source": "PubMed"}, {"chunk_id": "37709055_1", "pmid": "37709055", "title": "Advancements in computer-assisted diagnosis of Alzheimer's disease: A comprehensive survey of neuroimaging methods and AI techniques for early detection.", "authors": "Shanmugavadivel K, Sathishkumar VE, Cho J et al.", "year": "2023", "journal": "Ageing research reviews", "keywords": "None", "chunk": "AD diagnosis datasets, the study provides a comprehensive understanding of the diversity of input types, subjects, and classes used in AD research. Summarizing 60 papers on methodologies gives researchers a succinct overview of various approaches that contribute to enhancing detection accuracy. From the review, data are acquired and pre-processed form multiple modalities of neuroimaging. This paper mainly focused on review of different datasets used, various feature extraction methods, parameters used in neuro images. To diagnosis the Alzheimer's disease, the existing methods utilized three most common artificial intelligence techniques such as machine learning, deep learning, and transfer learning. We conclude this survey work by providing future perspectives for AD diagnosis at early stage.", "source": "PubMed"}, {"chunk_id": "36189728_0", "pmid": "36189728", "title": "Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.", "authors": "Warren-Gash C, Cadogan SL, Nicholas JM et al.", "year": "2022", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope -", "source": "PubMed"}, {"chunk_id": "36189728_1", "pmid": "36189728", "title": "Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.", "authors": "Warren-Gash C, Cadogan SL, Nicholas JM et al.", "year": "2022", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD.", "source": "PubMed"}, {"chunk_id": "36189728_2", "pmid": "36189728", "title": "Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.", "authors": "Warren-Gash C, Cadogan SL, Nicholas JM et al.", "year": "2022", "journal": "Annals of clinical and translational neurology", "keywords": "None", "chunk": "individuals at high risk of early-onset AD.", "source": "PubMed"}, {"chunk_id": "37746412_0", "pmid": "37746412", "title": "Comparative Study of Safety and Efficacy of Angiotensin-Receptor Blockers and Anti Amyloid-\u00df Monoclonal Antibodies for the Treatment of Alzheimer's Disease: A Systematic Review.", "authors": "Shahid K, Tamene Y, Mody SP et al.", "year": "2023", "journal": "Cureus", "keywords": "alzheimer's dementia, alzheimer's disease, angiotensin-receptor blockers, anti-amyloid therapy, monoclonal antibodies", "chunk": "Amyloid-\u00df (A\u00df) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the exploration of Anti-A\u00df monoclonal antibodies and angiotensin-receptor blockers (ARBs). The antibodies can decrease plaque formation or remove already formed plaques. ARBs increase angiotensin II (AT2) levels and decrease the effect of AT2 on the AT1 receptor (AT1R). This systematic analysis reviews evidence of monoclonal antibodies (Aducanumab, Lecanemab, Donanemab, and Solanezumab) and ARBs in managing AD. An in-depth methodical search was conducted across PubMed, Science Direct, and Mendeley. PRISMA 2020 guidelines were followed for this study. Randomized control trials for antibodies and ARBs and one retrospective cohort study were included. The comparison was made among studies that shared similar measured outcomes. Antibodies were found to be more effective than ARBs, with Aducanumab and Lecanemab being the most effective. ARBs, on the other hand, were found to", "source": "PubMed"}, {"chunk_id": "37746412_1", "pmid": "37746412", "title": "Comparative Study of Safety and Efficacy of Angiotensin-Receptor Blockers and Anti Amyloid-\u00df Monoclonal Antibodies for the Treatment of Alzheimer's Disease: A Systematic Review.", "authors": "Shahid K, Tamene Y, Mody SP et al.", "year": "2023", "journal": "Cureus", "keywords": "alzheimer's dementia, alzheimer's disease, angiotensin-receptor blockers, anti-amyloid therapy, monoclonal antibodies", "chunk": "that shared similar measured outcomes. Antibodies were found to be more effective than ARBs, with Aducanumab and Lecanemab being the most effective. ARBs, on the other hand, were found to be the safer choice. Further trials of longer duration and larger sample sizes are needed to explore both groups' long-term safety and efficacy.", "source": "PubMed"}, {"chunk_id": "34380878_0", "pmid": "34380878", "title": "Promise of metformin for preventing age-related cognitive dysfunction.", "authors": "Madhu LN, Kodali M, Shetty AK", "year": "2022", "journal": "Neural regeneration research", "keywords": "activated microglia, aging, autophagy, cognitive dysfunction, mTOR signaling, memory, metformin, neuroinflammation", "chunk": "The expanded lifespan of people, while a positive advance, has also amplified the prevalence of age-related disorders, which include mild cognitive impairment, dementia, and Alzheimer's disease. Therefore, competent therapies that could improve the healthspan of people have great significance. Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age. Metformin, a drug widely used for treating diabetes, is one such candidate that could alleviate age-related cognitive dysfunction. However, the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies. While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people, its efficacy in the nondiabetic population is still unclear. Moreover, a previous animal model study implied that metformin could adversely affect cognitive function", "source": "PubMed"}, {"chunk_id": "34380878_1", "pmid": "34380878", "title": "Promise of metformin for preventing age-related cognitive dysfunction.", "authors": "Madhu LN, Kodali M, Shetty AK", "year": "2022", "journal": "Neural regeneration research", "keywords": "activated microglia, aging, autophagy, cognitive dysfunction, mTOR signaling, memory, metformin, neuroinflammation", "chunk": "and Alzheimer's disease in aged diabetic people, its efficacy in the nondiabetic population is still unclear. Moreover, a previous animal model study implied that metformin could adversely affect cognitive function in the aged. However, a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age. The study also revealed that cognition-enhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase, diminished neuroinflammation, inhibition of the mammalian target of rapamycin signaling, and augmented autophagy in the hippocampus. The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function. Nonetheless, additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are", "source": "PubMed"}, {"chunk_id": "34380878_2", "pmid": "34380878", "title": "Promise of metformin for preventing age-related cognitive dysfunction.", "authors": "Madhu LN, Kodali M, Shetty AK", "year": "2022", "journal": "Neural regeneration research", "keywords": "activated microglia, aging, autophagy, cognitive dysfunction, mTOR signaling, memory, metformin, neuroinflammation", "chunk": "additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.", "source": "PubMed"}, {"chunk_id": "34305568_0", "pmid": "34305568", "title": "Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline.", "authors": "Xu X, Wang T, Li W et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "functional network, morphological network, multiple kernel learning, structural network, subjective cognitive decline", "chunk": "Subjective cognitive decline (SCD) is considered the earliest stage of the clinical manifestations of the continuous progression of Alzheimer's Disease (AD). Previous studies have suggested that multimodal brain networks play an important role in the early diagnosis and mechanisms underlying SCD. However, most of the previous studies focused on a single modality, and lacked correlation analysis between different modal biomarkers and brain regions. In order to further explore the specific characteristic of the multimodal brain networks in the stage of SCD, 22 individuals with SCD and 20 matched healthy controls (HCs) were recruited in the present study. We constructed the individual morphological, structural and functional brain networks based on 3D-T1 structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. A <i>t</i>-test was used to select the connections with significant difference, and a multi-kernel support vector machine (MK-SVM) was applied to combine the", "source": "PubMed"}, {"chunk_id": "34305568_1", "pmid": "34305568", "title": "Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline.", "authors": "Xu X, Wang T, Li W et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "functional network, morphological network, multiple kernel learning, structural network, subjective cognitive decline", "chunk": "resting-state functional magnetic resonance imaging (rs-fMRI), respectively. A <i>t</i>-test was used to select the connections with significant difference, and a multi-kernel support vector machine (MK-SVM) was applied to combine the selected multimodal connections to distinguish SCD from HCs. Moreover, we further identified the consensus connections of brain networks as the most discriminative features to explore the pathological mechanisms and potential biomarkers associated with SCD. Our results shown that the combination of three modal connections using MK-SVM achieved the best classification performance, with an accuracy of 92.68%, sensitivity of 95.00%, and specificity of 90.48%. Furthermore, the consensus connections and hub nodes based on the morphological, structural, and functional networks identified in our study exhibited abnormal cortical-subcortical connections in individuals with SCD. In addition, the functional networks presented more discriminative connections and hubs in the cortical-subcortical regions, and were found to perform better in distinguishing SCD from HCs. Therefore, our findings highlight", "source": "PubMed"}, {"chunk_id": "34305568_2", "pmid": "34305568", "title": "Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline.", "authors": "Xu X, Wang T, Li W et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "functional network, morphological network, multiple kernel learning, structural network, subjective cognitive decline", "chunk": "In addition, the functional networks presented more discriminative connections and hubs in the cortical-subcortical regions, and were found to perform better in distinguishing SCD from HCs. Therefore, our findings highlight the role of the cortical-subcortical circuit in individuals with SCD from the perspective of a multimodal brain network, providing potential biomarkers for the diagnosis and prediction of the preclinical stage of AD.", "source": "PubMed"}, {"chunk_id": "37721286_0", "pmid": "37721286", "title": "Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases.", "authors": "Gonzalez-Cano SI, Flores G, Guevara J et al.", "year": "2024", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Vanadium species, antidiabetic, brain, cognition, diabetes, insulin, neurodegeneration, neuroinflammation, oxidative stress", "chunk": "Aging is a natural phenomenon characterized by a progressive decline in physiological integrity, leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases, including cardiovascular diseases, osteoporosis, cancer, diabetes, and neurodegeneration. Aging is considered the major risk factor for Parkinson's and Alzheimer's disease develops. Likewise, diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders. Currently, no treatment can effectively reverse these neurodegenerative pathologies. However, some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes. In the previous framework, Vanadium species have demonstrated a notable antidiabetic effect. Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome. The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms. This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the", "source": "PubMed"}, {"chunk_id": "37721286_1", "pmid": "37721286", "title": "Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases.", "authors": "Gonzalez-Cano SI, Flores G, Guevara J et al.", "year": "2024", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Vanadium species, antidiabetic, brain, cognition, diabetes, insulin, neurodegeneration, neuroinflammation, oxidative stress", "chunk": "with metabolic syndrome. The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms. This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain, constituting a therapeutic alternative for aging and neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "38113746_0", "pmid": "38113746", "title": "Brain magnetic resonance imaging findings six months after critical COVID-19: A prospective cohort study.", "authors": "Ollila H, Pihlajamaa J, Martola J et al.", "year": "2024", "journal": "Journal of critical care", "keywords": "Brain MRI, COVID-19, Intensive care, Long-term", "chunk": "COVID-19 patients suffered from neurological symptoms in the acute phase. Whether this led to long-term consequences was unknown. We studied long-term brain MRI findings in ICU-treated COVID-19 patients and compared them with findings in groups with less severe acute disease. In this prospective cohort study, 69 ICU-treated, 46 ward-treated, and 46 home-isolated patients, as well as 53 non-COVID-19 controls, underwent brain MRI six months after acute COVID-19. Plasma neurofilament light chain (NfL), a biomarker of neuroaxonal injury, was measured simultaneously. Ischaemic infarctions existed in 5.8% of ICU-treated patients. Cerebral microbleeds (CMBs) existed in 27 (39.1%) ICU-treated, 13 (28.3%) ward-treated, 8 (17.4%) home-isolated COVID-19 patients, and 12 (22.6%) non-COVID controls. Patients with CMBs were older (p < 0.001), had a higher level of plasma NfL (p = 0.003), and higher supplementary oxygen days (p < 0.001). In multivariable analysis, age (OR 1.06, 95% CI 1.02-1.09) and supplementary oxygen days (OR 1.07,", "source": "PubMed"}, {"chunk_id": "38113746_1", "pmid": "38113746", "title": "Brain magnetic resonance imaging findings six months after critical COVID-19: A prospective cohort study.", "authors": "Ollila H, Pihlajamaa J, Martola J et al.", "year": "2024", "journal": "Journal of critical care", "keywords": "Brain MRI, COVID-19, Intensive care, Long-term", "chunk": "level of plasma NfL (p = 0.003), and higher supplementary oxygen days (p < 0.001). In multivariable analysis, age (OR 1.06, 95% CI 1.02-1.09) and supplementary oxygen days (OR 1.07, 95% CI 1.02-1.13) were associated with CMBs. The ICU group showed prevalent distribution of CMBs in deep regions. Age and supplementary oxygen days were independently associated with CMBs; COVID-19 status showed no association. Accumulation of risk factors in the ICU group may explain the higher prevalence of CMBs. ClinicalTrials.govNCT04864938, registered February 9, 2021.", "source": "PubMed"}, {"chunk_id": "32388925_0", "pmid": "32388925", "title": "Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and <sup>18</sup> F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.", "authors": "Nadebaum DP, Krishnadas N, Poon AMT et al.", "year": "2021", "journal": "Internal medicine journal", "keywords": "18F-fluoro-2-deoxyglucose, Alzheimer disease, positron emission tomography, single-photon emission computed tomography imaging", "chunk": "Clinical diagnosis of Alzheimer disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. While widely accepted that <sup>18</sup> F-fluoro-2-deoxyglucose positron emission tomography (<sup>18</sup> F-FDG PET) has superior accuracy to CBF-SPECT for AD, there are very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard. To compare directly the accuracy of CBF-SPECT and <sup>18</sup> F-FDG PET in patients referred for diagnostic studies in detecting \u03b2-amyloid PET confirmed AD. A total of 126 patients, 56% with mild cognitive impairment and 44% with dementia, completed both CBF-SPECT and <sup>18</sup> F-FDG PET as part of their diagnostic assessment, and subsequently underwent \u03b2-amyloid PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of <sup>18</sup> F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data.", "source": "PubMed"}, {"chunk_id": "32388925_1", "pmid": "32388925", "title": "Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and <sup>18</sup> F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.", "authors": "Nadebaum DP, Krishnadas N, Poon AMT et al.", "year": "2021", "journal": "Internal medicine journal", "keywords": "18F-fluoro-2-deoxyglucose, Alzheimer disease, positron emission tomography, single-photon emission computed tomography imaging", "chunk": "PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of <sup>18</sup> F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data. Operators selected the most likely diagnosis and their diagnostic confidence. Accuracy analysis used final diagnosis incorporating \u03b2-amyloid PET as the reference standard. Clinicians reported high diagnostic confidence in 83% of <sup>18</sup> F-FDG PET compared to 67% for CBF-SPECT (P = 0.001). All reviewers showed individually higher accuracy using <sup>18</sup> F-FDG PET. Based on majority read, the combined area under the receiver operating characteristic curve in diagnosing AD was 0.71 for <sup>18</sup> F-FDG PET and 0.61 for CBF-SPECT (P = 0.02). The sensitivity of <sup>18</sup> F-FDG PET and CBF-SPECT was 76% versus 43% (P < 0.001), while specificity was 74% versus 83% (P = 0.45). <sup>18</sup> F-FDG PET is superior to CBF-SPECT in detecting AD among patients referred for the assessment", "source": "PubMed"}, {"chunk_id": "32388925_2", "pmid": "32388925", "title": "Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and <sup>18</sup> F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.", "authors": "Nadebaum DP, Krishnadas N, Poon AMT et al.", "year": "2021", "journal": "Internal medicine journal", "keywords": "18F-fluoro-2-deoxyglucose, Alzheimer disease, positron emission tomography, single-photon emission computed tomography imaging", "chunk": "versus 43% (P < 0.001), while specificity was 74% versus 83% (P = 0.45). <sup>18</sup> F-FDG PET is superior to CBF-SPECT in detecting AD among patients referred for the assessment of cognitive impairment.", "source": "PubMed"}, {"chunk_id": "37212119_0", "pmid": "37212119", "title": "Effect of Lecanemab in Early Alzheimer's Disease: Mechanistic Interpretation in the Amyloid Cascade Hypothesis 2.0 Perspective.", "authors": "Volloch V, Rits-Volloch S", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, Amyloid Cascade Hypothesis 2.0, A\u03b2PP-independent iA\u03b2 generation in AD, donanemab, intraneuronal A\u03b2, lecanemab", "chunk": "In clinical trials, lecanemab and donanemab showed statistically significant yet marginal slowdown of Alzheimer's disease (AD)-associated cognitive decline. This could be due to their sub-optimal design and/or deployment; alternatively, their limited efficiency could be intrinsic. Distinguishing between the two is of great importance considering the acute need of efficient AD therapy and tremendous resources being invested in its pursuit. The present study analyzes the mode of operation of lecanemab and donanemab within the framework of recently proposed Amyloid Cascade Hypothesis 2.0 and concludes that the second possibility is correct. It suggests that substantial improvement of the efficiency of these drugs in symptomatic AD is unlikely and proposes the alternative therapeutic strategy.", "source": "PubMed"}, {"chunk_id": "35327019_0", "pmid": "35327019", "title": "Differentiating Degenerative from Vascular Dementia with the Help of Optical Coherence Tomography Angiography Biomarkers.", "authors": "Chalkias E, Chalkias IN, Bakirtzis C et al.", "year": "2022", "journal": "Healthcare (Basel, Switzerland)", "keywords": "Alzheimer\u2019s, biomarkers, neurodegeneration, small vessel disease, vascular cognitive impairment", "chunk": "Alzheimer's disease and vascular dementia account for the majority of cases of cognitive decline in elderly people. These two main forms of dementia, under which various subtypes fall, are often overlapping and, in some cases, definitive diagnosis may only be possible post-mortem. This has implications for the quality of care and the design of individualized interventions for these patients. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality used to visualize the retinal layers and vessels which shows encouraging results in the study of various neurological conditions, including dementia. This review aims to succinctly sum up the present state of knowledge and provide critical insight into emerging patterns of OCTA biomarker values in Alzheimer's disease and vascular dementia. According to the current literature, vessel density seems to be a common biomarker for both forms; inner retinal layer thickness might represent a biomarker preferentially affected in degenerative dementia including Alzheimer's,", "source": "PubMed"}, {"chunk_id": "35327019_1", "pmid": "35327019", "title": "Differentiating Degenerative from Vascular Dementia with the Help of Optical Coherence Tomography Angiography Biomarkers.", "authors": "Chalkias E, Chalkias IN, Bakirtzis C et al.", "year": "2022", "journal": "Healthcare (Basel, Switzerland)", "keywords": "Alzheimer\u2019s, biomarkers, neurodegeneration, small vessel disease, vascular cognitive impairment", "chunk": "to the current literature, vessel density seems to be a common biomarker for both forms; inner retinal layer thickness might represent a biomarker preferentially affected in degenerative dementia including Alzheimer's, while, in contrast, the outer-layer thickness as a whole justifies attention as a potential vascular dementia biomarker. Radial peripapillary capillary density should also be further studied as a biomarker specifically linked to vascular dementia.", "source": "PubMed"}, {"chunk_id": "40284217_0", "pmid": "40284217", "title": "Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders.", "authors": "Fahey JW, Liu H, Batt H et al.", "year": "2025", "journal": "Nutrients", "keywords": "autism, broccoli, cognition, detoxication, glucoraphanin, neurologic, nutrition, psychiatric, schizophrenia", "chunk": "The brain accounts for about 2% of the body's weight, but it consumes about 20% of the body's energy at rest, primarily derived from ATP produced in mitochondria. The brain thus has a high mitochondrial density in its neurons because of its extensive energy demands for maintaining ion gradients, neurotransmission, and synaptic activity. The brain is also extremely susceptible to damage and dysregulation caused by inflammation (neuroinflammation) and oxidative stress. Many systemic challenges to the brain can be mitigated by the phytochemical sulforaphane (SF), which is particularly important in supporting mitochondrial function. SF or its biogenic precursor glucoraphanin, from broccoli seeds or sprouts, can confer neuroprotective and cognitive benefits via diverse physiological and biochemical mechanisms. SF is able to cross the blood-brain barrier as well as to protect it, and it mitigates the consequences of destructive neuroinflammation. It also protects against the neurotoxic effects of environmental pollutants, combats the tissue", "source": "PubMed"}, {"chunk_id": "40284217_1", "pmid": "40284217", "title": "Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders.", "authors": "Fahey JW, Liu H, Batt H et al.", "year": "2025", "journal": "Nutrients", "keywords": "autism, broccoli, cognition, detoxication, glucoraphanin, neurologic, nutrition, psychiatric, schizophrenia", "chunk": "the blood-brain barrier as well as to protect it, and it mitigates the consequences of destructive neuroinflammation. It also protects against the neurotoxic effects of environmental pollutants, combats the tissue and cell damage wrought by advanced glycation end products (detoxication), and supports healthy glucose metabolism. These effects are applicable to individuals of all ages, from the developing brains in periconception and infancy, to cognitively, developmentally, and traumatically challenged brains, to those in later life as well as those who are suffering with multiple chronic conditions including Parkinson's and Alzheimer's diseases.", "source": "PubMed"}, {"chunk_id": "37966285_0", "pmid": "37966285", "title": "Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.", "authors": "Bateman RJ, Smith J, Donohue MC et al.", "year": "2023", "journal": "The New England journal of medicine", "keywords": "None", "chunk": "Monoclonal antibodies that target amyloid-beta (A\u03b2) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-A\u03b2 IgG1 monoclonal antibody with highest affinity for aggregated A\u03b2 that has been tested for the treatment of Alzheimer's disease. We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. A total of 985 and 980 participants were enrolled in the GRADUATE I", "source": "PubMed"}, {"chunk_id": "37966285_1", "pmid": "37966285", "title": "Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.", "authors": "Bateman RJ, Smith J, Donohue MC et al.", "year": "2023", "journal": "The New England journal of medicine", "keywords": "None", "chunk": "of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval [CI], -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in", "source": "PubMed"}, {"chunk_id": "37966285_2", "pmid": "37966285", "title": "Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.", "authors": "Bateman RJ, Smith J, Donohue MC et al.", "year": "2023", "journal": "The New England journal of medicine", "keywords": "None", "chunk": "level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of A\u03b242 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%. Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).", "source": "PubMed"}, {"chunk_id": "37966285_3", "pmid": "37966285", "title": "Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.", "authors": "Bateman RJ, Smith J, Donohue MC et al.", "year": "2023", "journal": "The New England journal of medicine", "keywords": "None", "chunk": "but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).", "source": "PubMed"}, {"chunk_id": "41801601_0", "pmid": "41801601", "title": "Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, \u03b2-secretase and neuroinflammation.", "authors": "Anwer R, Ullah I, Khan AU et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Acetylcholinesterase, Alzheimer\u2019s disease, Neuroinflammation, Oxidative stress, Piperitone", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder linked with oxidative imbalance, cholinergic dysfunction and neuroinflammation, necessitates developing new multitarget natural compounds with potential disease-modifying action. Piperitone was evaluated using in-silico, in-vitro and in-vivo methods. In-silico study identified the pharmacokinetic parameters (PK) and the interaction stability of piperitone with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and \u03b2-secretase. In-vivo assessment of spatial memory in scopolamine-induced rat model was identified by behavioral assays with donepezil as a reference standard. In-vitro assays identified activity of cholinesterases, oxidative stress markers, levels of antioxidants and neuroinflammatory substrates, quantified with Reverse Transcription Polymerase Chain Reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Piperitone demonstrated favorable PK properties & docking scores comparable to Donepezil, Tacrine & QUD. Molecular dynamics simulations (MDS) confirmed stable associations with catalytic residues of cholinesterases and beta-secretase. Dose dependent reduction was recorded in cholinesterases, improvement in behavioral outcomes, and supplemented defenses of antioxidants including Glutathione (Reduced", "source": "PubMed"}, {"chunk_id": "41801601_1", "pmid": "41801601", "title": "Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, \u03b2-secretase and neuroinflammation.", "authors": "Anwer R, Ullah I, Khan AU et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Acetylcholinesterase, Alzheimer\u2019s disease, Neuroinflammation, Oxidative stress, Piperitone", "chunk": "(MDS) confirmed stable associations with catalytic residues of cholinesterases and beta-secretase. Dose dependent reduction was recorded in cholinesterases, improvement in behavioral outcomes, and supplemented defenses of antioxidants including Glutathione (Reduced Form (GSH), Glutathione S-Transferase (GST), Catalase (CAT), Superoxide Dismutase (SOD), and diminished Lipid Peroxidation (LPO), Nitric Oxide (NO), Tumor Necrosis Factor-alpha (TNF-\u03b1), Interleukin (IL)-1\u03b2, IL-18, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB), NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) and amyloid-\u03b2 production, while improving Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Piperitone showed significant neuroprotective and cognitive enhancement benefits by modulating cholinergic signaling, oxidative stress, and neuroinflammation. These multitarget actions advocate piperitone as a prospective lead candidate for the development of disease modifying treatments for AD.", "source": "PubMed"}, {"chunk_id": "16944667_0", "pmid": "16944667", "title": "Genetically increased risk of sleep disruption in Alzheimer's disease.", "authors": "Craig D, Hart DJ, Passmore AP", "year": "2006", "journal": "Sleep", "keywords": "None", "chunk": "To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD). A case-control association analysis. Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A). Patients with AD diagnosed according to standard criteria. Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number", "source": "PubMed"}, {"chunk_id": "16944667_1", "pmid": "16944667", "title": "Genetically increased risk of sleep disruption in Alzheimer's disease.", "authors": "Craig D, Hart DJ, Passmore AP", "year": "2006", "journal": "Sleep", "keywords": "None", "chunk": "Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods. Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype. We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.", "source": "PubMed"}, {"chunk_id": "36852969_0", "pmid": "36852969", "title": "A semi-parametric approach for time-dependent ROC curves with nonignorable missing biomarker.", "authors": "Cheng W, Li X,  ", "year": "2023", "journal": "Journal of biopharmaceutical statistics", "keywords": "Cox proportional hazards, Time-dependent ROC curves, instrumental variable, nonignorable missing data, semi-parametric location model", "chunk": "The main purpose of this paper is to survey the statistical inference for covariate-specific time-dependent receiver operating characteristic (ROC) curves with nonignorable missing continuous biomarker values. To construct time-dependent ROC curves, we consider a joint model which assumes that the failure time depends on the continuous biomarker and the covariates through a Cox proportional hazards model and that the continuous biomarker depends on the covariates through a semiparametric location model. Assuming a purely parametric model on the propensity score, we utilize instrumental variables to deal with the identifiable issue and estimate the unknown parameters of the propensity score by a simple and efficient method. In addition, when the propensity score is estimated, we develop HT and AIPW approaches to estimate our interested quantities. In the presence of nonignorable missing biomarker, our AIPW estimators of the interested quantities are still doubly robust when the true propensity score is a special parametric", "source": "PubMed"}, {"chunk_id": "36852969_1", "pmid": "36852969", "title": "A semi-parametric approach for time-dependent ROC curves with nonignorable missing biomarker.", "authors": "Cheng W, Li X,  ", "year": "2023", "journal": "Journal of biopharmaceutical statistics", "keywords": "Cox proportional hazards, Time-dependent ROC curves, instrumental variable, nonignorable missing data, semi-parametric location model", "chunk": "our interested quantities. In the presence of nonignorable missing biomarker, our AIPW estimators of the interested quantities are still doubly robust when the true propensity score is a special parametric logistic model. At last, simulation studies are conducted to assess the performance of our proposed approaches, and a real data analysis is also carried out to illustrate its application.", "source": "PubMed"}, {"chunk_id": "40392441_0", "pmid": "40392441", "title": "Multimorbidity and fluid biomarkers of Alzheimer's disease: a systematic review.", "authors": "Valletta M, Canevelli M, Gasparini F et al.", "year": "2025", "journal": "European geriatric medicine", "keywords": "Alzheimer\u2019s disease, Biomarkers, Blood, Cerebrospinal fluid, Chronic diseases, Multimorbidity", "chunk": "This systematic review aimed to summarize the evidence on the association between multimorbidity and fluid biomarkers of Alzheimer's disease (AD). We systematically searched PubMed, Web of Science, and Embase for studies investigating the association between multimorbidity-defined as the co-occurrence of multiple chronic conditions in the same individual-and levels of cerebrospinal fluid (CSF) or blood biomarkers of AD, focusing on the most established AD biomarkers (amyloid-beta, phosphorylated-tau, total-tau, neurofilament light chain, and glial fibrillary acidic protein). Studies were selected following PRISMA guidelines. Out of 3,104 records, we identified 10 cross-sectional studies. Four studies assessed CSF biomarkers in dementia-free participants with mean age between 61.8 and 66.6 years, yielding mixed findings with no consistent association between multimorbidity and CSF biomarkers. Six studies focused on blood biomarkers in participants with mean age ranging from 66.5 to 76.4 years, five of which included individuals with dementia. Most of these studies reported an association between", "source": "PubMed"}, {"chunk_id": "40392441_1", "pmid": "40392441", "title": "Multimorbidity and fluid biomarkers of Alzheimer's disease: a systematic review.", "authors": "Valletta M, Canevelli M, Gasparini F et al.", "year": "2025", "journal": "European geriatric medicine", "keywords": "Alzheimer\u2019s disease, Biomarkers, Blood, Cerebrospinal fluid, Chronic diseases, Multimorbidity", "chunk": "focused on blood biomarkers in participants with mean age ranging from 66.5 to 76.4 years, five of which included individuals with dementia. Most of these studies reported an association between multimorbidity and elevated blood biomarker levels. This review suggests a significant association between multimorbidity and AD blood biomarkers in older populations, while the results on CSF are mixed and inconsistent. Further research is needed, particularly longitudinal studies assessing both CSF and blood biomarkers within the same populations.", "source": "PubMed"}, {"chunk_id": "38154805_0", "pmid": "38154805", "title": "Blood-brain barrier disruption in dementia: Nano-solutions as new treatment options.", "authors": "Cooper CG, Kafetzis KN, Patabendige A et al.", "year": "2024", "journal": "The European journal of neuroscience", "keywords": "Alzheimer's disease, blood\u2013brain barrier, dementia, drug delivery, nanogels, nanoparticles", "chunk": "Candidate drugs targeting the central nervous system (CNS) demonstrate extremely low clinical success rates, with more than 98% of potential treatments being discontinued due to poor blood-brain barrier (BBB) permeability. Neurological conditions were shown to be the second leading cause of death globally in 2016, with the number of people currently affected by neurological disorders increasing rapidly. This increasing trend, along with an inability to develop BBB permeating drugs, is presenting a major hurdle in the treatment of CNS-related disorders, like dementia. To overcome this, it is necessary to understand the structure and function of the BBB, including the transport of molecules across its interface in both healthy and pathological conditions. The use of CNS drug carriers is rapidly gaining popularity in CNS research due to their ability to target BBB transport systems. Further research and development of drug delivery vehicles could provide essential information that can be used to", "source": "PubMed"}, {"chunk_id": "38154805_1", "pmid": "38154805", "title": "Blood-brain barrier disruption in dementia: Nano-solutions as new treatment options.", "authors": "Cooper CG, Kafetzis KN, Patabendige A et al.", "year": "2024", "journal": "The European journal of neuroscience", "keywords": "Alzheimer's disease, blood\u2013brain barrier, dementia, drug delivery, nanogels, nanoparticles", "chunk": "popularity in CNS research due to their ability to target BBB transport systems. Further research and development of drug delivery vehicles could provide essential information that can be used to develop novel treatments for neurological conditions. This review discusses the BBB and its transport systems and evaluates the potential of using nanoparticle-based delivery systems as drug carriers for CNS disease with a focus on dementia.", "source": "PubMed"}, {"chunk_id": "41775642_0", "pmid": "41775642", "title": "Isolated medial temporal lobe amnesia (MTLA): Predictor of cerebral amyloidosis or marker of phenotype-specific vulnerability?", "authors": "Pin G, Horowitz T, Guedj E et al.", "year": "2026", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Amnesia, Amyloid, Apolipoprotein E4", "chunk": "Medial temporal lobe amnestic syndrome (MTLA) is classically considered a hallmark of Alzheimer's disease (AD). However, emerging evidence suggests etiological heterogeneity, challenging the assumption that MTLA universally reflects AD pathology. To determine the prevalence of amyloid pathology in isolated MTLA, identify phenotypic and genetic risk factors, and characterize associated network vulnerabilities in amnestic mild cognitive impairment (aMCI). This retrospective observational study analyzed 55 patients with isolated MTLA at the aMCI stage. Participants underwent neuropsychological testing, cerebrospinal fluid (CSF) biomarker analysis, amyloid PET, and 18FDG-PET. Patients were stratified by amyloid status (positive/negative) and compared for APOE genotype, clinical features, and metabolic patterns. Statistical analyses included the Kruskal-Wallis test for non-parametric group comparisons and chi-square tests for categorical genetic associations. Amyloid pathology was observed in only 67% (37/55) of MTLA patients, dissociating the syndrome from AD in one-third of cases. Amyloid-positive patients demonstrated a significantly higher APOE \u025b4 carrier rate compared to", "source": "PubMed"}, {"chunk_id": "41775642_1", "pmid": "41775642", "title": "Isolated medial temporal lobe amnesia (MTLA): Predictor of cerebral amyloidosis or marker of phenotype-specific vulnerability?", "authors": "Pin G, Horowitz T, Guedj E et al.", "year": "2026", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Amnesia, Amyloid, Apolipoprotein E4", "chunk": "was observed in only 67% (37/55) of MTLA patients, dissociating the syndrome from AD in one-third of cases. Amyloid-positive patients demonstrated a significantly higher APOE \u025b4 carrier rate compared to amyloid-negative peers (\u03c7<sup>2</sup>=7.02, df=2, P=0.030), while 18FDG-PET revealed inferotemporal hypometabolism in amyloid-positive cases, marking early decontextualized memory impairment. MTLA syndrome is not homogeneous on the biological level and amyloid pathology and APOE \u025b4 genotype stratify patients into distinct subgroups. Amyloid-positive cases demonstrate inferotemporal hypometabolism, suggesting AD-related network vulnerability. By contrast, amyloid-negative MTLA group shows no systemic brain network vulnerabilities, likely due to its heterogeneous etiological origins. These findings advocate for a precision medicine framework integrating biomarkers to guide therapeutic strategies, moving beyond syndromic diagnoses to target underlying mechanisms.", "source": "PubMed"}, {"chunk_id": "41133969_0", "pmid": "41133969", "title": "Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis.", "authors": "Lindenborn P, Fabian R, Grehl T et al.", "year": "2026", "journal": "Annals of neurology", "keywords": "None", "chunk": "We aimed to evaluate the clinical utility of serum neurofilament light chain (sNfL) and cardiac troponin T (cTnT) in amyotrophic lateral sclerosis (ALS) and assess whether their combination improves diagnostic accuracy. We retrospectively analyzed 293 ALS patients, 85 neurodegenerative disease controls, and 29 healthy controls. A validation cohort of 501 ALS patients was analyzed to confirm reproducibility of the results. Receiver operating characteristic (ROC) curve analysis was performed for sNfL, cTnT, and their combination, and the area under the curve (AUC) was compared across groups. An ALS-specific cTnT cut-off of 8.35ng/L was determined using the Youden index and applied in subgroup analyses, in which \"biomarker-negative\" ALS patients were compared to \"biomarker-positive\" patients regarding disease duration and progression. sNfL showed excellent performance in discriminating ALS patients from healthy controls (AUC = 0.94), but only moderate performance in discriminating neurodegenerative disease controls (AUC = 0.82). Combining sNfL and cTnT improved diagnostic accuracy", "source": "PubMed"}, {"chunk_id": "41133969_1", "pmid": "41133969", "title": "Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis.", "authors": "Lindenborn P, Fabian R, Grehl T et al.", "year": "2026", "journal": "Annals of neurology", "keywords": "None", "chunk": "performance in discriminating ALS patients from healthy controls (AUC = 0.94), but only moderate performance in discriminating neurodegenerative disease controls (AUC = 0.82). Combining sNfL and cTnT improved diagnostic accuracy for ALS over neurodegenerative controls, with an AUC of 0.90, whereas cTnT alone showed an AUC of 0.77. The validation cohort showed similar AUCs. \"Biomarker-negative\" ALS patients had a longer disease duration (73.0 vs 18.0 months, p = 0.0003) and a lower progression rate (0.19 vs 0.70 points per months, p < 0.0001) than \"biomarker-positive\" patients. Although sNfL alone performs well in distinguishing ALS from healthy controls, repurposing cTnT for ALS provides additional value in discriminating ALS from disease controls. The combination of sNfL and cTnT improves diagnostic accuracy and may help identify prognostically distinct ALS subgroups. ANN NEUROL 2026;99:408-417.", "source": "PubMed"}, {"chunk_id": "41133969_2", "pmid": "41133969", "title": "Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis.", "authors": "Lindenborn P, Fabian R, Grehl T et al.", "year": "2026", "journal": "Annals of neurology", "keywords": "None", "chunk": "may help identify prognostically distinct ALS subgroups. ANN NEUROL 2026;99:408-417.", "source": "PubMed"}, {"chunk_id": "40250046_0", "pmid": "40250046", "title": "Blood biomarkers for brain injury in chronic subdural hematomas: postoperative dynamics and relation to long-term outcome.", "authors": "Svedung Wettervik T, Lindblad C, Axelsson F et al.", "year": "2025", "journal": "Journal of neurosurgery", "keywords": "biomarkers, chronic subdural hematoma, glial fibrillary acidic protein, neurofilament light chain, neuron-specific enolase, tau, traumatic brain injury", "chunk": "The aim of this study was to investigate whether the biomarkers neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau (total [t] and brain-derived [BD]) are elevated in plasma preoperatively; if there is a dynamic biomarker response to surgery; and if the biomarker levels are related to long-term outcome in chronic subdural hematomas (CSDHs). Eighty-five CSDH patients surgically treated between 2022 and 2023 at Uppsala University Hospital, Uppsala, Sweden, were included in this prospective, observational study. NSE, GFAP, NfL, t-tau, and BD-tau were evaluated in plasma pre- and postoperatively (6-24 hours after surgery) and in the CSDH fluid. Health-related quality of life was evaluated using the 5-level EQ-5D (EQ-5D-5L) at 6 months postoperatively. GFAP, NfL, and tau levels decreased after CSDH surgery (p < 0.02). NSE and BD-tau levels also decreased, but not significantly. Older age and larger CSDH volume were associated with higher preoperative", "source": "PubMed"}, {"chunk_id": "40250046_1", "pmid": "40250046", "title": "Blood biomarkers for brain injury in chronic subdural hematomas: postoperative dynamics and relation to long-term outcome.", "authors": "Svedung Wettervik T, Lindblad C, Axelsson F et al.", "year": "2025", "journal": "Journal of neurosurgery", "keywords": "biomarkers, chronic subdural hematoma, glial fibrillary acidic protein, neurofilament light chain, neuron-specific enolase, tau, traumatic brain injury", "chunk": "and tau levels decreased after CSDH surgery (p < 0.02). NSE and BD-tau levels also decreased, but not significantly. Older age and larger CSDH volume were associated with higher preoperative GFAP, NfL, and BD-tau levels (p < 0.05). Higher preoperative values and greater dynamics (\u0394 [postoperative value - preoperative value]) of GFAP, NfL, and BD-tau correlated significantly with worse levels of several EQ-5D-5L domains (p < 0.05). A higher preoperative NfL level in plasma was independently associated with a lower EQ-5D-5L visual analog scale score (p < 0.001). Surgical CSDH patients exhibit ongoing central nervous system cellular injury, demonstrated via increased fluid biomarkers for brain injury preoperatively, which immediately improved after surgery and was strongly related to long-term outcome. The extent of preoperative biomarker elevation could aid in the decision-making for surgical indication and urgency.", "source": "PubMed"}, {"chunk_id": "40250046_2", "pmid": "40250046", "title": "Blood biomarkers for brain injury in chronic subdural hematomas: postoperative dynamics and relation to long-term outcome.", "authors": "Svedung Wettervik T, Lindblad C, Axelsson F et al.", "year": "2025", "journal": "Journal of neurosurgery", "keywords": "biomarkers, chronic subdural hematoma, glial fibrillary acidic protein, neurofilament light chain, neuron-specific enolase, tau, traumatic brain injury", "chunk": "extent of preoperative biomarker elevation could aid in the decision-making for surgical indication and urgency.", "source": "PubMed"}, {"chunk_id": "40653764_0", "pmid": "40653764", "title": "A novel traditional Chinese medicine formula restores sleep and cognitive function in APP/PS1 mice by targeting glycolytic pathways and neuroinflammatory responses.", "authors": "Zhang J, Wang C, Chang K et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cognitive function, glycolysis, neuroinflammation, sleep, traditional Chinese medicine", "chunk": "BackgroundAlzheimer's disease (AD) is recognized as a multifactorial neurodegenerative disorder involving numerous cellular and molecular processes, such as sleep disturbance, imbalance in brain glucose metabolism and neuroinflammation; these dysregulations typically precede the onset of symptoms. Hence, the results of mono-target therapy after AD diagnosis are in many cases unsatisfactory.ObjectiveTraditional Chinese medicine (TCM) presents significant potential for treating AD. Sleep disorders are one of the early symptoms of AD; however, there is no effective solution to sleep disorders caused by AD. Some TCMs have been shown to treat sleep disorders by regulating energy metabolism or improving neuroinflammation. This study aims to investigate if XX-F administrated in advance could alleviate AD by improving sleep quality and neuroinflammation.MethodsMice were given <i>Xiexintongfu</i> formula (XX-F) intragastrically for three months. Morris water maze and pentobarbital-induced sleep test were performed to evaluate cognition and sleep. Determine changes in energy metabolism related to glycolysis through western blot and", "source": "PubMed"}, {"chunk_id": "40653764_1", "pmid": "40653764", "title": "A novel traditional Chinese medicine formula restores sleep and cognitive function in APP/PS1 mice by targeting glycolytic pathways and neuroinflammatory responses.", "authors": "Zhang J, Wang C, Chang K et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cognitive function, glycolysis, neuroinflammation, sleep, traditional Chinese medicine", "chunk": "intragastrically for three months. Morris water maze and pentobarbital-induced sleep test were performed to evaluate cognition and sleep. Determine changes in energy metabolism related to glycolysis through western blot and specific assay kits. Using immunofluorescence and western blot to detect neuroinflammation.ResultsShortened sleep duration and cognitive impairment were observed in 6-month-old APP/PS1 mice. XX-F significantly prolonged sleep duration and rescued cognition. In addition, XX-F reduced the number of amyloid-\u03b2 (A\u03b2) plaques and ameliorated neuroinflammation, and inhibited glycolysis by reducing pyruvate kinase M2 (PKM2) and lactate levels while rescuing adenosine triphosphate (ATP) deficiency.ConclusionsWe demonstrate that XX-F can improve sleep and cognition of AD mice by regulating energy metabolism and reducing neuroinflammation. This is a potential treatment method for AD and requires further in-depth research.", "source": "PubMed"}, {"chunk_id": "40653764_2", "pmid": "40653764", "title": "A novel traditional Chinese medicine formula restores sleep and cognitive function in APP/PS1 mice by targeting glycolytic pathways and neuroinflammatory responses.", "authors": "Zhang J, Wang C, Chang K et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cognitive function, glycolysis, neuroinflammation, sleep, traditional Chinese medicine", "chunk": "in-depth research.", "source": "PubMed"}, {"chunk_id": "36799538_0", "pmid": "36799538", "title": "Biomimetic Remodeling of Microglial Riboflavin Metabolism Ameliorates Cognitive Impairment by Modulating Neuroinflammation.", "authors": "Zhang M, Chen H, Zhang W et al.", "year": "2023", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "keywords": "Neuroinflammation, cognitive decline, flavin mononucleotide, microglial targeted delivery, riboflavin kinase", "chunk": "Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates cognitive impairment via anti-oxidative stress and anti-inflammation properties; however, the underlying mechanisms linking riboflavin metabolism and microglial function in cognitive impairment remain unclear. Here, it is demonstrated that riboflavin kinase (RFK), a critical enzyme in riboflavin metabolism, is specifically expressed in microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression via regulation of lysine-specific methyltransferase 2B (KMT2B). FMN supplementation attenuated the pro-inflammatory TNFR1/NF-\u03baB signaling pathway, and this effect is abolished by KMT2B overexpression. To improve the limited anti-inflammatory efficiency of free FMN, a biomimetic microglial nanoparticle strategy (designated as MNPs@FMN) is established, which penetrated the blood brain barrier with enhanced microglial-targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide-induced inflammatory mouse model and in a 5xFAD mouse model", "source": "PubMed"}, {"chunk_id": "36799538_1", "pmid": "36799538", "title": "Biomimetic Remodeling of Microglial Riboflavin Metabolism Ameliorates Cognitive Impairment by Modulating Neuroinflammation.", "authors": "Zhang M, Chen H, Zhang W et al.", "year": "2023", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "keywords": "Neuroinflammation, cognitive decline, flavin mononucleotide, microglial targeted delivery, riboflavin kinase", "chunk": "the blood brain barrier with enhanced microglial-targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide-induced inflammatory mouse model and in a 5xFAD mouse model of Alzheimer's disease. Taken together, biomimetic microglial delivery of FMN may serve as a potential therapeutic approach for inflammation-dependent cognitive decline.", "source": "PubMed"}, {"chunk_id": "41205698_0", "pmid": "41205698", "title": "Exploring biomarkers of neurodegenerative risk: associations of oxysterols, sex hormones, and reproductive characteristics in older women.", "authors": "Dunk MM, Delac L, Rapp SR et al.", "year": "2025", "journal": "Journal of lipid research", "keywords": "24(S)-hydroxycholesterol, Alzheimer\u2019s disease, CYP46A1, apolipoprotein E, cholesterol, estrogen, hormones, lipids, reproductive history, statins", "chunk": "Women face a higher lifetime risk of developing neurodegenerative diseases such as Alzheimer's disease and related dementias. The menopausal transition, characterized by a decline in estrogen levels, may affect cholesterol metabolism and neurodegenerative processes. Oxysterols, oxidized cholesterol derivatives, play a role in these pathways, with 24(S)-hydroxycholesterol (24HC) reflecting brain cholesterol turnover and 27-hydroxycholesterol (27HC) linked to systemic cholesterol metabolism. We investigated associations of plasma oxysterols with circulating sex hormones and characteristics of reproductive history in 1,974 postmenopausal women with no history of dementia from the Women's Health Initiative, taking into account APOE4 status and cholesterol-lowering medication. We found that higher levels of bioavailable estradiol were associated with higher 24HC and 27HC levels, and higher estrone was associated with higher 24HC (all P values <0.05). Associations of estradiol with 24HC and 27HC were stronger among APOE4 carriers and those not using cholesterol-lowering medication, with a significant interaction between bioavailable estradiol and", "source": "PubMed"}, {"chunk_id": "41205698_1", "pmid": "41205698", "title": "Exploring biomarkers of neurodegenerative risk: associations of oxysterols, sex hormones, and reproductive characteristics in older women.", "authors": "Dunk MM, Delac L, Rapp SR et al.", "year": "2025", "journal": "Journal of lipid research", "keywords": "24(S)-hydroxycholesterol, Alzheimer\u2019s disease, CYP46A1, apolipoprotein E, cholesterol, estrogen, hormones, lipids, reproductive history, statins", "chunk": "(all P values <0.05). Associations of estradiol with 24HC and 27HC were stronger among APOE4 carriers and those not using cholesterol-lowering medication, with a significant interaction between bioavailable estradiol and APOE4 in relation to 27HC (p for interaction = 0.04). Having an older age at menopause was associated with lower 24HC among those taking cholesterol medication (p for interaction = 0.03). Our findings suggest that 24HC and 27HC may be proxy biomarkers of neuronal health and estrogen status in postmenopausal women. The stronger associations between estradiol and oxysterols among APOE4 carriers and those not using cholesterol medication suggest the need to account for hormonal, genetic, and pharmacological factors when evaluating neurodegenerative risk. Longitudinal studies are warranted to further investigate oxysterols as potential early biomarkers of risk for Alzheimer's disease and related dementias.", "source": "PubMed"}, {"chunk_id": "41205698_2", "pmid": "41205698", "title": "Exploring biomarkers of neurodegenerative risk: associations of oxysterols, sex hormones, and reproductive characteristics in older women.", "authors": "Dunk MM, Delac L, Rapp SR et al.", "year": "2025", "journal": "Journal of lipid research", "keywords": "24(S)-hydroxycholesterol, Alzheimer\u2019s disease, CYP46A1, apolipoprotein E, cholesterol, estrogen, hormones, lipids, reproductive history, statins", "chunk": "as potential early biomarkers of risk for Alzheimer's disease and related dementias.", "source": "PubMed"}, {"chunk_id": "41143873_0", "pmid": "41143873", "title": "Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders.", "authors": "Tikkanen V, Paajanen TI, Heikkinen AL et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood-based biomarkers, digital cognitive assessment, early-onset dementia, glial fibrillary acidic protein, mild cognitive impairment, neurofilament light chain, neuropsychological tests", "chunk": "BackgroundEarly diagnosis of early-onset dementia (EOD) is often challenging. Executive dysfunction is a common symptom in EOD, including Alzheimer's disease (AD). Currently, no specific tools for screening EOD at the primary health care exist. The availability of neuropsychological assessment and biomarker analyses is often limited to specialized memory clinics. However, recent advances in blood-biomarkers and better accessible computerized cognitive tests provide new opportunities.ObjectiveTo investigate the ability of serum biomarkers neurofilament light chain and glial fibrillary acidic protein, combined with a novel computerized Flexible Attention Test (FAT) to distinguish early-onset neurodegenerative disorders from other conditions resulting cognitive symptoms in a diagnostically challenging memory clinic population.MethodsCohort consisted of 206 participants with symptom onset \u226465 years and followed up to 24 months: EOD (n = 54, including 29 AD cases), neurological mild cognitive impairment (MCI-n, n = 34), MCI due to other causes (n = 104), and subjective cognitive decline (n = 14).", "source": "PubMed"}, {"chunk_id": "41143873_1", "pmid": "41143873", "title": "Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders.", "authors": "Tikkanen V, Paajanen TI, Heikkinen AL et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood-based biomarkers, digital cognitive assessment, early-onset dementia, glial fibrillary acidic protein, mild cognitive impairment, neurofilament light chain, neuropsychological tests", "chunk": "(n = 54, including 29 AD cases), neurological mild cognitive impairment (MCI-n, n = 34), MCI due to other causes (n = 104), and subjective cognitive decline (n = 14). Serum biomarkers were analyzed using single-molecule array, and discriminative accuracy of individual and combined tests was assessed using Receiver Operating Characteristic and discriminant analyses. FAT was compared to traditional neuropsychological tests.ResultsCombining serum biomarkers with cognitive tests were more accurate in detecting EOD and MCI-n from other conditions (area under the curve, AUC = 0.872) compared to each method individually (AUC = 0.633-0.783). Combination of the FAT and serum biomarkers reached 82.1% accuracy, comparable to traditional neuropsychological tests and biomarkers together (82.3%).ConclusionsIntegrating serum biomarkers with computerized FAT offers a promising strategy for screening EOD early and identifying patients for further evaluation.", "source": "PubMed"}, {"chunk_id": "41143873_2", "pmid": "41143873", "title": "Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders.", "authors": "Tikkanen V, Paajanen TI, Heikkinen AL et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood-based biomarkers, digital cognitive assessment, early-onset dementia, glial fibrillary acidic protein, mild cognitive impairment, neurofilament light chain, neuropsychological tests", "chunk": "for screening EOD early and identifying patients for further evaluation.", "source": "PubMed"}, {"chunk_id": "30372683_0", "pmid": "30372683", "title": "Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease: Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers.", "authors": "Nasoohi S, Parveen K, Ishrat T", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, brain insulin resistance, inflammasomes, metabolic syndrome, oxidative stress, thioredoxin-interacting protein (TXNIP), type 3 diabetes", "chunk": "Empirical evidence indicates a strong association between insulin resistance and pathological alterations related to Alzheimer's disease (AD) in different cerebral regions. While cerebral insulin resistance is not essentially parallel with systemic metabolic derangements, type 2 diabetes mellitus (T2DM) has been established as a risk factor for AD. The circulating \"toxic metabolites\" emerging in metabolic syndrome may engage several biochemical pathways to promote oxidative stress and neuroinflammation leading to impair insulin function in the brain or \"type 3 diabetes\". Thioredoxin-interacting protein (TXNIP) as an intracellular amplifier of oxidative stress and inflammasome activation may presumably mediate central insulin resistance. Emerging data including those from our recent studies has demonstrated a sharp TXNIP upregulation in stroke, aging and AD and well underlining the significance of this hypothesis. With the main interest to illustrate TXNIP place in type 3 diabetes, the present review primarily briefs the potential mechanisms contributing to cerebral insulin resistance in", "source": "PubMed"}, {"chunk_id": "30372683_1", "pmid": "30372683", "title": "Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease: Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers.", "authors": "Nasoohi S, Parveen K, Ishrat T", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, brain insulin resistance, inflammasomes, metabolic syndrome, oxidative stress, thioredoxin-interacting protein (TXNIP), type 3 diabetes", "chunk": "significance of this hypothesis. With the main interest to illustrate TXNIP place in type 3 diabetes, the present review primarily briefs the potential mechanisms contributing to cerebral insulin resistance in a metabolically deranged environment. Then with a particular focus on plausible TXNIP functions to drive and associate with AD pathology, we present the most recent evidence supporting TXNIP as a promising therapeutic target in AD as an age-associated dementia.", "source": "PubMed"}, {"chunk_id": "41638367_0", "pmid": "41638367", "title": "Multi-omics dissection of Parkinson's patients in subgroups associated with motor and cognitive severity.", "authors": "Athieniti E, Afxenti S, Minadakis G et al.", "year": "2026", "journal": "Neurobiology of disease", "keywords": "Disease staging, Factor analysis, Monitoring markers, Multi-omics, Parkinson\u2019s disease, Severity", "chunk": "Heterogeneity in the severity of Parkinson's disease (PD) inhibits the effective interpretation of clinical trial outcomes. Multi-omics analysis may help explain the pathological mechanisms underlying disease progression and reveal biomarkers of clinical severity. We performed Multi-Omics Factor Analysis (MOFA) on whole blood RNA, miRNA and cerebrospinal fluid (CSF) and blood plasma proteomics from the Parkinson's Progression Marker Initiative (PPMI), to identify molecular factors correlated with motor (MDS-UPDRS3) and cognitive (Semantic Fluency Test, SFT) function. Three molecular factors significantly correlated with the MDS-UPDRS3 score and two with SFT, which remained significant after adjusting for age, sex, and medication dose. We used the identified factors to stratify patients into subgroups with distinct motor and cognitive severity. The severe motor clusters showed deregulation of cytotoxic natural killer cell mechanisms in peripheral blood, and changes to proteins associated with the endoplasmic reticulum and dense core vesicle in CSF. The severe cognitive clusters showed changes", "source": "PubMed"}, {"chunk_id": "41638367_1", "pmid": "41638367", "title": "Multi-omics dissection of Parkinson's patients in subgroups associated with motor and cognitive severity.", "authors": "Athieniti E, Afxenti S, Minadakis G et al.", "year": "2026", "journal": "Neurobiology of disease", "keywords": "Disease staging, Factor analysis, Monitoring markers, Multi-omics, Parkinson\u2019s disease, Severity", "chunk": "of cytotoxic natural killer cell mechanisms in peripheral blood, and changes to proteins associated with the endoplasmic reticulum and dense core vesicle in CSF. The severe cognitive clusters showed changes in the complement system and synaptic dysfunction. Our analysis capitalizes on multi-omics data integration to enrich our understanding of the mechanisms driving motor and cognitive decline in PD, to support precision medicine.", "source": "PubMed"}, {"chunk_id": "41280080_0", "pmid": "41280080", "title": "Hippocampal grey matter changes across scales in Alzheimer's Disease.", "authors": "Karat BG, Farahani MV, Davidson M et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disease of the central nervous system, characterized by deterioration in cognitive function including extensive memory impairment. The hippocampus, a medial temporal lobe region, is a key orchestrator in the encoding and retrieval of memory and is believed to be one of the first regions to deteriorate in AD. In this work we examined hippocampal macrostructure (specifically gyrification and thickness) and microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI) relative to healthy aged controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We first utilized an iterative training paradigm to adapt an existing deep learning approach for capturing hippocampal topology to elderly individuals as well as individuals with potential hippocampal degeneration. Using this new model, we found notable decreases in both thickness and gyrification in AD and MCI across both the subfields and anterior-posterior axis. Using the diffusion tensor representation", "source": "PubMed"}, {"chunk_id": "41280080_1", "pmid": "41280080", "title": "Hippocampal grey matter changes across scales in Alzheimer's Disease.", "authors": "Karat BG, Farahani MV, Davidson M et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "degeneration. Using this new model, we found notable decreases in both thickness and gyrification in AD and MCI across both the subfields and anterior-posterior axis. Using the diffusion tensor representation derived from diffusion MRI data, we found significant increases in the mean diffusivity across the extent of the hippocampus in AD and MCI, which may be related to a number of changes such as loss of neuronal cells, decreased fiber density, demyelination, and increased presence of CSF. Examining the primary direction of diffusion relative to canonical hippocampal axes, we found distinct diffusion orientation shifts in AD and MCI throughout the anterior-posterior extent of the subiculum and CA1. Specifically, we found a decrease in diffusion oriented tangentially, and an increase in diffusion oriented along the long-axis. This could potentially be related to the known degeneration of the perforant path, which is greatly affected in AD and is a largely tangential oriented", "source": "PubMed"}, {"chunk_id": "41280080_2", "pmid": "41280080", "title": "Hippocampal grey matter changes across scales in Alzheimer's Disease.", "authors": "Karat BG, Farahani MV, Davidson M et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "diffusion oriented along the long-axis. This could potentially be related to the known degeneration of the perforant path, which is greatly affected in AD and is a largely tangential oriented pathway. The AD-related changes in diffusion orientations were found to not have significant spatial overlap with AD-related changes in mean diffusivity, suggesting that they may be capturing distinct spatially-localized disease processes. Finally, we showed that the macro- and microstructure of the hippocampus in AD changed less across age relative to MCI and controls. As well, the age-related hippocampal macrostructure changes in MCI appeared indistinguishable from healthy aging.", "source": "PubMed"}, {"chunk_id": "40612382_0", "pmid": "40612382", "title": "Biologically inspired hybrid model for Alzheimer's disease classification using structural MRI in the ADNI dataset.", "authors": "Slimi H, Cherif I, Abid S et al.", "year": "2025", "journal": "Frontiers in artificial intelligence", "keywords": "Alzheimer\u2019s disease (AD), MRI images, convolution neural networks (CNN), cross-validation, spiking neural networks (SNN)", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and structural brain alterations such as cortical atrophy and hippocampal degeneration. Early diagnosis remains challenging due to subtle neuroanatomical changes in early stages. This study proposes a hybrid convolutional neural network-spiking neural network (CNN-SNN) architecture to classify AD stages using structural MRI (sMRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The model synergizes CNNs for hierarchical spatial feature extraction and SNNs for biologically inspired temporal dynamics processing. The CNN component processes image slices through convolutional layers, batch normalization, and dropout, while the SNN employs leaky integrate-and-fire (LIF) neurons across 25 time steps to simulate temporal progression of neurodegeneration-even with static sMRI inputs. Trained on a three-class task [AD, mild cognitive impairment (MCI), and cognitively normal (CN) subjects], the hybrid network optimizes mean squared error (MSE) loss with L2 regularization and Adam, incorporating early stopping to enhance generalization.", "source": "PubMed"}, {"chunk_id": "40612382_1", "pmid": "40612382", "title": "Biologically inspired hybrid model for Alzheimer's disease classification using structural MRI in the ADNI dataset.", "authors": "Slimi H, Cherif I, Abid S et al.", "year": "2025", "journal": "Frontiers in artificial intelligence", "keywords": "Alzheimer\u2019s disease (AD), MRI images, convolution neural networks (CNN), cross-validation, spiking neural networks (SNN)", "chunk": "[AD, mild cognitive impairment (MCI), and cognitively normal (CN) subjects], the hybrid network optimizes mean squared error (MSE) loss with L2 regularization and Adam, incorporating early stopping to enhance generalization. Evaluation on ADNI data demonstrates robust performance, with training/validation accuracy and loss tracked over 30 epochs. Classification metrics (precision, recall, <i>F</i> <sub>1</sub>-score) highlight the model's ability to disentangle complex spatiotemporal patterns in neurodegeneration. Visualization of learning curves further validates stability during training. An ablation study demonstrates the SNN's critical role, with its removal reducing accuracy from 99.58 to 75.67%, underscoring the temporal module's importance. The SNN introduces architectural sparsity via spike-based computation, reducing overfitting and enhancing generalization while aligning with neuromorphic principles for energy-efficient deployment. By bridging deep learning with neuromorphic principles, this work advances AD diagnostic frameworks, offering a computationally efficient and biologically plausible approach for clinical neuroimaging. The results underscore the potential of hybrid CNN-SNN architectures to improve", "source": "PubMed"}, {"chunk_id": "40612382_2", "pmid": "40612382", "title": "Biologically inspired hybrid model for Alzheimer's disease classification using structural MRI in the ADNI dataset.", "authors": "Slimi H, Cherif I, Abid S et al.", "year": "2025", "journal": "Frontiers in artificial intelligence", "keywords": "Alzheimer\u2019s disease (AD), MRI images, convolution neural networks (CNN), cross-validation, spiking neural networks (SNN)", "chunk": "neuromorphic principles, this work advances AD diagnostic frameworks, offering a computationally efficient and biologically plausible approach for clinical neuroimaging. The results underscore the potential of hybrid CNN-SNN architectures to improve early detection and stratification of neurodegenerative diseases, paving the way for future applications in neuromorphic healthcare systems.", "source": "PubMed"}, {"chunk_id": "41411732_0", "pmid": "41411732", "title": "IL-24 ameliorates cognitive dysfunction via the inhibition PERK-eIF2\u03b1 Signaling pathway in Alzheimer's disease.", "authors": "Du Y, Zheng X, Yue X et al.", "year": "2026", "journal": "International immunopharmacology", "keywords": "Alzheimer's disease, Amnestic mild cognitive impairment, Endoplasmic reticulum stress, Interleukin-24, T cell subsets", "chunk": "The role of inflammation in the etiology and progression of Alzheimer's disease (AD) has attracted increasing attention; however, the effect of peripheral adaptive immune cells and IL-24 expression on amnestic mild cognitive impairment (aMCI)/AD remains unclear. We detected a reduction in CD4<sup>+</sup> central memory T cells (T<sub>CM</sub>) and an increase in effector memory T cells (T<sub>EM</sub>) in AD compared with aMCI and controls. CD4<sup>+</sup> T cells from patients with AD showed enhanced proliferation, reduced secretion levels of IL-24, and increased secretion levels of IFN-\u03b3 and TNF-\u03b1. The decrease in IL-24 expression in patients with AD was positively associated with cognition. IL-24 overexpression significantly ameliorated the cognitive deficits, neuropathological injury, and cytotoxicity in AD in vivo and in vitro, potentially through PERK-eIF2\u03b1 pathway inhibition. Altogether, T cell subset analyses supported a shift towards senescence of the adaptive immune system in AD. IL-24 is a new therapeutic target and strategy for AD.", "source": "PubMed"}, {"chunk_id": "41411732_1", "pmid": "41411732", "title": "IL-24 ameliorates cognitive dysfunction via the inhibition PERK-eIF2\u03b1 Signaling pathway in Alzheimer's disease.", "authors": "Du Y, Zheng X, Yue X et al.", "year": "2026", "journal": "International immunopharmacology", "keywords": "Alzheimer's disease, Amnestic mild cognitive impairment, Endoplasmic reticulum stress, Interleukin-24, T cell subsets", "chunk": "PERK-eIF2\u03b1 pathway inhibition. Altogether, T cell subset analyses supported a shift towards senescence of the adaptive immune system in AD. IL-24 is a new therapeutic target and strategy for AD.", "source": "PubMed"}, {"chunk_id": "39032019_0", "pmid": "39032019", "title": "Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders.", "authors": "Dobson H, Al Maawali S, Malpas C et al.", "year": "2024", "journal": "Epilepsia", "keywords": "biomarker, epilepsy, glial fibrillary acidic protein, neurofilament light chain, nonepileptic seizures", "chunk": "Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders. We recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy. A total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age", "source": "PubMed"}, {"chunk_id": "39032019_1", "pmid": "39032019", "title": "Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders.", "authors": "Dobson H, Al Maawali S, Malpas C et al.", "year": "2024", "journal": "Epilepsia", "keywords": "biomarker, epilepsy, glial fibrillary acidic protein, neurofilament light chain, nonepileptic seizures", "chunk": "104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03). An elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics", "source": "PubMed"}, {"chunk_id": "39032019_2", "pmid": "39032019", "title": "Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders.", "authors": "Dobson H, Al Maawali S, Malpas C et al.", "year": "2024", "journal": "Epilepsia", "keywords": "biomarker, epilepsy, glial fibrillary acidic protein, neurofilament light chain, nonepileptic seizures", "chunk": "diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.", "source": "PubMed"}, {"chunk_id": "30010132_0", "pmid": "30010132", "title": "MRI-Based Screening of Preclinical Alzheimer's Disease for Prevention Clinical Trials.", "authors": "Casamitjana A, Petrone P, Tucholka A et al.", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Amyloid pathology, clinical trial, machine learning, preclinical Alzheimer\u2019s disease, screening, secondaryprevention", "chunk": "The identification of healthy individuals harboring amyloid pathology represents one important challenge for secondary prevention clinical trials in Alzheimer's disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% of unnecessary CSF/PET tests and to reduce 47% of the cost of recruitment. This recruitment strategy capitalizes on available MR scans to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD.", "source": "PubMed"}, {"chunk_id": "30010132_1", "pmid": "30010132", "title": "MRI-Based Screening of Preclinical Alzheimer's Disease for Prevention Clinical Trials.", "authors": "Casamitjana A, Petrone P, Tucholka A et al.", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Amyloid pathology, clinical trial, machine learning, preclinical Alzheimer\u2019s disease, screening, secondaryprevention", "chunk": "tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD.", "source": "PubMed"}, {"chunk_id": "41573397_0", "pmid": "41573397", "title": "Sensor-based quantification of items used in the MDS-UPDRS-III scale: repetitive lower-limb movements in healthy human participants.", "authors": "Hunziker S, Vogel D, Kalt D et al.", "year": "2025", "journal": "Frontiers in neurology", "keywords": "MDS-UPDRS, Parkinson\u2019s disease, inertial measurement unit, leg agility, quantitative assessment, toe tapping", "chunk": "The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is used as a standardized approach to assess motor function in Parkinson's disease (PD). This assessment is based on the examiner's subjective judgement and is therefore variable. While quantitative approaches have been evaluated for upper-limb movements, data is scarce on lower-limb movements. Thus, our aim was to implement and assess a setup to quantify lower-limb movements as defined in the MDS-UPDRS in healthy participants introducing new parameters for smoothness and acceleration patterns. Twenty-three participants (age-range = 21-31 years) performed five 20-s trials for both lower-limb movement tasks from the MDS-UPDRS-III, i.e., toe tapping (item 3.7) and leg agility (item 3.8). Foot and leg movements were recorded using four inertial measurement units (two per leg: one mounted on the foot and one on the ankle). Biomarkers such as kinematic parameters (e.g., frequency, angular amplitude, movement smoothness, acceleration-based parameters) were extracted to", "source": "PubMed"}, {"chunk_id": "41573397_1", "pmid": "41573397", "title": "Sensor-based quantification of items used in the MDS-UPDRS-III scale: repetitive lower-limb movements in healthy human participants.", "authors": "Hunziker S, Vogel D, Kalt D et al.", "year": "2025", "journal": "Frontiers in neurology", "keywords": "MDS-UPDRS, Parkinson\u2019s disease, inertial measurement unit, leg agility, quantitative assessment, toe tapping", "chunk": "units (two per leg: one mounted on the foot and one on the ankle). Biomarkers such as kinematic parameters (e.g., frequency, angular amplitude, movement smoothness, acceleration-based parameters) were extracted to characterize foot-movement dynamics (dominant vs. non-dominant leg), with statistical analyses including linear mixed-effects models applied to four consecutive, non-overlapping 5-s intervals. A paired Wilcoxon test showed no significant differences in parameters for toe tapping and leg agility based on leg dominance. For toe tapping, the relationship between frequency and angle displayed non-linearity, with a clear decrease in angle with 17.41\u00b0 -0.83\u00b0/interval*t (t = 1-4 time intervals) and no clear decrease in frequency with 2.75 Hz - 0.02 Hz/interval*t. The median frequency and angle for toe tapping were 2.8 Hz and 16\u00b0 respectively. The median frequency for leg agility was 2.6 Hz. Reference values could be determined for all parameters including smoothness and acceleration patterns. The quantitative assessment of two MDS-UPDRS-III", "source": "PubMed"}, {"chunk_id": "41573397_2", "pmid": "41573397", "title": "Sensor-based quantification of items used in the MDS-UPDRS-III scale: repetitive lower-limb movements in healthy human participants.", "authors": "Hunziker S, Vogel D, Kalt D et al.", "year": "2025", "journal": "Frontiers in neurology", "keywords": "MDS-UPDRS, Parkinson\u2019s disease, inertial measurement unit, leg agility, quantitative assessment, toe tapping", "chunk": "16\u00b0 respectively. The median frequency for leg agility was 2.6 Hz. Reference values could be determined for all parameters including smoothness and acceleration patterns. The quantitative assessment of two MDS-UPDRS-III items shows that temporal changes and adaptation-mechanisms significantly influenced leg-movement dynamics. Reducing exercise duration to 10 s and implementing a metronome with defined frequency could enhance measurement accuracy and reliability, offering more precise parameters for future applications in PD-patients.", "source": "PubMed"}, {"chunk_id": "36948139_0", "pmid": "36948139", "title": "Role of hippocampal subfields in neurodegenerative disease progression analyzed with a multi-scale attention-based network.", "authors": "Xu H, Liu Y, Wang L et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Deep learning, Hippocampal subfields, Mild cognitive impairment, Parkinson disease", "chunk": "Both Alzheimer's disease (AD) and Parkinson's disease (PD) are progressive neurodegenerative diseases. Early identification is very important for the prevention and intervention of their progress. Hippocampus plays a crucial role in cognition, in which there are correlations between atrophy of Hippocampal subfields and cognitive impairment in neurodegenerative diseases. Exploring biomarkers in the prediction of early cognitive impairment in AD and PD is significant for understanding the progress of neurodegenerative diseases. A multi-scale attention-based deep learning method is proposed to perform computer-aided diagnosis for neurodegenerative disease based on Hippocampal subfields. First, the two dimensional (2D) Hippocampal Mapping Image (HMI) is constructed and used as input of three branches of the following network. Second, the multi-scale module and attention module are integrated into the 2D residual network to improve the diversity of the extracted features and capture significance of various voxels for classification. Finally, the role of Hippocampal subfields in the progression", "source": "PubMed"}, {"chunk_id": "36948139_1", "pmid": "36948139", "title": "Role of hippocampal subfields in neurodegenerative disease progression analyzed with a multi-scale attention-based network.", "authors": "Xu H, Liu Y, Wang L et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Deep learning, Hippocampal subfields, Mild cognitive impairment, Parkinson disease", "chunk": "into the 2D residual network to improve the diversity of the extracted features and capture significance of various voxels for classification. Finally, the role of Hippocampal subfields in the progression of different neurodegenerative diseases is analyzed using the proposed method. Classification experiments between normal control (NC), mild cognitive impairment (MCI), AD, PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) are carried out using the proposed method. Experimental results show that subfields subiculum, presubiculum, CA1, and molecular layer are strongly correlated with cognitive impairment in AD and MCI, subfields GC-DG and fimbria are sensitive in detecting early stage of cognitive impairment in MCI, subfields CA3, CA4, GC-DG, and CA1 show significant atrophy in PD. For exploring the role of Hippocampal subfields in PD cognitive impairment, we find that left parasubiculum, left HATA and left presubiculum could be important biomarkers for predicting conversion from PD-NC to PD-MCI. The", "source": "PubMed"}, {"chunk_id": "36948139_2", "pmid": "36948139", "title": "Role of hippocampal subfields in neurodegenerative disease progression analyzed with a multi-scale attention-based network.", "authors": "Xu H, Liu Y, Wang L et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Deep learning, Hippocampal subfields, Mild cognitive impairment, Parkinson disease", "chunk": "role of Hippocampal subfields in PD cognitive impairment, we find that left parasubiculum, left HATA and left presubiculum could be important biomarkers for predicting conversion from PD-NC to PD-MCI. The proposed multi-scale attention-based network can effectively discover the correlation between subfields and neurodegenerative diseases. Experimental results are consistent with previous clinical studies, which will be useful for further exploring the role of Hippocampal subfields in neurodegenerative disease progression.", "source": "PubMed"}, {"chunk_id": "41767317_0", "pmid": "41767317", "title": "Comparison of binocular vision indices in Parkinson's disease patients <i>vs</i> age-sex-matched healthy controls.", "authors": "Shariati-Moghaddam R, Shoeibi A, Ahmad MA et al.", "year": "2026", "journal": "International journal of ophthalmology", "keywords": "Parkinson's disease, binocular vision, fusional vergence, heterophoria, near point of convergence, saccadic eye movement", "chunk": "To evaluate the differences in near point of convergence (NPC), fusional vergence, saccadic eye movements, versional eye movements, and heterophoria between patients diagnosed with Parkinson's disease (PD) and healthy subjects. A cross-sectional comparative study was conducted, enrolling two cohorts: a PD group and a healthy control group. The PD group was recruited <i>via</i> non-random convenience sampling, while the control group was selected randomly from individuals without PD. All participants were screened according to predefined inclusion and exclusion criteria before undergoing a comprehensive optometric assessment, which included measurements of uncorrected visual acuity, corrected visual acuity, and objective and subjective refraction. Subsequently, binocular vision function evaluations were performed, covering NPC measurement, fusional vergence reserve assessment at both distance and near, saccadic eye movement testing, and versional eye movement and heterophoria assessment. A total of 42 PD patients and 41 healthy controls were included in the final analysis. The two groups were well-matched", "source": "PubMed"}, {"chunk_id": "41767317_1", "pmid": "41767317", "title": "Comparison of binocular vision indices in Parkinson's disease patients <i>vs</i> age-sex-matched healthy controls.", "authors": "Shariati-Moghaddam R, Shoeibi A, Ahmad MA et al.", "year": "2026", "journal": "International journal of ophthalmology", "keywords": "Parkinson's disease, binocular vision, fusional vergence, heterophoria, near point of convergence, saccadic eye movement", "chunk": "movement testing, and versional eye movement and heterophoria assessment. A total of 42 PD patients and 41 healthy controls were included in the final analysis. The two groups were well-matched in terms of sex distribution [29 males (69.0%) in the PD group <i>vs</i> 29 males (70.7%) in the control group, <i>P</i>=0.867] and mean age (55.3\u00b19.6y in the PD group <i>vs</i> 54.9\u00b19.8y in the control group, <i>P</i>=0.866). The prevalence of abnormal versional eye movements was significantly higher in the PD group than in the control group (23.81%, 95%CI: 12.05%-39.45% <i>vs</i> 7.32%, 95%CI: 1.54%-19.92%; <i>P</i>=0.025). Near exophoria was more prevalent in PD patients (61.90%, 95%CI: 45.64%-76.43%) than in controls (17.07%, 95%CI: 7.15%-32.06%), with a significant difference [odds ratio (OR)=7.99; 95%CI: 2.83-21.99; <i>P</i><0.001]. The mean NPC was significantly greater (more receded) in the PD group than in the control group (9.01\u00b13.74 cm <i>vs</i> 7.20\u00b12.15 cm; <i>P</i>=0.007). A statistically significant positive correlation was observed", "source": "PubMed"}, {"chunk_id": "41767317_2", "pmid": "41767317", "title": "Comparison of binocular vision indices in Parkinson's disease patients <i>vs</i> age-sex-matched healthy controls.", "authors": "Shariati-Moghaddam R, Shoeibi A, Ahmad MA et al.", "year": "2026", "journal": "International journal of ophthalmology", "keywords": "Parkinson's disease, binocular vision, fusional vergence, heterophoria, near point of convergence, saccadic eye movement", "chunk": "The mean NPC was significantly greater (more receded) in the PD group than in the control group (9.01\u00b13.74 cm <i>vs</i> 7.20\u00b12.15 cm; <i>P</i>=0.007). A statistically significant positive correlation was observed between PD severity and NPC values (Pearson's correlation coefficient=0.309; <i>P</i>=0.046). Except for distance base-out break and distance base-out recovery values, all other fusional vergence parameters were significantly lower in the PD group than in the control group (<i>P</i><0.05). The mean saccadic test score was significantly lower in PD patients than in controls (3.29\u00b10.57 <i>vs</i> 3.78\u00b10.42; <i>P</i><0.001). Among all fusional vergence indices, near base-in blur yielded the highest area under the curve (AUC=0.877), with a sensitivity of 69% and specificity of 90%, followed by distance base-out blur (AUC=0.824, sensitivity=97.6%, specificity=66.7%), near base-out blur (AUC=0.814, sensitivity=76.2%, specificity=72.7%), near base-out break (AUC=0.749, sensitivity=78.6%, specificity=67.6%), and near base-out recovery (AUC=0.749, sensitivity=95.2%, specificity=50%). PD is associated with significant binocular vision function impairment, with receded NPC", "source": "PubMed"}, {"chunk_id": "41767317_3", "pmid": "41767317", "title": "Comparison of binocular vision indices in Parkinson's disease patients <i>vs</i> age-sex-matched healthy controls.", "authors": "Shariati-Moghaddam R, Shoeibi A, Ahmad MA et al.", "year": "2026", "journal": "International journal of ophthalmology", "keywords": "Parkinson's disease, binocular vision, fusional vergence, heterophoria, near point of convergence, saccadic eye movement", "chunk": "base-out blur (AUC=0.814, sensitivity=76.2%, specificity=72.7%), near base-out break (AUC=0.749, sensitivity=78.6%, specificity=67.6%), and near base-out recovery (AUC=0.749, sensitivity=95.2%, specificity=50%). PD is associated with significant binocular vision function impairment, with receded NPC and reduced near fusional vergence reserves being the most prominent disorders. These findings highlight the potential value of binocular vision assessment as a non-invasive biomarker for the early detection and clinical monitoring of PD.", "source": "PubMed"}, {"chunk_id": "35988315_0", "pmid": "35988315", "title": "Effective high-density lipoprotein cholesterol is associated with carotid intima-media thickness and vascular events after acute ischemic stroke.", "authors": "Schwedhelm E, Tiedt S, Lezius S et al.", "year": "2022", "journal": "Atherosclerosis", "keywords": "Biomarker, Major cardiovascular events, Outcome, Stroke", "chunk": "Effective high density lipoprotein cholesterol (HDL-C) is a measure of HDL functionality. We evaluated if HDL-C is associated with carotid intima-media thickness (cIMT) and incident major adverse cardiovascular events (MACE) in patients with acute ischemic stroke from two prospective cohort studies. In the MARK-STROKE cohort, 299 patients with acute ischemic stroke or TIA were included. Outcome was available in 219 patients during a median follow-up of 294 days. In CIRCULAS, 382 acute ischemic stroke patients were included and a 90-day follow-up was available in 213 patients. HDL-C was calculated based on symmetric dimethylarginine (SDMA) and HDL cholesterol concentrations. Main outcome was incident MACE (death, stroke, and myocardial infarction) and the main measure was cIMT. In both studies, HDL-C was inversely associated with cIMT in linear regression analysis adjusted for age, sex and creatinine. In MARK-STROKE, the adjusted hazard for MACE was significantly reduced for patients with one unit increase (mg/dL)", "source": "PubMed"}, {"chunk_id": "35988315_1", "pmid": "35988315", "title": "Effective high-density lipoprotein cholesterol is associated with carotid intima-media thickness and vascular events after acute ischemic stroke.", "authors": "Schwedhelm E, Tiedt S, Lezius S et al.", "year": "2022", "journal": "Atherosclerosis", "keywords": "Biomarker, Major cardiovascular events, Outcome, Stroke", "chunk": "associated with cIMT in linear regression analysis adjusted for age, sex and creatinine. In MARK-STROKE, the adjusted hazard for MACE was significantly reduced for patients with one unit increase (mg/dL) of HDL-C (hazard ratio 0.95 [95% confidence interval (CI): 0.92, 0.99]). In the CIRCULAS cohort, stroke patients with higher HDL-C had less incident MACE during 90 days of follow-up (odds ratio: 0.97 [95% CI: 0.94, 0.99] for one unit increase). Neither SDMA nor HDL cholesterol predicted outcome. Our findings imply a protective role of biologically effective HDL after acute cerebral ischemia for secondary events and emphasize the relevance of lipoprotein functionality in these patients.", "source": "PubMed"}, {"chunk_id": "40585705_0", "pmid": "40585705", "title": "Exploring the Association Between Myocardial Infarction and Cognitive Decline: A Narrative Review.", "authors": "Issimdar IA, Mudegowdar R, Gupta AR et al.", "year": "2025", "journal": "Cureus", "keywords": "acute myocardial infarction (ami), cognitive decline, cognitive impairment, dementia, myocardial infarction, post-acute myocardial infarction", "chunk": "The association between cognitive impairment (CI) and myocardial infarction (MI) has been highlighted in recent years. Several studies have reported an increased incidence of cognitive decline (CD) following MI, emphasizing the need for early identification and intervention in such patients. Previous research findings have been inconsistent due to the presence of various unaccounted factors potentially contributing to CD and disparities in the methods utilized to assess cognition such as the Mini-Mental State Examination, Mini-Cog and self-evaluation questionnaires. This emphasizes the potential for a more standardized tool of assessment to investigate the onset of CD amongst MI patients in a reliable manner. This literature review delineates the correlation between MI and CI, exploring the pathogenesis, risk factors, management and preventive strategies. Cerebral hypoperfusion, underlying atherosclerosis and neuroinflammation are crucial in the development of CD after MI. Hence, it is important to consider the 'heart-brain axis' for targeted therapy of CD in", "source": "PubMed"}, {"chunk_id": "40585705_1", "pmid": "40585705", "title": "Exploring the Association Between Myocardial Infarction and Cognitive Decline: A Narrative Review.", "authors": "Issimdar IA, Mudegowdar R, Gupta AR et al.", "year": "2025", "journal": "Cureus", "keywords": "acute myocardial infarction (ami), cognitive decline, cognitive impairment, dementia, myocardial infarction, post-acute myocardial infarction", "chunk": "Cerebral hypoperfusion, underlying atherosclerosis and neuroinflammation are crucial in the development of CD after MI. Hence, it is important to consider the 'heart-brain axis' for targeted therapy of CD in MI patients. Old age is a common risk factor for CD and MI. However, the impact of variables including gender and comorbidities is underreported, which can potentially alter the relationship between cognitive outcomes and MI. The implementation of multidisciplinary-oriented cardiac rehabilitation programs and a universal screening tool to follow up on patients with established CI post-MI has shown favorable outcomes and has reduced the risk of adverse health consequences. Optimizing medical management and regular monitoring of serum brain natriuretic peptide (BNP) and hemoglobin levels are essential in preventing CD after MI. Psychological evaluation and counselling also help attenuate CD. Additionally, preventive strategies addressing modifiable risk factors and implementing anti-inflammatory diets have proven beneficial. Ongoing research is focused on the study", "source": "PubMed"}, {"chunk_id": "40585705_2", "pmid": "40585705", "title": "Exploring the Association Between Myocardial Infarction and Cognitive Decline: A Narrative Review.", "authors": "Issimdar IA, Mudegowdar R, Gupta AR et al.", "year": "2025", "journal": "Cureus", "keywords": "acute myocardial infarction (ami), cognitive decline, cognitive impairment, dementia, myocardial infarction, post-acute myocardial infarction", "chunk": "MI. Psychological evaluation and counselling also help attenuate CD. Additionally, preventive strategies addressing modifiable risk factors and implementing anti-inflammatory diets have proven beneficial. Ongoing research is focused on the study of novel interventions targeting the neuroinflammatory process. Recently a new member of the C-reactive protein family, pentraxin 3, has been identified as a specific vascular inflammatory biomarker produced by cells in atherosclerotic lesions that can potentially aid in recognizing CD. It is imperative to establish uniform guidelines to recognize and manage CI among patients following MI to improve quality of life among the elderly population.", "source": "PubMed"}, {"chunk_id": "38778071_0", "pmid": "38778071", "title": "A deep learning model for brain segmentation across pediatric and adult populations.", "authors": "Simarro J, Meyer MI, Van Eyndhoven S et al.", "year": "2024", "journal": "Scientific reports", "keywords": "None", "chunk": "Automated quantification of brain tissues on MR images has greatly contributed to the diagnosis and follow-up of neurological pathologies across various life stages. However, existing solutions are specifically designed for certain age ranges, limiting their applicability in monitoring brain development from infancy to late adulthood. This retrospective study aims to develop and validate a brain segmentation model across pediatric and adult populations. First, we trained a deep learning model to segment tissues and brain structures using T1-weighted MR images from 390 patients (age range: 2-81 years) across four different datasets. Subsequently, the model was validated on a cohort of 280 patients from six distinct test datasets (age range: 4-90 years). In the initial experiment, the proposed deep learning-based pipeline, icobrain-dl, demonstrated segmentation accuracy comparable to both pediatric and adult-specific models across diverse age groups. Subsequently, we evaluated intra- and inter-scanner variability in measurements of various tissues and structures in both", "source": "PubMed"}, {"chunk_id": "38778071_1", "pmid": "38778071", "title": "A deep learning model for brain segmentation across pediatric and adult populations.", "authors": "Simarro J, Meyer MI, Van Eyndhoven S et al.", "year": "2024", "journal": "Scientific reports", "keywords": "None", "chunk": "demonstrated segmentation accuracy comparable to both pediatric and adult-specific models across diverse age groups. Subsequently, we evaluated intra- and inter-scanner variability in measurements of various tissues and structures in both pediatric and adult populations computed by icobrain-dl. Results demonstrated significantly higher reproducibility compared to similar brain quantification tools, including childmetrix, FastSurfer, and the medical device icobrain v5.9 (p-value< 0.01). Finally, we explored the potential clinical applications of icobrain-dl measurements in diagnosing pediatric patients with Cerebral Visual Impairment and adult patients with Alzheimer's Disease.", "source": "PubMed"}, {"chunk_id": "39434814_0", "pmid": "39434814", "title": "Individualized and Biomarker-Based Prognosis of Longitudinal Cognitive Decline in Early Symptomatic Alzheimer's Disease.", "authors": "Wang X, Ye T, Huang Z et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer\u2019s disease, cognitive decline, individualized prediction, mild cognitive impairment, nomogram", "chunk": "Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain. We aimed to develop prognostic models for individualized prediction of cognitive change in early AD. A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years. A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R<sup>2</sup> of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude", "source": "PubMed"}, {"chunk_id": "39434814_1", "pmid": "39434814", "title": "Individualized and Biomarker-Based Prognosis of Longitudinal Cognitive Decline in Early Symptomatic Alzheimer's Disease.", "authors": "Wang X, Ye T, Huang Z et al.", "year": "2024", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer\u2019s disease, cognitive decline, individualized prediction, mild cognitive impairment, nomogram", "chunk": "provided the best predictive performance, achieving an overfitting-corrected R<sup>2</sup> of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD. Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.", "source": "PubMed"}, {"chunk_id": "41009720_0", "pmid": "41009720", "title": "p.N370S <i>GBA1</i> Mutation Influences the Morphology and Lipid Composition of Extracellular Vesicles in Blood Plasma from Patients with Parkinson's Disease.", "authors": "Usenko TS, Kopytova AE, Izyumchenko AD et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "GBA1, Parkinson\u2019s disease, cryo-electron microscopy, extracellular vesicles, lipidomics, proteomics", "chunk": "Parkinson's disease, associated with mutations in the <i>GBA1</i> gene (GBA1-PD), is the most common genetic form of Parkinson's disease (PD), marked by clinical heterogeneity influenced by mutation type. Extracellular vesicles (EVs), key mediators of intercellular communication, are implicated in PD pathogenesis through the transport of pathological proteins and lipids. In this study, we analyzed blood plasma-derived EVs from GBA1-PD patients carrying p.N370S and p.L444P mutations and from healthy controls using cryo-electron microscopy, lipidomics, and proteomics. EVs from GBA1-PD patients were significantly larger than those from controls, with the largest size and most multilayered vesicles observed in p.N370S carriers. Lipidomic profiling identified 237 lipid species; of these, 186 lipids were altered in p.N370S and 24 in p.L444P versus controls. Mutation carriers showed distinct lipid signatures, with p.L444P samples enriched predominantly in sphingolipids, while p.N370S carriers exhibited more extensive lipid remodeling across multiple classes, including triglycerides, cholesteryl esters, and phospholipids. Notably, Cer", "source": "PubMed"}, {"chunk_id": "41009720_1", "pmid": "41009720", "title": "p.N370S <i>GBA1</i> Mutation Influences the Morphology and Lipid Composition of Extracellular Vesicles in Blood Plasma from Patients with Parkinson's Disease.", "authors": "Usenko TS, Kopytova AE, Izyumchenko AD et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "GBA1, Parkinson\u2019s disease, cryo-electron microscopy, extracellular vesicles, lipidomics, proteomics", "chunk": "showed distinct lipid signatures, with p.L444P samples enriched predominantly in sphingolipids, while p.N370S carriers exhibited more extensive lipid remodeling across multiple classes, including triglycerides, cholesteryl esters, and phospholipids. Notably, Cer 23:0 was elevated across all GBA1-PD groups. Proteomic analysis revealed enrichment in pathways related to lipid transport, immune regulation, and vesicle-mediated processes. Overall, GBA1-PD patients share a distinct lipidomic EV signature, with mutation-specific patterns reflecting differing mechanisms of lysosomal dysfunction. These findings support the potential of EV profiling to unravel disease heterogeneity and identify biomarkers.", "source": "PubMed"}, {"chunk_id": "41258220_0", "pmid": "41258220", "title": "Neuropsychological insights into creativity in people with Parkinson's disease.", "authors": "Zeggio S, Steyrl D, Pelowski M et al.", "year": "2025", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Creativity, the capacity and motivation to produce novel and personally meaningful ideas or behaviors, can be influenced by Parkinson's disease (PD). Non-motor neuropsychological symptoms, such as apathy and negative schizotypy have been linked to reduced creativity, while dopaminergic treatments are associated with increased creative engagement. Building on epidemiological findings investigating changes in creativity, we examined possible drivers of increased and decreased creative activity. In a cross-sectional study, 360 participants with PD completed a questionnaire assessing self-reported creativity changes and associated factors, including personality (Big-Five, Multidimensional-Schizotypy-Scale), lifestyle (e.g., creative lifestyle, free time), and clinical (HY-scores, MoCA, dopaminergic treatments). Using machine learning (gradient-boosted decision-trees), we explained 23% of variance in creativity changes. Dopamine agonists, extraversion, free time, and a creative lifestyle since symptom onset predicted increased creativity, while disorganized schizotypy predicted decreases. The findings provide new insights for future research on creativity as part of PD's neuropsychological spectrum and for person-centered treatment.", "source": "PubMed"}, {"chunk_id": "41258220_1", "pmid": "41258220", "title": "Neuropsychological insights into creativity in people with Parkinson's disease.", "authors": "Zeggio S, Steyrl D, Pelowski M et al.", "year": "2025", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "symptom onset predicted increased creativity, while disorganized schizotypy predicted decreases. The findings provide new insights for future research on creativity as part of PD's neuropsychological spectrum and for person-centered treatment.", "source": "PubMed"}, {"chunk_id": "38761289_0", "pmid": "38761289", "title": "Enhancing clinical diagnostics: novel denoising methodology for brain MRI with adaptive masking and modified non-local block.", "authors": "Velayudham A, Kumar KM, Priya M S K", "year": "2024", "journal": "Medical & biological engineering & computing", "keywords": "Brain MRI images, Deep learning, Denoising, Dynamic mask generation, Edge enhancement, Image processing", "chunk": "Medical image denoising has been a subject of extensive research, with various techniques employed to enhance image quality and facilitate more accurate diagnostics. The evolution of denoising methods has highlighted impressive results but struggled to strike equilibrium between noise reduction and edge preservation which limits its applicability in various domains. This paper manifests the novel methodology that integrates an adaptive masking strategy, transformer-based U-Net Prior generator, edge enhancement module, and modified non-local block (MNLB) for denoising brain MRI clinical images. The adaptive masking strategy maintains the vital information through dynamic mask generation while the prior generator by capturing hierarchical features regenerates the high-quality prior MRI images. Finally, these images are fed to the edge enhancement module to boost structural information by maintaining crucial edge details, and the MNLB produces the denoised output by deriving non-local contextual information. The comprehensive experimental assessment is performed by employing two datasets namely the brain", "source": "PubMed"}, {"chunk_id": "38761289_1", "pmid": "38761289", "title": "Enhancing clinical diagnostics: novel denoising methodology for brain MRI with adaptive masking and modified non-local block.", "authors": "Velayudham A, Kumar KM, Priya M S K", "year": "2024", "journal": "Medical & biological engineering & computing", "keywords": "Brain MRI images, Deep learning, Denoising, Dynamic mask generation, Edge enhancement, Image processing", "chunk": "by maintaining crucial edge details, and the MNLB produces the denoised output by deriving non-local contextual information. The comprehensive experimental assessment is performed by employing two datasets namely the brain tumor MRI dataset and Alzheimer's dataset for diverse metrics and compared with conventional denoising approaches. The proposed denoising methodology achieves a PSNR of 40.965 and SSIM of 0.938 on the Alzheimer's dataset and also achieves a PSNR of 40.002 and SSIM of 0.926 on the brain tumor MRI dataset at a noise level of 50% revealing its supremacy in noise minimization. Furthermore, the impact of different masking ratios on denoising performance is analyzed which reveals that the proposed method showed PSNR of 40.965, SSIM of 0.938, MAE of 5.847, and MSE of 3.672 at the masking ratio of 60%. Moreover, the findings pave the way for the advancement of clinical image processing, facilitating precise detection of tumors in clinical MRI", "source": "PubMed"}, {"chunk_id": "38761289_2", "pmid": "38761289", "title": "Enhancing clinical diagnostics: novel denoising methodology for brain MRI with adaptive masking and modified non-local block.", "authors": "Velayudham A, Kumar KM, Priya M S K", "year": "2024", "journal": "Medical & biological engineering & computing", "keywords": "Brain MRI images, Deep learning, Denoising, Dynamic mask generation, Edge enhancement, Image processing", "chunk": "MSE of 3.672 at the masking ratio of 60%. Moreover, the findings pave the way for the advancement of clinical image processing, facilitating precise detection of tumors in clinical MRI images.", "source": "PubMed"}, {"chunk_id": "38658167_0", "pmid": "38658167", "title": "Altered Hierarchical Gradients of Intrinsic Neural Timescales in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Zhang A, Wengler K, Zhu X et al.", "year": "2024", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "AD, INT, MCI, rs-fMRI", "chunk": "Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the United States. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit. Such heterogeneity of the timescales forms a basis of the brain functional hierarchy and captures an aspect of circuit dynamics relevant to excitation/inhibition balance, which is broadly relevant for cognitive functions. Given that, we applied rs-fMRI to test whether distinct changes of INT at different hierarchies are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed-effect model was implemented to detect altered hierarchical gradients across populations", "source": "PubMed"}, {"chunk_id": "38658167_1", "pmid": "38658167", "title": "Altered Hierarchical Gradients of Intrinsic Neural Timescales in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Zhang A, Wengler K, Zhu X et al.", "year": "2024", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "AD, INT, MCI, rs-fMRI", "chunk": "are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed-effect model was implemented to detect altered hierarchical gradients across populations followed by pairwise comparisons to identify regional differences. High similarities between AD and Converter were observed. Specifically, the inferior temporal, caudate, and pallidum areas exhibit significant alterations in both AD and Converter. Distinct INT-related pathological changes in MCI and AD were found. For AD/Converter, neural information is stored for a longer time in lower hierarchical areas, while higher levels of hierarchy seem to be preferentially impaired in MCI leading to a less pronounced hierarchical gradient. These results inform that the INT holds great potential as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.", "source": "PubMed"}, {"chunk_id": "38658167_2", "pmid": "38658167", "title": "Altered Hierarchical Gradients of Intrinsic Neural Timescales in Mild Cognitive Impairment and Alzheimer's Disease.", "authors": "Zhang A, Wengler K, Zhu X et al.", "year": "2024", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "AD, INT, MCI, rs-fMRI", "chunk": "prediction, even a stable biomarker for clinical diagnosis.", "source": "PubMed"}, {"chunk_id": "41148189_0", "pmid": "41148189", "title": "Diagnostic utility of speech-based biomarkers in mild cognitive impairment: a systematic review and meta-analysis.", "authors": "Jafari Z, Andrew MK, Rockwood KJ", "year": "2025", "journal": "Age and ageing", "keywords": "accuracy, automatic speech recognition, machine learning, mild cognitive impairment, older adults, sensitivity, specificity, speech analysis, subjective cognitive decline, systematic review", "chunk": "Among various tools developed for mild cognitive impairment (MCI) detection, analysing speech features is a non-invasive and cost-effective approach that shows promise for early detection. This review aimed to systematically synthesise and analyse current evidence on the diagnostic utility of speech-based biomarkers for identifying MCI. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Scopus, Ovid Medline and PsycINFO databases were searched up to April 2025 without restrictions on language, article status or year. Of 4432 identified records, 54 peer-reviewed articles met the inclusion criteria. Fixed-effects meta-analyses showed pooled estimates of 80.0% 'accuracy' [95% confidence intervals (CI): 70.0%-89.0%, P < .001, n = 21], 78.0% 'area under the curve' (95% CI: 70.0%-86.0%, P < .001, n = 21), 80.0% 'sensitivity' (95% CI: 71.0%-90.0%, P < .001, n = 22), and 77.0% 'specificity' (95% CI: 65.0%-89.0%, P < .001, n = 15)", "source": "PubMed"}, {"chunk_id": "41148189_1", "pmid": "41148189", "title": "Diagnostic utility of speech-based biomarkers in mild cognitive impairment: a systematic review and meta-analysis.", "authors": "Jafari Z, Andrew MK, Rockwood KJ", "year": "2025", "journal": "Age and ageing", "keywords": "accuracy, automatic speech recognition, machine learning, mild cognitive impairment, older adults, sensitivity, specificity, speech analysis, subjective cognitive decline, systematic review", "chunk": "70.0%-86.0%, P < .001, n = 21), 80.0% 'sensitivity' (95% CI: 71.0%-90.0%, P < .001, n = 22), and 77.0% 'specificity' (95% CI: 65.0%-89.0%, P < .001, n = 15) in differentiating MCI from cognitively unimpaired (CU) individuals. Egger's regression tests indicated no publication bias (P \u2265 .299), and the I2 statistic revealed no heterogeneity across studies (I2 = 0.00%, P = 1.00). Four studies also included a subjective cognitive decline group, reporting significant differences in certain speech features compared to CU. Speech analysis demonstrates moderate classification performance, with balanced sensitivity and specificity, in distinguishing MCI from CU, suggesting its potential as an accurate and cost-effective diagnostic tool for MCI detection. Further research is needed to address variations in study methodologies, refine speech analysis protocols and validate findings in diverse populations to enhance generalisability.", "source": "PubMed"}, {"chunk_id": "41148189_2", "pmid": "41148189", "title": "Diagnostic utility of speech-based biomarkers in mild cognitive impairment: a systematic review and meta-analysis.", "authors": "Jafari Z, Andrew MK, Rockwood KJ", "year": "2025", "journal": "Age and ageing", "keywords": "accuracy, automatic speech recognition, machine learning, mild cognitive impairment, older adults, sensitivity, specificity, speech analysis, subjective cognitive decline, systematic review", "chunk": "methodologies, refine speech analysis protocols and validate findings in diverse populations to enhance generalisability.", "source": "PubMed"}, {"chunk_id": "40319433_0", "pmid": "40319433", "title": "Characterizing the Journey of Early Alzheimer's Disease in Patients Initiating Lecanemab Treatment in the United States: A Real-World Evidence Study.", "authors": "Sabbagh MN, Zhao C, Mahendran M et al.", "year": "2025", "journal": "Neurology and therapy", "keywords": "Administrative claims, Alzheimer\u2019s disease, Diagnostic patterns, Disease-modifying therapy, Lecanemab, Retrospective study, Treatment patterns", "chunk": "With the advent of disease-modifying therapies for early Alzheimer's disease (AD), a comprehensive characterization of patients initiating lecanemab in the USA is needed to understand its use in real-world settings. This retrospective observational study used administrative claims from the Komodo Research Database (1/1/2023-6/30/2024). Eligible patients had \u2265 1 lecanemab administration (first claim defined the index date) and \u2265 12 months of clinical activity/insurance eligibility before the index date. Patient characteristics, diagnostic process, and AD-related medications were evaluated within 12 months before the index date (baseline), whereas lecanemab treatment patterns and concomitant medications were evaluated on or after the index date (follow-up). Outcomes were reported using descriptive statistics and persistence to lecanemab was evaluated using Kaplan-Meier analysis. Of 3155 patients included in the study, mean age was 75.0 years, 55.8% were female, 44.2% were male, and most (93.3%) received their index lecanemab administration in an urban setting. Diagnoses of AD (83.8%)", "source": "PubMed"}, {"chunk_id": "40319433_1", "pmid": "40319433", "title": "Characterizing the Journey of Early Alzheimer's Disease in Patients Initiating Lecanemab Treatment in the United States: A Real-World Evidence Study.", "authors": "Sabbagh MN, Zhao C, Mahendran M et al.", "year": "2025", "journal": "Neurology and therapy", "keywords": "Administrative claims, Alzheimer\u2019s disease, Diagnostic patterns, Disease-modifying therapy, Lecanemab, Retrospective study, Treatment patterns", "chunk": "in the study, mean age was 75.0 years, 55.8% were female, 44.2% were male, and most (93.3%) received their index lecanemab administration in an urban setting. Diagnoses of AD (83.8%) and mild cognitive impairment (60.8%) were common at baseline, and 67.6% of patients used AD symptomatic medications. Average time from earliest diagnosis to first lecanemab administration was 4.9 months among patients with a diagnosis in January 2023 (accelerated approval date) or onwards. Over a mean follow-up of 138.8 days, the monthly mean number of administrations of lecanemab was 1.9, with an average of 16.5 days between consecutive administrations and 47.4 days to the first follow-up head magnetic resonance imaging. Persistence to lecanemab was 87.6% at 4 months after treatment initiation. Lecanemab was utilized in appropriate patient populations according to the prescribing information approved by the US Food and Drug Administration. Findings from our study provide first insights into the real-world", "source": "PubMed"}, {"chunk_id": "40319433_2", "pmid": "40319433", "title": "Characterizing the Journey of Early Alzheimer's Disease in Patients Initiating Lecanemab Treatment in the United States: A Real-World Evidence Study.", "authors": "Sabbagh MN, Zhao C, Mahendran M et al.", "year": "2025", "journal": "Neurology and therapy", "keywords": "Administrative claims, Alzheimer\u2019s disease, Diagnostic patterns, Disease-modifying therapy, Lecanemab, Retrospective study, Treatment patterns", "chunk": "Lecanemab was utilized in appropriate patient populations according to the prescribing information approved by the US Food and Drug Administration. Findings from our study provide first insights into the real-world use of lecanemab in the USA and shed light on the need for increased and timely lecanemab initiation for the long-term management of early AD.", "source": "PubMed"}, {"chunk_id": "33034769_0", "pmid": "33034769", "title": "Application of deep learning in detecting neurological disorders from magnetic resonance images: a survey on the detection of Alzheimer's disease, Parkinson's disease and schizophrenia.", "authors": "Noor MBT, Zenia NZ, Kaiser MS et al.", "year": "2020", "journal": "Brain informatics", "keywords": "Alzheimer\u2019s disease, Machine learning, Neuroimaging, Parkinson\u2019s disease, Schizophrenia", "chunk": "Neuroimaging, in particular magnetic resonance imaging (MRI), has been playing an important role in understanding brain functionalities and its disorders during the last couple of decades. These cutting-edge MRI scans, supported by high-performance computational tools and novel ML techniques, have opened up possibilities to unprecedentedly identify neurological disorders. However, similarities in disease phenotypes make it very difficult to detect such disorders accurately from the acquired neuroimaging data. This article critically examines and compares performances of the existing deep learning (DL)-based methods to detect neurological disorders-focusing on Alzheimer's disease, Parkinson's disease and schizophrenia-from MRI data acquired using different modalities including functional and structural MRI. The comparative performance analysis of various DL architectures across different disorders and imaging modalities suggests that the Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.", "source": "PubMed"}, {"chunk_id": "33034769_1", "pmid": "33034769", "title": "Application of deep learning in detecting neurological disorders from magnetic resonance images: a survey on the detection of Alzheimer's disease, Parkinson's disease and schizophrenia.", "authors": "Noor MBT, Zenia NZ, Kaiser MS et al.", "year": "2020", "journal": "Brain informatics", "keywords": "Alzheimer\u2019s disease, Machine learning, Neuroimaging, Parkinson\u2019s disease, Schizophrenia", "chunk": "Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.", "source": "PubMed"}, {"chunk_id": "37833015_0", "pmid": "37833015", "title": "Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.", "authors": "Sharma A, Feng L, Muresanu DF et al.", "year": "2023", "journal": "International review of neurobiology", "keywords": "Amyloid beta peptide, Blood\u2013brain barrier, Blood\u2013spinal cord barrier, CD86, Cerebrolysin, Iba1, Microglia, Monoclonal antibodies therapy, Nanowired delivery, Phosphorylated-tau, Serotonin, Spinal cord edema, Spinal cord injury, Tumor necrosis factor-alpha", "chunk": "Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-\u03b1) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid", "source": "PubMed"}, {"chunk_id": "37833015_1", "pmid": "37833015", "title": "Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.", "authors": "Sharma A, Feng L, Muresanu DF et al.", "year": "2023", "journal": "International review of neurobiology", "keywords": "Amyloid beta peptide, Blood\u2013brain barrier, Blood\u2013spinal cord barrier, CD86, Cerebrolysin, Iba1, Microglia, Monoclonal antibodies therapy, Nanowired delivery, Phosphorylated-tau, Serotonin, Spinal cord edema, Spinal cord injury, Tumor necrosis factor-alpha", "chunk": "peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-\u03b1) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (A\u03b2P), p-tau", "source": "PubMed"}, {"chunk_id": "37833015_2", "pmid": "37833015", "title": "Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.", "authors": "Sharma A, Feng L, Muresanu DF et al.", "year": "2023", "journal": "International review of neurobiology", "keywords": "Amyloid beta peptide, Blood\u2013brain barrier, Blood\u2013spinal cord barrier, CD86, Cerebrolysin, Iba1, Microglia, Monoclonal antibodies therapy, Nanowired delivery, Phosphorylated-tau, Serotonin, Spinal cord edema, Spinal cord injury, Tumor necrosis factor-alpha", "chunk": "as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (A\u03b2P), p-tau and TNF-\u03b1 significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-\u03b1 levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.", "source": "PubMed"}, {"chunk_id": "40324849_0", "pmid": "40324849", "title": "Tau PET probes for Alzheimer's disease detection and their structural characterization.", "authors": "Chinnathambi S, Malik S, Chandrashekar M", "year": "2025", "journal": "Advances in protein chemistry and structural biology", "keywords": "Alzheimer\u2019s disease, First- and second-generation Tau PET probes, Neurofibrillary tangles, Tau, Tau PET imaging", "chunk": "There are two hallmarks for the Alzheimer's disease that are currently used to identify the disease- the presence of the proteins Amyloid-\u03b2 and Tau. Amyloid PET has been studied for a long time and many effective probes have been introduced, some approved by the FDA, including [<sup>18</sup>F]-florbetaben (Neuraceq), [<sup>18</sup>F]-florbetapir (Amyvid), [<sup>18</sup>F]-flutemetamol (Vizamyl). However, it was found that imaging of NFTs could give more accurate results as the accumulation of Tau could directly be correlated with neurodegeneration, which isn't the case for Amyloid-\u03b2. Amyloid PET is thereby a diagnostic tool, which can rather be used for confirming the absence of Alzheimer's Disease. Tau PET, which was found to be a potentially useful diagnostic tool was explored further as it can directly be associated with the extent of spread of the disease. This led to the discovery of many probes for Tau PET. The initial ones were non-selective for Tau over A\u03b2.", "source": "PubMed"}, {"chunk_id": "40324849_1", "pmid": "40324849", "title": "Tau PET probes for Alzheimer's disease detection and their structural characterization.", "authors": "Chinnathambi S, Malik S, Chandrashekar M", "year": "2025", "journal": "Advances in protein chemistry and structural biology", "keywords": "Alzheimer\u2019s disease, First- and second-generation Tau PET probes, Neurofibrillary tangles, Tau, Tau PET imaging", "chunk": "be associated with the extent of spread of the disease. This led to the discovery of many probes for Tau PET. The initial ones were non-selective for Tau over A\u03b2. Further exploration suggested two generations of Tau probes, both with higher selectivity for Tau over A\u03b2. A second generation was introduced to overcome the shortcomings of the first generation which are examined in this review. Much research on effective Tau PET probes has led to an FDA-approved Tau probe, <sup>18</sup>F-flortaucipir. This systematic review discusses the characteristics and effectiveness of the first-generation probes, second-generation probes and other newer probes. It discusses the structural changes made in the probes over time that led to the enhancement of their properties as a Tau probe, that is, increased affinity and selectivity for Tau. It also discusses the shortcomings of probes developed so far and the ideal characteristics for Tau probes.", "source": "PubMed"}, {"chunk_id": "40324849_2", "pmid": "40324849", "title": "Tau PET probes for Alzheimer's disease detection and their structural characterization.", "authors": "Chinnathambi S, Malik S, Chandrashekar M", "year": "2025", "journal": "Advances in protein chemistry and structural biology", "keywords": "Alzheimer\u2019s disease, First- and second-generation Tau PET probes, Neurofibrillary tangles, Tau, Tau PET imaging", "chunk": "probe, that is, increased affinity and selectivity for Tau. It also discusses the shortcomings of probes developed so far and the ideal characteristics for Tau probes.", "source": "PubMed"}, {"chunk_id": "36433486_0", "pmid": "36433486", "title": "Zoom-In Neural Network Deep-Learning Model for Alzheimer's Disease Assessments.", "authors": "Wang B, Lim JS", "year": "2022", "journal": "Sensors (Basel, Switzerland)", "keywords": "AAL functional regions, Alzheimer\u2019s disease, deep neural networks, discriminative regions of interest of Alzheimer\u2019s disease, metacognitive learning, resting-state fMRI", "chunk": "Deep neural networks have been successfully applied to generate predictive patterns from medical and diagnostic data. This paper presents an approach for assessing persons with Alzheimer's disease (AD) mild cognitive impairment (MCI), compared with normal control (NC) persons, using the zoom-in neural network (ZNN) deep-learning algorithm. ZNN stacks a set of zoom-in learning units (ZLUs) in a feedforward hierarchy without backpropagation. The resting-state fMRI (rs-fMRI) dataset for AD assessments was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The Automated Anatomical Labeling (AAL-90) atlas, which provides 90 neuroanatomical functional regions, was used to assess and detect the implicated regions in the course of AD. The features of the ZNN are extracted from the 140-time series rs-fMRI voxel values in a region of the brain. ZNN yields the three classification accuracies of AD versus MCI and NC, NC versus AD and MCI, and MCI versus AD and NC of 97.7%, 84.8%,", "source": "PubMed"}, {"chunk_id": "36433486_1", "pmid": "36433486", "title": "Zoom-In Neural Network Deep-Learning Model for Alzheimer's Disease Assessments.", "authors": "Wang B, Lim JS", "year": "2022", "journal": "Sensors (Basel, Switzerland)", "keywords": "AAL functional regions, Alzheimer\u2019s disease, deep neural networks, discriminative regions of interest of Alzheimer\u2019s disease, metacognitive learning, resting-state fMRI", "chunk": "region of the brain. ZNN yields the three classification accuracies of AD versus MCI and NC, NC versus AD and MCI, and MCI versus AD and NC of 97.7%, 84.8%, and 72.7%, respectively, with the seven discriminative regions of interest (ROIs) in the AAL-90.", "source": "PubMed"}, {"chunk_id": "32144992_0", "pmid": "32144992", "title": "Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer's Disease.", "authors": "Aschenbrenner AJ, Gordon BA, Fagan AM et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, attention, cerebrospinal fluid, memory, neurofilament light", "chunk": "Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer's disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration. To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort. A total of 255 participants (55% female; mean age = 66.2 years, range = 42.5-86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline", "source": "PubMed"}, {"chunk_id": "32144992_1", "pmid": "32144992", "title": "Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer's Disease.", "authors": "Aschenbrenner AJ, Gordon BA, Fagan AM et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, attention, cerebrospinal fluid, memory, neurofilament light", "chunk": "assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels. Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status. These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer's disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition.", "source": "PubMed"}, {"chunk_id": "39727939_0", "pmid": "39727939", "title": "Neurological Sequelae of Post-COVID-19 Fatigue: A Narrative Review of Dipeptidyl Peptidase IV-Mediated Cerebrovascular Complications.", "authors": "Che Mohd Nassir CMN, Che Ramli MD, Jaffer U et al.", "year": "2024", "journal": "Current issues in molecular biology", "keywords": "SARS-CoV-2, cerebrovascular, dipeptidyl peptidase IV, neurodegenerative diseases, post-COVID-19 fatigue", "chunk": "Coronavirus disease 2019 (COVID-19) has been a global pandemic affecting millions of people's lives, which has led to 'post-COVID-19 fatigue'. Alarmingly, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) not only infects the lungs but also influences the heart and brain. Endothelial cell dysfunction and hypercoagulation, which we know occur with this infection, lead to thrombo-inflammation that can manifest as many myriad cardio-cerebrovascular disorders, such as brain fog, fatigue, cognitive dysfunction, etc. Additionally, SARS-CoV-2 has been associated with oxidative stress, protein aggregation, cytokine storm, and mitochondrial dysfunction in neurodegenerative diseases. Accordingly, the identification of molecular targets involved in these actions could provide strategies for preventing and treating this disease. In particular, the very common enzyme dipeptidyl peptidase IV (DPPIV) has recently been identified as a candidate co-receptor for the cell entry of the SARS-CoV-2 virus with its involvement in infection. In addition, DPPIV has been reported as a co-receptor for some viruses", "source": "PubMed"}, {"chunk_id": "39727939_1", "pmid": "39727939", "title": "Neurological Sequelae of Post-COVID-19 Fatigue: A Narrative Review of Dipeptidyl Peptidase IV-Mediated Cerebrovascular Complications.", "authors": "Che Mohd Nassir CMN, Che Ramli MD, Jaffer U et al.", "year": "2024", "journal": "Current issues in molecular biology", "keywords": "SARS-CoV-2, cerebrovascular, dipeptidyl peptidase IV, neurodegenerative diseases, post-COVID-19 fatigue", "chunk": "identified as a candidate co-receptor for the cell entry of the SARS-CoV-2 virus with its involvement in infection. In addition, DPPIV has been reported as a co-receptor for some viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV). It mediates immunologic reactions and diseases such as type 2 diabetes mellitus, obesity, and hypertension, which have been considered the prime risk factors for stroke among other types of cardio-cerebrovascular diseases. Unlike angiotensin-converting enzyme 2 (ACE2), DPPIV has been implicated in aggravating the course of infection due to its disruptive effect on inflammatory signaling networks and the neuro-glia-vascular unit. Regarding the neurological, physiological, and molecular grounds governing post-COVID-19 fatigue, this review focuses on DPPIV as one of such reasons that progressively establishes cerebrovascular grievances following SARS-CoV infection.", "source": "PubMed"}, {"chunk_id": "39727939_2", "pmid": "39727939", "title": "Neurological Sequelae of Post-COVID-19 Fatigue: A Narrative Review of Dipeptidyl Peptidase IV-Mediated Cerebrovascular Complications.", "authors": "Che Mohd Nassir CMN, Che Ramli MD, Jaffer U et al.", "year": "2024", "journal": "Current issues in molecular biology", "keywords": "SARS-CoV-2, cerebrovascular, dipeptidyl peptidase IV, neurodegenerative diseases, post-COVID-19 fatigue", "chunk": "grievances following SARS-CoV infection.", "source": "PubMed"}, {"chunk_id": "24412277_0", "pmid": "24412277", "title": "Immunotherapy for Alzheimer's disease.", "authors": "Wisniewski T, Go\u00f1i F", "year": "2014", "journal": "Biochemical pharmacology", "keywords": "Alzheimer's disease, Amyloid \u03b2, Immunomodulation, Tau, Transgenic mice, Vaccination", "chunk": "Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD the normal soluble amyloid \u03b2 (sA\u03b2) peptide is converted into oligomeric/fibrillar A\u03b2. The oligomeric forms of A\u03b2 are thought to be the most toxic, while fibrillar A\u03b2 becomes deposited as amyloid plaques and congophilic angiopathy, which serve as neuropathological markers of the disease. In addition the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is a critical part of the pathology. Numerous therapeutic interventions are under investigation to prevent and treat AD. Among the more exciting and advanced of these approaches is vaccination. Active and passive Immunotherapy targeting only A\u03b2 has been successful in many AD model animal trials; however, the more limited human data has shown much less benefit so far, with encephalitis occurring in a minority of patients treated with active immunization and vasogenic edema or amyloid-related imaging abnormalities (ARIA)", "source": "PubMed"}, {"chunk_id": "24412277_1", "pmid": "24412277", "title": "Immunotherapy for Alzheimer's disease.", "authors": "Wisniewski T, Go\u00f1i F", "year": "2014", "journal": "Biochemical pharmacology", "keywords": "Alzheimer's disease, Amyloid \u03b2, Immunomodulation, Tau, Transgenic mice, Vaccination", "chunk": "limited human data has shown much less benefit so far, with encephalitis occurring in a minority of patients treated with active immunization and vasogenic edema or amyloid-related imaging abnormalities (ARIA) being a complication in some passive immunization trials. Therapeutic intervention targeting only tau has been tested only in mouse models; and no approaches targeting both pathologies concurrently has been attempted, until very recently. The immune approaches tried so far were targeting a self-protein, albeit in an abnormal conformation; however, effective enhanced clearance of the disease associated conformer has to be balanced with the potential risk of stimulating excessive toxic inflammation. The design of future more effective immunomodulatory approaches will need to target all aspects of AD pathology, as well as specifically targeting pathological oligomeric conformers, without the use of any self-antigen.", "source": "PubMed"}, {"chunk_id": "24412277_2", "pmid": "24412277", "title": "Immunotherapy for Alzheimer's disease.", "authors": "Wisniewski T, Go\u00f1i F", "year": "2014", "journal": "Biochemical pharmacology", "keywords": "Alzheimer's disease, Amyloid \u03b2, Immunomodulation, Tau, Transgenic mice, Vaccination", "chunk": "specifically targeting pathological oligomeric conformers, without the use of any self-antigen.", "source": "PubMed"}, {"chunk_id": "41605308_0", "pmid": "41605308", "title": "Higher CSF sTREM2 is related to slower hippocampal atrophy and cognitive decline independently of pTau181 levels.", "authors": "Stephenson HG, Betthauser TJ, Jonaitis E et al.", "year": "2026", "journal": "Brain, behavior, and immunity", "keywords": "AD, Atrophy, CSF biomarkers, Cognition, Cognitive decline, MRI, Preclinical AD, Volumetrics, pTau181, sTREM2", "chunk": "Heightened TREM2-dependent microglial activation is thought to protect against the negative effects of Alzheimer's disease (AD) neuropathology, but data in preclinical disease and in the context of aging are lacking. This study examined the association of longitudinal hippocampal atrophy and memory composite scores with baseline soluble TREM2 (sTREM2) in the cerebrospinal fluid in two large, well-characterized samples of elderly individuals. It was hypothesized that higher sTREM2 would be associated with slower atrophy and cognitive decline and that this effect would be stronger in those with higher AD neuropathology. Linear mixed effects models predicting hippocampal volume and cognitive decline tested interactions between sTREM2 and time (years since baseline) to see whether higher sTREM2 was associated with slower atrophy and cognitive decline, controlling for pTau181 and its interaction with time. A three-way interaction between pTau181, sTREM2, and time was then added to determine whether AD pathology moderated effects of sTREM2. Results showed", "source": "PubMed"}, {"chunk_id": "41605308_1", "pmid": "41605308", "title": "Higher CSF sTREM2 is related to slower hippocampal atrophy and cognitive decline independently of pTau181 levels.", "authors": "Stephenson HG, Betthauser TJ, Jonaitis E et al.", "year": "2026", "journal": "Brain, behavior, and immunity", "keywords": "AD, Atrophy, CSF biomarkers, Cognition, Cognitive decline, MRI, Preclinical AD, Volumetrics, pTau181, sTREM2", "chunk": "controlling for pTau181 and its interaction with time. A three-way interaction between pTau181, sTREM2, and time was then added to determine whether AD pathology moderated effects of sTREM2. Results showed that higher sTREM2 was associated with slower hippocampal atrophy and cognitive decline independently of pTau181 levels. Further analysis showed that cognitive effects were moderated by pTau181 levels such that beneficial effects of sTREM2 were stronger at higher levels of pTau181, though this effect was very small, and the interaction between sTREM2 and time remained significant. These findings suggest that higher TREM2-dependent microglial activation, as indexed by sTREM2, may indicate subtle resilience not just to the effects of AD but to age-related neurodegeneration more broadly.", "source": "PubMed"}, {"chunk_id": "39647777_0", "pmid": "39647777", "title": "Skin autofluorescence of advanced glycation end-products, glycemic memory, and diabetes complications.", "authors": "Rigalleau V, Pucheux Y, Couffinhal T et al.", "year": "2025", "journal": "Diabetes & metabolism", "keywords": "Advanced glycation end-products, Diabetes complications, Skin autofluorescence", "chunk": "Since the pionneer work of Meerwaldt and the Groningen team, who related skin autofluorescence (SAF) to the dermal concentrations of advanced glycation end-products (AGEs), hundreds of articles have been devoted to its application in diabetes. Due to the slow turnover of the AGEs formed on collagen of the skin, the SAF can reflect the progressive accumulation of AGEs and hence be a marker of long-term glucose exposure. Accordingly, relations with HbA1c from the previous 3-10 years have been established in both type 1 and type 2 diabetes, and even in gestational diabetes mellitus. Other important determinants of SAF exist however, notably age, renal function, diet, and genetics. SAF is also related to current and future micro- and macrovascular complications of diabetes, as expected for a marker of glycemic memory. It is also related to some important emerging diabetes complications and comorbidities such as cancer, cognitive decline and liver disease. Quantitative", "source": "PubMed"}, {"chunk_id": "39647777_1", "pmid": "39647777", "title": "Skin autofluorescence of advanced glycation end-products, glycemic memory, and diabetes complications.", "authors": "Rigalleau V, Pucheux Y, Couffinhal T et al.", "year": "2025", "journal": "Diabetes & metabolism", "keywords": "Advanced glycation end-products, Diabetes complications, Skin autofluorescence", "chunk": "diabetes, as expected for a marker of glycemic memory. It is also related to some important emerging diabetes complications and comorbidities such as cancer, cognitive decline and liver disease. Quantitative information on glucose exposure during the previous years may be pertinent to personnalize care for patients with diabetes: priority for glucose control when SAF is low, and for screening for complications once SAF is high.", "source": "PubMed"}, {"chunk_id": "41777345_0", "pmid": "41777345", "title": "Efficacy and safety of adjunctive acupuncture for depression and motor symptoms in Parkinson's disease: study protocol for a randomized controlled trial.", "authors": "Liao K, Fan JQ, Xiao L et al.", "year": "2026", "journal": "Frontiers in psychiatry", "keywords": "Parkinson\u2019s disease, Parkinson\u2019s disease with depression, acupuncture, motor symptoms, randomized controlled trial", "chunk": "Depression is one of the most prevalent and disabling non-motor symptoms in Parkinson's disease (PD), forming a bidirectional relationship with motor dysfunction that worsens quality of life. Pharmacological treatments exhibit limited and inconsistent efficacy, and may lead to adverse interactions. Acupuncture may improve both depressive and motor symptoms by regulating the neuro-immune-endocrine network, but high-quality evidence remains insufficient. This study aims to evaluate the efficacy and safety of acupuncture as an adjunctive therapy for depression in PD and to explore potential biological correlates of clinical changes using predefined serum biomarkers. In this single-center, evaluator-blinded, randomized controlled trial, 88 patients with PD and comorbid depression will be randomly assigned to an acupuncture group or a waitlist control group. The primary outcome is the change in the Montgomery-Asberg Depression Rating Scale (MADRS) score. Secondary outcomes include motor function, anxiety, sleep quality, and overall quality of life. Exploratory analyses will assess serum inflammatory", "source": "PubMed"}, {"chunk_id": "41777345_1", "pmid": "41777345", "title": "Efficacy and safety of adjunctive acupuncture for depression and motor symptoms in Parkinson's disease: study protocol for a randomized controlled trial.", "authors": "Liao K, Fan JQ, Xiao L et al.", "year": "2026", "journal": "Frontiers in psychiatry", "keywords": "Parkinson\u2019s disease, Parkinson\u2019s disease with depression, acupuncture, motor symptoms, randomized controlled trial", "chunk": "is the change in the Montgomery-Asberg Depression Rating Scale (MADRS) score. Secondary outcomes include motor function, anxiety, sleep quality, and overall quality of life. Exploratory analyses will assess serum inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and kynurenine/tryptophan (KYN/TRP) ratio. We hypothesize that adjunctive acupuncture may improve depressive and motor symptoms compared with the control. Exploratory analyses will examine whether clinical changes are associated with changes in relevant biomarkers. This study will provide rigorous evidence for acupuncture as an adjunctive therapy, offering a non-pharmacological strategy to optimize the comprehensive management of PD and disrupt the bidirectional emotion-motor interplay. https://www.chictr.org.cn/, identifier ChiCTR2500113443.", "source": "PubMed"}, {"chunk_id": "41050022_0", "pmid": "41050022", "title": "Magnetic Resonance Spectroscopy in the Evaluation of Biopsy-Indeterminate Primary Central Nervous System Lymphoma: A Case Report.", "authors": "Marino MD, Kardasis W, Mader JP et al.", "year": "2025", "journal": "Cureus", "keywords": "corticosteroids, diffuse large b cell lymphoma, immunohistochemistry, magnetic resonance imaging (mri), magnetic resonance spectroscopy (mrs), neuroradiology, primary central nervous system lymphoma (pcnsl), stereotactic brain biopsy", "chunk": "Primary central nervous system lymphoma (PCNSL) is a rare, aggressive extra-nodal non-Hodgkin lymphoma restricted to the central nervous system without systemic involvement at diagnosis. PCNSL can present with a wide array of symptoms, including cognitive dysfunction, focal neurologic deficits, or seizures. This case report utilizes a chart review of the history, physical examination, laboratory tests, imaging findings, and pathology reports recorded during this patient's hospital encounters. We present the case of a middle-aged woman with a past medical history of traumatic brain injury and seizures with incidental neuroimaging findings on head computed tomography showing right parietal lobe and subcortical edema. She reported subacute onset of diffuse paresthesia, generalized weakness, severe migraine headaches, poor balance, and falls. She was admitted to the hospital for further evaluation of her neurological symptoms and was started on prophylactic dexamethasone. Magnetic resonance imaging (MRI) demonstrated avidly enhancing lesions in the bilateral cingulate gyri and periventricular", "source": "PubMed"}, {"chunk_id": "41050022_1", "pmid": "41050022", "title": "Magnetic Resonance Spectroscopy in the Evaluation of Biopsy-Indeterminate Primary Central Nervous System Lymphoma: A Case Report.", "authors": "Marino MD, Kardasis W, Mader JP et al.", "year": "2025", "journal": "Cureus", "keywords": "corticosteroids, diffuse large b cell lymphoma, immunohistochemistry, magnetic resonance imaging (mri), magnetic resonance spectroscopy (mrs), neuroradiology, primary central nervous system lymphoma (pcnsl), stereotactic brain biopsy", "chunk": "the hospital for further evaluation of her neurological symptoms and was started on prophylactic dexamethasone. Magnetic resonance imaging (MRI) demonstrated avidly enhancing lesions in the bilateral cingulate gyri and periventricular regions, right frontoparietal region, right temporal lobe, corpus callosum, hypothalamus, and basal ganglia, with vasogenic edema and midline shift. Magnetic resonance spectroscopy (MRS) yielded an elevated choline-to-creatinine ratio, decreased N-acetylaspartate peak, normal myoinositol, and a prominent lipid peak - findings consistent with PCNSL. Steroids were continued after discharge to treat cerebral edema, and a stereotactic biopsy performed 28 days later was non-diagnostic. Subsequent brain MRI showed marked disease regression, and cerebrospinal fluid analysis failed to confirm a diagnosis. Steroids were discontinued, and a repeat biopsy was performed two months later after symptomatic and radiologic progression. Pathology analysis determined a diagnosis of diffuse large B-cell lymphoma. This case highlights the classic imaging and MRS findings associated with PCNSL and underscores the", "source": "PubMed"}, {"chunk_id": "41050022_2", "pmid": "41050022", "title": "Magnetic Resonance Spectroscopy in the Evaluation of Biopsy-Indeterminate Primary Central Nervous System Lymphoma: A Case Report.", "authors": "Marino MD, Kardasis W, Mader JP et al.", "year": "2025", "journal": "Cureus", "keywords": "corticosteroids, diffuse large b cell lymphoma, immunohistochemistry, magnetic resonance imaging (mri), magnetic resonance spectroscopy (mrs), neuroradiology, primary central nervous system lymphoma (pcnsl), stereotactic brain biopsy", "chunk": "after symptomatic and radiologic progression. Pathology analysis determined a diagnosis of diffuse large B-cell lymphoma. This case highlights the classic imaging and MRS findings associated with PCNSL and underscores the diagnostic challenges posed by continued corticosteroid use, which can lead to false-negative biopsy, cytology, and flow cytometry. Avoiding unnecessary delays in diagnosing PCNSL is critical, as timely initiation of targeted chemotherapy improves outcomes. When MRI and MRS findings support a diagnosis of PCNSL, physicians may opt for early biopsy and avoid steroids even if cerebral edema is present. This case also supports the growing role of MRS as a valuable adjunct in characterizing CNS lesions - especially when biopsy is non-diagnostic or contraindicated. Further research and standardization of MRS techniques may enhance its utility in non-invasively diagnosing PCNSL in the future.", "source": "PubMed"}, {"chunk_id": "41050022_3", "pmid": "41050022", "title": "Magnetic Resonance Spectroscopy in the Evaluation of Biopsy-Indeterminate Primary Central Nervous System Lymphoma: A Case Report.", "authors": "Marino MD, Kardasis W, Mader JP et al.", "year": "2025", "journal": "Cureus", "keywords": "corticosteroids, diffuse large b cell lymphoma, immunohistochemistry, magnetic resonance imaging (mri), magnetic resonance spectroscopy (mrs), neuroradiology, primary central nervous system lymphoma (pcnsl), stereotactic brain biopsy", "chunk": "may enhance its utility in non-invasively diagnosing PCNSL in the future.", "source": "PubMed"}, {"chunk_id": "39908690_0", "pmid": "39908690", "title": "Clinical trials targeting tau should be halted.", "authors": "Olluri A", "year": "2025", "journal": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia", "keywords": "Alzheimer\u2019s disease, Amyloid, Antibody, Clinical trial, Dementia, Medicine, Tau", "chunk": "Experimental drugs lowering brain tau are heralded as improvements in the treatment of Alzheimer's disease. However, the outcomes in clinical trials testing these agents have consistently failed to improve patient outcomes, i.e. slow down disease or improving cognition. Furthermore, the scientific rationale behind such drugs is rather poor in the first place and has been questioned. Therefore, I argue that trials of anti-tau drugs should be halted.", "source": "PubMed"}, {"chunk_id": "40579790_0", "pmid": "40579790", "title": "Gait variability as a marker of white matter integrity in individuals with Down syndrome.", "authors": "Leach EM, Powell DK, Glueck AC et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "DTI, MRI, amyloid beta, dementia, gross motor skills, trisomy 21", "chunk": "Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age \u00b1 SD 37 \u00b1 7.5 years). DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Gait variability linked to white matter integrity", "source": "PubMed"}, {"chunk_id": "40579790_1", "pmid": "40579790", "title": "Gait variability as a marker of white matter integrity in individuals with Down syndrome.", "authors": "Leach EM, Powell DK, Glueck AC et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "DTI, MRI, amyloid beta, dementia, gross motor skills, trisomy 21", "chunk": "correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.", "source": "PubMed"}, {"chunk_id": "41830915_0", "pmid": "41830915", "title": "Self-Improved LeNet and Modified SegNet for Alzheimer's Disease Classification using MRI.", "authors": "Rs R, G S G, S S et al.", "year": "2026", "journal": "The International journal of neuroscience", "keywords": "Alzheimer\u2019s disease, Disease classification, MPL5 Classifier, MRI, Segmentation", "chunk": "Alzheimer's disease (AD) is the leading cause of dementia, typically affecting the elderly. It results in cognitive and memory loss with progression that can lead to death. Although the exact cause remains unclear, it is believed to involve genetics, diet and environment. One key sign of AD is the shrinkage of the hippocampus and frontal lobe cortex. MRI is frequently used to diagnose AD due to its ability to capture detailed images of soft tissues. This study proposes an innovative Multi-head Parallel LeNet5-based Alzheimer's Disease Classification (MPL5-ADC) framework. The proposed MPL5-ADC system processes MRI images through several key steps. First, the Modified Wiener Filter (MWF) is applied for noise reduction during preprocessing. Next, Pyramid Convolutional Kernels-based SegNet (PCK-SgN) performs segmentation to isolate relevant brain regions. In the feature extraction phase, Improved Local Gabor Binary Pattern Histogram Sequence (ILGBPHS), shape features and deep features from VGG16 and ResNet are used to", "source": "PubMed"}, {"chunk_id": "41830915_1", "pmid": "41830915", "title": "Self-Improved LeNet and Modified SegNet for Alzheimer's Disease Classification using MRI.", "authors": "Rs R, G S G, S S et al.", "year": "2026", "journal": "The International journal of neuroscience", "keywords": "Alzheimer\u2019s disease, Disease classification, MPL5 Classifier, MRI, Segmentation", "chunk": "to isolate relevant brain regions. In the feature extraction phase, Improved Local Gabor Binary Pattern Histogram Sequence (ILGBPHS), shape features and deep features from VGG16 and ResNet are used to capture both texture and structural details. These features are augmented and then input into a Multi-head Parallel LeNet-5 (MPL5) classifier, which produces the final classified output for accurate and early detection of AD. The MPL5-ADC model predicts a higher accuracy score of 98% to confirm that it more consistently classifies Alzheimer's disease using MRI.", "source": "PubMed"}, {"chunk_id": "37443334_0", "pmid": "37443334", "title": "CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease.", "authors": "Horie K, Salvad\u00f3 G, Barth\u00e9lemy NR et al.", "year": "2023", "journal": "Nature medicine", "keywords": "None", "chunk": "Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219). MTBR-tau243 was most strongly associated with tau-positron emission tomography (PET) and cognition, whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 \u2264 R<sup>2</sup> \u2264 0.75) and the performance in", "source": "PubMed"}, {"chunk_id": "37443334_1", "pmid": "37443334", "title": "CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease.", "authors": "Horie K, Salvad\u00f3 G, Barth\u00e9lemy NR et al.", "year": "2023", "journal": "Nature medicine", "keywords": "None", "chunk": "whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 \u2264 R<sup>2</sup> \u2264 0.75) and the performance in predicting cognitive measures (0.34 \u2264 R<sup>2</sup> \u2264 0.48) approached that of tau-PET (0.44 \u2264 R<sup>2</sup> \u2264 0.52). MTBR-tau243 levels longitudinally increased with insoluble tau aggregates, unlike CSF p-tau species. CSF MTBR-tau243 is a specific biomarker of tau aggregate pathology, which may be utilized in interventional trials and in the diagnosis of patients. Based on these findings, we propose to revise the A/T/(N) criteria to include MTBR-tau243 as representing insoluble tau aggregates ('T').", "source": "PubMed"}, {"chunk_id": "38384997_0", "pmid": "38384997", "title": "<i>APOE</i> \u025b4 exacerbates age-dependent deficits in cortical microstructure.", "authors": "Mak E, Dounavi ME, Operto G et al.", "year": "2024", "journal": "Brain communications", "keywords": "NODDI, cognitive impairment, neurodegeneration, preclinical dementia", "chunk": "The apolipoprotein E \u025b4 allele is the primary genetic risk factor for the sporadic type of Alzheimer's disease. However, the mechanisms by which apolipoprotein E \u025b4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein \u025b4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers and 757 apolipoprotein E \u025b4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on (i) the main effects of apolipoprotein E \u025b4, and (ii) the interactions of apolipoprotein E \u025b4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis", "source": "PubMed"}, {"chunk_id": "38384997_1", "pmid": "38384997", "title": "<i>APOE</i> \u025b4 exacerbates age-dependent deficits in cortical microstructure.", "authors": "Mak E, Dounavi ME, Operto G et al.", "year": "2024", "journal": "Brain communications", "keywords": "NODDI, cognitive impairment, neurodegeneration, preclinical dementia", "chunk": "main effects of apolipoprotein E \u025b4, and (ii) the interactions of apolipoprotein E \u025b4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E \u025b4 \u00d7 age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E \u025b4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E \u025b4 carriers with lower years of education. We demonstrated that apolipoprotein E \u025b4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer's disease. This finding also suggests that apolipoprotein E \u025b4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index.", "source": "PubMed"}, {"chunk_id": "38384997_2", "pmid": "38384997", "title": "<i>APOE</i> \u025b4 exacerbates age-dependent deficits in cortical microstructure.", "authors": "Mak E, Dounavi ME, Operto G et al.", "year": "2024", "journal": "Brain communications", "keywords": "NODDI, cognitive impairment, neurodegeneration, preclinical dementia", "chunk": "cortical Orientation Dispersion Index.", "source": "PubMed"}, {"chunk_id": "36446820_0", "pmid": "36446820", "title": "A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson's disease.", "authors": "Xiang C, Cong S, Tan X et al.", "year": "2022", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Biomarkers play important roles in the diagnosis and differential diagnosis of Parkinson's disease (PD). Thus, we carried out a systematic review and meta-analysis evaluating the diagnostic utility of cerebrospinal fluid (CSF) biomarkers to distinguish PD from atypical parkinsonian syndromes (APSs) and controls. Data for PD and APS and controls were extracted from 123 studies that reported the concentration of CSF biomarkers. Comparisons were presented using pooled Hedges' g. Sources of heterogeneity were evaluated using meta-regression, and subgroup and sensitivity analyses. We found that compared with controls, PD patients had lower levels of amyloid beta 1-42, phosphorylated tau, total tau, total \u03b1-synuclein, Zn, DJ-1, and YKL-40, and higher levels of oligomeric and phosphorylated \u03b1-synuclein. Moreover, lower CSF levels of neurofilament light chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of", "source": "PubMed"}, {"chunk_id": "36446820_1", "pmid": "36446820", "title": "A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson's disease.", "authors": "Xiang C, Cong S, Tan X et al.", "year": "2022", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of A\u03b242 compared with patients with progressive supranuclear palsy. Reduced levels of p-tau and t-tau and higher A\u03b242 levels were found in PD patients compared with patients with dementia with Lewy bodies. Finally, reduced NFL levels were found in patients with PD compared with patients with cortical basal degeneration. Therefore, we believe that the combinations of t-\u03b1-syn, A\u03b242, and NFL could be promising biomarkers for the differential diagnosis of PD and APSs.", "source": "PubMed"}, {"chunk_id": "35860682_0", "pmid": "35860682", "title": "Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the \u03b2-amyloid precursor protein (APP) on thrombosis and cancer.", "authors": "Nguyen KV", "year": "2022", "journal": "AIMS neuroscience", "keywords": "APP-like protein-1 (APLP1), APP-like protein-2 (APLP2), Alternative splicing, Antisense drugs, Antithrombin (AT), Cancer, Central nervous system (CNS), Cerebral venous thrombosis (CVT), Deep venous thrombosis (DVT), Encephalomalacia/gliosis, Epigenetics, Epistasis, Human homologue of the murine double minute 2 protein (HDM2), Hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene, Hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, Kidney cancer, Lesch-Nyhan disease (LND), Low-molecular-weight heparin (LMWH), Pulmonary embolism (PE), Thrombosis, Tumor suppressor protein p53 (TP53), Venous thromboembolism (VTE), Warfarin, \u03b2-amyloid precursor protein (APP)", "chunk": "A heterozygous Arg393His point mutation at the reactive site of antithrombin (AT) gene causing thrombosis in a Vietnamese patient is reported and named as Arg393His in AT-Hanoi. The present variant is characterized by a severe reduction of functionally active AT plasma concentration to 42% of normal resulting in multiple severe thrombotic events such as cerebral venous thrombosis (CVT) (encephalomalacia/gliosis), recurrent deep venous thrombosis (DVT) and the development of kidney cancer. Today the complexity of thrombophilia has grown with appreciation that multiple inherited and acquired risk factors may interact to result in a clinically thrombotic phenotype. This article focuses on the following issues: (1) pathophysiology and clinical conditions of Arg393His in AT-Hanoi; (2) \"two way association\" between cancer and thrombosis in which venous thromboembolism (VTE) can be both a presenting sign and a complication of cancer; (3) efficacy of anticoagulants used for the prevention of cancer-related thrombosis; (4) conditions of acquired", "source": "PubMed"}, {"chunk_id": "35860682_1", "pmid": "35860682", "title": "Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the \u03b2-amyloid precursor protein (APP) on thrombosis and cancer.", "authors": "Nguyen KV", "year": "2022", "journal": "AIMS neuroscience", "keywords": "APP-like protein-1 (APLP1), APP-like protein-2 (APLP2), Alternative splicing, Antisense drugs, Antithrombin (AT), Cancer, Central nervous system (CNS), Cerebral venous thrombosis (CVT), Deep venous thrombosis (DVT), Encephalomalacia/gliosis, Epigenetics, Epistasis, Human homologue of the murine double minute 2 protein (HDM2), Hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene, Hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, Kidney cancer, Lesch-Nyhan disease (LND), Low-molecular-weight heparin (LMWH), Pulmonary embolism (PE), Thrombosis, Tumor suppressor protein p53 (TP53), Venous thromboembolism (VTE), Warfarin, \u03b2-amyloid precursor protein (APP)", "chunk": "which venous thromboembolism (VTE) can be both a presenting sign and a complication of cancer; (3) efficacy of anticoagulants used for the prevention of cancer-related thrombosis; (4) conditions of acquired risk factors such as cancer or genetic disorders via epigenetic modifications in gene-gene (epistasis) and/or gene-environment interactions such as in Lesch-Nyhan disease (LND), in which the \u03b2-amyloid precursor protein (APP) that may interact to predispose a patient to thrombosis and cancer. It is also necessary to study the hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, AT, and APP using expression vectors for exploring their impact on LND, thrombosis as well as other human diseases, especially the ones related to APP such as Alzheimer's disease (AD) and cancer. For such a purpose, the construction of expression vectors for HGprt and APP, with or without the glycosyl-phosphatidylinositol (GPI) anchor, was performed as described in Ref. #148 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L.", "source": "PubMed"}, {"chunk_id": "35860682_2", "pmid": "35860682", "title": "Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the \u03b2-amyloid precursor protein (APP) on thrombosis and cancer.", "authors": "Nguyen KV", "year": "2022", "journal": "AIMS neuroscience", "keywords": "APP-like protein-1 (APLP1), APP-like protein-2 (APLP2), Alternative splicing, Antisense drugs, Antithrombin (AT), Cancer, Central nervous system (CNS), Cerebral venous thrombosis (CVT), Deep venous thrombosis (DVT), Encephalomalacia/gliosis, Epigenetics, Epistasis, Human homologue of the murine double minute 2 protein (HDM2), Hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene, Hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, Kidney cancer, Lesch-Nyhan disease (LND), Low-molecular-weight heparin (LMWH), Pulmonary embolism (PE), Thrombosis, Tumor suppressor protein p53 (TP53), Venous thromboembolism (VTE), Warfarin, \u03b2-amyloid precursor protein (APP)", "chunk": "of expression vectors for HGprt and APP, with or without the glycosyl-phosphatidylinositol (GPI) anchor, was performed as described in Ref. #148 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L. Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). <i>Nucleosides Nucleotides Nucleic Acids</i> 2020, 39: 905-922). In the same manner, the construction of expression vectors for AT and APP can be performed as shown in Figure 6. These expressions vectors, with or without GPI anchor, could be used as tools for (a) studying the effects of Arg393His mutation in AT; (b) studying the emerging role of Arg393His mutation in AT and cancer; (c) studying intermolecular interactions between APP and AT. Furthermore, the construction of expression vectors as described in Ref. #148, especially the one with GPI, can be used as a model for the construction of expression vectors for any protein targeting", "source": "PubMed"}, {"chunk_id": "35860682_3", "pmid": "35860682", "title": "Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the \u03b2-amyloid precursor protein (APP) on thrombosis and cancer.", "authors": "Nguyen KV", "year": "2022", "journal": "AIMS neuroscience", "keywords": "APP-like protein-1 (APLP1), APP-like protein-2 (APLP2), Alternative splicing, Antisense drugs, Antithrombin (AT), Cancer, Central nervous system (CNS), Cerebral venous thrombosis (CVT), Deep venous thrombosis (DVT), Encephalomalacia/gliosis, Epigenetics, Epistasis, Human homologue of the murine double minute 2 protein (HDM2), Hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene, Hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, Kidney cancer, Lesch-Nyhan disease (LND), Low-molecular-weight heparin (LMWH), Pulmonary embolism (PE), Thrombosis, Tumor suppressor protein p53 (TP53), Venous thromboembolism (VTE), Warfarin, \u03b2-amyloid precursor protein (APP)", "chunk": "construction of expression vectors as described in Ref. #148, especially the one with GPI, can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [155],[156], for example).", "source": "PubMed"}, {"chunk_id": "35771851_0", "pmid": "35771851", "title": "Study protocol for the Alzheimer and music therapy study: An RCT to compare the efficacy of music therapy and physical activity on brain plasticity, depressive symptoms, and cognitive decline, in a population with and at risk for Alzheimer's disease.", "authors": "Flo BK, Matziorinis AM, Skouras S et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "There is anecdotal evidence for beneficial effects of music therapy in patients with Alzheimer's Disease (AD). However, there is a lack of rigorous research investigating this issue. The aim of this study is to evaluate the effects of music therapy and physical activity on brain plasticity, mood, and cognition in a population with AD and at risk for AD. One-hundred and thirty-five participants with memory complaints will be recruited for a parallel, three-arm Randomized Controlled Trial (RCT). Inclusion criteria are a diagnosis of mild (early) AD or mild cognitive impairment (MCI), or memory complaints without other neuropsychiatric pathology. Participants are randomised into either a music therapy intervention (singing lessons), an active control group (physical activity) or a passive control group (no intervention) for 12 months. The primary outcomes are the brain age gap, measured via magnetic resonance imaging (MRI), and depressive symptoms. Secondary outcomes include cognitive performance, activities of daily", "source": "PubMed"}, {"chunk_id": "35771851_1", "pmid": "35771851", "title": "Study protocol for the Alzheimer and music therapy study: An RCT to compare the efficacy of music therapy and physical activity on brain plasticity, depressive symptoms, and cognitive decline, in a population with and at risk for Alzheimer's disease.", "authors": "Flo BK, Matziorinis AM, Skouras S et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "(no intervention) for 12 months. The primary outcomes are the brain age gap, measured via magnetic resonance imaging (MRI), and depressive symptoms. Secondary outcomes include cognitive performance, activities of daily living, brain structure (voxel-based morphometry and diffusion tensor imaging), and brain function (resting-state functional MRI). Screening of participants began in April 2018. A total of 84 participants have been recruited and started intervention, out of which 48 participants have completed 12 months of intervention and post-intervention assessment. Addressing the need for rigorous longitudinal data for the effectiveness of music therapy in people with and at risk for developing AD, this trial aims to enhance knowledge regarding cost-effective interventions with potentially high clinical applicability. ClinicalTrials.gov identifier: NCT03444181, registered on February 23, 2018.", "source": "PubMed"}, {"chunk_id": "35771851_2", "pmid": "35771851", "title": "Study protocol for the Alzheimer and music therapy study: An RCT to compare the efficacy of music therapy and physical activity on brain plasticity, depressive symptoms, and cognitive decline, in a population with and at risk for Alzheimer's disease.", "authors": "Flo BK, Matziorinis AM, Skouras S et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "2018.", "source": "PubMed"}, {"chunk_id": "39310044_0", "pmid": "39310044", "title": "Insight into the Brain: Application of the Retinal Microvasculature as a Biomarker for Cerebrovascular Diseases through Optical Coherence Tomography Angiography.", "authors": "Wang L, Shah S, Llaneras CN et al.", "year": "2024", "journal": "Current ophthalmology reports", "keywords": "Carotid Artery Stenosis, Cerebral Small Vessel Disease, Cerebrovascular Disease, Dementia, Ischemic Stroke, Optical Coherence Tomography Angiography, Retinal Microvasculature", "chunk": "The present article serves as a comprehensive review of the published research literature surrounding the retinal microvasculature, characterized through the optical coherence tomography angiography (OCTA) and its potential clinical value for understanding and detecting cerebrovascular diseases. Studies from the past 3 years (2020-2023) have identified a degeneration of the retinal microvasculature, commonly defined through the loss of vascular density, in ischemic stroke, dementia, carotid artery stenosis, cerebral small vessel disease, and a series of rare, potentially inherited cerebrovascular disorders. These retinal microvascular changes often correlate with structure and functional changes in the brain and sometimes occur prior to debilitating neurodegeneration. While further investigations with longitudinal data and larger sample sizes are necessary, OCTA shows promising results for characterizing the retinal microvasculature as a potential imaging biomarker in reflecting the changes in the cerebral microvasculature for early detection, prevention, and treatment of cerebrovascular diseases.", "source": "PubMed"}, {"chunk_id": "39310044_1", "pmid": "39310044", "title": "Insight into the Brain: Application of the Retinal Microvasculature as a Biomarker for Cerebrovascular Diseases through Optical Coherence Tomography Angiography.", "authors": "Wang L, Shah S, Llaneras CN et al.", "year": "2024", "journal": "Current ophthalmology reports", "keywords": "Carotid Artery Stenosis, Cerebral Small Vessel Disease, Cerebrovascular Disease, Dementia, Ischemic Stroke, Optical Coherence Tomography Angiography, Retinal Microvasculature", "chunk": "microvasculature as a potential imaging biomarker in reflecting the changes in the cerebral microvasculature for early detection, prevention, and treatment of cerebrovascular diseases.", "source": "PubMed"}, {"chunk_id": "37206236_0", "pmid": "37206236", "title": "Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease.", "authors": "Zhang B, Zhao Y, Guo K et al.", "year": "2023", "journal": "Bioengineering & translational medicine", "keywords": "Alzheimer's disease, drug delivery, hyaluronic acid, polyphenols, reactive oxygen species", "chunk": "Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood-brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate", "source": "PubMed"}, {"chunk_id": "37206236_1", "pmid": "37206236", "title": "Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease.", "authors": "Zhang B, Zhao Y, Guo K et al.", "year": "2023", "journal": "Bioengineering & translational medicine", "keywords": "Alzheimer's disease, drug delivery, hyaluronic acid, polyphenols, reactive oxygen species", "chunk": "issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood-brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6-RES-OPC-HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6-RES-OPC-HA nanoparticles have the potential to prevent and alleviate early AD.", "source": "PubMed"}, {"chunk_id": "34237390_0", "pmid": "34237390", "title": "Caveolin-1, a novel player in cognitive decline.", "authors": "Tang W, Li Y, Li Y et al.", "year": "2021", "journal": "Neuroscience and biobehavioral reviews", "keywords": "Brain development, Caveolin-1, Cognitive decline-related diseases, Pathophysiologic mechanisms", "chunk": "Cognitive decline (CD), which related to vascular dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and diabetes mellitus, is a growing health concern that has a great impact on the patients' quality of life. Although extensive efforts, the mechanisms of CD are still far from being clarified, not to mention the effective treatment and prevention strategies. Caveolin-1 (Cav-1), a trans-membrane protein, is a major component of the caveolae structure and scaffolding proteins. Recently, ample evidence depicts a strong correlation between Cav-1 and CD, however, the specific role of Cav-1 in CD has not been clearly examined and how they might be connected have yet to be identified. This review seeks to provide a comprehensive overview about how Cav-1 modulates pathogeneses of CD-associated diseases. In summary, Cav-1 can promote structural and functional plasticity of neurons, improve neurogenesis, relieve mitochondrial dysfunction, inhibit inflammation and suppress oxidative stress, which have shed", "source": "PubMed"}, {"chunk_id": "34237390_1", "pmid": "34237390", "title": "Caveolin-1, a novel player in cognitive decline.", "authors": "Tang W, Li Y, Li Y et al.", "year": "2021", "journal": "Neuroscience and biobehavioral reviews", "keywords": "Brain development, Caveolin-1, Cognitive decline-related diseases, Pathophysiologic mechanisms", "chunk": "modulates pathogeneses of CD-associated diseases. In summary, Cav-1 can promote structural and functional plasticity of neurons, improve neurogenesis, relieve mitochondrial dysfunction, inhibit inflammation and suppress oxidative stress, which have shed light on the idea that Cav-1 may be an efficacious therapeutic target to treat CD.", "source": "PubMed"}, {"chunk_id": "40947636_0", "pmid": "40947636", "title": "Coupling CZE, Liquid-Phase Ion Mobility, to MS/MS for Quantitative Top-Down Proteomics: Revealing Significant Proteoform Differences Between Healthy and Alzheimer's Disease Brains.", "authors": "Falamarzi Askarani M, Fang F, Counts SE et al.", "year": "2025", "journal": "Proteomics", "keywords": "Alzheimer's disease, CZE\u2010MS/MS, human brain, proteoform, tau phosphorylation, top\u2010down proteomics", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and pathological protein aggregation. Comprehensive quantitative proteomics of brain tissues from AD patients is critical for pursuing a better understanding of the molecular mechanisms that drive AD progression. Here, we present one of the first quantitative top-down proteomics (TDP) studies of postmortem cortex samples from AD patients and healthy controls to profile their proteoform differences by coupling capillary zone electrophoresis (CZE, liquid-phase ion mobility) to tandem mass spectrometry (MS/MS). We identified 3191 unique proteoforms and uncovered a drastic transformation in the proteoform profile in AD compared to healthy controls. Over 2200 proteoforms were exclusively identified in either AD or healthy control samples, and 157 proteoforms identified in both AD and control samples showed statistically significant abundance differences between the two conditions. Gene Ontology and pathway analysis of the genes associated with those proteoforms revealed broad changes in biological processes", "source": "PubMed"}, {"chunk_id": "40947636_1", "pmid": "40947636", "title": "Coupling CZE, Liquid-Phase Ion Mobility, to MS/MS for Quantitative Top-Down Proteomics: Revealing Significant Proteoform Differences Between Healthy and Alzheimer's Disease Brains.", "authors": "Falamarzi Askarani M, Fang F, Counts SE et al.", "year": "2025", "journal": "Proteomics", "keywords": "Alzheimer's disease, CZE\u2010MS/MS, human brain, proteoform, tau phosphorylation, top\u2010down proteomics", "chunk": "and control samples showed statistically significant abundance differences between the two conditions. Gene Ontology and pathway analysis of the genes associated with those proteoforms revealed broad changes in biological processes in AD brains, for example, telomere organization, substantia nigra development, amyloid fibril formation, microtubule cytoskeleton organization, progressive neurological disorders, long-term synaptic potentiation, and axogenesis. These biological processes are highly associated with the development of AD. Our study revealed a pool of potential novel proteoform biomarkers of AD in human brain samples for early diagnosis and therapy development. SUMMARY: Alzheimer's disease (AD) is a chronic neurodegenerative disease, destroying brain cells and causing thinking ability and memory to decline over time. Proteins (e.g., amyloid and tau) play key roles in the development of AD. Global and accurate protein measurement of human brains of AD patients and healthy controls will shed new light on the molecular mechanisms driving AD progression and discover new", "source": "PubMed"}, {"chunk_id": "40947636_2", "pmid": "40947636", "title": "Coupling CZE, Liquid-Phase Ion Mobility, to MS/MS for Quantitative Top-Down Proteomics: Revealing Significant Proteoform Differences Between Healthy and Alzheimer's Disease Brains.", "authors": "Falamarzi Askarani M, Fang F, Counts SE et al.", "year": "2025", "journal": "Proteomics", "keywords": "Alzheimer's disease, CZE\u2010MS/MS, human brain, proteoform, tau phosphorylation, top\u2010down proteomics", "chunk": "of AD. Global and accurate protein measurement of human brains of AD patients and healthy controls will shed new light on the molecular mechanisms driving AD progression and discover new biomarkers for AD diagnosis and therapeutic development. Here, we performed the first CZE-MS/MS-based quantitative top-down proteomics (TDP) of a small cohort of AD human brain samples and healthy controls (5 AD and 5 control) to determine the differentially quantified proteoforms between the two health conditions. Over 3000 proteoforms were identified, and only about 700 proteoforms were detected in both conditions, indicating drastically different proteoform profiles between the two conditions. The differentially quantified proteoforms (e.g., tau, neurogranin, and calmodulin-1 proteoforms) are associated with biological processes relevant to AD development, for example, amyloid fibril formation, microtubule disruption, synaptic transmission, and axogenesis. The results offer a deep view of the proteoform transformation in the AD human brain compared to the healthy control, providing", "source": "PubMed"}, {"chunk_id": "40947636_3", "pmid": "40947636", "title": "Coupling CZE, Liquid-Phase Ion Mobility, to MS/MS for Quantitative Top-Down Proteomics: Revealing Significant Proteoform Differences Between Healthy and Alzheimer's Disease Brains.", "authors": "Falamarzi Askarani M, Fang F, Counts SE et al.", "year": "2025", "journal": "Proteomics", "keywords": "Alzheimer's disease, CZE\u2010MS/MS, human brain, proteoform, tau phosphorylation, top\u2010down proteomics", "chunk": "amyloid fibril formation, microtubule disruption, synaptic transmission, and axogenesis. The results offer a deep view of the proteoform transformation in the AD human brain compared to the healthy control, providing potential proteoform biomarkers for AD diagnosis and proteoform targets for therapeutic development.", "source": "PubMed"}, {"chunk_id": "36120786_0", "pmid": "36120786", "title": "High Soluble Amyloid-\u03b242 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations.", "authors": "Sturchio A, Dwivedi AK, Malm T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, FDG-PET, amyloid-\u03b2, atrophy, cognition", "chunk": "In amyloid-positive individuals at risk for Alzheimer's disease (AD), high soluble 42-amino acid amyloid-\u03b2 (A\u03b242) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort. To test the hypothesis that high A\u03b242 preserves normal cognition in amyloid-positive individuals with Alzheimer's disease (AD)-causing mutations (APP, PSEN1, or PSEN2) to a greater extent than lower levels of brain amyloid, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), or total tau (t-tau). Cognitive progression was defined as any increase in Clinical Dementia Rating (CDR = 0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) \u22651.42 by Pittsburgh compound-B positron emission tomography (PiB-PET). We used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity", "source": "PubMed"}, {"chunk_id": "36120786_1", "pmid": "36120786", "title": "High Soluble Amyloid-\u03b242 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations.", "authors": "Sturchio A, Dwivedi AK, Malm T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, FDG-PET, amyloid-\u03b2, atrophy, cognition", "chunk": "used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity analyses, including Cox regression. Of 232 mutation carriers, 108 were PiB-PET-positive at baseline, with 43 (39.8%) meeting criteria for progression after 3.3\u00b12.0 years. Soluble A\u03b242 levels were higher among CDR non-progressors than CDR progressors. Higher A\u03b242 predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19-0.67; p = 0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68-0.96; p = 0.018). CSF A\u03b242 levels predicting lower risk of progression increased with higher SUVR levels. High CSF A\u03b242 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations.", "source": "PubMed"}, {"chunk_id": "36120786_2", "pmid": "36120786", "title": "High Soluble Amyloid-\u03b242 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations.", "authors": "Sturchio A, Dwivedi AK, Malm T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, FDG-PET, amyloid-\u03b2, atrophy, cognition", "chunk": "genetic mutations.", "source": "PubMed"}, {"chunk_id": "38696263_0", "pmid": "38696263", "title": "The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.", "authors": "Kalaria R, Maestre G, Mahinrad S et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, dementia, diversity, high\u2010income countries, low\u2010 and middle\u2010income countries, risk factors, vascular dementia", "chunk": "Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS:", "source": "PubMed"}, {"chunk_id": "38696263_1", "pmid": "38696263", "title": "The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.", "authors": "Kalaria R, Maestre G, Mahinrad S et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, dementia, diversity, high\u2010income countries, low\u2010 and middle\u2010income countries, risk factors, vascular dementia", "chunk": "options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.", "source": "PubMed"}, {"chunk_id": "41486173_0", "pmid": "41486173", "title": "GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.", "authors": "Silva-Llanes I, Smith LA, Abdelkader-Guill\u00e9n A et al.", "year": "2026", "journal": "Journal of biomedical science", "keywords": "Alzheimer\u2019s disease (AD), Dimethyl fumarate (DMF), Frontotemporal dementia (FTD), GASDERMIN D, NLRP3, Pyroptosis, TAU", "chunk": "Recent research has revealed a strong connection between neuroinflammation and TAU protein-related neurodegeneration. A key discovery shows that the NLRP3 inflammasome, when activated, can significantly impact TAU pathology and subsequent neuronal death. This process involves pyroptosis, a lytic form of programmed cell death driven by inflammasome activation, leading to GASDERMIN D (GSDMD) cleavage and the subsequent release of inflammatory molecules IL-1\u03b2 and IL-18. In this study, we explore the role of pyroptosis and GSDMD in Alzheimer's disease (AD) and tauopathy models, focusing on the TAU-induced neuroinflammatory process and its correlation with synaptic plasticity loss. Hippocampal tissue from AD patients at Braak stage II-III has been analyzed using qPCR to assess pyroptosis-related gene expression. To determine the role of TAU in pyroptosis and neuroinflammation, we used two different models: one based on intracerebral injection of an adeno-associated virus that specifically overexpresses TAU in the neurons of the hippocampus (AAV-TAU<sup>P301L</sup>), and a", "source": "PubMed"}, {"chunk_id": "41486173_1", "pmid": "41486173", "title": "GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.", "authors": "Silva-Llanes I, Smith LA, Abdelkader-Guill\u00e9n A et al.", "year": "2026", "journal": "Journal of biomedical science", "keywords": "Alzheimer\u2019s disease (AD), Dimethyl fumarate (DMF), Frontotemporal dementia (FTD), GASDERMIN D, NLRP3, Pyroptosis, TAU", "chunk": "pyroptosis and neuroinflammation, we used two different models: one based on intracerebral injection of an adeno-associated virus that specifically overexpresses TAU in the neurons of the hippocampus (AAV-TAU<sup>P301L</sup>), and a transgenic mouse model Tg-TAU<sup>P301S</sup> at 8 and 10 months of age. Gene expression, protein levels, and neuroinflammation markers were evaluated using qPCR and immunofluorescence. Additionally, both genetic (GSDMD-deficient mice) and pharmacological (dimethyl fumarate, DMF) interventions targeting pyroptosis have been explored to assess their impact on neuroinflammation and synaptic plasticity. AD patients exhibited increased expression of pyroptosis-related genes, supporting the involvement of pyroptosis in neurodegeneration. Furthermore, TAU overexpression induced pyroptosis in both mouse models, and GSDMD protein levels increased alongside reactive microglial morphology. Our data supports that TAU-induced neuroinflammation correlated with synaptic plasticity impairment. GSDMD deficiency significantly reduced pyroptosis-related markers associated to TAU, but unexpectedly worsened synaptic plasticity deficits, suggesting GSDMD may play a dual role in inflammation and synaptic function.", "source": "PubMed"}, {"chunk_id": "41486173_2", "pmid": "41486173", "title": "GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.", "authors": "Silva-Llanes I, Smith LA, Abdelkader-Guill\u00e9n A et al.", "year": "2026", "journal": "Journal of biomedical science", "keywords": "Alzheimer\u2019s disease (AD), Dimethyl fumarate (DMF), Frontotemporal dementia (FTD), GASDERMIN D, NLRP3, Pyroptosis, TAU", "chunk": "synaptic plasticity impairment. GSDMD deficiency significantly reduced pyroptosis-related markers associated to TAU, but unexpectedly worsened synaptic plasticity deficits, suggesting GSDMD may play a dual role in inflammation and synaptic function. Finally, we showed that DMF treatment suppressed pyroptosis gene expression, reduced GSDMD levels, and alleviated neuroinflammation, correlating with improved synaptic marker expression. Our findings demonstrate that TAU-induced pyroptosis contributes to neuroinflammation and synaptic dysfunction. While GSDMD inhibition mitigates inflammation, its absence exacerbates synaptic impairment, highlighting its complex role in tauopathies. Our results indicate that DMF treatment could offer a promising therapeutic avenue to modulate pyroptosis and neuroinflammation, and restore synaptic integrity in tauopathies.", "source": "PubMed"}, {"chunk_id": "41184000_0", "pmid": "41184000", "title": "Utility of Locus Coeruleus Signal Intensity on High-resolution T1-weighted MR Imaging with Magnetization Transfer for Differentiating Parkinson's Disease from Atypical Parkinsonism.", "authors": "Yoshimatsu Y, Ide S, Ogawa N et al.", "year": "2026", "journal": "Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine", "keywords": "Parkinson\u2019s disease, T1-weighted imaging with magnetization transfer, atypical parkinsonism, locus coeruleus", "chunk": "This study aimed to evaluate the diagnostic utility of locus coeruleus (LC) signal intensity on high-resolution T1-weighted imaging with magnetization transfer (T1WI with MT) for distinguishing Parkinson's disease (PD) from a broad range of atypical parkinsonism (AP) subtypes, including early-stage cases. We retrospectively analyzed T1WI with MT data from 214 participants, including patients with PD (n = 125), corticobasal syndrome (CBS, n = 12), multiple system atrophy (MSA, n = 16), progressive supranuclear palsy (PSP, n = 19), essential tremor (n = 17), vascular parkinsonism (n = 4), drug-induced parkinsonism (DIP, n = 7), and healthy subjects (HS, n = 14). Circular ROIs were placed on the LC and substantia nigra pars compacta to calculate contrast ratios (CRs). Conventional MRI findings of AP, focusing on characteristic regional atrophy patterns, were also evaluated. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. A subanalysis was performed for early-stage cases (within", "source": "PubMed"}, {"chunk_id": "41184000_1", "pmid": "41184000", "title": "Utility of Locus Coeruleus Signal Intensity on High-resolution T1-weighted MR Imaging with Magnetization Transfer for Differentiating Parkinson's Disease from Atypical Parkinsonism.", "authors": "Yoshimatsu Y, Ide S, Ogawa N et al.", "year": "2026", "journal": "Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine", "keywords": "Parkinson\u2019s disease, T1-weighted imaging with magnetization transfer, atypical parkinsonism, locus coeruleus", "chunk": "findings of AP, focusing on characteristic regional atrophy patterns, were also evaluated. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. A subanalysis was performed for early-stage cases (within 2 years of onset). Three independent neuroradiologists evaluated T1WI with MT, and interobserver agreement was assessed using intraclass correlation coefficients (ICC). The LC-CR was significantly lower in PD than in HS (P < 0.01) and all AP subtypes except DIP (P = 0.37). ROC analysis revealed that LC-CR had the highest diagnostic accuracy for differentiating PD from AP (area under the curve [AUC] = 0.83, sensitivity = 67%, specificity = 90%). In early-stage cases, LC-CR maintained high specificity (98%) with an AUC of 0.80. The diagnostic utility of LC-CR was comparable or superior to conventional MRI findings in distinguishing PD from CBS, MSA, and PSP. Interobserver agreement for LC-CR measurements was good, with an ICC of 0.87 (95% confidence interval:", "source": "PubMed"}, {"chunk_id": "41184000_2", "pmid": "41184000", "title": "Utility of Locus Coeruleus Signal Intensity on High-resolution T1-weighted MR Imaging with Magnetization Transfer for Differentiating Parkinson's Disease from Atypical Parkinsonism.", "authors": "Yoshimatsu Y, Ide S, Ogawa N et al.", "year": "2026", "journal": "Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine", "keywords": "Parkinson\u2019s disease, T1-weighted imaging with magnetization transfer, atypical parkinsonism, locus coeruleus", "chunk": "comparable or superior to conventional MRI findings in distinguishing PD from CBS, MSA, and PSP. Interobserver agreement for LC-CR measurements was good, with an ICC of 0.87 (95% confidence interval: 0.85-0.89). LC-CR measured on T1WI with MT serves as a reliable imaging biomarker for differentiating PD from various forms of AP, even in early disease stages.", "source": "PubMed"}, {"chunk_id": "37536279_0", "pmid": "37536279", "title": "How should we be using biomarkers in trials of disease modification in Parkinson's disease?", "authors": "Vijiaratnam N, Foltynie T", "year": "2023", "journal": "Brain : a journal of neurology", "keywords": "Parkinson\u2019s disease, biomarkers, clinical trials, disease modification", "chunk": "The recent validation of the \u03b1-synuclein seed amplification assay as a biomarker with high sensitivity and specificity for the diagnosis of Parkinson's disease has formed the backbone for a proposed staging system for incorporation in Parkinson's disease clinical studies and trials. The routine use of this biomarker should greatly aid in the accuracy of diagnosis during recruitment of Parkinson's disease patients into trials (as distinct from patients with non-Parkinson's disease parkinsonism or non-Parkinson's disease tremors). There remain, however, further challenges in the pursuit of biomarkers for clinical trials of disease modifying agents in Parkinson's disease, namely: optimizing the distinction between different \u03b1-synucleinopathies; the selection of subgroups most likely to benefit from a candidate disease modifying agent; a sensitive means of confirming target engagement; and the early prediction of longer-term clinical benefit. For example, levels of CSF proteins such as the lysosomal enzyme \u03b2-glucocerebrosidase may assist in prognostication or allow enrichment", "source": "PubMed"}, {"chunk_id": "37536279_1", "pmid": "37536279", "title": "How should we be using biomarkers in trials of disease modification in Parkinson's disease?", "authors": "Vijiaratnam N, Foltynie T", "year": "2023", "journal": "Brain : a journal of neurology", "keywords": "Parkinson\u2019s disease, biomarkers, clinical trials, disease modification", "chunk": "confirming target engagement; and the early prediction of longer-term clinical benefit. For example, levels of CSF proteins such as the lysosomal enzyme \u03b2-glucocerebrosidase may assist in prognostication or allow enrichment of appropriate patients into disease modifying trials of agents with this enzyme as the target; the presence of coexisting Alzheimer's disease-like pathology (detectable through CSF levels of amyloid-\u03b242 and tau) can predict subsequent cognitive decline; imaging techniques such as free-water or neuromelanin MRI may objectively track decline in Parkinson's disease even in its later stages. The exploitation of additional biomarkers to the \u03b1-synuclein seed amplification assay will, therefore, greatly add to our ability to plan trials and assess the disease modifying properties of interventions. The choice of which biomarker(s) to use in the context of disease modifying clinical trials will depend on the intervention, the stage (at risk, premotor, motor, complex) of the population recruited and the aims of the", "source": "PubMed"}, {"chunk_id": "37536279_2", "pmid": "37536279", "title": "How should we be using biomarkers in trials of disease modification in Parkinson's disease?", "authors": "Vijiaratnam N, Foltynie T", "year": "2023", "journal": "Brain : a journal of neurology", "keywords": "Parkinson\u2019s disease, biomarkers, clinical trials, disease modification", "chunk": "use in the context of disease modifying clinical trials will depend on the intervention, the stage (at risk, premotor, motor, complex) of the population recruited and the aims of the trial. The progress already made lends hope that panels of fluid biomarkers in tandem with structural or functional imaging may provide sensitive and objective methods of confirming that an intervention is modifying a key pathophysiological process of Parkinson's disease. However, correlation with clinical progression does not necessarily equate to causation, and the ongoing validation of quantitative biomarkers will depend on insightful clinical-genetic-pathophysiological comparisons incorporating longitudinal biomarker changes from those at genetic risk with evidence of onset of the pathophysiology and those at each stage of manifest clinical Parkinson's disease.", "source": "PubMed"}, {"chunk_id": "41276030_0", "pmid": "41276030", "title": "MDM2 in the signaling pathways related to neurological diseases.", "authors": "Shi C, Xue Y, Li J et al.", "year": "2025", "journal": "Neurobiology of disease", "keywords": "Autophagy, CNS diseases, MDM2, Mitochondria, Therapeutic target, p53", "chunk": "Mouse double minute 2 homolog (MDM2) is a key negative regulator of the p53 pathway, functioning through its E3 ubiquitin ligase activity to control cell-cycle progression, DNA damage response, and apoptosis. Recent findings reveal that MDM2 also plays multifaceted roles in the central nervous system (CNS), extending beyond its canonical oncogenic functions. Increasingly, MDM2 has been implicated in the pathogenesis and progression of neurodegenerative diseases, brain injury, neuroinflammation, and cognitive dysfunction.This review integrates current advances on the non-canonical roles of MDM2 in CNS disorders, focusing on its involvement in mitochondrial homeostasis, autophagy regulation, synaptic plasticity, immune modulation, and metabolic signaling. Unlike previous reviews that addressed MDM2 mainly in oncogenesis or single neurological conditions, this work establishes a stage- and cell-type-specific framework of MDM2 regulation within the CNS. It distinguishes p53-dependent stress-surveillance mechanisms from p53-independent repair and metabolic pathways and introduces a therapeutic-window concept that balances neuroprotection with adaptive stress responses.Together,", "source": "PubMed"}, {"chunk_id": "41276030_1", "pmid": "41276030", "title": "MDM2 in the signaling pathways related to neurological diseases.", "authors": "Shi C, Xue Y, Li J et al.", "year": "2025", "journal": "Neurobiology of disease", "keywords": "Autophagy, CNS diseases, MDM2, Mitochondria, Therapeutic target, p53", "chunk": "framework of MDM2 regulation within the CNS. It distinguishes p53-dependent stress-surveillance mechanisms from p53-independent repair and metabolic pathways and introduces a therapeutic-window concept that balances neuroprotection with adaptive stress responses.Together, these perspectives position MDM2 as a dynamic molecular switch orchestrating neuronal fate, providing conceptual foundations for context-specific therapeutic strategies in neurological disease.", "source": "PubMed"}, {"chunk_id": "39964126_0", "pmid": "39964126", "title": "The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders.", "authors": "McIntyre RS, Rasgon N, Goldberg J et al.", "year": "2025", "journal": "CNS spectrums", "keywords": "Neuroplasticity, apoptosis, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), neuroprotection", "chunk": "Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs) mimic naturally occurring GLP-1 and GIP and are highly effective anti-diabetic and anti-obesity agents. In addition to their robust acute and long-term effects on weight, metabolism, and blood pressure, these agents also reduce cardiovascular mortality as well as stroke risk and associated consequences. A replicated and convergent body of preclinical evidence also indicates that incretin receptor agonists activate molecular effectors critical to neuroplasticity, neuroprotection, and anti-apoptosis. Herein, we propose that GLP-1 RAs and GIP RAs are promising transdiagnostic mechanistically informed therapeutics in the treatment and prevention of multiple domains of psychopathology, including general cognitive, reward, and motivation systems and mental disorders. Major neurocognitive disorders (eg, Alzheimer's Disease, Parkinson's Disease), alcohol and substance use disorders, traumatic brain injury, and depressive disorders are near-term therapeutic targets. In addition, GLP-1 RAs and GIP RAs have robust effects on comorbidities that differentially affect", "source": "PubMed"}, {"chunk_id": "39964126_1", "pmid": "39964126", "title": "The effect of glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptor agonists on neurogenesis, differentiation, and plasticity (Neuro-GDP): potential mechanistically informed therapeutics in the treatment and prevention of mental disorders.", "authors": "McIntyre RS, Rasgon N, Goldberg J et al.", "year": "2025", "journal": "CNS spectrums", "keywords": "Neuroplasticity, apoptosis, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), neuroprotection", "chunk": "alcohol and substance use disorders, traumatic brain injury, and depressive disorders are near-term therapeutic targets. In addition, GLP-1 RAs and GIP RAs have robust effects on comorbidities that differentially affect persons with mental disorders (eg, cardiovascular, cerebrovascular, and metabolic disorders) and psychotropic drug-related weight gain.", "source": "PubMed"}, {"chunk_id": "41488982_0", "pmid": "41488982", "title": "A value assessment of patient-level outcomes and productivity loss for intravenous and subcutaneous lecanemab for patients with early Alzheimer's disease.", "authors": "Ressa R, Ettinger J, Chowdhury E et al.", "year": "2025", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, I12, I15, economic analysis, intravenous, lecanemab, subcutaneous, value", "chunk": "Intravenous (IV) lecanemab is approved for the treatment of patients with early Alzheimer's disease (AD); a subcutaneous (SC) option may offer additional benefits. We assessed the overall value of SC treatments, and direct/indirect outcomes associated with IV and SC lecanemab. For the narrative review, PubMed was searched (February 2025) for studies comparing patient preferences for IV/SC treatment administration published between 2015-2025. Study eligibility was determined using patient, intervention, comparator, outcomes, and study criteria. For the decision-analytic model, a Markov model was developed with four lecanemab treatment scenarios. Scenarios one to three included IV initiation (10 mg/kg biweekly) to month 18, followed by either IV initiation continued (10 mg/kg biweekly), SC maintenance (250 mg weekly) or IV maintenance (10 mg/kg every 4 weeks). Scenario four included SC initiation (500 mg weekly) for an 18-month period, followed by SC maintenance (250 mg weekly). Outcomes were administration time/frequency; patient, caregiver, and healthcare professional", "source": "PubMed"}, {"chunk_id": "41488982_1", "pmid": "41488982", "title": "A value assessment of patient-level outcomes and productivity loss for intravenous and subcutaneous lecanemab for patients with early Alzheimer's disease.", "authors": "Ressa R, Ettinger J, Chowdhury E et al.", "year": "2025", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, I12, I15, economic analysis, intravenous, lecanemab, subcutaneous, value", "chunk": "4 weeks). Scenario four included SC initiation (500 mg weekly) for an 18-month period, followed by SC maintenance (250 mg weekly). Outcomes were administration time/frequency; patient, caregiver, and healthcare professional time; and caregiver productivity loss. Forty-three publications reported patient treatment preferences. Most (88.4%) reported that patients preferred SC over IV. Key reasons for this were time savings (<i>n</i> = 13/43 studies; 30.2%), convenience (<i>n</i> = 11/43; 25.6%), treatment frequency (<i>n</i> = 12/43; 27.9%). Two studies (<i>n</i> = 2/43; 4.7%) reported an IV preference over SC; for three studies (<i>n</i> = 3/43; 7.0%), treatment preference was driven by administration frequency. Decision-analytic modeling of lecanemab treatment scenarios revealed that IV initiation to IV maintenance had the lowest number of administrations, whereas SC initiation to SC maintenance had the lowest number of treatment hours and caregiver productivity losses. Caution must be taken when generalizing these results for all AD patients. SC treatments show", "source": "PubMed"}, {"chunk_id": "41488982_2", "pmid": "41488982", "title": "A value assessment of patient-level outcomes and productivity loss for intravenous and subcutaneous lecanemab for patients with early Alzheimer's disease.", "authors": "Ressa R, Ettinger J, Chowdhury E et al.", "year": "2025", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, I12, I15, economic analysis, intravenous, lecanemab, subcutaneous, value", "chunk": "initiation to SC maintenance had the lowest number of treatment hours and caregiver productivity losses. Caution must be taken when generalizing these results for all AD patients. SC treatments show value as a therapeutic option. IV and SC lecanemab availability may offer benefits to patients, caregivers, and society, and improve shared decision making.", "source": "PubMed"}, {"chunk_id": "41694458_0", "pmid": "41694458", "title": "Gut-kidney-brain axis and daytime sleepiness in Parkinson's disease and chronic kidney disease: an expert narrative review.", "authors": "Yang S, Zhu C, Xiong S et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Parkinson's disease, blood-brain barrier permeability, chronic kidney disease, excessive daytime sleepiness, gut-kidney-brain axis, precision medicine", "chunk": "Excessive daytime sleepiness (EDS) is a debilitating comorbidity in over 80% of patients with Parkinson's disease (PD) and chronic kidney disease (CKD). Evidence implicates dysregulation of the gut-kidney-brain axis as a may contribute of EDS pathogenesis, though detailed mechanistic insights remain limited. This review evaluates the efficacy of interventions targeting the gut-kidney-brain axis in ameliorating EDS among PD and CKD patients, benchmarking outcomes against standard care protocols. We systematically queried PubMed, Cochrane Library, Embase, Web of Science, and Scopus for studies published between January 2000 and December 2025. Our search encompassed experimental, observational, and qualitative designs. Two reviewers independently conducted study selection and data extraction. Data synthesis incorporated random-effects models to address methodological heterogeneity. Analysis of 68 included studies (<i>n</i> = 15,392 participants) demonstrated that interventions such as specific probiotics significantly reduced Epworth Sleepiness Scale (ESS) scores by 8.2 points (95% CI: 7.1-9.3; I<sup>2</sup> = 65%). Furthermore, biomarker-guided personalized strategies", "source": "PubMed"}, {"chunk_id": "41694458_1", "pmid": "41694458", "title": "Gut-kidney-brain axis and daytime sleepiness in Parkinson's disease and chronic kidney disease: an expert narrative review.", "authors": "Yang S, Zhu C, Xiong S et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Parkinson's disease, blood-brain barrier permeability, chronic kidney disease, excessive daytime sleepiness, gut-kidney-brain axis, precision medicine", "chunk": "= 15,392 participants) demonstrated that interventions such as specific probiotics significantly reduced Epworth Sleepiness Scale (ESS) scores by 8.2 points (95% CI: 7.1-9.3; I<sup>2</sup> = 65%). Furthermore, biomarker-guided personalized strategies (BBPI) yielded a 3.2-fold higher improvement in EDS outcomes (OR = 3.2, 95% CI: 1.9-5.4). Targeting the gut-kidney-brain axis holds substantial promise for managing EDS, supported by moderate-certainty evidence for BBPI-based approaches. However, clinical translation necessitates personalized intervention frameworks and validation through large-scale multicenter trials.", "source": "PubMed"}, {"chunk_id": "41476028_0", "pmid": "41476028", "title": "Six-month follow-up of ARIA-H and iron deposition in real-world lecanemab therapy for Alzheimer's disease: Evidence from a Chinese 7T MRI cohort.", "authors": "Zhang W, Liu H, Zhang C et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "7T MRI, ARIA\u2010H, Alzheimer's disease, Chinese cohort, iron deposition, lecanemab", "chunk": "With the approval of lecanemab for treating Alzheimer's disease (AD), there is an urgent need to evaluate its safety and treatment effects on biomarkers in real-world practice. Patients receiving lecanemab (n = 72) underwent routine 3T and 7T magnetic resonance imaging (MRI) for amyloid-related imaging abnormality (ARIA) monitoring. Longitudinal changes of iron deposition assessed by quantitative susceptibility mapping (QSM) and its association with plasma biomarkers were further evaluated. With use of 7T MRI, we identified characteristic perivascular features and detected ARIA with hemorrhages/hemosiderin deposition (ARIA-H) \u22484 months earlier than with 3T. QSM detected post-treatment regional susceptibility reductions. Decreased susceptibility in the temporal, frontal lobes, and the thalamus was associated with plasma amyloid beta 42 (A\u03b242) and tau phosphorylated at threonine 217 (p-tau217) changes. 7T MRI provides superior ARIA-H detection and iron dynamics monitoring, supporting its role in risk stratification and therapy assessment for lecanemab-treated patients. Iron deposition measured by QSM", "source": "PubMed"}, {"chunk_id": "41476028_1", "pmid": "41476028", "title": "Six-month follow-up of ARIA-H and iron deposition in real-world lecanemab therapy for Alzheimer's disease: Evidence from a Chinese 7T MRI cohort.", "authors": "Zhang W, Liu H, Zhang C et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "7T MRI, ARIA\u2010H, Alzheimer's disease, Chinese cohort, iron deposition, lecanemab", "chunk": "217 (p-tau217) changes. 7T MRI provides superior ARIA-H detection and iron dynamics monitoring, supporting its role in risk stratification and therapy assessment for lecanemab-treated patients. Iron deposition measured by QSM may serve as a promising neuroimaging marker for amyloid-targeting treatments. Using 7T magnetic resonance imaging (MRI), this study for the first time visualized amyloid-related imaging abnormality with hemorrhages/hemosiderin deposition (ARIA-H) at a submillimeter resolution, characterized by aggregated, clustered cerebral microbleeds in a perivascular distribution, suggesting overlapping pathology with cerebral amyloid angiopathy. The susceptibility-weighted imaging sequence on 7T MRI enabled detection of ARIA-H up to 4 months earlier. Plasma amyloid beta 42 (A\u03b242) and tau phosphorylated at threonine 217 (p-tau 217) levels are sensitive biomarkers for amyloid targeted therapy. Quantitative susceptibility mapping (QSM) analysis demonstrated reduced cortical iron burden post-treatment, which has significant associations with plasma A\u03b242 and p-tau 217 levels, highlighting QSM-derived iron quantification as a promising neuroimaging indicator for", "source": "PubMed"}, {"chunk_id": "41476028_2", "pmid": "41476028", "title": "Six-month follow-up of ARIA-H and iron deposition in real-world lecanemab therapy for Alzheimer's disease: Evidence from a Chinese 7T MRI cohort.", "authors": "Zhang W, Liu H, Zhang C et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "7T MRI, ARIA\u2010H, Alzheimer's disease, Chinese cohort, iron deposition, lecanemab", "chunk": "mapping (QSM) analysis demonstrated reduced cortical iron burden post-treatment, which has significant associations with plasma A\u03b242 and p-tau 217 levels, highlighting QSM-derived iron quantification as a promising neuroimaging indicator for amyloid-targeted therapeutics.", "source": "PubMed"}, {"chunk_id": "41565969_0", "pmid": "41565969", "title": "Association of a five-metabolite and early-symptom profile with Parkinson's disease and its clinical progression.", "authors": "Oropeza Valdez JJ, Elizalde-D\u00edaz JP, Antonio OR et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Biomarker, Metabolomics, Parkinson", "chunk": "Parkinson's disease (PD) urgently requires blood-based markers that flag pathology before disabling motor decline. This study measured absolute concentrations of 144 plasma metabolites in 20 neurologically healthy adults and in 40 PD patients clinically classified as intermediate (PD-I) or progressive (PD-II). A multinomial logistic regression model was built to examine how changes in metabolite concentrations relate to disease stage and to assess their exploratory discriminative performance in this cohort. Five metabolites: glutamine, butyric acid, indoleacetic acid, phosphatidylcholine aa C40:2, and acylcarnitine C12:1 emerged as the smallest biomarker set that consistently separated controls, PD-I, and PD-II. When three non-motor manifestations often present in the prodromal phase (drooling, REM behavior disorder and depression) were added, the combined profile clearly distinguished controls from early-stage patients and improved classification of intermediate versus progressive disease. The selected metabolites play roles in gut-derived signaling, mitochondrial \u03b2-oxidation, and membrane lipid homeostasis, while the clinical variables mirror the", "source": "PubMed"}, {"chunk_id": "41565969_1", "pmid": "41565969", "title": "Association of a five-metabolite and early-symptom profile with Parkinson's disease and its clinical progression.", "authors": "Oropeza Valdez JJ, Elizalde-D\u00edaz JP, Antonio OR et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Biomarker, Metabolomics, Parkinson", "chunk": "early-stage patients and improved classification of intermediate versus progressive disease. The selected metabolites play roles in gut-derived signaling, mitochondrial \u03b2-oxidation, and membrane lipid homeostasis, while the clinical variables mirror the recognized early spread of \u03b1-synuclein pathology, together offering a coherent snapshot of systemic changes across PD progression. Because the panel can be quantified from a single small plasma aliquot and a brief clinical interview, it represents a promising exploratory finding that requires validation in larger, independent cohorts before any consideration for clinical application or pre-symptomatic screening.", "source": "PubMed"}, {"chunk_id": "41641148_0", "pmid": "41641148", "title": "Raspberry protective role in inflammatory diseases: An overview.", "authors": "Arya P, Sharma V, Singh P et al.", "year": "2026", "journal": "Iranian journal of basic medical sciences", "keywords": "Alzheimer\u2019s, Atherosclerosis, Cancer, Cardiovascular, Inflammation, Neuroinflammation, Parkinson\u2019s, Raspberry", "chunk": "Inflammation is a natural immune response triggered by multiple factors such as pathogens, damaged cells, and toxic substances. These triggers can lead to both acute and chronic inflammatory reactions in different tissues, contributing to the development of several inflammatory disorders, including cardiovascular diseases, neuroinflammation, arthritis, and cancer. Both infectious and non-infectious stimuli activate immune cells and initiate critical inflammatory signaling pathways. Raspberries (<i>Rubus idaeus</i>) are abundant in bioactive constituents, especially polyphenols like anthocyanins, flavanols, phenolic acids, urolithin A, and ellagic acid, all of which possess notable anti-inflammatory and anti-oxidant activities. These compounds have been shown to regulate various inflammatory signaling pathways, including MAPKs, NF-\u03baB, PI3K/Akt, AP-1, IL-6, TNF-\u03b1, IL-1\u03b2, CD40, nitric oxide (NO), caspases, and the JAK-STAT pathway. Studies have emphasized their broad pharmacological effects, such as anti-inflammatory, anti-oxidant, hepatoprotective, cardioprotective, gastroprotective, anti-obesity, skin depigmenting, and bone-regenerative properties. This review emphasizes mechanistic insights into raspberries' protective roles in managing inflammatory-related", "source": "PubMed"}, {"chunk_id": "41641148_1", "pmid": "41641148", "title": "Raspberry protective role in inflammatory diseases: An overview.", "authors": "Arya P, Sharma V, Singh P et al.", "year": "2026", "journal": "Iranian journal of basic medical sciences", "keywords": "Alzheimer\u2019s, Atherosclerosis, Cancer, Cardiovascular, Inflammation, Neuroinflammation, Parkinson\u2019s, Raspberry", "chunk": "emphasized their broad pharmacological effects, such as anti-inflammatory, anti-oxidant, hepatoprotective, cardioprotective, gastroprotective, anti-obesity, skin depigmenting, and bone-regenerative properties. This review emphasizes mechanistic insights into raspberries' protective roles in managing inflammatory-related disorders, particularly cardiovascular diseases, neurodegenerative conditions, and cancer, and highlights their therapeutic potential.", "source": "PubMed"}, {"chunk_id": "41830037_0", "pmid": "41830037", "title": "Effects of Laurocerasus Officinalis Roem (Cherry Laurel) on Cognitive Function and Neurobiochemical Pathways in a Streptozotocin-Induced Nontransgenic Alzheimer's Disease Model.", "authors": "Ozsoy F, Yanar K, Sayili U et al.", "year": "2026", "journal": "Nutrients", "keywords": "Alzheimer\u2019s disease, GSK3-\u03b2, Moris Water Maze, cherry laurel, type 2 diabetes", "chunk": "<b>Background:</b> This study investigated the effects of <i>Laurocerasus officinalis</i> Roem (cherry laurel; CL), a traditionally consumed fruit, on cognitive performance and selected neurobiochemical and metabolic pathways in a nontransgenic streptozotocin (STZ)-induced Alzheimer's disease (i.c.v. STZ) model and an STZ-induced type 2 diabetes mellitus (T2DM; i.p. STZ) model. <b>Method:</b> Fifty-seven adult male Sprague-Dawley rats were allocated to control, T2DM, and Alzheimer (ALZ) model groups, with subgroup interventions including CL supplementation and, in the T2DM model, metformin as a comparator. Spatial learning and memory were assessed using the Morris Water Maze. Serum and brain tissue levels of GSK3-\u03b2, glutathione (GSH), interleukin-1 (IL-1), GLUT4, GLP-1, \u03b2-amyloid (A\u03b2), and acetylcholinesterase (AChE) were quantified. <b>Results:</b> Serum GSK3-\u03b2 levels did not differ significantly between groups, whereas brain tissue GSK3-\u03b2 showed significant between-group differences. CL increased GSH levels in both models, with significant elevations in serum and brain tissue GSH in the ALZ model following CL administration;", "source": "PubMed"}, {"chunk_id": "41830037_1", "pmid": "41830037", "title": "Effects of Laurocerasus Officinalis Roem (Cherry Laurel) on Cognitive Function and Neurobiochemical Pathways in a Streptozotocin-Induced Nontransgenic Alzheimer's Disease Model.", "authors": "Ozsoy F, Yanar K, Sayili U et al.", "year": "2026", "journal": "Nutrients", "keywords": "Alzheimer\u2019s disease, GSK3-\u03b2, Moris Water Maze, cherry laurel, type 2 diabetes", "chunk": "brain tissue GSK3-\u03b2 showed significant between-group differences. CL increased GSH levels in both models, with significant elevations in serum and brain tissue GSH in the ALZ model following CL administration; in the T2DM model, GSH increased after both CL and metformin. In the ALZ model, CL was associated with decreased serum A\u03b2 and AChE levels and improved Morris Water Maze performance, reflected by reduced escape latencies. <b>Conclusions:</b> CL supplementation was associated with antioxidant enhancement and modulation of amyloid- and cholinergic-related measures, alongside improved spatial learning performance in the STZ-induced nontransgenic ALZ model. In addition, CL reduced blood glucose in the T2DM model. Given the likely contribution of fruit phytochemicals (including total phenolics), further studies are warranted to better define the bioactive composition and mechanisms underlying these effects.", "source": "PubMed"}, {"chunk_id": "41830037_2", "pmid": "41830037", "title": "Effects of Laurocerasus Officinalis Roem (Cherry Laurel) on Cognitive Function and Neurobiochemical Pathways in a Streptozotocin-Induced Nontransgenic Alzheimer's Disease Model.", "authors": "Ozsoy F, Yanar K, Sayili U et al.", "year": "2026", "journal": "Nutrients", "keywords": "Alzheimer\u2019s disease, GSK3-\u03b2, Moris Water Maze, cherry laurel, type 2 diabetes", "chunk": "bioactive composition and mechanisms underlying these effects.", "source": "PubMed"}, {"chunk_id": "41683444_0", "pmid": "41683444", "title": "Neuroinflammation as a Central Mechanism in Alzheimer's Disease: Therapeutic Insights from Schiff Base Derivatives.", "authors": "Abdullah SK, See-Too WS, Mohd Mohidin TB et al.", "year": "2026", "journal": "Molecules (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, Schiff bases, neuroinflammation", "chunk": "Despite decades of intensive research, an effective cure for Alzheimer's disease (AD) remains elusive. Although AD is classically linked to amyloid-beta (A\u03b2) aggregation, growing evidence highlights neuroinflammation as a major driver of disease progression. Neuroinflammation forms a self-amplifying cycle involving various factors such as cytokines, chemokines, oxidative stress, and glial cell activation, emphasizing the need for multi-target therapeutic strategies. Schiff bases have emerged as promising candidates, especially metal-incorporated Schiff bases, as numerous preclinical studies have demonstrated their ability to modulate key pathological processes, including inflammation, oxidative stress, reactive oxygen species (ROS) impairment, metal dysregulation, A\u03b2 aggregation, and cholinergic dysfunction. Additionally, some preclinical studies even revealed the neuroprotective and anti-amnesic potential of Schiff bases. Nevertheless, these activities have been investigated across diverse structures of Schiff bases, and systematic evaluation of metal-incorporated Schiff bases remains limited. Although Schiff base-based anti-AD investigations have remained exclusively at the preclinical level, the huperzine A prodrug", "source": "PubMed"}, {"chunk_id": "41683444_1", "pmid": "41683444", "title": "Neuroinflammation as a Central Mechanism in Alzheimer's Disease: Therapeutic Insights from Schiff Base Derivatives.", "authors": "Abdullah SK, See-Too WS, Mohd Mohidin TB et al.", "year": "2026", "journal": "Molecules (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, Schiff bases, neuroinflammation", "chunk": "diverse structures of Schiff bases, and systematic evaluation of metal-incorporated Schiff bases remains limited. Although Schiff base-based anti-AD investigations have remained exclusively at the preclinical level, the huperzine A prodrug ZT-1 progressed to early-phase clinical trials before its development was discontinued. Comprehensive studies assessing their multi-target potential with their pharmacokinetic profiles are therefore essential to advance their development as prospective anti-AD agents.", "source": "PubMed"}, {"chunk_id": "41540037_0", "pmid": "41540037", "title": "UQCRC1 deficiency impairs mitophagy via PINK1-dependent mechanisms in Parkinson's disease.", "authors": "Li JL, Huang SY, Huang PY et al.", "year": "2026", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Oxidative phosphorylation (OXPHOS) and mitophagy are functionally interconnected cellular processes, the defects of which are considered key driving forces behind the pathogenesis of Parkinson's disease (PD). UQCRC1, a core subunit of the mitochondrial respiratory chain complex III, is a recently identified familial PD gene whose pathogenic mutations result in OXPHOS stress. Given its importance, however, the role of UQCRC1 in idiopathic PD as well as mitophagy has not been investigated. In this study, we collected 19 datasets comprising postmortem substantia nigra from 150 cases of non-disease controls and 185 cases of PD or incidental Lewy body disease (iLBD), and the meta-analysis of the UQCRC1 mRNA level showed reduced expression in idiopathic PD, suggesting the potential of UQCRC1 as a biomarker. Leveraging the SH-SY5Y cells and fly models, we showed that mitophagy was impaired upon UQCRC1 mutation or depletion. Notably, insufficiency of PINK1 mRNA was associated with UQCRC1 deficiency, and overexpression", "source": "PubMed"}, {"chunk_id": "41540037_1", "pmid": "41540037", "title": "UQCRC1 deficiency impairs mitophagy via PINK1-dependent mechanisms in Parkinson's disease.", "authors": "Li JL, Huang SY, Huang PY et al.", "year": "2026", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Leveraging the SH-SY5Y cells and fly models, we showed that mitophagy was impaired upon UQCRC1 mutation or depletion. Notably, insufficiency of PINK1 mRNA was associated with UQCRC1 deficiency, and overexpression of Pink1 rescued the locomotion and mitophagy defects in the fly models with neuronal loss of uqcrc1. Treatment with two PINK1 activators, kinetin and MTK458, resulted in similar protective effects in the fly and cell models. Overall, we identified OXPHOS stress led by deficiency of UQCRC1 as an etiology of mitophagy defects in PD and PINK1 as a therapeutic target for UQCRC1-associated PD.", "source": "PubMed"}, {"chunk_id": "40850187_0", "pmid": "40850187", "title": "AlzFormer: Multi-modal framework for Alzheimer's classification using MRI and graph-embedded demographics guided by adaptive attention gating.", "authors": "Hussain SS, Degang X, Shah PM et al.", "year": "2025", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "AlzFormer, Alzheimer disease, MRIs, Transformer", "chunk": "Alzheimer's disease (AD) is the most common neurodegenerative progressive disorder and the fifth-leading cause of death in older people. The detection of AD is a very challenging task for clinicians and radiologists due to the complex nature of this disease, thus requiring automatic data-driven machine-learning models to enhance diagnostic accuracy and support expert decision-making. However, machine learning models are hindered by three key limitations, in AD classification:(i) diffuse and subtle structural changes in the brain that make it difficult to capture global pathology (ii) non-uniform alterations across MRI planes, which limit single-view learning and (iii) the lack of deep integration of demographic context, which is often ignored despite its clinical importance. To address these challenges in this paper, we propose a novel multi-modal deep learning framework, named AlzFormer, that dynamically integrates 3D MRI with demographic features represented as knowledge graph embeddings for AD classification. Specifically, (i) to capture global and", "source": "PubMed"}, {"chunk_id": "40850187_1", "pmid": "40850187", "title": "AlzFormer: Multi-modal framework for Alzheimer's classification using MRI and graph-embedded demographics guided by adaptive attention gating.", "authors": "Hussain SS, Degang X, Shah PM et al.", "year": "2025", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "AlzFormer, Alzheimer disease, MRIs, Transformer", "chunk": "a novel multi-modal deep learning framework, named AlzFormer, that dynamically integrates 3D MRI with demographic features represented as knowledge graph embeddings for AD classification. Specifically, (i) to capture global and volumetric features, a 3D CNN is employed; (ii) to model plane-specific information, three parallel 2D CNNs are used for tri-planar processing (axial, coronal, sagittal), combined with a Transformer encoder; and (iii) to incorporate demographic context, we integrate demographic features as knowledge graph embeddings through a novel Adaptive Attention Gating mechanism that balances contributions from both modalities (i.e., MRI and demographics). Comprehensive experiments on two real-world datasets, including generalization tests, ablation studies, and robustness evaluation under noisy conditions, demonstrate that the proposed model provides a robust and effective solution for AD diagnosis. These results suggest strong potential for integration into Clinical Decision Support Systems (CDSS), offering a more interpretable and personalized approach to early Alzheimer's detection.", "source": "PubMed"}, {"chunk_id": "40850187_2", "pmid": "40850187", "title": "AlzFormer: Multi-modal framework for Alzheimer's classification using MRI and graph-embedded demographics guided by adaptive attention gating.", "authors": "Hussain SS, Degang X, Shah PM et al.", "year": "2025", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "AlzFormer, Alzheimer disease, MRIs, Transformer", "chunk": "diagnosis. These results suggest strong potential for integration into Clinical Decision Support Systems (CDSS), offering a more interpretable and personalized approach to early Alzheimer's detection.", "source": "PubMed"}, {"chunk_id": "39008616_0", "pmid": "39008616", "title": "Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias.", "authors": "Cai H, Zhao T, Pang Y et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, ageing, complement, interleukin, longitudinal, systemic inflammation", "chunk": "Systemic inflammation with alterations in inflammatory markers is involved in ageing and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during ageing and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both ageing and the development of Alzheimer's disease. However, only complement C3, interleukin-1\u03b2 and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their", "source": "PubMed"}, {"chunk_id": "39008616_1", "pmid": "39008616", "title": "Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias.", "authors": "Cai H, Zhao T, Pang Y et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, ageing, complement, interleukin, longitudinal, systemic inflammation", "chunk": "markers significantly altered during both ageing and the development of Alzheimer's disease. However, only complement C3, interleukin-1\u03b2 and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrated specificity to Alzheimer's disease, while interleukin-1\u03b2 and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the ageing process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful ageing and in the prevention and treatment of Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41411715_0", "pmid": "41411715", "title": "SGK1 downregulation co-occurs with leukocyte oligomeric \u03b1-synuclein accumulation in Parkinson's disease.", "authors": "Veltri F, Sancesario GM, Rosina M et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "Biomarker, Neuroinflammation, PBMCs, Parkinson's disease, SGK1, \u03b1-synuclein", "chunk": "Serum and glucocorticoid-inducible kinase 1 (SGK1) is a ubiquitous kinase with cytoprotective and immune-specific functions. Parkinson's disease (PD) animal models disclosed interactions between SGK1 and the critical pathogenic pathways of the disease, whereas human-based evidence is lacking. We investigated the SGK1 contribution to the biological dynamics of PD ex vivo, at immune and systemic level. Thirty-two well-phenotyped PD patients and 34 controls were enrolled. Peripheral blood mononuclear cells (PBMCs) and serum were obtained. PBMCs levels of SGK1, \u03b1-synuclein total and oligomeric forms (\u03b1-syn<sup>tot</sup>, \u03b1-syn<sup>olig</sup>) were measured by Western blot and ELISA, respectively. SGK1 levels were tested in the serum by ELISA. Group differences were assessed using age-adjusted, rank-based linear regression models; ROC analysis was performed using age-adjusted PBMC SGK1 residuals and a Youden-derived cutpoint; associations with clinical variables were tested using age-adjusted regressions. PD PBMCs exhibited lower SGK1 (p < 0.001) and higher \u03b1-syn<sup>olig</sup> levels than controls (p = 0.026).", "source": "PubMed"}, {"chunk_id": "41411715_1", "pmid": "41411715", "title": "SGK1 downregulation co-occurs with leukocyte oligomeric \u03b1-synuclein accumulation in Parkinson's disease.", "authors": "Veltri F, Sancesario GM, Rosina M et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "Biomarker, Neuroinflammation, PBMCs, Parkinson's disease, SGK1, \u03b1-synuclein", "chunk": "and a Youden-derived cutpoint; associations with clinical variables were tested using age-adjusted regressions. PD PBMCs exhibited lower SGK1 (p < 0.001) and higher \u03b1-syn<sup>olig</sup> levels than controls (p = 0.026). SGK1 serum levels were also lower in PD patients (p = 0.040). ROC analysis showed that PBMC SGK1 significantly discriminated PD from controls (AUC = 0.85,[95 % CI 0.75-0.95],p < 0.001). The optimal cutpoint yielded a sensitivity of 1.00 and a specificity of 0.60. No significant correlations were found between biological and clinical parameters. In PD patients, SGK1 was downregulated in both PBMCs and serum. Given the preliminary nature of these findings and the co-occurrence of \u03b1-syn<sup>olig</sup> accumulation in leukocytes, common mechanistic pathways might be supposed, although pending confirmation. Nevertheless, SGK1 emerged as a potential target in PD, for both biomarker and therapeutic purposes.", "source": "PubMed"}, {"chunk_id": "41411715_2", "pmid": "41411715", "title": "SGK1 downregulation co-occurs with leukocyte oligomeric \u03b1-synuclein accumulation in Parkinson's disease.", "authors": "Veltri F, Sancesario GM, Rosina M et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "Biomarker, Neuroinflammation, PBMCs, Parkinson's disease, SGK1, \u03b1-synuclein", "chunk": "SGK1 emerged as a potential target in PD, for both biomarker and therapeutic purposes.", "source": "PubMed"}, {"chunk_id": "36764305_0", "pmid": "36764305", "title": "Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration.", "authors": "Kelty TJ, Dashek RJ, Arnold WD et al.", "year": "2023", "journal": "Seminars in liver disease", "keywords": "None", "chunk": "The association between liver and brain health has gained attention as biomarkers of liver function have been revealed to predict neurodegeneration. The liver is a central regulator in metabolic homeostasis. However, in nonalcoholic fatty liver disease (NAFLD), homeostasis is disrupted which can result in extrahepatic organ pathologies. Emerging literature provides insight into the mechanisms behind the liver-brain health axis. These include the increased production of liver-derived factors that promote insulin resistance and loss of neuroprotective factors under conditions of NAFLD that increase insulin resistance in the central nervous system. In addition, elevated proinflammatory cytokines linked to NAFLD negatively impact the blood-brain barrier and increase neuroinflammation. Furthermore, exacerbated dyslipidemia associated with NAFLD and hepatic dysfunction can promote altered brain bioenergetics and oxidative stress. In this review, we summarize the current knowledge of the crosstalk between liver and brain as it relates to the pathophysiology between NAFLD and neurodegeneration, with an emphasis", "source": "PubMed"}, {"chunk_id": "36764305_1", "pmid": "36764305", "title": "Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration.", "authors": "Kelty TJ, Dashek RJ, Arnold WD et al.", "year": "2023", "journal": "Seminars in liver disease", "keywords": "None", "chunk": "oxidative stress. In this review, we summarize the current knowledge of the crosstalk between liver and brain as it relates to the pathophysiology between NAFLD and neurodegeneration, with an emphasis on Alzheimer's disease. We also highlight knowledge gaps and future areas for investigation to strengthen the potential link between NAFLD and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "35992936_0", "pmid": "35992936", "title": "Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer's disease: Current trends and future perspectives.", "authors": "La Barbera L, Mauri E, D'Amelio M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, blood-brain barrier, drug delivery, nanomedicine, nanotheranostics, neurodegeneration, polymeric nanoparticles", "chunk": "Alzheimer's disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including", "source": "PubMed"}, {"chunk_id": "35992936_1", "pmid": "35992936", "title": "Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer's disease: Current trends and future perspectives.", "authors": "La Barbera L, Mauri E, D'Amelio M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, blood-brain barrier, drug delivery, nanomedicine, nanotheranostics, neurodegeneration, polymeric nanoparticles", "chunk": "has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the blood-brain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications", "source": "PubMed"}, {"chunk_id": "35992936_2", "pmid": "35992936", "title": "Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer's disease: Current trends and future perspectives.", "authors": "La Barbera L, Mauri E, D'Amelio M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, blood-brain barrier, drug delivery, nanomedicine, nanotheranostics, neurodegeneration, polymeric nanoparticles", "chunk": "treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease.", "source": "PubMed"}, {"chunk_id": "38578117_0", "pmid": "38578117", "title": "Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.", "authors": "Garcia-Cordero I, Anastassiadis C, Khoja A et al.", "year": "2024", "journal": "Annals of neurology", "keywords": "None", "chunk": "To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups. Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance", "source": "PubMed"}, {"chunk_id": "38578117_1", "pmid": "38578117", "title": "Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.", "authors": "Garcia-Cordero I, Anastassiadis C, Khoja A et al.", "year": "2024", "journal": "Annals of neurology", "keywords": "None", "chunk": "gray matter volume and functional networks connectivity were compared across groups. Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD. AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109.", "source": "PubMed"}, {"chunk_id": "38578117_2", "pmid": "38578117", "title": "Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.", "authors": "Garcia-Cordero I, Anastassiadis C, Khoja A et al.", "year": "2024", "journal": "Annals of neurology", "keywords": "None", "chunk": "with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109.", "source": "PubMed"}, {"chunk_id": "37357282_0", "pmid": "37357282", "title": "Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force.", "authors": "Angioni D, Hansson O, Bateman RJ et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid, monitoring, randomized clinical trials, screening, tau", "chunk": "In randomized clinical trials (RCTs) for Alzheimer's Disease (AD), cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are currently used for the detection and monitoring of AD pathological features. The use of less resource-intensive plasma biomarkers could decrease the burden to study volunteers and limit costs and time for study enrollment. Blood-based markers (BBMs) could thus play an important role in improving the design and the conduct of RCTs on AD. It remains to be determined if the data available on BBMs are strong enough to replace CSF and PET biomarkers as entry criteria and monitoring tools in RCTs.", "source": "PubMed"}, {"chunk_id": "40654235_0", "pmid": "40654235", "title": "Differential effects of a multidomain intervention on cognitive decline in older adults with type 2 diabetes according to white matter hyperintensity status: A secondary analysis of the J-MIND-Diabetes.", "authors": "Sugimoto T, Omura T, Araki A et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "cerebral small\u2010vessel disease, cognitive decline, diet, exercise, multidomain intervention, social participation, type 2 diabetes, white matter hyperintensity", "chunk": "White matter hyperintensities (WMHs) are commonly observed in older adults with type 2 diabetes. The current study aimed to investigate whether WMH modifies the effects of multidomain intervention in preventing cognitive decline among older adults with type 2 diabetes and mild cognitive impairment. This secondary analysis of the Japan-Multidomain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes included 154 participants aged 70-85 years who presented with type 2 diabetes and mild cognitive impairment. They were randomized into the intervention (vascular risk management, exercise, nutritional counselling and promotion of social activities) and control (provision of health-related information) groups. The primary outcome was a change in average Z-scores from all of the neuropsychological tests combined, and secondary outcomes were domain-specific composite scores (memory, executive function and processing speed) from baseline to 18 months. The presence of WMH was assessed using the Fazekas scale. The associations between the intervention and", "source": "PubMed"}, {"chunk_id": "40654235_1", "pmid": "40654235", "title": "Differential effects of a multidomain intervention on cognitive decline in older adults with type 2 diabetes according to white matter hyperintensity status: A secondary analysis of the J-MIND-Diabetes.", "authors": "Sugimoto T, Omura T, Araki A et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "cerebral small\u2010vessel disease, cognitive decline, diet, exercise, multidomain intervention, social participation, type 2 diabetes, white matter hyperintensity", "chunk": "domain-specific composite scores (memory, executive function and processing speed) from baseline to 18 months. The presence of WMH was assessed using the Fazekas scale. The associations between the intervention and baseline WMH were evaluated using a mixed-effects model for repeated measures. Among 90 participants included in the analyses, 34 had moderate to severe WMH. At the 18-month follow-up, a significant intervention-WMH interaction (p = 0.017) was found for the primary outcome. The intervention effect was significant in individuals with WMH (Z-score difference: +0.335, 95% confidence interval [CI]: +0.045 to +0.624), but not in individuals without WMH (Z-score difference: -0.121, 95% CI: -0.353 to +0.110). Older adults with type 2 diabetes and WMH may benefit from multidomain interventions. Further studies should be performed to validate this finding.", "source": "PubMed"}, {"chunk_id": "40654235_2", "pmid": "40654235", "title": "Differential effects of a multidomain intervention on cognitive decline in older adults with type 2 diabetes according to white matter hyperintensity status: A secondary analysis of the J-MIND-Diabetes.", "authors": "Sugimoto T, Omura T, Araki A et al.", "year": "2025", "journal": "Diabetes, obesity & metabolism", "keywords": "cerebral small\u2010vessel disease, cognitive decline, diet, exercise, multidomain intervention, social participation, type 2 diabetes, white matter hyperintensity", "chunk": "be performed to validate this finding.", "source": "PubMed"}, {"chunk_id": "41270820_0", "pmid": "41270820", "title": "The effect of CysLTR1 inhibition on cells of the retinal neurovascular unit in 5xFAD Alzheimer mice.", "authors": "Mayr D, Preishuber-Pfl\u00fcgl J, Koller A et al.", "year": "2026", "journal": "Experimental eye research", "keywords": "(1\u20137), 5xFAD mouse model, Alzheimer's disease, Cysteinyl leukotriene receptor 1 (CysLTR1), Microglial cells, Montelukast, Neurovascular unit, Pericytes", "chunk": "Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that affects both the brain and the retina. Many cerebral-associated AD pathologies, including neuroinflammation and vascular changes, have been reported to manifest in the retina. Furthermore, the neurovascular unit (NVU), composed of vascular cells, glia and neurons, regulates blood flow and neuronal metabolic activity and has been described to be dysfunctional in AD brains and retinas. As leukotrienes are modulators of both neuroinflammation and the vasculature, their receptors have been recognized as potential targets for ameliorating AD pathology. Therefore, the present study investigated the effects of the cysteinyl leukotriene receptor 1 (CysLTR1) antagonist montelukast (MTK) on retinal NVU cells in the 5xFAD mouse model of AD. Retinal analyses were performed in male and female 8-month-old 5xFAD mice and after 13-weeks of treatment with low and high doses of MTK or vehicle, and in age-matched controls. The retinal pericyte (PC) coverage was unchanged", "source": "PubMed"}, {"chunk_id": "41270820_1", "pmid": "41270820", "title": "The effect of CysLTR1 inhibition on cells of the retinal neurovascular unit in 5xFAD Alzheimer mice.", "authors": "Mayr D, Preishuber-Pfl\u00fcgl J, Koller A et al.", "year": "2026", "journal": "Experimental eye research", "keywords": "(1\u20137), 5xFAD mouse model, Alzheimer's disease, Cysteinyl leukotriene receptor 1 (CysLTR1), Microglial cells, Montelukast, Neurovascular unit, Pericytes", "chunk": "and female 8-month-old 5xFAD mice and after 13-weeks of treatment with low and high doses of MTK or vehicle, and in age-matched controls. The retinal pericyte (PC) coverage was unchanged in AD, but CysLTR1 inhibition resulted in increased PC coverage in AD mice. Furthermore, an AD-associated decrease in capillary diameter was observed, which was not affected by CysLTR1 inhibition. The number of retinal microglial cells was increased in AD, independent of treatment. In addition, the astrocyte area and retinal ganglion cell density were not affected by either AD or CysLTR1 inhibition. In conclusion, the present study revealed minor AD-associated changes in retinal NVU cells in the 5xFAD mouse model. MTK treatment increased dose-independently PC coverage, but it remains to be clarified whether this affects the vessel tightness and blood flow.", "source": "PubMed"}, {"chunk_id": "41270820_2", "pmid": "41270820", "title": "The effect of CysLTR1 inhibition on cells of the retinal neurovascular unit in 5xFAD Alzheimer mice.", "authors": "Mayr D, Preishuber-Pfl\u00fcgl J, Koller A et al.", "year": "2026", "journal": "Experimental eye research", "keywords": "(1\u20137), 5xFAD mouse model, Alzheimer's disease, Cysteinyl leukotriene receptor 1 (CysLTR1), Microglial cells, Montelukast, Neurovascular unit, Pericytes", "chunk": "clarified whether this affects the vessel tightness and blood flow.", "source": "PubMed"}, {"chunk_id": "40958704_0", "pmid": "40958704", "title": "Focused transcranial ultrasound stimulation: a breakthrough approach to treating brain disorders.", "authors": "Vanneste S, Reynolds J, De Ridder D", "year": "2025", "journal": "Expert review of medical devices", "keywords": "Focused transcranial ultrasound stimulation, blood-brain barrier applications, drug delivery, neuromodulation, thermal ablation", "chunk": "Focused transcranial ultrasound stimulation (fTUS) has emerged as a novel noninvasive technique with promising therapeutic potential for various neurological and psychiatric conditions. The aim of this review is to evaluate current research on fTUS, examining its mechanisms, therapeutic applications, challenges, and future potential in neurological and psychiatric disorders. High-intensity fTUS leads to heat-induced thermoablation, which has shown efficacy in treating essential tremor and tremor-dominant Parkinson's disease, with promising outcomes in clinical trials. fTUS has been explored for blood-brain barrier opening, facilitating drug delivery for conditions like glioblastoma and Alzheimer's disease. Low-intensity fTUS can also be used as a novel neuromodulation tool which has shown potential in alleviating chronic pain, depression, and cognitive decline. Challenges remain, including technical refinements, standardization of parameters, and optimization of therapeutic protocols. Emerging approaches like hyperthermia therapy, sonodynamic therapy, and sonothrombolysis hold promise for future applications. With ongoing research and collaboration, the next decade holds immense", "source": "PubMed"}, {"chunk_id": "40958704_1", "pmid": "40958704", "title": "Focused transcranial ultrasound stimulation: a breakthrough approach to treating brain disorders.", "authors": "Vanneste S, Reynolds J, De Ridder D", "year": "2025", "journal": "Expert review of medical devices", "keywords": "Focused transcranial ultrasound stimulation, blood-brain barrier applications, drug delivery, neuromodulation, thermal ablation", "chunk": "parameters, and optimization of therapeutic protocols. Emerging approaches like hyperthermia therapy, sonodynamic therapy, and sonothrombolysis hold promise for future applications. With ongoing research and collaboration, the next decade holds immense potential for further advancements in fTUS technology and its clinical integration.", "source": "PubMed"}, {"chunk_id": "37073873_0", "pmid": "37073873", "title": "Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.", "authors": "Radavelli-Bagatini S, Macpherson H, Scott D et al.", "year": "2023", "journal": "Journal of cachexia, sarcopenia and muscle", "keywords": "Alzheimer's disease, Cognitive function, Grip strength, Timed-up-and-go", "chunk": "Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E <sub>\u2107</sub> 4 (APOE <sub>\u2107</sub> 4) genotype. Grip strength and TUG were assessed in community-dwelling older women (mean \u00b1 SD; age 75.0 \u00b1 2.6 years) at baseline (n = 1225) and 5 years (n = 1052). Incident 14.5-year late-life dementia events (dementia-related hospitalization/death) were obtained from linked health records. Cardiovascular risk factors (Framingham Risk Score), APOE genotyping, prevalent atherosclerotic vascular disease and cardiovascular-related medications were evaluated at baseline. These were included in multivariable-adjusted Cox-proportional hazards models assessing the relationship between muscle function measures and late-life-dementia", "source": "PubMed"}, {"chunk_id": "37073873_1", "pmid": "37073873", "title": "Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.", "authors": "Radavelli-Bagatini S, Macpherson H, Scott D et al.", "year": "2023", "journal": "Journal of cachexia, sarcopenia and muscle", "keywords": "Alzheimer's disease, Cognitive function, Grip strength, Timed-up-and-go", "chunk": "APOE genotyping, prevalent atherosclerotic vascular disease and cardiovascular-related medications were evaluated at baseline. These were included in multivariable-adjusted Cox-proportional hazards models assessing the relationship between muscle function measures and late-life-dementia events. Over follow-up, 207 (16.9%) women had a late-life dementia event. Compared with women with the highest grip strength (Quartile [Q] 4, 25.8 kg), those with the lowest grip strength (Q1, 16.0 kg) had greater hazard for a late-life dementia event (HR 2.27 95% CI 1.54-3.35, P < 0.001). For TUG, the slowest women (Q4, 12.4 vs. Q1, 7.4 s) also recorded a greater hazard for a late-life dementia event (HR 2.10 95% CI 1.42-3.10, P = 002). Weak hand grip (<22 kg) or slow TUG (>10.2 s) provided independent information to the presence of an APOE <sub>\u2107</sub> 4 allele (n = 280, 22.9%). Compared with women with no weakness and no APOE <sub>\u2107</sub> 4 allele, those with weakness and", "source": "PubMed"}, {"chunk_id": "37073873_2", "pmid": "37073873", "title": "Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.", "authors": "Radavelli-Bagatini S, Macpherson H, Scott D et al.", "year": "2023", "journal": "Journal of cachexia, sarcopenia and muscle", "keywords": "Alzheimer's disease, Cognitive function, Grip strength, Timed-up-and-go", "chunk": "information to the presence of an APOE <sub>\u2107</sub> 4 allele (n = 280, 22.9%). Compared with women with no weakness and no APOE <sub>\u2107</sub> 4 allele, those with weakness and APOE <sub>\u2107</sub> 4 allele had a greater hazard (HR 3.19 95% CI 2.09-4.88, P < 0.001) for a late-life dementia event. Women presenting with slowness and the APOE <sub>\u2107</sub> 4 allele also recorded a greater hazard for a late-life dementia event (HR 2.59 95% CI 1.64-4.09, P < 0.001). For 5-year muscle function changes, compared with women with the lowest performance decrement (Q1), those with the largest decrement (Q4) had higher hazards for a late-life dementia event (grip strength HR 1.94 95% CI 1.22-3.08, P = 0.006; TUG HR 2.52 95% CI 1.59-3.98, P < 0.001) over the next 9.5 years. Weaker grip strength and slower TUG, and a greater decline over 5 years, were significant risk factors for a", "source": "PubMed"}, {"chunk_id": "37073873_3", "pmid": "37073873", "title": "Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.", "authors": "Radavelli-Bagatini S, Macpherson H, Scott D et al.", "year": "2023", "journal": "Journal of cachexia, sarcopenia and muscle", "keywords": "Alzheimer's disease, Cognitive function, Grip strength, Timed-up-and-go", "chunk": "95% CI 1.59-3.98, P < 0.001) over the next 9.5 years. Weaker grip strength and slower TUG, and a greater decline over 5 years, were significant risk factors for a late-life-dementia event in community-dwelling older women, independent of lifestyle and genetic risk factors. Incorporating muscle function measures as part of dementia screening appears useful to identify high-risk individuals who might benefit from primary prevention programmes.", "source": "PubMed"}, {"chunk_id": "40911721_0", "pmid": "40911721", "title": "Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer's disease continuum.", "authors": "Lee SY, Diaz VE, Emanuel OM et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "ATN, Alzheimer's disease, GFAP, astrocyte reactivity, cognition, glial fibrillary acidic protein, inflammation, neurodegeneration, neuroinflammation, neuropathology, plasma GFAP, plasma biomarkers", "chunk": "Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer's pathology at early disease stages. GFAP moderation of Alzheimer's disease (AD)-related neurodegeneration and cognition is unclear. We examined plasma GFAP moderation of AD biomarkers (amyloid beta [A\u03b2]-positron emission tomography [PET][A]; plasma phosphorylated tau-181 [p-tau181][T<sub>1</sub>]), neurodegeneration (plasma NfL[N<sub>plasma</sub>]; structural magnetic resonance imaging [MRI][N<sub>MRI</sub>]), and cognition (Cog<sub>memory</sub>; Cog<sub>executive</sub>) in two cohorts: University of California San Francisco (UCSF) (N = 212, 91.0% non-Hispanic/Latino White [NHLW], age = 74.7 [7.6] years, 75.9% cognitively unimpaired [CU]) and 1Florida Alzheimer's Disease Research Centers (1FLADRC; N = 582, 32.8% NHLW, age = 70.7 [8.5] years, 28.9% CU). Plasma GFAP consistently moderated A-T<sub>1</sub> (UCSF: \u03b2 = 0.46, p = 0.012; 1FLADRC: \u03b2 = 0.12, p = 0.029). The association between elevated A\u03b2-PET and increased (p-tau) was strengthened at higher GFAP concentrations. In 1FLADRC, GFAP moderated T<sub>1</sub>-N<sub>plasma/MRI.</sub> In UCSF, GFAP moderated T<sub>1</sub>-Cog<sub>memory/executive</sub> and N<sub>MRI</sub>-Cog<sub>memory/executive</sub>. Higher GFAP consistently related to worse", "source": "PubMed"}, {"chunk_id": "40911721_1", "pmid": "40911721", "title": "Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer's disease continuum.", "authors": "Lee SY, Diaz VE, Emanuel OM et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "ATN, Alzheimer's disease, GFAP, astrocyte reactivity, cognition, glial fibrillary acidic protein, inflammation, neurodegeneration, neuroinflammation, neuropathology, plasma GFAP, plasma biomarkers", "chunk": "between elevated A\u03b2-PET and increased (p-tau) was strengthened at higher GFAP concentrations. In 1FLADRC, GFAP moderated T<sub>1</sub>-N<sub>plasma/MRI.</sub> In UCSF, GFAP moderated T<sub>1</sub>-Cog<sub>memory/executive</sub> and N<sub>MRI</sub>-Cog<sub>memory/executive</sub>. Higher GFAP consistently related to worse neurodegeneration and cognition (main effects). Across demographically and clinically heterogeneous cohorts, plasma GFAP is a key moderator of AD and may help identify individuals at greatest risk of AD-related neurodegeneration and cognitive decline. AD biomarkers were measured in two demographically and clinically distinct cohorts. Plasma GFAP moderated A\u03b2-PET to p-tau associations in both UCSF and 1FLADRC. Cohort-dependent, GFAP moderated p-tau to neurodegeneration and cognition associations. All moderations revealed strengthened disease associations with higher plasma GFAP. Plasma GFAP may help identify individuals at greatest risk of AD-related decline.", "source": "PubMed"}, {"chunk_id": "39540665_0", "pmid": "39540665", "title": "Evaluation of ComBat Harmonization for Reducing Across-Tracer Differences in Regional Amyloid PET Analyses.", "authors": "Yang B, Earnest T, Kumar S et al.", "year": "2024", "journal": "Human brain mapping", "keywords": "Centiloid, ComBat, amyloid\u2010\u03b2, harmonization, positron emission tomography", "chunk": "Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-\u03b2 uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [<sup>18</sup>F]-florbetapir (FBP) and [<sup>11</sup>C]-Pittsburgh compound-B (PiB). One hundred thirteen head-to-head FBP-PiB scan pairs, scanned from the same subject within 90 days, were selected from the Open Access Series of Imaging Studies 3 (OASIS-3) dataset. The Centiloid scale, ComBat with no covariates, ComBat with biological covariates, and GAM-ComBat with biological covariates were used to harmonize both global and regional amyloid standardized uptake value ratios (SUVR). Variants of ComBat, including longitudinal ComBat and PEACE, were also tested. Intraclass correlation coefficient (ICC) and mean absolute error (MAE) were computed to measure the absolute agreement between tracers. Additionally, longitudinal amyloid SUVRs from", "source": "PubMed"}, {"chunk_id": "39540665_1", "pmid": "39540665", "title": "Evaluation of ComBat Harmonization for Reducing Across-Tracer Differences in Regional Amyloid PET Analyses.", "authors": "Yang B, Earnest T, Kumar S et al.", "year": "2024", "journal": "Human brain mapping", "keywords": "Centiloid, ComBat, amyloid\u2010\u03b2, harmonization, positron emission tomography", "chunk": "longitudinal ComBat and PEACE, were also tested. Intraclass correlation coefficient (ICC) and mean absolute error (MAE) were computed to measure the absolute agreement between tracers. Additionally, longitudinal amyloid SUVRs from an anti-amyloid drug trial were simulated using linear mixed effects modeling. Differences in rates-of-change between simulated treatment and placebo groups were tested, and change in statistical power/Type-I error after harmonization was quantified. In the head-to-head tracer comparison, ComBat with no covariates was the best at increasing ICC and decreasing MAE of both global summary and regional amyloid PET SUVRs between scan pairs of the same group of subjects. In the clinical trial simulation, harmonization with both Centiloid and ComBat increased statistical power of detecting true rate-of-change differences between groups and decreased false discovery rate in the absence of a treatment effect. The greatest benefit of harmonization was observed when groups exhibited differing FBP-to-PiB proportions. ComBat outperformed the Centiloid scale in", "source": "PubMed"}, {"chunk_id": "39540665_2", "pmid": "39540665", "title": "Evaluation of ComBat Harmonization for Reducing Across-Tracer Differences in Regional Amyloid PET Analyses.", "authors": "Yang B, Earnest T, Kumar S et al.", "year": "2024", "journal": "Human brain mapping", "keywords": "Centiloid, ComBat, amyloid\u2010\u03b2, harmonization, positron emission tomography", "chunk": "decreased false discovery rate in the absence of a treatment effect. The greatest benefit of harmonization was observed when groups exhibited differing FBP-to-PiB proportions. ComBat outperformed the Centiloid scale in harmonizing both global and regional amyloid estimates. Additionally, ComBat improved the detection of rate-of-change differences between clinical trial groups. Our findings suggest that ComBat is a viable alternative to Centiloid for harmonizing regional amyloid PET analyses.", "source": "PubMed"}, {"chunk_id": "34839208_0", "pmid": "34839208", "title": "Structural brain network correlations with amyloid burden in elderly individuals at risk of Alzheimer's disease.", "authors": "Ota M, Numata Y, Kitabatake A et al.", "year": "2022", "journal": "Psychiatry research. Neuroimaging", "keywords": "Alzheimer's disease, Beta-amyloid, Betweenness centrality, Clustering coefficient, Degree, Small world properties", "chunk": "Alzheimer's disease (AD) has a long preclinical phase during which beta-amyloid accumulates in the brain without cognitive impairment. However, the pattern of brain network alterations in this early stage of the disease remains to be clarified. In this study we examined the relationships between regional brain network indices and beta-amyloid deposits. Twenty-four elderly subjects with the APOE4 allele underwent both a 1.5-Tesla magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan using [<sup>18</sup>F]Florbetapir. We computed network metrics such as the degree, betweenness centrality, and clustering coefficient, and examined the relationships between the beta-amyloid accumulation and these regional brain network connectivity metrics. We found a significant positive correlation between the global standardized uptake value ratio (SUVR) of [<sup>18</sup>F]Florbetapir and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our", "source": "PubMed"}, {"chunk_id": "34839208_1", "pmid": "34839208", "title": "Structural brain network correlations with amyloid burden in elderly individuals at risk of Alzheimer's disease.", "authors": "Ota M, Numata Y, Kitabatake A et al.", "year": "2022", "journal": "Psychiatry research. Neuroimaging", "keywords": "Alzheimer's disease, Beta-amyloid, Betweenness centrality, Clustering coefficient, Degree, Small world properties", "chunk": "and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our data suggest a relationship between the beta-amyloid accumulation and the regional brain network connectivity in subjects at risk of AD. The brain connectome may provide an adjunct biomarker for the early detection of AD.", "source": "PubMed"}, {"chunk_id": "38501315_0", "pmid": "38501315", "title": "Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease.", "authors": "Huang SY, Zhang YR, Guo Y et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid, analysis along the perivascular space, cognitive decline, glymphatic, neurodegeneration, progression", "chunk": "Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid-positive transition and clinical progression, and faster rates of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. Glymphatic failure may precede amyloid", "source": "PubMed"}, {"chunk_id": "38501315_1", "pmid": "38501315", "title": "Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease.", "authors": "Huang SY, Zhang YR, Guo Y et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, amyloid, analysis along the perivascular space, cognitive decline, glymphatic, neurodegeneration, progression", "chunk": "of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD. The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (A\u03b2) positron emission tomography (PET) burden and A\u03b2-positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid A\u03b242 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. A\u03b2 PET and brain atrophy mediated the link of ALPS index with cognitive decline.", "source": "PubMed"}, {"chunk_id": "39460815_0", "pmid": "39460815", "title": "Tuning multispectral fluorescence quantum dot-based identification of short-length amyloid \u03b2 peptides by applying Cu(II) ions.", "authors": "G\u0142owacz K, Tokarska W, Olechowska A et al.", "year": "2024", "journal": "Mikrochimica acta", "keywords": "Amyloid \u03b2, Chemical tongue, Competitive assay, Multispectral fluorescence, PLS-DA, Quantum dots", "chunk": "Currently available methods for detecting amyloid \u03b2 (A\u03b2) derivatives are mainly dedicated to determining the long forms A\u03b2<sub>1-42</sub> and A\u03b2<sub>1-40</sub>. At the same time, the number of physiologically occurring A\u03b2 analogs is much higher, including those truncated at the N- and C-termini. Their identification using standard methods is challenging due to the structural similarity of various A\u03b2 analogs, but could highly benefit from both biomarkers discovery and pathophysiological studies of Alzheimer's disease. Therefore a \"chemical tongue\" sensing strategy was employed for the detection of seven A\u03b2 peptide derivatives: A\u03b2<sub>1-16</sub>, A\u03b2<sub>4-16</sub>, A\u03b2<sub>4-9</sub>, A\u03b2<sub>5-16</sub>, A\u03b2<sub>5-12</sub>, A\u03b2<sub>5-9</sub>, A\u03b2<sub>12-16</sub>. The proposed sensing system is based on competitive interactions between quantum dots, Cu(II) ions, and A\u03b2 peptides, providing unique fluorescence fingerprints useful for the identification of analytes. After carefully evaluating the A\u03b2 sample preparation protocol, perfect determination of all studied A\u03b2 peptides was achieved using partial least square-discriminant analysis (PLS-DA). The developed PLS-DA models are", "source": "PubMed"}, {"chunk_id": "39460815_1", "pmid": "39460815", "title": "Tuning multispectral fluorescence quantum dot-based identification of short-length amyloid \u03b2 peptides by applying Cu(II) ions.", "authors": "G\u0142owacz K, Tokarska W, Olechowska A et al.", "year": "2024", "journal": "Mikrochimica acta", "keywords": "Amyloid \u03b2, Chemical tongue, Competitive assay, Multispectral fluorescence, PLS-DA, Quantum dots", "chunk": "of analytes. After carefully evaluating the A\u03b2 sample preparation protocol, perfect determination of all studied A\u03b2 peptides was achieved using partial least square-discriminant analysis (PLS-DA). The developed PLS-DA models are characterized by excellent accuracy, sensitivity, precision, and specificity of analyte determination, emphasizing the potential of the proposed sensing strategy.", "source": "PubMed"}, {"chunk_id": "41454064_0", "pmid": "41454064", "title": "Impaired glymphatic function is associated with synaptic loss in cognitive impairment.", "authors": "He K, Wang J, Wu J et al.", "year": "2026", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Diffusion tensor imaging, Glial fibrillary acidic protein, Synaptic vesicle glycoprotein 2A", "chunk": "To investigate the correlation between glymphatic impairment and synaptic loss and to explore whether this relationship is affected by amyloid-\u03b2 (A\u03b2) pathology or reactive astrocytes in individuals spanning the Alzheimer's disease-related pathological spectrum. We investigated the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as a biomarker of the glymphatic system. A total of 182 participants underwent synaptic vesicle glycoprotein 2 A (SV2A) PET/MRI and amyloid-\u03b2 (A\u03b2) PET/CT imaging, with SV2A serving as a biomarker of synaptic density. Additionally, plasma A\u03b242/40 ratios were measured in 139 participants, and glial fibrillary acidic protein (GFAP) levels were assessed in 143 participants. Controlling for age, sex, years of education, and cognitive status, we investigated the relationships between glymphatic system impairment and synaptic density, along with other biomarkers. Mediation analyses were conducted using the SPSS PROCESS macro (version 3.3) to examine whether synaptic density mediates the relationship between the ALPS index and", "source": "PubMed"}, {"chunk_id": "41454064_1", "pmid": "41454064", "title": "Impaired glymphatic function is associated with synaptic loss in cognitive impairment.", "authors": "He K, Wang J, Wu J et al.", "year": "2026", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Diffusion tensor imaging, Glial fibrillary acidic protein, Synaptic vesicle glycoprotein 2A", "chunk": "synaptic density, along with other biomarkers. Mediation analyses were conducted using the SPSS PROCESS macro (version 3.3) to examine whether synaptic density mediates the relationship between the ALPS index and cognitive performance. A lower ALPS index, indicating greater glymphatic impairment, was significantly associated with reduced synaptic density. The ALPS index was also significantly positively associated with the residual SV2A PET standardized uptake value ratio (SUVr) in the hippocampus of participants with A\u03b2 deposition or greater plasma GFAP concentrations. The correlation between hippocampal synaptic loss and cerebral A\u03b2 was stronger in participants with a lower ALPS index. In addition, the hippocampal synaptic density fully mediated the association between ALPS index and global cognition. Glymphatic system impairment is significantly correlated with synaptic density loss. GFAP levels and cerebral A\u03b2 plaques may strengthened this association. These findings suggest a potential link between glymphatic dysfunction and synaptic degeneration in AD, which may have implications", "source": "PubMed"}, {"chunk_id": "41454064_2", "pmid": "41454064", "title": "Impaired glymphatic function is associated with synaptic loss in cognitive impairment.", "authors": "He K, Wang J, Wu J et al.", "year": "2026", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Diffusion tensor imaging, Glial fibrillary acidic protein, Synaptic vesicle glycoprotein 2A", "chunk": "density loss. GFAP levels and cerebral A\u03b2 plaques may strengthened this association. These findings suggest a potential link between glymphatic dysfunction and synaptic degeneration in AD, which may have implications for understanding disease mechanisms and therapeutic monitoring.", "source": "PubMed"}, {"chunk_id": "38623196_0", "pmid": "38623196", "title": "Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease.", "authors": "Han Z, Yang X, Huang S", "year": "2024", "journal": "Heliyon", "keywords": "Alzheimer's disease, Disease progression, Mechanisms, Risk factor, Sleep deprivation, Tau protein, \u03b2-amyloid", "chunk": "Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting in insufficient sleep. It is often caused by sleep disorders, work demands (e.g., night shifts), and study pressure. Sleep deprivation promotes A\u03b2 deposition and tau hyperphosphorylation, which is a risk factor for the pathogenesis and progression of Alzheimer's disease (AD). Recent research has demonstrated the potential involvement of sleep deprivation in both the pathogenesis and progression of AD through glial cell activation, the glial lymphatic system, orexin system, circadian rhythm system, inflammation, and the gut microbiota. Thus, investigating the molecular mechanisms underlying the association between sleep deprivation and AD is crucial, which may contribute to the development of preventive and therapeutic strategies for AD. This review aims to analyze the impact of sleep deprivation on AD, exploring the underlying pathological mechanisms that link sleep deprivation to the initiation and progression of AD, which offers a theoretical foundation", "source": "PubMed"}, {"chunk_id": "38623196_1", "pmid": "38623196", "title": "Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease.", "authors": "Han Z, Yang X, Huang S", "year": "2024", "journal": "Heliyon", "keywords": "Alzheimer's disease, Disease progression, Mechanisms, Risk factor, Sleep deprivation, Tau protein, \u03b2-amyloid", "chunk": "to analyze the impact of sleep deprivation on AD, exploring the underlying pathological mechanisms that link sleep deprivation to the initiation and progression of AD, which offers a theoretical foundation for the development of drugs aimed at preventing and treating AD.", "source": "PubMed"}, {"chunk_id": "30376881_0", "pmid": "30376881", "title": "Secondary prevention of Alzheimer's dementia: neuroimaging contributions.", "authors": "Ten Kate M, Ingala S, Schwarz AJ et al.", "year": "2018", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Clinical trials, Neuroimaging, Secondary prevention", "chunk": "In Alzheimer's disease (AD), pathological changes may arise up to 20 years before the onset of dementia. This pre-dementia window provides a unique opportunity for secondary prevention. However, exposing non-demented subjects to putative therapies requires reliable biomarkers for subject selection, stratification, and monitoring of treatment. Neuroimaging allows the detection of early pathological changes, and longitudinal imaging can assess the effect of interventions on markers of molecular pathology and rates of neurodegeneration. This is of particular importance in pre-dementia AD trials, where clinical outcomes have a limited ability to detect treatment effects within the typical time frame of a clinical trial. We review available evidence for the use of neuroimaging in clinical trials in pre-dementia AD. We appraise currently available imaging markers for subject selection, stratification, outcome measures, and safety in the context of such populations. Amyloid positron emission tomography (PET) is a validated in-vivo marker of fibrillar amyloid plaques. It", "source": "PubMed"}, {"chunk_id": "30376881_1", "pmid": "30376881", "title": "Secondary prevention of Alzheimer's dementia: neuroimaging contributions.", "authors": "Ten Kate M, Ingala S, Schwarz AJ et al.", "year": "2018", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Clinical trials, Neuroimaging, Secondary prevention", "chunk": "markers for subject selection, stratification, outcome measures, and safety in the context of such populations. Amyloid positron emission tomography (PET) is a validated in-vivo marker of fibrillar amyloid plaques. It is appropriate for inclusion in trials targeting the amyloid pathway, as well as to monitor treatment target engagement. Amyloid PET, however, has limited ability to stage the disease and does not perform well as a prognostic marker within the time frame of a pre-dementia AD trial. Structural magnetic resonance imaging (MRI), providing markers of neurodegeneration, can improve the identification of subjects at risk of imminent decline and hence play a role in subject inclusion. Atrophy rates (either hippocampal or whole brain), which can be reliably derived from structural MRI, are useful in tracking disease progression and have the potential to serve as outcome measures. MRI can also be used to assess comorbid vascular pathology and define homogeneous groups for inclusion", "source": "PubMed"}, {"chunk_id": "30376881_2", "pmid": "30376881", "title": "Secondary prevention of Alzheimer's dementia: neuroimaging contributions.", "authors": "Ten Kate M, Ingala S, Schwarz AJ et al.", "year": "2018", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Clinical trials, Neuroimaging, Secondary prevention", "chunk": "useful in tracking disease progression and have the potential to serve as outcome measures. MRI can also be used to assess comorbid vascular pathology and define homogeneous groups for inclusion or for subject stratification. Finally, MRI also plays an important role in trial safety monitoring, particularly the identification of amyloid-related imaging abnormalities (ARIA). Tau PET to measure neurofibrillary tangle burden is currently under development. Evidence to support the use of advanced MRI markers such as resting-state functional MRI, arterial spin labelling, and diffusion tensor imaging in pre-dementia AD is preliminary and requires further validation. We propose a strategy for longitudinal imaging to track early signs of AD including quantitative amyloid PET and yearly multiparametric MRI.", "source": "PubMed"}, {"chunk_id": "19362884_0", "pmid": "19362884", "title": "Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study.", "authors": "Knopman DS, Mosley TH, Catellier DJ et al.", "year": "2009", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "None", "chunk": "Strokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited. We describe the relationships of APOE genotype, stroke, and vascular risk factors with cognitive change over a 14-year follow-up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age. Participants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990-1992 and 2004-2006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990-1992. Incident stroke was recorded over the 14 years of follow-up. There were 1130 participants (mean age, 59 +/- 4.3 [SD] years; 62% women; 52% African-American) with longitudinal", "source": "PubMed"}, {"chunk_id": "19362884_1", "pmid": "19362884", "title": "Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study.", "authors": "Knopman DS, Mosley TH, Catellier DJ et al.", "year": "2009", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "None", "chunk": "visit in 1990-1992. Incident stroke was recorded over the 14 years of follow-up. There were 1130 participants (mean age, 59 +/- 4.3 [SD] years; 62% women; 52% African-American) with longitudinal data. In multivariate, random-effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE epsilon4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not. For DWR, stroke and APOE epsilon4 genotype were independent predictors of decline (both P < .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all P < .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found. The vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE epsilon4 genotype independently contribute to cognitive decline in", "source": "PubMed"}, {"chunk_id": "19362884_2", "pmid": "19362884", "title": "Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study.", "authors": "Knopman DS, Mosley TH, Catellier DJ et al.", "year": "2009", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "None", "chunk": "gender, or interactions between risk factors was found. The vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE epsilon4 genotype independently contribute to cognitive decline in late middle age and early elderly years.", "source": "PubMed"}, {"chunk_id": "37357285_0", "pmid": "37357285", "title": "Outreach, Screening, and Randomization of APOE \u03b54 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program.", "authors": "Walsh T, Duff L, Riviere ME et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "APOE, Alzheimer\u2019s disease, participant outreach, participant recruitment, participant screening, prevention trial, registries", "chunk": "Alzheimer's disease (AD) prevention trials require a large outreach and screening funnel to identify cognitively unimpaired adults who meet the study's inclusion criteria, such as certain clinical or demographic criteria, genetic risk factors, and/or biomarker evidence of the disease. Describe tactics and strategies to identify and enroll cognitively unimpaired adults with one (heterozygotes [HT]) or two (homozygotes [HM]) copies of the APOE \u03b54 allele, a genetic risk factor for dementia due to AD, into the Alzheimer's Prevention Initiative (API) Generation Program, the largest and only prevention trials for late onset AD using this enrichment technique. The Generation Program was comprised of two global, randomized, double-blind, placebo-controlled, parallel group adaptive design with variable treatment duration clinical trials. Generation Study 1 randomized participants into one of two cohorts: Cohort 1 which evaluated CAD106 vs. placebo or Cohort 2 which evaluated umibecestat vs placebo. Generation Study 2 randomized participants into two doses of", "source": "PubMed"}, {"chunk_id": "37357285_1", "pmid": "37357285", "title": "Outreach, Screening, and Randomization of APOE \u03b54 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program.", "authors": "Walsh T, Duff L, Riviere ME et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "APOE, Alzheimer\u2019s disease, participant outreach, participant recruitment, participant screening, prevention trial, registries", "chunk": "participants into one of two cohorts: Cohort 1 which evaluated CAD106 vs. placebo or Cohort 2 which evaluated umibecestat vs placebo. Generation Study 2 randomized participants into two doses of umibecestat vs. placebo. The Generation Program was terminated early in 2019, while enrollment was still occurring. Both Generation Study 1 and Generation Study 2 enrolled cognitively unimpaired APOE \u03b54 HMs aged 60-75; Generation Study 2 also enrolled APOE \u03b54 HTs ages 60-75 with elevated brain amyloid. Describe results of the centralized and localized outreach, recruitment, screening strategies and tactics as well as characteristics of sites successful at enrolling genetically eligible participants, with a particular focus on APOE \u03b54 HMs given the 2-3% prevalence of this genotype. At the time the trial program was terminated, 35,333 individuals had consented to the optional prescreening ICF1a/ICFA and provided a sample of DNA for APOE genotyping, 1,138 APOE \u03b54 HMs consented to screening for", "source": "PubMed"}, {"chunk_id": "37357285_2", "pmid": "37357285", "title": "Outreach, Screening, and Randomization of APOE \u03b54 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program.", "authors": "Walsh T, Duff L, Riviere ME et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "APOE, Alzheimer\u2019s disease, participant outreach, participant recruitment, participant screening, prevention trial, registries", "chunk": "trial program was terminated, 35,333 individuals had consented to the optional prescreening ICF1a/ICFA and provided a sample of DNA for APOE genotyping, 1,138 APOE \u03b54 HMs consented to screening for Generation Study 1 (ICF1b), and 1,626 APOE \u03b54 carriers were randomized into either Generation Study 1 or Generation Study 2. Genetic testing registries, partnerships with genetic testing/counseling companies, and the optional prescreening ICF1a/ICFA were the most successful strategies for identifying genetically eligible participants for screening. It is feasible to recruit, screen and randomize cognitively unimpaired APOE \u03b54 carriers, particularly APOE \u03b54 HMs for a global AD prevention trial. The Generation Program was on track to complete enrollment by end of 2019. Factors that were key to this success included: working with sites to develop customizable outreach, recruitment, and screening programs specific to their site needs, providing forums for sites to exchange best practices, and developing partnerships between the sponsor team", "source": "PubMed"}, {"chunk_id": "37357285_3", "pmid": "37357285", "title": "Outreach, Screening, and Randomization of APOE \u03b54 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program.", "authors": "Walsh T, Duff L, Riviere ME et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "APOE, Alzheimer\u2019s disease, participant outreach, participant recruitment, participant screening, prevention trial, registries", "chunk": "with sites to develop customizable outreach, recruitment, and screening programs specific to their site needs, providing forums for sites to exchange best practices, and developing partnerships between the sponsor team and trial sites.", "source": "PubMed"}, {"chunk_id": "40955506_0", "pmid": "40955506", "title": "Revised Diagnostic Criteria for Vascular Cognitive Impairment and Dementia-The VasCog-2-WSO Criteria.", "authors": " , Sachdev PS, Bentvelzen AC et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "Several sets of diagnostic criteria have been proposed for vascular cognitive impairment and dementia (VCID). The International Society for Vascular Behavioural and Cognitive Disorders (VasCog) working group published comprehensive operationalized criteria in 2014. Considering subsequent advances in the field, a revision was needed. To update the VasCog criteria to achieve consensus on diagnosis of VCID. VasCog criteria and other published diagnostic guidelines, aided by literature review of recent developments in VCID, were used as reference points for an online Delphi survey (minimum 3 rounds, \u226575% threshold for agreement), including operationalization of criteria and guidance on potential biomarkers. Seventy international experts from diverse international regions were invited to participate in 2023. Three survey rounds included 49 to 54 participants that agreed on VasCog-2 diagnostic criteria for preclinical, mild, and major dementia levels of vascular cognitive impairment (under the overarching term VCID). Research guidelines, including the use of novel neuroimaging and fluid", "source": "PubMed"}, {"chunk_id": "40955506_1", "pmid": "40955506", "title": "Revised Diagnostic Criteria for Vascular Cognitive Impairment and Dementia-The VasCog-2-WSO Criteria.", "authors": " , Sachdev PS, Bentvelzen AC et al.", "year": "2025", "journal": "JAMA neurology", "keywords": "None", "chunk": "on VasCog-2 diagnostic criteria for preclinical, mild, and major dementia levels of vascular cognitive impairment (under the overarching term VCID). Research guidelines, including the use of novel neuroimaging and fluid biomarkers, were also agreed on. The World Stroke Organization (WSO) endorsed the criteria, hence named VasCog-2-WSO. The VasCog-2-WSO criteria update the VasCog criteria for the diagnosis of VCID, providing operationalization and additional guidance on potential neuroimaging and fluid biomarkers. VasCog-2-WSO should provide an international standard for VCID diagnosis, facilitating diagnostic consistency among clinicians and researchers.", "source": "PubMed"}, {"chunk_id": "38806521_0", "pmid": "38806521", "title": "Predictive value for cerebrospinal fluid Alzheimer's disease profile of different measures of verbal episodic memory in patients with MCI.", "authors": "Salvadori N, Torrigiani EG, Paoletti FP et al.", "year": "2024", "journal": "Scientific reports", "keywords": "A/T/(N) classification, Alzheimer\u2019s disease, CSF biomarkers, Mild Cognitive Impairment, Verbal episodic memory", "chunk": "Neuropsychological evidence of memory impairment represents the main feature of the clinical onset of typical Alzheimer's disease (AD). Rey's Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) are two tests both assessing verbal episodic memory, widely used in clinical practice. Our aim was to investigate the added value of their combined use in predicting cerebrospinal fluid (CSF) AD biomarkers positivity in a retrospective consecutive series of patients with mild cognitive impairment (MCI). 169 MCI patients were included. For all of them neuropsychological assessment and CSF analysis were available. According to CSF A/T/(N) profile, 109 were defined as MCI due to AD (A+T+), and 60 were non-AD MCI (A-T-). Logistic regression model and receiver-operating characteristic (ROC) curves were analyzed to evaluate the discriminatory power of single and combined sub-measures between AD and non-AD patients. The combination of RAVLT-del with LM could acceptably discriminate the two groups (AUC: 0.69, CI 95%", "source": "PubMed"}, {"chunk_id": "38806521_1", "pmid": "38806521", "title": "Predictive value for cerebrospinal fluid Alzheimer's disease profile of different measures of verbal episodic memory in patients with MCI.", "authors": "Salvadori N, Torrigiani EG, Paoletti FP et al.", "year": "2024", "journal": "Scientific reports", "keywords": "A/T/(N) classification, Alzheimer\u2019s disease, CSF biomarkers, Mild Cognitive Impairment, Verbal episodic memory", "chunk": "evaluate the discriminatory power of single and combined sub-measures between AD and non-AD patients. The combination of RAVLT-del with LM could acceptably discriminate the two groups (AUC: 0.69, CI 95% 0.617-0.761, sens: 0.75, spec. 0.58, p < 0.001), while the single tests did not show sufficient discriminative performance. Our study shows that the combination of RAVLT delayed recall with LM better predicts the biological AD diagnosis (A+T+), showing a good discriminative power between MCI-AD from non-AD MCI. Since RAVLT and LM assess different components of verbal episodic memory, they should be considered as complementary, rather than interchangeable, tests.", "source": "PubMed"}, {"chunk_id": "41226793_0", "pmid": "41226793", "title": "ABC Transporters, APOE, CYP46A1, and LRP1 Gene Polymorphisms as Markers of Dementia Development in Patients with Hyperlipidemia.", "authors": "Machowska M, Leszek J, R\u0105czy-Krzemianowska M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "ABCA1, ABCB1, APOE, CYP46A1, LRP, dementia, hyperlipidemia, markers, polymorphism", "chunk": "In an aging society, solving problems associated with the diagnosis and treatment of dementia-related diseases represents a serious challenge. The aim of the study was to evaluate the possibility of applying molecular biology methods to test polymorphisms recognized in the global literature as potentially useful in assessing the risk of developing dementia in a group of patients with hyperlipidemia. A sample of 203 patients: 109 diagnosed with both dementia and hyperlipidemia, 94 with hyperlipidemia, and 101 individuals as an allele frequency control group-were genotyped. Additional data about cognitive decline and neuropsychological assessment were collected. Among all the studied polymorphisms, the frequency of the <i>ABCA1</i> rs2230806 polymorphism differed between the analyzed groups. The GG genotype (<i>p</i> = 0.0002, RR = 3.22, CI = 1.63 \u00f7 6.37) and the G allele (<i>p</i> = 0.0007, RR = 1.53, CI = 1.19 \u00f7 1.97) were more frequent in patients diagnosed with dementia, specifically in", "source": "PubMed"}, {"chunk_id": "41226793_1", "pmid": "41226793", "title": "ABC Transporters, APOE, CYP46A1, and LRP1 Gene Polymorphisms as Markers of Dementia Development in Patients with Hyperlipidemia.", "authors": "Machowska M, Leszek J, R\u0105czy-Krzemianowska M et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "ABCA1, ABCB1, APOE, CYP46A1, LRP, dementia, hyperlipidemia, markers, polymorphism", "chunk": "CI = 1.63 \u00f7 6.37) and the G allele (<i>p</i> = 0.0007, RR = 1.53, CI = 1.19 \u00f7 1.97) were more frequent in patients diagnosed with dementia, specifically in those with Alzheimer's disease. Furthermore, the GG genotype was more common in individuals with a shorter disease duration and lower scores on the Montreal Cognitive Assessment (MoCA) scale, and consequently, with greater cognitive function deficits during early stages of the diagnostic process. <i>ABCA1</i> rs2230806 genotyping is a potential marker for the early identification of dementia risk in patients with hyperlipidemia, which supports the validity of exploring options for incorporating diagnostics based on molecular biology methods.", "source": "PubMed"}, {"chunk_id": "35986297_0", "pmid": "35986297", "title": "Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial.", "authors": "Fu QH, Pei J, Zhou HG et al.", "year": "2022", "journal": "Trials", "keywords": "Acupuncture, Alzheimer\u2019s disease, Randomized controlled trial, Study protocol, Syndrome differentiation", "chunk": "There has been a rapid increase in the worldwide prevalence of Alzheimer's disease (AD). Previous studies have shown that acupuncture can improve neurological and cognitive function; however, the utility of applying acupuncture in patients with AD remains unclear. This study protocol describes a clinical trial for evaluating the efficacy and safety of acupuncture based on syndrome differentiation with donepezil hydrochloride on cognitive function in patients with AD. This multicenter randomized controlled trial commenced on February 1, 2019, at the Shanghai Longhua Hospital of TCM, Shanghai Huashan Hospital of Fudan University, and Shanghai Mental Health Center, and will conclude on June 30, 2022. The study will recruit 184 patients randomly divided into an acupuncture group or a control group at a 1:1 ratio. All participants will receive donepezil hydrochloride (5 mg/day), and those in the acupuncture group will receive acupuncture based on syndrome differentiation with donepezil for 12 weeks. The primary", "source": "PubMed"}, {"chunk_id": "35986297_1", "pmid": "35986297", "title": "Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial.", "authors": "Fu QH, Pei J, Zhou HG et al.", "year": "2022", "journal": "Trials", "keywords": "Acupuncture, Alzheimer\u2019s disease, Randomized controlled trial, Study protocol, Syndrome differentiation", "chunk": "1:1 ratio. All participants will receive donepezil hydrochloride (5 mg/day), and those in the acupuncture group will receive acupuncture based on syndrome differentiation with donepezil for 12 weeks. The primary outcome will be the post-treatment change in the Alzheimer's Disease Assessment Scale-cognition score at 12 weeks. The secondary outcomes will be the efficacy scores of the Minimum Mental State Examination, Alzheimer's Disease Cooperative Research Activity-Daily Life, and Quality of Life-Alzheimer's Disease. All assessments will be performed at baseline, after treatment (week 12), and at follow-up (weeks 24 and 36). This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of AD. The results of this study will be published in peer-reviewed journals. ClinicalTrials.gov NCT03810794 . Registered on 17 January 2019.", "source": "PubMed"}, {"chunk_id": "35986297_2", "pmid": "35986297", "title": "Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial.", "authors": "Fu QH, Pei J, Zhou HG et al.", "year": "2022", "journal": "Trials", "keywords": "Acupuncture, Alzheimer\u2019s disease, Randomized controlled trial, Study protocol, Syndrome differentiation", "chunk": "on 17 January 2019.", "source": "PubMed"}, {"chunk_id": "37722875_0", "pmid": "37722875", "title": "A circadian rhythm-restricted diet regulates autophagy to improve cognitive function and prolong lifespan.", "authors": "Hu X, Peng J, Tang W et al.", "year": "2023", "journal": "Bioscience trends", "keywords": "biological clock, intermittent fasting, metabolism, protein aggregation, quality control, sleep", "chunk": "Diet and circadian rhythms have been found to have a profound impact on health, disease, and aging. Skipping breakfast, eating late, and overeating have adverse effects on the body's metabolism and increase the risk of cardiovascular and metabolic diseases. Disturbance of circadian rhythms has been associated with increased risk of atherosclerosis, Alzheimer's disease, Parkinson's disease, and other diseases. Abnormal deposition of amyloid \u03b2 (A\u03b2) and tau proteins in the brain and impaired synaptic function are linked to cognitive dysfunction. A restrictive diet following the circadian rhythm can affect the metabolism of lipids, glucose, and amino acids such as branched chain amino acids and cysteine. These metabolic changes contribute to autophagy through molecular mechanisms such as adenosine monophosphate-activated protein kinase (AMPK), rapamycin (mTOR), D-\u03b2-hydroxybutyrate (D-BHB), and neuropeptide Y (NPY). Autophagy, in turn, promotes the removal of abnormally deposited proteins and damaged organelles and improves cognitive function, ultimately prolonging lifespan. In addition,", "source": "PubMed"}, {"chunk_id": "37722875_1", "pmid": "37722875", "title": "A circadian rhythm-restricted diet regulates autophagy to improve cognitive function and prolong lifespan.", "authors": "Hu X, Peng J, Tang W et al.", "year": "2023", "journal": "Bioscience trends", "keywords": "biological clock, intermittent fasting, metabolism, protein aggregation, quality control, sleep", "chunk": "rapamycin (mTOR), D-\u03b2-hydroxybutyrate (D-BHB), and neuropeptide Y (NPY). Autophagy, in turn, promotes the removal of abnormally deposited proteins and damaged organelles and improves cognitive function, ultimately prolonging lifespan. In addition, a diet restricted to the circadian rhythm induces increased expression of brain-derived neurotrophic factor (BDNF) in the forebrain region, regulating autophagy and increasing synaptic plasticity, thus enhancing cognitive function. Consequently, circadian rhythm-restricted diets could serve as a promising non-pharmacological treatment for preventing and improving cognitive dysfunction and prolonging lifespan.", "source": "PubMed"}, {"chunk_id": "40062731_0", "pmid": "40062731", "title": "Neuropathological links between T2DM and LOAD: systematic review and meta-analysis.", "authors": "Lemche E, Hortob\u00e1gyi T, Kiecker C et al.", "year": "2025", "journal": "Physiological reviews", "keywords": "Alzheimer\u2019s disease, biomarkers, blood-brain barrier, diabetes, encephalopathy", "chunk": "Recent decades have described parallel neuropathological mechanisms increasing the risk for developing late-onset Alzheimer's dementia (LOAD) in type 2 diabetes mellitus (T2DM); however, still little is known of the role of diabetic encephalopathy and brain atrophy in LOAD. The aim of this systematic review is to provide a comprehensive view on diabetic encephalopathy/cerebral atrophy, taking into account neuroimaging data, neuropathology, metabolic and endocrine mechanisms, amyloid formation, brain perfusion impairments, neuroimmunology, and inflammasome activation. Key switches were identified, to further meta-analyze genomic candidate loci and epigenetic modifications. For the qualitative meta-analysis of genomic bases extracted, human linkage studies were examined; for epigenetic mechanisms, data from both human and animal studies are described. For the systematic review of pathophysiological mechanisms, 1,259 publications were evaluated and 93 gene loci extracted for candidate risk linkages. Sixty-six publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight the insulin signaling", "source": "PubMed"}, {"chunk_id": "40062731_1", "pmid": "40062731", "title": "Neuropathological links between T2DM and LOAD: systematic review and meta-analysis.", "authors": "Lemche E, Hortob\u00e1gyi T, Kiecker C et al.", "year": "2025", "journal": "Physiological reviews", "keywords": "Alzheimer\u2019s disease, biomarkers, blood-brain barrier, diabetes, encephalopathy", "chunk": "were evaluated and 93 gene loci extracted for candidate risk linkages. Sixty-six publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight the insulin signaling system, vascular markers, inflammation and inflammasome pathways, amylin interactions, and glycosylation mechanisms. The protocol was registered with PROSPERO (ID: CRD42023440535).", "source": "PubMed"}, {"chunk_id": "37204119_0", "pmid": "37204119", "title": "Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.", "authors": "Li Q, Zhao Y, Guo H et al.", "year": "2023", "journal": "Autophagy", "keywords": "TREM1, hippocampus, lipid droplets, lipophagy, neuroinflammation, type 2 diabetes mellitus", "chunk": "Neuroinflammation caused by microglial activation and consequent neurological impairment are prominent features of diabetes-associated cognitive impairment (DACI). Microglial lipophagy, a significant fraction of autophagy contributing to lipid homeostasis and inflammation, had mostly been ignored in DACI. Microglial lipid droplets (LDs) accumulation is a characteristic of aging, however, little is known about the pathological role of microglial lipophagy and LDs in DACI. Therefore, we hypothesized that microglial lipophagy could be an Achilles's heel exploitable to develop effective strategies for DACI therapy. Here, starting with characterization of microglial accumulation of LDs in leptin receptor-deficient (db/db) mice and in high-fat diet and STZ (HFD/STZ) induced T2DM mice, as well as in high-glucose (HG)-treated mice BV2, human HMC3 and primary mice microglia, we revealed that HG-dampened lipophagy was responsible for LDs accumulation in microglia. Mechanistically, accumulated LDs colocalized with the microglial specific inflammatory amplifier TREM1 (triggering receptor expressed on myeloid cells 1), resulting in", "source": "PubMed"}, {"chunk_id": "37204119_1", "pmid": "37204119", "title": "Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.", "authors": "Li Q, Zhao Y, Guo H et al.", "year": "2023", "journal": "Autophagy", "keywords": "TREM1, hippocampus, lipid droplets, lipophagy, neuroinflammation, type 2 diabetes mellitus", "chunk": "that HG-dampened lipophagy was responsible for LDs accumulation in microglia. Mechanistically, accumulated LDs colocalized with the microglial specific inflammatory amplifier TREM1 (triggering receptor expressed on myeloid cells 1), resulting in the buildup of microglial TREM1, which in turn aggravates HG-induced lipophagy damage and subsequently promoted HG-induced neuroinflammatory cascades via NLRP3 (NLR family pyrin domain containing 3) inflammasome. Moreover, pharmacological blockade of TREM1 with LP17 in db/db mice and HFD/STZ mice inhibited accumulation of LDs and TREM1, reduced hippocampal neuronal inflammatory damage, and consequently improved cognitive functions. Taken together, these findings uncover a previously unappreciated mechanism of impaired lipophagy-induced TREM1 accumulation in microglia and neuroinflammation in DACI, suggesting its translational potential as an attractive therapeutic target for delaying diabetes-associated cognitive decline.<b>Abbreviations:</b> ACTB: beta actin; AIF1/IBA1: allograft inflammatory factor 1; ALB: albumin; ARG1: arginase 1; ATG3: autophagy related 3; Baf: bafilomycin A<sub>1</sub>; BECN1: beclin 1, autophagy related; BW: body weight; CNS: central", "source": "PubMed"}, {"chunk_id": "37204119_2", "pmid": "37204119", "title": "Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.", "authors": "Li Q, Zhao Y, Guo H et al.", "year": "2023", "journal": "Autophagy", "keywords": "TREM1, hippocampus, lipid droplets, lipophagy, neuroinflammation, type 2 diabetes mellitus", "chunk": "ACTB: beta actin; AIF1/IBA1: allograft inflammatory factor 1; ALB: albumin; ARG1: arginase 1; ATG3: autophagy related 3; Baf: bafilomycin A<sub>1</sub>; BECN1: beclin 1, autophagy related; BW: body weight; CNS: central nervous system; Co-IP: co-immunoprecipitation; DACI: diabetes-associated cognitive impairment; DAPI: 4',6-diamidino-2-phenylindole; DGs: dentate gyrus; DLG4/PSD95: discs large MAGUK scaffold protein 4; DMEM: Dulbecco's modified Eagle's medium; DSST: digit symbol substitution test; EDTA: ethylenedinitrilotetraacetic acid; ELISA: enzyme linked immunosorbent assay; GFAP: glial fibrillary acidic protein; HFD: high-fat diet; HG: high glucose; IFNG/IFN-\u03b3: interferon gamma; IL1B/IL-1\u03b2: interleukin 1 beta; IL4: interleukin 4; IL6: interleukin 6; IL10: interleukin 10; LDs: lipid droplets; LPS: lipopolysaccharide; MAP2: microtubule associated protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MWM: morris water maze; NFKB/NF-\u03baB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3: NLR family pyrin domain containing 3; NOS2/iNOS: nitric oxide synthase 2, inducible; NOR: novel object recognition; OA: oleic acid;", "source": "PubMed"}, {"chunk_id": "37204119_3", "pmid": "37204119", "title": "Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.", "authors": "Li Q, Zhao Y, Guo H et al.", "year": "2023", "journal": "Autophagy", "keywords": "TREM1, hippocampus, lipid droplets, lipophagy, neuroinflammation, type 2 diabetes mellitus", "chunk": "factor of kappa light polypeptide gene enhancer in B cells; NLRP3: NLR family pyrin domain containing 3; NOS2/iNOS: nitric oxide synthase 2, inducible; NOR: novel object recognition; OA: oleic acid; PA: palmitic acid; PBS: phosphate-buffered saline; PFA: paraformaldehyde; PLIN2: perilipin 2; PLIN3: perilipin 3; PS: penicillin-streptomycin solution; RAPA: rapamycin; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; RELA/p65: RELA proto-oncogene, NF-kB subunit; ROS: reactive oxygen species; RT: room temperature; RT-qPCR: Reverse transcription quantitative real-time polymerase chain reaction; STZ: streptozotocin; SQSTM1/p62: sequestosome 1; SYK: spleen asociated tyrosine kinase; SYP: synaptophysin; T2DM: type 2 diabetes mellitus; TNF/TNF-\u03b1: tumor necrosis factor; TREM1: triggering receptor expressed on myeloid cells 1; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling.", "source": "PubMed"}, {"chunk_id": "39657969_0", "pmid": "39657969", "title": "Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.", "authors": "Wang D, Honnorat N, Toledo JB et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Lewy body dementia, MRI, deep learning, neuropathology, vascular dementia", "chunk": "Concurrent neurodegenerative and vascular pathologies pose a diagnostic challenge in the clinical setting, with histopathology remaining the definitive modality for dementia-type diagnosis. To address this clinical challenge, we introduce a neuropathology-based, data-driven, multi-label deep-learning framework to identify and quantify in vivo biomarkers for Alzheimer's disease (AD), vascular dementia (VD) and Lewy body dementia (LBD) using antemortem T1-weighted MRI scans of 423 demented and 361 control participants from National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative datasets. Based on the best-performing deep-learning model, explainable heat maps were extracted to visualize disease patterns, and the novel Deep Signature of Pathology Atrophy REcognition (DeepSPARE) indices were developed, where a higher DeepSPARE score indicates more brain alterations associated with that specific pathology. A substantial discrepancy in clinical and neuropathological diagnosis was observed in the demented patients: 71% had more than one pathology, but 67% were diagnosed clinically as AD only. Based on these", "source": "PubMed"}, {"chunk_id": "39657969_1", "pmid": "39657969", "title": "Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.", "authors": "Wang D, Honnorat N, Toledo JB et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Lewy body dementia, MRI, deep learning, neuropathology, vascular dementia", "chunk": "substantial discrepancy in clinical and neuropathological diagnosis was observed in the demented patients: 71% had more than one pathology, but 67% were diagnosed clinically as AD only. Based on these neuropathological diagnoses and leveraging cross-validation principles, the deep-learning model achieved the best performance, with a balanced accuracy of 0.844, 0.839 and 0.623 for AD, VD and LBD, respectively, and was used to generate the explainable deep-learning heat maps and DeepSPARE indices. The explainable deep-learning heat maps revealed distinct neuroimaging brain alteration patterns for each pathology: (i) the AD heat map highlighted bilateral hippocampal regions; (ii) the VD heat map emphasized white matter regions; and (iii) the LBD heat map exposed occipital alterations. The DeepSPARE indices were validated by examining their associations with cognitive testing and neuropathological and neuroimaging measures using linear mixed-effects models. The DeepSPARE-AD index was associated with Mini-Mental State Examination, the Trail Making Test B, memory, hippocampal volume,", "source": "PubMed"}, {"chunk_id": "39657969_2", "pmid": "39657969", "title": "Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.", "authors": "Wang D, Honnorat N, Toledo JB et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Lewy body dementia, MRI, deep learning, neuropathology, vascular dementia", "chunk": "associations with cognitive testing and neuropathological and neuroimaging measures using linear mixed-effects models. The DeepSPARE-AD index was associated with Mini-Mental State Examination, the Trail Making Test B, memory, hippocampal volume, Braak stages, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores and Thal phases [false-discovery rate (FDR)-adjusted P < 0.05]. The DeepSPARE-VD index was associated with white matter hyperintensity volume and cerebral amyloid angiopathy (FDR-adjusted P < 0.001), and the DeepSPARE-LBD index was associated with Lewy body stages (FDR-adjusted P < 0.05). The findings were replicated in an out-of-sample Alzheimer's Disease Neuroimaging Initiative dataset by testing associations with cognitive, imaging, plasma and CSF measures. CSF and plasma tau phosphorylated at threonine-181 (pTau181) were significantly associated with DeepSPARE-AD in the AD and mild cognitive impairment amyloid-\u03b2 positive (AD/MCI\u0391\u03b2+) group (FDR-adjusted P < 0.001), and CSF \u03b1-synuclein was associated solely with DeepSPARE-LBD (FDR-adjusted P = 0.036). Overall, these findings demonstrate the", "source": "PubMed"}, {"chunk_id": "39657969_3", "pmid": "39657969", "title": "Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.", "authors": "Wang D, Honnorat N, Toledo JB et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, Lewy body dementia, MRI, deep learning, neuropathology, vascular dementia", "chunk": "AD and mild cognitive impairment amyloid-\u03b2 positive (AD/MCI\u0391\u03b2+) group (FDR-adjusted P < 0.001), and CSF \u03b1-synuclein was associated solely with DeepSPARE-LBD (FDR-adjusted P = 0.036). Overall, these findings demonstrate the advantages of our innovative deep-learning framework in detecting antemortem neuroimaging signatures linked to different pathologies. The newly deep-learning-derived DeepSPARE indices are precise, pathology-sensitive and single-valued non-invasive neuroimaging metrics, bridging the traditional widely available in vivo T1 imaging with histopathology.", "source": "PubMed"}, {"chunk_id": "38642716_0", "pmid": "38642716", "title": "Exosome-Based Macromolecular neurotherapeutic drug delivery approaches in overcoming the Blood-Brain barrier for treating brain disorders.", "authors": "Yadav K, Vijayalakshmi R, Kumar Sahu K et al.", "year": "2024", "journal": "European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V", "keywords": "Blood\u2013brain barrier, Brain disorders, Drug delivery, Exosomes, Extracellular vesicles, Neurotherapeutic", "chunk": "Delivering drugs to the brain is a complex challenge in medical research, particularly for disorders like Alzheimer's and Parkinson's. The blood-brain barrier restricts the entry of many therapeutic molecules, hindering their effectiveness. Nanoparticles, a potential solution, face issues like toxicity and limited approvals. A new avenue explores the use of small extracellular vesicles (sEVs), i.e., exosomes, as natural carriers for drug delivery. sEVs, tiny structures below 150 nm, show promise due to their minimal immune response and ability to precisely deliver drugs. This review focuses on the potential of sEVs-based drug delivery systems for treating neurological disorders, brain cancers, and other brain-related issues. Notably, bioengineered sEVs-carrying therapeutic compounds exhibit promise in early studies. The unique features of sEVs, such as their small size and natural properties, position them as candidates to overcome challenges in drug delivery to the brain. Ongoing clinical trials and research into sEVs behavior within the body", "source": "PubMed"}, {"chunk_id": "38642716_1", "pmid": "38642716", "title": "Exosome-Based Macromolecular neurotherapeutic drug delivery approaches in overcoming the Blood-Brain barrier for treating brain disorders.", "authors": "Yadav K, Vijayalakshmi R, Kumar Sahu K et al.", "year": "2024", "journal": "European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V", "keywords": "Blood\u2013brain barrier, Brain disorders, Drug delivery, Exosomes, Extracellular vesicles, Neurotherapeutic", "chunk": "their small size and natural properties, position them as candidates to overcome challenges in drug delivery to the brain. Ongoing clinical trials and research into sEVs behavior within the body further highlight their potential for revolutionizing drug delivery and addressing complex brain conditions.", "source": "PubMed"}, {"chunk_id": "41633894_0", "pmid": "41633894", "title": "Folate receptor 1 activation suppresses high glucose-induced amyloidogenesis in neurons via STAT3/Nrf2 pathway-dependent mitigation of mitochondrial oxidative stress.", "authors": "Kim DH, Jo HY, Oh YJ et al.", "year": "2026", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Amyloid-beta, Diabetic encephalopathy, Folate receptor 1, Folic acid, Mitochondrial oxidative stress, Nrf2", "chunk": "Diabetes is a major risk factor for diabetic encephalopathy (DE), which is closely associated with sporadic Alzheimer's disease. Folic acid (FA) receptor signaling can suppress generation of neuropathogenic amyloid-beta (A\u03b2) induced by high extracellular glucose, suggesting that enhanced activation of this pathway could be a therapeutic strategy against DE-associated dementia, but the precise molecular signaling mechanisms are unclear. We report that high glucose levels increased the expression of amyloid precursor protein (APP) and \u03b2-secretase (BACE1) in cultured neurons and concomitantly induced amyloidogenesis, while FA treatment suppressed high glucose-stimulated expression of APP and BACE1, A\u03b2 release, and accumulation of mitochondrial reactive oxygen species. Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was minimal under high glucose conditions, but was significantly upregulated together with downstream antioxidant enzymes following FA co-treatment. High glucose stimulation also increased folate receptor 1 (FOLR1) mRNA expression, suggesting a compensatory protective response. While treatment with 5-methyltetrahydrofolate (5-MTHF),", "source": "PubMed"}, {"chunk_id": "41633894_1", "pmid": "41633894", "title": "Folate receptor 1 activation suppresses high glucose-induced amyloidogenesis in neurons via STAT3/Nrf2 pathway-dependent mitigation of mitochondrial oxidative stress.", "authors": "Kim DH, Jo HY, Oh YJ et al.", "year": "2026", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Amyloid-beta, Diabetic encephalopathy, Folate receptor 1, Folic acid, Mitochondrial oxidative stress, Nrf2", "chunk": "upregulated together with downstream antioxidant enzymes following FA co-treatment. High glucose stimulation also increased folate receptor 1 (FOLR1) mRNA expression, suggesting a compensatory protective response. While treatment with 5-methyltetrahydrofolate (5-MTHF), the activated form of folate, did not significantly alter high glucose-induced upregulation of APP and BACE1, knockdown of FOLR1 mRNA reduced high glucose-stimulated Nrf2 expression and further augmented APP and BACE1 expression under high glucose conditions. Treatment with the STAT3 inhibitor 5'15-DPP also abolished high glucose-stimulated Nrf2 expression and increased APP and BACE1 expression levels. These findings indicate that FA/FOLR1 activation suppresses high glucose-induced amyloidogenesis by mitigating mitochondrial oxidative stress via STAT3/Nrf2 pathway signaling. In conclusion, present study suggests that the FA/FOLR1/STAT3/Nrf2 pathway is an effective therapeutic target for DE.", "source": "PubMed"}, {"chunk_id": "39170552_0", "pmid": "39170552", "title": "Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery.", "authors": "Zeynalzadeh E, Khodadadi E, Khodadadi E et al.", "year": "2024", "journal": "Heliyon", "keywords": "Blood-brain barrier, Drug delivery, Lipid nanoparticles", "chunk": "The blood-brain interface poses formidable obstacles in addressing neurological conditions such as Alzheimer's, Multiple Sclerosis, brain cancers, and cerebrovascular accidents. Serving as a safeguard against potential threats in the blood, this barrier hinders direct drug delivery to affected cells, necessitating specialized transport mechanisms. Within the realm of nanotechnology, the creation of nanoscale carriers, including macromolecules such as polymers, lipids, and metallic nanoparticles, is gaining prominence. These carriers, tailored in diverse forms and sizes and enriched with specific functional groups for enhanced penetration and targeting, are capturing growing interest. This revised abstract explores the macromolecular dimension in understanding how nanoparticles interact with the blood-brain barrier. It re-evaluates the structure and function of the blood-brain barrier, highlighting macromolecular nanocarriers utilized in drug delivery to the brain. The discussion delves into the intricate pathways through which drugs navigate the blood-brain barrier, emphasizing the distinctive attributes of macromolecular nanocarriers. Additionally, it explores recent innovations", "source": "PubMed"}, {"chunk_id": "39170552_1", "pmid": "39170552", "title": "Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery.", "authors": "Zeynalzadeh E, Khodadadi E, Khodadadi E et al.", "year": "2024", "journal": "Heliyon", "keywords": "Blood-brain barrier, Drug delivery, Lipid nanoparticles", "chunk": "delivery to the brain. The discussion delves into the intricate pathways through which drugs navigate the blood-brain barrier, emphasizing the distinctive attributes of macromolecular nanocarriers. Additionally, it explores recent innovations in nanotechnology and unconventional approaches to drug delivery. Ultimately, the paper addresses the intricacies and considerations in developing macromolecular-based nanomedicines for the brain, aiming to advance the creation and evolution of nanomedicines for neurological ailments.", "source": "PubMed"}, {"chunk_id": "37587767_0", "pmid": "37587767", "title": "Artificial intelligence for dementia drug discovery and trials optimization.", "authors": "Doherty T, Yao Z, Khleifat AAL et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's Disease, artificial Intelligence, big data, clinical trials, dementia, drug discovery, machine learning", "chunk": "Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi-disciplinary approach can promote data-driven decision-making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation.", "source": "PubMed"}, {"chunk_id": "37587767_1", "pmid": "37587767", "title": "Artificial intelligence for dementia drug discovery and trials optimization.", "authors": "Doherty T, Yao Z, Khleifat AAL et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's Disease, artificial Intelligence, big data, clinical trials, dementia, drug discovery, machine learning", "chunk": "review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation.", "source": "PubMed"}, {"chunk_id": "39969227_0", "pmid": "39969227", "title": "Integrating Machine Learning and Environmental and Genetic Risk Factors for the Early Detection of Preclinical Alzheimer's Disease.", "authors": "Al-Hammadi N, Abouelyazid M, Brown DC et al.", "year": "2025", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Area deprivation index, Biomarkers, Naturalistic driving behavior, Predictive modeling, Resampling/bootstrapping methods", "chunk": "This study classified preclinical Alzheimer's disease (AD) using cognitive screening, neighborhood deprivation via the area deprivation index (ADI), and sociodemographic and genetic risk factors. Additionally, it compared the predictive accuracy of multiple machine learning algorithms and examined model performance with two bootstrapping procedures. Data were drawn from a longitudinal cohort that required participants to be age 65 or older, cognitively normal at baseline, and active drivers, defined as taking at least one trip a week. Naturalistic driving data were collected using a commercial datalogger. Biomarker positivity was determined via amyloid pathology using cerebrospinal fluid and positron emission tomography imaging. ADI was captured based on geocoding latitude and longitude to derive a national ranking for the specific location (home or unique destination). Machine learning algorithms classified preclinical AD. Each individual model's predictive ability was confirmed in a 20% testing dataset with 100 rounds of resampling with and without replacement. Among 292", "source": "PubMed"}, {"chunk_id": "39969227_1", "pmid": "39969227", "title": "Integrating Machine Learning and Environmental and Genetic Risk Factors for the Early Detection of Preclinical Alzheimer's Disease.", "authors": "Al-Hammadi N, Abouelyazid M, Brown DC et al.", "year": "2025", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Area deprivation index, Biomarkers, Naturalistic driving behavior, Predictive modeling, Resampling/bootstrapping methods", "chunk": "destination). Machine learning algorithms classified preclinical AD. Each individual model's predictive ability was confirmed in a 20% testing dataset with 100 rounds of resampling with and without replacement. Among 292 participants (n = 2,792 observations), including ADI of trip destinations, participants' home ADI, and frequency of trips to the same ADI led to a slight but notable improvement in predicting preclinical AD. The ensemble model demonstrated superior predictive performance, highlighting the potential of integrating multiple models for early AD detection. Our findings underscore the importance of incorporating socioeconomic and environmental variables, such as neighborhood deprivation, in predicting preclinical AD. Addressing socioeconomic disparities through public health strategies is crucial for mitigating AD risk and enhancing the quality of life for older adults.", "source": "PubMed"}, {"chunk_id": "39969227_2", "pmid": "39969227", "title": "Integrating Machine Learning and Environmental and Genetic Risk Factors for the Early Detection of Preclinical Alzheimer's Disease.", "authors": "Al-Hammadi N, Abouelyazid M, Brown DC et al.", "year": "2025", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Area deprivation index, Biomarkers, Naturalistic driving behavior, Predictive modeling, Resampling/bootstrapping methods", "chunk": "adults.", "source": "PubMed"}, {"chunk_id": "40524460_0", "pmid": "40524460", "title": "Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome.", "authors": "Ledreux A, Carmona-Iragui M, Videla L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, amyloid\u2010beta, biomarker, dementia, extracellular vesicle, neurofilament\u2010light, phosphorylated Tau", "chunk": "Individuals with Down syndrome (DS) are at an ultra-high risk of developing Alzheimer's disease (AD). Diagnosis of AD onset in people with DS can be challenging due to the variable degrees of intellectual disability and cognitive impairment among individuals. Plasma samples from individuals with DS diagnosed with AD dementia (n = 33), prodromal AD (n = 31), or cognitively stable (n = 43) were enriched for neuron-derived extracellular vesicles (NDEV) using immunocapture with the L1CAM antibody. We used single-molecule array technology to quantify amyloid-\u03b2 (A\u03b2) peptides, Tau, phosphorylated Tau, neurofilament light chain (NfL), and synaptosomal-associated protein 25 (SNAP25) across diagnostic groups. NDEV levels of A\u03b240, A\u03b242, Tau, pTauT181, pTauT231, NfL, and SNAP25 were significantly higher in people with DS diagnosed with prodromal AD compared to those with no cognitive decline. Middle-aged or older women had higher levels of NDEV biomarkers compared to males. NDEV biomarker levels can inform on the", "source": "PubMed"}, {"chunk_id": "40524460_1", "pmid": "40524460", "title": "Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome.", "authors": "Ledreux A, Carmona-Iragui M, Videla L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, amyloid\u2010beta, biomarker, dementia, extracellular vesicle, neurofilament\u2010light, phosphorylated Tau", "chunk": "with prodromal AD compared to those with no cognitive decline. Middle-aged or older women had higher levels of NDEV biomarkers compared to males. NDEV biomarker levels can inform on the onset of AD in individuals with DS. Diagnosis of Alzheimer's dementia in individuals with Down syndrome (DS)is challenging. Neuron-derived extracellular vesicles were enriched from plasma of adults with Down syndrome. Alzheimer's disease biomarkers were measured using single molecule array technology. NDEV biomarkers accurately predicted the prodromal stage of dementia in people with DS.", "source": "PubMed"}, {"chunk_id": "40466640_0", "pmid": "40466640", "title": "Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma.", "authors": "Liu J, Liu Y, Yin D et al.", "year": "2025", "journal": "Cell chemical biology", "keywords": "Alzheimer\u2019s disease, SLC7A11, calyx of held, edge of cleft, electrochemical sensor, glutamate, hemichannels, nanoelectrode, neurotransmitter, oxygen glucose deprivation", "chunk": "Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of \u223c60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds. More importantly, protein engineering of residue mutation and linker peptides flexibility expanded linear range from 10 \u03bcM to 6 mM, accelerated on/off times down to 35/40 ms. This toolkit realized real-time quantifying of Glu both at edge of cleft and peri-soma, we discovered that Glu was almost released through SLC7A11 channels in calyx of held synapse upon oxygen-glucose-deprivation, while Glu was mainly released through hemichannels upon \u03b2-amyloid<sub>42</sub> stimulation. Our work provided a methodology for investigating Glu release and reuptake and offered insights for Glu related pathology.", "source": "PubMed"}, {"chunk_id": "40466640_1", "pmid": "40466640", "title": "Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma.", "authors": "Liu J, Liu Y, Yin D et al.", "year": "2025", "journal": "Cell chemical biology", "keywords": "Alzheimer\u2019s disease, SLC7A11, calyx of held, edge of cleft, electrochemical sensor, glutamate, hemichannels, nanoelectrode, neurotransmitter, oxygen glucose deprivation", "chunk": "upon oxygen-glucose-deprivation, while Glu was mainly released through hemichannels upon \u03b2-amyloid<sub>42</sub> stimulation. Our work provided a methodology for investigating Glu release and reuptake and offered insights for Glu related pathology.", "source": "PubMed"}, {"chunk_id": "39565520_0", "pmid": "39565520", "title": "Development and validation of Galectin-3 and CVAI-based model for predicting cognitive impairment in type 2 diabetes.", "authors": "Zhou X, Dai N, Yu D et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "CVAI, Galectin-3, Mild cognitive impairment, Nomogram, Type 2 diabetes", "chunk": "The objective of this study is to develop a predictive model combining multiple indicators to quantify the risk of mild cognitive impairment (MCI) in T2DM patients. This study included Chinese T2DM patients who were hospitalized at Zhongda Hospital between November 2021 and May 2023. Clinical data, including demographics, medical history, biochemical tests, and cognitive status, were collected. Cognitive assessment was performed using neuropsychological tests, and MCI was diagnosed based on the Montreal Cognitive Assessment (MoCA) scores. The dataset was randomly divided into a training set and a validation set in a 7:3 ratio. Logistic regression analysis was conducted to identify factors influencing MCI in the training set. A nomogram-based scoring model was then developed by integrating these findings with high-risk clinical variables, and its performance was validated in the validation set. In this study, T2DM patients were divided into a training set and a validation set in a 7:3 ratio.", "source": "PubMed"}, {"chunk_id": "39565520_1", "pmid": "39565520", "title": "Development and validation of Galectin-3 and CVAI-based model for predicting cognitive impairment in type 2 diabetes.", "authors": "Zhou X, Dai N, Yu D et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "CVAI, Galectin-3, Mild cognitive impairment, Nomogram, Type 2 diabetes", "chunk": "clinical variables, and its performance was validated in the validation set. In this study, T2DM patients were divided into a training set and a validation set in a 7:3 ratio. There were no significant differences in MCI incidence, demographics, or clinical characteristics between the two groups, confirming the appropriateness of model construction. In the training set, Galectin-3 and CVAI were significantly negatively correlated with cognitive function (MoCA and MMSE scores), and this negative correlation remained after adjusting for confounding variables. Logistic regression analysis revealed that age, CVAI, and Galectin-3 significantly increased the risk of MCI, while years of education had a protective effect. The constructed nomogram model, which integrated age, sex, education level, hypertension, CVAI, and Galectin-3 levels, exhibited high predictive performance (C-index of 0.816), with AUCs of 0.816 in the training set and 0.858 in the validation set, outperforming single indicators. PR curve analysis further validated the superiority of", "source": "PubMed"}, {"chunk_id": "39565520_2", "pmid": "39565520", "title": "Development and validation of Galectin-3 and CVAI-based model for predicting cognitive impairment in type 2 diabetes.", "authors": "Zhou X, Dai N, Yu D et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "CVAI, Galectin-3, Mild cognitive impairment, Nomogram, Type 2 diabetes", "chunk": "predictive performance (C-index of 0.816), with AUCs of 0.816 in the training set and 0.858 in the validation set, outperforming single indicators. PR curve analysis further validated the superiority of the nomogram model. The straightforward, highly accurate, and interactive nomogram model developed in this study facilitate the early risk prediction of MCI in individuals with T2DM by incorporating Galectin-3, CVAI, and other common clinical risk factors.", "source": "PubMed"}, {"chunk_id": "41620655_0", "pmid": "41620655", "title": "Investigating the dynamic association of multiple risk factors on cognitive impairment in older people: a retrospective cohort study in Baisha Town, Hepu County, China.", "authors": "Zhao W, Huang R, Li N et al.", "year": "2026", "journal": "BMC geriatrics", "keywords": "Cognitive impairment, Older people, Retrospective cohort study, Risk factors", "chunk": "With the acceleration of global aging, cognitive impairment has become a critical public health issue. However, evidence delineating the dynamic and multifactorial trajectories of its progression remains scarce. Early identification of modifiable lifestyle and clinical risk factors is therefore essential to enable timely and effective prevention and intervention. This retrospective cohort study included 6,462 older adults from Baisha Town, Hepu County, Guangxi, China, who underwent health examinations between 2019 and 2024. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Correlation analysis, logistic regression, Cox proportional hazards models, restricted cubic splines (RCS), and linear mixed-effects models (LMMs) for longitudinal data were employed to examine the dynamic associations of multiple risk factors on cognitive impairment. Multivariable binary logistic regression showed that lower educational attainment, physical inactivity, poor dental status, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), abnormal high-density lipoprotein cholesterol (HDL-C), and elevated fasting blood glucose (FBG) were", "source": "PubMed"}, {"chunk_id": "41620655_1", "pmid": "41620655", "title": "Investigating the dynamic association of multiple risk factors on cognitive impairment in older people: a retrospective cohort study in Baisha Town, Hepu County, China.", "authors": "Zhao W, Huang R, Li N et al.", "year": "2026", "journal": "BMC geriatrics", "keywords": "Cognitive impairment, Older people, Retrospective cohort study, Risk factors", "chunk": "that lower educational attainment, physical inactivity, poor dental status, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), abnormal high-density lipoprotein cholesterol (HDL-C), and elevated fasting blood glucose (FBG) were associated with cognitive impairment in older individuals. Cox proportional hazards models indicated that lower educational attainment, physical inactivity, poor dental status, abnormal HDL-C, and elevated FBG were associated with a higher hazard of incident cognitive impairment. Kaplan-Meier survival curves showed longer maintenance of normal cognition among participants with higher education and regular exercise, whereas the presence of dentures or missing teeth, abnormal HDL-C, and elevated FBG were associated with shorter durations of preserved cognition. LMMs demonstrated sustained or time-varying associations of educational attainment, exercise frequency, dental status, and metabolic factors with trajectories of cognitive function over time. This study indicates that educational attainment, frequency of physical activity, oral health status, and metabolic factors are associated with temporal variation in the", "source": "PubMed"}, {"chunk_id": "41620655_2", "pmid": "41620655", "title": "Investigating the dynamic association of multiple risk factors on cognitive impairment in older people: a retrospective cohort study in Baisha Town, Hepu County, China.", "authors": "Zhao W, Huang R, Li N et al.", "year": "2026", "journal": "BMC geriatrics", "keywords": "Cognitive impairment, Older people, Retrospective cohort study, Risk factors", "chunk": "with trajectories of cognitive function over time. This study indicates that educational attainment, frequency of physical activity, oral health status, and metabolic factors are associated with temporal variation in the risk of cognitive impairment among older adults. Focusing on these modifiable factors may inform feasible, actionable screening and prevention strategies in primary care and community settings. Our findings also underscore the importance of dynamic monitoring of these indicators and suggest their potential value in slowing cognitive decline.", "source": "PubMed"}, {"chunk_id": "41675591_0", "pmid": "41675591", "title": "Distinct CSF lipidomic profiles are associated with five proteomic subtypes in patients with Alzheimer's disease.", "authors": "Malliou G, Reus LM, Pijnenburg YAL et al.", "year": "2026", "journal": "Molecular neurodegeneration advances", "keywords": "Alzheimer\u2019s disease, Heterogeneity, Lipid metabolism, Lipidomics, Molecular subtypes", "chunk": "Alzheimer's disease (AD) is molecularly heterogeneous. In our previous cerebrospinal fluid (CSF) proteomic study in AD, we identified and validated five distinct molecular subtypes characterized by neuronal hyperplasticity (subtype 1), innate immune activation (subtype 2), RNA dysregulation (subtype 3), choroid plexus dysfunction (subtype 4) and blood-brain barrier impairment (subtype 5). These subtypes also differed in the CSF levels of proteins involved in lipid metabolism, suggesting that lipid dysregulation in AD might be subtype specific. We performed untargeted lipidomics on CSF samples from 601 individuals in the Amsterdam Dementia Cohort who were previously included in our proteomic study (n = 416 AD, 185 controls). Using the CSH-QTOF platform for complex lipids, 3,532 lipids were detected in CSF, 270 of which could be mapped to 13 different lipid classes. Lipid levels were compared between each AD subtype and controls using linear regression models adjusted for age and sex (R v4.2.1). Lipids with", "source": "PubMed"}, {"chunk_id": "41675591_1", "pmid": "41675591", "title": "Distinct CSF lipidomic profiles are associated with five proteomic subtypes in patients with Alzheimer's disease.", "authors": "Malliou G, Reus LM, Pijnenburg YAL et al.", "year": "2026", "journal": "Molecular neurodegeneration advances", "keywords": "Alzheimer\u2019s disease, Heterogeneity, Lipid metabolism, Lipidomics, Molecular subtypes", "chunk": "be mapped to 13 different lipid classes. Lipid levels were compared between each AD subtype and controls using linear regression models adjusted for age and sex (R v4.2.1). Lipids with significantly different levels (p < 0.05) were included for pathway enrichment analysis with MetaboAnalyst6.0. We observed alterations in the levels of 1,893 lipids, with the majority associated with a single AD subtype. Subtype 3 (RNA dysregulation) exhibited the most pronounced alterations, with altered CSF levels of 669 lipids, including triglycerides and fatty acids, which were reduced compared to controls. Subtype 4 (choroid plexus dysfunction) and subtype 5 (blood-brain barrier dysfunction) both had alterations in the same set of 150 lipids, but with changes occurring in opposite directions (i.e., decreased in subtype 4, and increased in subtype 5). These lipids were associated with sphingolipid metabolism and lipid transport. Subtype 1 (neuronal hyperplasticity) and subtype 2 (innate immune activation) had less pronounced", "source": "PubMed"}, {"chunk_id": "41675591_2", "pmid": "41675591", "title": "Distinct CSF lipidomic profiles are associated with five proteomic subtypes in patients with Alzheimer's disease.", "authors": "Malliou G, Reus LM, Pijnenburg YAL et al.", "year": "2026", "journal": "Molecular neurodegeneration advances", "keywords": "Alzheimer\u2019s disease, Heterogeneity, Lipid metabolism, Lipidomics, Molecular subtypes", "chunk": "subtype 4, and increased in subtype 5). These lipids were associated with sphingolipid metabolism and lipid transport. Subtype 1 (neuronal hyperplasticity) and subtype 2 (innate immune activation) had less pronounced differences compared to the other subtypes. Subtype 1 had increased levels of several phospholipids, indicating neuronal membrane remodeling, and subtype 2 decreased arachidonic acid levels, a precursor of immunoregulatory oxylipins. Our findings reveal subtype-specific lipid metabolism alterations in AD. Currently, five lipid-targeting drugs are in phase 1 and 2 trials. Our results suggest that treatment efficacy may vary by subtype. Understanding these molecular differences can inform trial design and analysis, advancing the development of tailored therapies for AD. The online version contains supplementary material available at 10.1186/s44477-026-00018-z.", "source": "PubMed"}, {"chunk_id": "41630626_0", "pmid": "41630626", "title": "Care preferences for persons with cognitive impairment: A discrete choice experiment.", "authors": "Regier DA, Taylor JO, Ho A et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "care partners, care preferences, cognitive impairment, dementia, discrete choice experiment, dyads, personhood, person\u2010centered care, preferences, supportive care, transitions", "chunk": "Evidence is limited on preferences of persons with cognitive decline and their care partners (CPs) regarding care. Our aim was to identify preferences and preference evolution for transitions in supportive care. We conducted a discrete choice experiment (DCE) (repeated measures baseline, 6-months) with older adults with mild cognitive impairment or mild to moderate dementia and CPs. Tasks were anchored to health states describing progressive memory and function decline. Split-sample mixed logit models estimated part-worth utilities. Baseline DCEs were completed by 131 cognitively impaired older adults and 137 CPs; 118 and 132 completed 6-month DCEs. At both timepoints, respondents preferred in-home care with moderate support when considering moderate or severe cognitive impairment. As impairment worsened, the acceptability of assisted living increased, especially among CPs. Persons with cognitive decline engaged in future-oriented decisions. Preferences were stable across time for both samples, and assisted living was more acceptable for CPs.", "source": "PubMed"}, {"chunk_id": "41630626_1", "pmid": "41630626", "title": "Care preferences for persons with cognitive impairment: A discrete choice experiment.", "authors": "Regier DA, Taylor JO, Ho A et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "care partners, care preferences, cognitive impairment, dementia, discrete choice experiment, dyads, personhood, person\u2010centered care, preferences, supportive care, transitions", "chunk": "especially among CPs. Persons with cognitive decline engaged in future-oriented decisions. Preferences were stable across time for both samples, and assisted living was more acceptable for CPs.", "source": "PubMed"}, {"chunk_id": "37907134_0", "pmid": "37907134", "title": "Repurposing and clinical attributes of antidiabetic drugs for the treatment of neurodegenerative disorders.", "authors": "Birajdar SV, Mazahir F, Alam MI et al.", "year": "2023", "journal": "European journal of pharmacology", "keywords": "AMPK/mTOR/BACE1, Antidiabetic drugs, Insulin degrading enzyme (IDE), Insulin resistance, Neurodegenerative disorders, Oxidative stress", "chunk": "The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid \u03b2 metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions. The insulin signaling via IP3 activation upregulates the IDE and could be a promising approach to regulate neurodegeneration. The repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial", "source": "PubMed"}, {"chunk_id": "37907134_1", "pmid": "37907134", "title": "Repurposing and clinical attributes of antidiabetic drugs for the treatment of neurodegenerative disorders.", "authors": "Birajdar SV, Mazahir F, Alam MI et al.", "year": "2023", "journal": "European journal of pharmacology", "keywords": "AMPK/mTOR/BACE1, Antidiabetic drugs, Insulin degrading enzyme (IDE), Insulin resistance, Neurodegenerative disorders, Oxidative stress", "chunk": "glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile and neuroinflammation in the brain. Antidiabetic medications reduce the risk of neuroinflammation, oxidative stress, and A\u03b2 deposition by enhancing their clearance rate. The downregulation of IDE alters the degradation of A\u03b2 monomers in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced mice model. Thus, the primary intention of this review is to explore the link between T2DM and neurodegenerative disorders, and the possible role of various antidiabetic drugs in the management of neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "37907134_2", "pmid": "37907134", "title": "Repurposing and clinical attributes of antidiabetic drugs for the treatment of neurodegenerative disorders.", "authors": "Birajdar SV, Mazahir F, Alam MI et al.", "year": "2023", "journal": "European journal of pharmacology", "keywords": "AMPK/mTOR/BACE1, Antidiabetic drugs, Insulin degrading enzyme (IDE), Insulin resistance, Neurodegenerative disorders, Oxidative stress", "chunk": "of neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "39034660_0", "pmid": "39034660", "title": "How will the emergence of lecanemab change dementia treatment?", "authors": "Iwata A", "year": "2024", "journal": "Geriatrics & gerontology international", "keywords": "Alzheimer's disease, amyloid\u2010related imaging abnormalities, amyloid\u2010\u03b2, lecanemab", "chunk": "The introduction of lecanemab has dramatically changed the field of dementia medicine. Lecanemab, defined as an anti-amyloid-\u03b2 (A\u03b2) drug, comprises an antibody against A\u03b2, a protein structure believed to cause Alzheimer's disease. This drug represents a new direction in dementia treatment. In a phase III study, lecanemab was found to significantly slow cognitive decline, while showing manageable levels of amyloid-related imaging abnormalities, which are side-effects of lecanemab. Furthermore, lecanemab has been shown to effectively reduce A\u03b2 accumulation in patients with early Alzheimer's disease, which might contribute not only to delaying the progression of cognitive decline, but also to improving the quality of life of patients and their families. However, there are conditions for the use of lecanemab, for which the Ministry of Health, Labor and Welfare has issued the Guidelines for Promotion of Optimal Use. These guidelines specify requirements for appropriate patient selection, prescribing physicians and administering medical institutions to", "source": "PubMed"}, {"chunk_id": "39034660_1", "pmid": "39034660", "title": "How will the emergence of lecanemab change dementia treatment?", "authors": "Iwata A", "year": "2024", "journal": "Geriatrics & gerontology international", "keywords": "Alzheimer's disease, amyloid\u2010related imaging abnormalities, amyloid\u2010\u03b2, lecanemab", "chunk": "Ministry of Health, Labor and Welfare has issued the Guidelines for Promotion of Optimal Use. These guidelines specify requirements for appropriate patient selection, prescribing physicians and administering medical institutions to ensure safe and effective use. Particular emphasis is placed on the confirmation of amyloid-\u03b2 accumulation, amyloid-related imaging abnormalities risk management and appropriate handling of side-effects. The clinical use of lecanemab represents an important advancement in the treatment of dementia; however, the understanding and cooperation of healthcare professionals, patients and families are essential to maximize its efficacy and safety. Future issues to be addressed include the sustainability and long-term efficacy of treatment, improvement of clinical symptoms after removal of A\u03b2 and motivation to administer the drug. Although lecanemab offers hope for the treatment of dementia, its use requires careful management. Geriatr Gerontol Int 2024; 24: 841-844.", "source": "PubMed"}, {"chunk_id": "39034660_2", "pmid": "39034660", "title": "How will the emergence of lecanemab change dementia treatment?", "authors": "Iwata A", "year": "2024", "journal": "Geriatrics & gerontology international", "keywords": "Alzheimer's disease, amyloid\u2010related imaging abnormalities, amyloid\u2010\u03b2, lecanemab", "chunk": "the treatment of dementia, its use requires careful management. Geriatr Gerontol Int 2024; 24: 841-844.", "source": "PubMed"}, {"chunk_id": "41688474_0", "pmid": "41688474", "title": "Neuromelanin imaging outperforms free water imaging in diagnosing early Parkinson's disease: a comparative MRI study.", "authors": "Roh YH, Youn J, Kim SY et al.", "year": "2026", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Early and accurate diagnosis of Parkinson's disease (PD) remains challenging due to reliance on clinical assessment of motor symptoms. This retrospective study compared the diagnostic performance of neuromelanin (NM)-sensitive MRI and free water (FW) imaging in 247 patients with early PD and 78 controls from a single tertiary center, with independent external validation in a separate cohort acquired at another institution. NM volumes were measured in the substantia nigra pars compacta and its functional subregions (limbic, associative, and sensorimotor), while FW values were extracted from corresponding substantia nigra regions using diffusion tensor imaging. A combined NM model incorporating subregional volumes was developed through multivariable logistic regression. NM volumes were reduced across all regions in early PD patients compared to controls, while FW values showed no significant group differences. NM measurements consistently outperformed FW imaging across all regions, with the combined NM model achieving superior diagnostic accuracy, and NM-based measures also", "source": "PubMed"}, {"chunk_id": "41688474_1", "pmid": "41688474", "title": "Neuromelanin imaging outperforms free water imaging in diagnosing early Parkinson's disease: a comparative MRI study.", "authors": "Roh YH, Youn J, Kim SY et al.", "year": "2026", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "while FW values showed no significant group differences. NM measurements consistently outperformed FW imaging across all regions, with the combined NM model achieving superior diagnostic accuracy, and NM-based measures also demonstrated higher diagnostic performance than FW in the external validation cohort. These results highlight the clinical utility of NM-MRI for early diagnostic assessment and its potential integration into emerging multimodal biomarker frameworks for PD.", "source": "PubMed"}, {"chunk_id": "39562718_0", "pmid": "39562718", "title": "Large-scale proteomic analyses of incident Alzheimer's disease reveal new pathophysiological insights and potential therapeutic targets.", "authors": "Zhang Y, Guo Y, He Y et al.", "year": "2025", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "Pathophysiological evolutions in early-stage Alzheimer's disease (AD) are not well understood. We used data of 2923 Olink plasma proteins from 51,296 non-demented middle-aged adults. During a follow-up of 15 years, 689 incident AD cases occurred. Cox-proportional hazard models were applied to identify AD-associated proteins in different time intervals. Through linking to protein categories, changing sequences of protein z-scores can reflect pathophysiological evolutions. Mendelian randomization using blood protein quantitative loci data provided causal evidence for potentially druggable proteins. We identified 48 AD-related proteins, with CEND1, GFAP, NEFL, and SYT1 being top hits in both near-term (HR:1.15-1.77; P:9.11 \u00d7 10<sup>-65</sup>-2.78 \u00d7 10<sup>-6</sup>) and long-term AD risk (HR:1.20-1.54; P:2.43 \u00d7 10<sup>-21</sup>-3.95 \u00d7 10<sup>-6</sup>). These four proteins increased 15 years before AD diagnosis and progressively escalated, indicating early and sustained dysfunction in synapse and neurons. Proteins related to extracellular matrix organization, apoptosis, innate immunity, coagulation, and lipid homeostasis showed early disturbances, followed by malfunctions", "source": "PubMed"}, {"chunk_id": "39562718_1", "pmid": "39562718", "title": "Large-scale proteomic analyses of incident Alzheimer's disease reveal new pathophysiological insights and potential therapeutic targets.", "authors": "Zhang Y, Guo Y, He Y et al.", "year": "2025", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "progressively escalated, indicating early and sustained dysfunction in synapse and neurons. Proteins related to extracellular matrix organization, apoptosis, innate immunity, coagulation, and lipid homeostasis showed early disturbances, followed by malfunctions in metabolism, adaptive immunity, and final synaptic and neuronal loss. Combining CEND1, GFAP, NEFL, and SYT1 with demographics generated desirable predictions for 10-year (AUC = 0.901) and over-10-year AD (AUC = 0.864), comparable to full model. Mendelian randomization supports potential genetic link between CEND1, SYT1, and AD as outcome. Our findings highlight the importance of exploring the pathophysiological evolutions in early stages of AD, which is essential for the development of early biomarkers and precision therapeutics.", "source": "PubMed"}, {"chunk_id": "38450963_0", "pmid": "38450963", "title": "Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.", "authors": "Maimaitituerxun R, Chen W, Xiang J et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "decision tree, mild cognitive impairment, predictor variable, type 2 diabetes mellitus", "chunk": "As the population ages, mild cognitive impairment (MCI) and type 2 diabetes mellitus (T2DM) become common conditions that often coexist. Evidence has shown that MCI could lead to reduced treatment compliance, medication management, and self-care ability in T2DM patients. Therefore, early identification of those with increased risk of MCI is crucial from a preventive perspective. Given the growing utilization of decision trees in prediction of health-related outcomes, this study aimed to identify MCI in T2DM patients using the decision tree approach. This hospital-based case-control study was performed in the Endocrinology Department of Xiangya Hospital affiliated to Central South University between March 2021 and December 2022. MCI was defined based on the Petersen criteria. Demographic characteristics, lifestyle factors, and T2DM-related information were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was", "source": "PubMed"}, {"chunk_id": "38450963_1", "pmid": "38450963", "title": "Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.", "authors": "Maimaitituerxun R, Chen W, Xiang J et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "decision tree, mild cognitive impairment, predictor variable, type 2 diabetes mellitus", "chunk": "were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was established using the chi-square automatic interaction detection (CHAID) algorithm to identify key predictor variables associated with MCI. The area under the curve (AUC) value was used to evaluate the performance of the established decision tree model, and the performance of multivariate regression model was also evaluated for comparison. A total of 1001 participants (705 in the training set and 296 in the validation set) were included in this study. The mean age of participants in the training and validation sets was 60.2 \u00b1 10.3 and 60.4 \u00b1 9.5 years, respectively. There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI,", "source": "PubMed"}, {"chunk_id": "38450963_2", "pmid": "38450963", "title": "Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.", "authors": "Maimaitituerxun R, Chen W, Xiang J et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "decision tree, mild cognitive impairment, predictor variable, type 2 diabetes mellitus", "chunk": "There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI, including age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy. The established decision tree model had 15 nodes composed of 4 layers, and age is the most significant predictor variable. It performed well (AUC = .75 [95% confidence interval (CI): .71-.78] and .67 [95% CI: .61-.74] in the training and validation sets, respectively), was internally validated, and had comparable predictive value compared to the multivariate logistic regression model (AUC = .76 [95% CI: .72-.80] and .69 [95% CI: .62-.75] in the training and validation sets, respectively). The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate", "source": "PubMed"}, {"chunk_id": "38450963_3", "pmid": "38450963", "title": "Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.", "authors": "Maimaitituerxun R, Chen W, Xiang J et al.", "year": "2024", "journal": "Brain and behavior", "keywords": "decision tree, mild cognitive impairment, predictor variable, type 2 diabetes mellitus", "chunk": "The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate logistic regression model and was internally validated. Due to its superior classification accuracy and simple presentation as well as interpretation of collected data, the decision tree model is more recommended for the prediction of MCI in T2DM patients in clinical practice.", "source": "PubMed"}, {"chunk_id": "40813364_0", "pmid": "40813364", "title": "Biobank-scale genetic characterization of Alzheimer's disease and related dementias across diverse ancestries.", "authors": "Khani M, Ak\u00e7imen F, Grant SM et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "Alzheimer's disease and related dementias (AD/ADRDs) pose a significant global public health challenge. To effectively implement personalized therapeutic interventions on a global scale, it is essential to identify disease-causing, risk, and resilience factors across diverse ancestral backgrounds. This study leveraged biobank-scale data to conduct a large multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We thoroughly explored the role of protein-coding and splicing variants from key genes associated with AD/ADRDs across 11 ancestries, utilizing data from five distinct biobanks, including a total of 25,001 cases and 93,542 controls. We compiled the most extensive catalog of known and novel genetic variation in AD/ADRDs in a global context, providing clinical insights into their genetic-phenotypic correlations. A thorough assessment of APOE revealed ancestry-driven modulation of APOE-associated AD/ADRDs, as well as disease-modifying effects conferred by several variants among APOE \u03b54 carriers. Finally, we present an accessible and user-friendly platform to support future ADRD research ( https://niacard.shinyapps.io/MAMBARD_browser/", "source": "PubMed"}, {"chunk_id": "40813364_1", "pmid": "40813364", "title": "Biobank-scale genetic characterization of Alzheimer's disease and related dementias across diverse ancestries.", "authors": "Khani M, Ak\u00e7imen F, Grant SM et al.", "year": "2025", "journal": "Nature communications", "keywords": "None", "chunk": "APOE-associated AD/ADRDs, as well as disease-modifying effects conferred by several variants among APOE \u03b54 carriers. Finally, we present an accessible and user-friendly platform to support future ADRD research ( https://niacard.shinyapps.io/MAMBARD_browser/ ).", "source": "PubMed"}, {"chunk_id": "41103292_0", "pmid": "41103292", "title": "Uncovering the Hidden Connections Between PCOS and Alzheimer's Disease: A Two-Sample Mendelian Randomization Perspective.", "authors": "Motafeghi FS, Akbarzadeh M, Talebi S et al.", "year": "2025", "journal": "International journal of endocrinology and metabolism", "keywords": "Alzheimer Disease, Causality, Genetic Epidemiology, Mendelian Randomization Analysis, Polycystic Ovary Syndrome", "chunk": "Polycystic ovary syndrome (PCOS) and Alzheimer's disease (AD) are two prevalent and complex conditions characterized by overlapping features such as metabolic dysfunction, hormonal imbalance, and chronic inflammation. These commonalities raise the possibility of a shared causal pathway. However, observational studies often face limitations due to confounding factors, complicating causal inference. The present study aimed to explore the causal link between PCOS and AD through Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis using summary-level data from two large genome-wide association studies (GWAS). For the exposure, genetic variants strongly associated with PCOS were obtained from a GWAS meta-analysis involving 10,074 cases and 103,164 controls of European ancestry. For the outcome, AD data were sourced from a separate GWAS comprising 1,036,225 cases and 90,338 controls, also of European descent. Multiple MR approaches were employed, with inverse variance weighted (IVW) as the primary method, supported by MR-Egger, weighted median, and weighted", "source": "PubMed"}, {"chunk_id": "41103292_1", "pmid": "41103292", "title": "Uncovering the Hidden Connections Between PCOS and Alzheimer's Disease: A Two-Sample Mendelian Randomization Perspective.", "authors": "Motafeghi FS, Akbarzadeh M, Talebi S et al.", "year": "2025", "journal": "International journal of endocrinology and metabolism", "keywords": "Alzheimer Disease, Causality, Genetic Epidemiology, Mendelian Randomization Analysis, Polycystic Ovary Syndrome", "chunk": "1,036,225 cases and 90,338 controls, also of European descent. Multiple MR approaches were employed, with inverse variance weighted (IVW) as the primary method, supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses were performed to assess the robustness of the findings. The two-sample MR analysis did not provide evidence for a significant causal effect of genetically predicted PCOS on AD risk. The initial IVW analysis using all instrumental variables (IVs) yielded an odds ratio (OR) of 0.967 [95% confidence interval (CI): 0.905 - 1.03; P = 0.311]. After removing outlier single nucleotide polymorphisms (SNPs) based on sensitivity analyses, the refined IVW model showed an OR of 0.93 (95% CI: 0.866 - 1.002; P = 0.057), indicating no statistically significant association. The results were consistent across various MR methods, and sensitivity tests confirmed the robustness of the findings. This MR study found no evidence of a significant causal relationship", "source": "PubMed"}, {"chunk_id": "41103292_2", "pmid": "41103292", "title": "Uncovering the Hidden Connections Between PCOS and Alzheimer's Disease: A Two-Sample Mendelian Randomization Perspective.", "authors": "Motafeghi FS, Akbarzadeh M, Talebi S et al.", "year": "2025", "journal": "International journal of endocrinology and metabolism", "keywords": "Alzheimer Disease, Causality, Genetic Epidemiology, Mendelian Randomization Analysis, Polycystic Ovary Syndrome", "chunk": "significant association. The results were consistent across various MR methods, and sensitivity tests confirmed the robustness of the findings. This MR study found no evidence of a significant causal relationship between genetically predicted PCOS and AD. These findings suggest that genetic predisposition to PCOS does not increase the risk of AD, indicating that previously observed associations in epidemiological studies may not reflect a causal link. Further studies are needed to explore alternative explanations beyond genetic causality.", "source": "PubMed"}, {"chunk_id": "40948091_0", "pmid": "40948091", "title": "Pathophysiology of cognitive impairment in chronic kidney disease.", "authors": "Merlino L, Tollitt J, Dunne RA et al.", "year": "2025", "journal": "Current opinion in nephrology and hypertension", "keywords": "chronic kidney disease, cognitive impairment, neurological resilience, neurovascular dysfunction, uremic toxins", "chunk": "Cognitive impairment (CI) is a frequent and disabling complication in individuals with chronic kidney disease (CKD). With rising CKD prevalence, especially in aging populations, there is a pressing need to understand the complex and multifactorial mechanisms linking kidney dysfunction to cognitive decline. Emerging evidence highlights the multifactorial pathogenesis of CKD-related CI, involving vascular dysfunction, blood-brain barrier disruption, glymphatic impairment, systemic inflammation, uremic toxin accumulation, hormonal dysregulation, and gut-brain axis alterations. Additionally, mental health comorbidities, sarcopenia, sleep disorders, and renal replacement therapies further modulate cognitive outcomes. Advances in biomarker research and the identification of neuroprotective factors like Klotho may reshape diagnostic and therapeutic strategies. CI in CKD results from a convergence of systemic and neural insults, modulated by resilience mechanisms and shaped by aging and comorbidities. Future research should explore interventions targeting modifiable contributors, such as vascular health, inflammation, and uremic toxicity, as well as enhancing neuroresilience to preserve cognitive function", "source": "PubMed"}, {"chunk_id": "40948091_1", "pmid": "40948091", "title": "Pathophysiology of cognitive impairment in chronic kidney disease.", "authors": "Merlino L, Tollitt J, Dunne RA et al.", "year": "2025", "journal": "Current opinion in nephrology and hypertension", "keywords": "chronic kidney disease, cognitive impairment, neurological resilience, neurovascular dysfunction, uremic toxins", "chunk": "shaped by aging and comorbidities. Future research should explore interventions targeting modifiable contributors, such as vascular health, inflammation, and uremic toxicity, as well as enhancing neuroresilience to preserve cognitive function in this high-risk population.", "source": "PubMed"}, {"chunk_id": "41591746_0", "pmid": "41591746", "title": "Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials.", "authors": "Cummings JL, Chumki SR, Chang D et al.", "year": "2026", "journal": "Clinical drug investigation", "keywords": "None", "chunk": "This analysis aimed to evaluate the efficacy of brexpiprazole 2 or 3 mg/day for the treatment of agitation associated with dementia due to Alzheimer's disease, on the basis of pooled clinical trial data. Data were pooled from two similarly designed, phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled trials of fixed-dose brexpiprazole in participants in care facilities or community-based settings who had agitation associated with dementia due to Alzheimer's disease. Efficacy outcomes included Cohen-Mansfield Agitation Inventory (CMAI) total score (which measures the frequency of 29 different agitation symptoms), Clinical Global Impression-Severity of illness (CGI-S) score, CMAI factor scores (aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors), and response rates. A sensitivity analysis included a third trial with flexible dosing. In total, 621 participants were randomized (brexpiprazole, 368; placebo, 253), and completion rates were 320/368 (87.0%) and 225/253 (88.9%), respectively. Mean (SD) baseline CMAI total scores were: brexpiprazole 76.9 (17.2) points", "source": "PubMed"}, {"chunk_id": "41591746_1", "pmid": "41591746", "title": "Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials.", "authors": "Cummings JL, Chumki SR, Chang D et al.", "year": "2026", "journal": "Clinical drug investigation", "keywords": "None", "chunk": "total, 621 participants were randomized (brexpiprazole, 368; placebo, 253), and completion rates were 320/368 (87.0%) and 225/253 (88.9%), respectively. Mean (SD) baseline CMAI total scores were: brexpiprazole 76.9 (17.2) points and placebo 75.5 (18.0) points. Over 12 weeks, CMAI total scores improved by least squares mean (SE) - 22.8 (0.8) points for brexpiprazole and - 18.3 (1.0) points for placebo, with a least squares mean difference between treatment arms of - 4.50 points (95% CI - 6.90 to - 2.10; p < 0.001; Cohen's d 0.30). CGI-S, CMAI factor, and response analyses also showed greater improvement with brexpiprazole versus placebo. The sensitivity analysis was supportive. Brexpiprazole 2 or 3 mg/day reduced agitation symptoms compared with placebo over 12 weeks in this large, pooled sample of participants with dementia due to Alzheimer's disease. ClinicalTrials.gov identifiers: NCT01862640, NCT03548584, and NCT01922258.", "source": "PubMed"}, {"chunk_id": "41591746_2", "pmid": "41591746", "title": "Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials.", "authors": "Cummings JL, Chumki SR, Chang D et al.", "year": "2026", "journal": "Clinical drug investigation", "keywords": "None", "chunk": "this large, pooled sample of participants with dementia due to Alzheimer's disease. ClinicalTrials.gov identifiers: NCT01862640, NCT03548584, and NCT01922258.", "source": "PubMed"}, {"chunk_id": "40392146_0", "pmid": "40392146", "title": "Association between metabolic syndrome and cognitive impairment: a meta-analysis of analytical observational studies.", "authors": "Azami M, Afraie M, Mohammadzadeh P et al.", "year": "2025", "journal": "Cognitive neuropsychiatry", "keywords": "Alzheimer\u2019s disease, Metabolic syndrome, Mets, cognitive impairment, meta-analysis", "chunk": "The potential link between metabolic syndrome (MetS) and the risk of dementia or cognitive impairment remains uncertain. This study aimed to assess the association between MetS and cognitive decline through a comprehensive review and meta-analysis of the existing literature. A systematic search was conducted in Medline (PubMed), Web of Science, Scopus and Embase up to January 2023. Eligible studies included cohort and case-control designs. Statistical analyses were performed using STATA version 17. A total of 20 studies comprising 5,727,594 participants were included. The pooled relative risk (RR) of cognitive impairment among individuals with MetS was 1.34 (95% CI: 1.25-1.43), indicating a significant association. Subgroup analyses revealed that the NCEP-ATP III criteria more effectively identified this relationship compared to other diagnostic methods. The association appeared strongest in Asian populations, followed by European and American groups. This meta-analysis supports a significant association between MetS and cognitive impairment. Geographic variation in the strength", "source": "PubMed"}, {"chunk_id": "40392146_1", "pmid": "40392146", "title": "Association between metabolic syndrome and cognitive impairment: a meta-analysis of analytical observational studies.", "authors": "Azami M, Afraie M, Mohammadzadeh P et al.", "year": "2025", "journal": "Cognitive neuropsychiatry", "keywords": "Alzheimer\u2019s disease, Metabolic syndrome, Mets, cognitive impairment, meta-analysis", "chunk": "methods. The association appeared strongest in Asian populations, followed by European and American groups. This meta-analysis supports a significant association between MetS and cognitive impairment. Geographic variation in the strength of this relationship may be influenced by differences in diagnostic criteria and lifestyle factors. The findings underscore the importance of early screening and the development of region-specific public health interventions to mitigate cognitive decline in individuals with MetS.", "source": "PubMed"}, {"chunk_id": "25698435_0", "pmid": "25698435", "title": "Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis.", "authors": "Cooper C, Sommerlad A, Lyketsos CG et al.", "year": "2015", "journal": "The American journal of psychiatry", "keywords": "None", "chunk": "Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition. The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies. There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or", "source": "PubMed"}, {"chunk_id": "25698435_1", "pmid": "25698435", "title": "Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis.", "authors": "Cooper C, Sommerlad A, Lyketsos CG et al.", "year": "2015", "journal": "The American journal of psychiatry", "keywords": "None", "chunk": "syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies. Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.", "source": "PubMed"}, {"chunk_id": "41754191_0", "pmid": "41754191", "title": "Berry Consumption and Its Role in the Modulation of Obesity and Mild Cognitive Impairment.", "authors": "Santos GAAD, Moraes CPM, Mar\u00f3stica J\u00fanior MR", "year": "2026", "journal": "Nutrients", "keywords": "anthocyanins, berries, mild cognitive impairment, obesity, polyphenols", "chunk": "Most dementias are preceded by mild cognitive impairment (MCI), a transitional clinical stage characterized by cognitive decline that does not yet significantly interfere with activities of daily living. Obesity and diabetes are among the major risk factors for MCI and are strongly associated with unhealthy lifestyle patterns. The growing global prevalence of obesity has intensified the need for effective dietary strategies that promote both weight control and neuroprotection. Red fruits, which are rich in bioactive compounds such as anthocyanins, have demonstrated potential roles in modulating metabolic pathways and cognitive function. This systematic review aimed to identify and synthesize evidence from human studies published over the past two decades that examined the effects of red fruit consumption on obesity-related mechanisms and cognitive outcomes, as well as its influence on key neurodegenerative biomarkers, including TAU protein, \u03b2-amyloid, and neurofilament light chain. A systematic search was conducted in major scientific databases to identify", "source": "PubMed"}, {"chunk_id": "41754191_1", "pmid": "41754191", "title": "Berry Consumption and Its Role in the Modulation of Obesity and Mild Cognitive Impairment.", "authors": "Santos GAAD, Moraes CPM, Mar\u00f3stica J\u00fanior MR", "year": "2026", "journal": "Nutrients", "keywords": "anthocyanins, berries, mild cognitive impairment, obesity, polyphenols", "chunk": "cognitive outcomes, as well as its influence on key neurodegenerative biomarkers, including TAU protein, \u03b2-amyloid, and neurofilament light chain. A systematic search was conducted in major scientific databases to identify human clinical trials evaluating the metabolic and neuroprotective effects of berry-derived compounds. Eligible studies were screened for outcomes related to cognitive performance, obesity-related parameters, and relevant molecular biomarkers. The included studies reported modest improvements in cognitive domains, with the most consistent effects observed in memory-related outcomes. Berry-derived bioactive compounds demonstrated potential in attenuating TAU protein hyperphosphorylation and reducing \u03b2-amyloid accumulation; however, the available evidence remains limited and requires further confirmation. Human clinical studies remain scarce, and although some trials reported favorable metabolic effects, these findings are still inconclusive. Reported outcomes included improvements in insulin sensitivity, regulation of leptin levels, and modulation of the gut-brain axis, which may collectively contribute to a reduced risk of obesity. Based on the studies evaluated", "source": "PubMed"}, {"chunk_id": "41754191_2", "pmid": "41754191", "title": "Berry Consumption and Its Role in the Modulation of Obesity and Mild Cognitive Impairment.", "authors": "Santos GAAD, Moraes CPM, Mar\u00f3stica J\u00fanior MR", "year": "2026", "journal": "Nutrients", "keywords": "anthocyanins, berries, mild cognitive impairment, obesity, polyphenols", "chunk": "included improvements in insulin sensitivity, regulation of leptin levels, and modulation of the gut-brain axis, which may collectively contribute to a reduced risk of obesity. Based on the studies evaluated in this review, there remains a limited number of human clinical trials that robustly support the neuroprotective and complementary metabolic effects of berry-derived bioactive compounds. Nevertheless, the available evidence suggests that dietary strategies incorporating wild fruits rich in polyphenols may represent a promising complementary approach for the prevention of mild cognitive impairment (MCI) and obesity, with potential implications for reducing the risk of dementia progression.", "source": "PubMed"}, {"chunk_id": "41637998_0", "pmid": "41637998", "title": "Microglial, astrocytic, oligodendrocyte, B-/T-cell and neutrophil dysregulation in neuroinflammation of Alzheimer's disease and related dementias.", "authors": "Singh AS, Naqvi AR, Chanu MT", "year": "2026", "journal": "Journal of psychiatric research", "keywords": "Alzheimer's disease, Astrocytic, Chemokines, Cognitive impairment, Cytokines, Dementia, Microglia, Neuroinflammation, Neutrophils, Oligodendrocyte, Other forms of dementia or related dementia, T cell and B cell", "chunk": "Wide number of basic, preclinical and clinical research have led to increase our knowledge on understanding the potential roles of neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD). In fact, neuroinflammation is considered as one of the key pathological factors of neuronal dysfunction leading to dementia in AD and other forms of dementias or related dementias (RD). Central nervous system (CNS) network communicates and control the immune system signaling pathways within the brain as well as peripheral part of the body. Hence, disturbance in the physiological immune system regulation is susceptible to the etiology or pathogenesis of the diseases. Microglia, astrocytes, oligodendrocytes, B-/T-cells and neutrophils are potential regulatory cells in keeping our immune system in balance. The imbalance in the regulatory function of these cells results to inflammatory consequences and has direct or indirect influence in the AD trajectory. In the brain, neuroinflammation is strongly linked to the accumulation", "source": "PubMed"}, {"chunk_id": "41637998_1", "pmid": "41637998", "title": "Microglial, astrocytic, oligodendrocyte, B-/T-cell and neutrophil dysregulation in neuroinflammation of Alzheimer's disease and related dementias.", "authors": "Singh AS, Naqvi AR, Chanu MT", "year": "2026", "journal": "Journal of psychiatric research", "keywords": "Alzheimer's disease, Astrocytic, Chemokines, Cognitive impairment, Cytokines, Dementia, Microglia, Neuroinflammation, Neutrophils, Oligodendrocyte, Other forms of dementia or related dementia, T cell and B cell", "chunk": "the regulatory function of these cells results to inflammatory consequences and has direct or indirect influence in the AD trajectory. In the brain, neuroinflammation is strongly linked to the accumulation of A\u03b2 plaques and tau tangles which lead to pathogenesis underlying dementia of AD. Currently, neuroinflammation is considered as one of the pathological hallmarks of AD, alongside A\u03b2 plaques and tau tangles. Various research and review articles have described the dysregulation of immune system cells leading to neuroinflammation in AD and RD pathogenesis. However, how these immune cells become coordinately imbalanced in the disease pathogenesis has been rarely reported, which is necessary for deeper understanding of the disease pathology and therapeutic development. In this review, we intend to highlight and discuss the neuroinflammatory pathways mediated via dysregulation of microglia, astrocyte, oligodendrocyte, neutrophil, B-cell and T-cell functions, which leads to neuronal dysfunction, dementia or cognitive decline in AD and RD. We", "source": "PubMed"}, {"chunk_id": "41637998_2", "pmid": "41637998", "title": "Microglial, astrocytic, oligodendrocyte, B-/T-cell and neutrophil dysregulation in neuroinflammation of Alzheimer's disease and related dementias.", "authors": "Singh AS, Naqvi AR, Chanu MT", "year": "2026", "journal": "Journal of psychiatric research", "keywords": "Alzheimer's disease, Astrocytic, Chemokines, Cognitive impairment, Cytokines, Dementia, Microglia, Neuroinflammation, Neutrophils, Oligodendrocyte, Other forms of dementia or related dementia, T cell and B cell", "chunk": "discuss the neuroinflammatory pathways mediated via dysregulation of microglia, astrocyte, oligodendrocyte, neutrophil, B-cell and T-cell functions, which leads to neuronal dysfunction, dementia or cognitive decline in AD and RD. We believe that the narrative in this review will be helpful in the future basic/clinical research and therapeutic development for AD and RD.", "source": "PubMed"}, {"chunk_id": "41555795_0", "pmid": "41555795", "title": "The capacity for Alzheimer's disease confirmatory testing in the United States: The current situation and simulations for future increase.", "authors": "Roth S, Yan J, Patru MM et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, United States, amyloid-\u03b2 peptides, biomarkers, medical economics, positron emission tomography", "chunk": "BackgroundWith recent advances in disease-modifying therapies for Alzheimer's disease (AD), demand for confirmatory biomarker testing such as via cerebrospinal fluid (CSF) analysis or amyloid positron emission tomography (PET) will increase considerably for diagnosis.ObjectiveTo assess the current capacity and estimating the anticipated future need of AD confirmatory testing in the United States (US).MethodsA population-based decision tree model was employed to simulate the AD diagnostic pathway for patients presenting with symptoms of mild cognitive impairment or mild dementia in primary and secondary care in the US. All patients were assumed to be enrolled in Medicare. The study was conducted from the US payer's perspective over a 5-year period. Four scenarios assessed the impact of different utilization patterns: (1) reference scenario (current use in AD diagnostic pathway: < 1% amyloid-PET; 3.5% CSF analysis); (2) increased CSF analysis utilization scenario (50% utilization); (3) amyloid-PET only; and (4) CSF analysis only.ResultsScenario 1 fails to meet", "source": "PubMed"}, {"chunk_id": "41555795_1", "pmid": "41555795", "title": "The capacity for Alzheimer's disease confirmatory testing in the United States: The current situation and simulations for future increase.", "authors": "Roth S, Yan J, Patru MM et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, United States, amyloid-\u03b2 peptides, biomarkers, medical economics, positron emission tomography", "chunk": "in AD diagnostic pathway: < 1% amyloid-PET; 3.5% CSF analysis); (2) increased CSF analysis utilization scenario (50% utilization); (3) amyloid-PET only; and (4) CSF analysis only.ResultsScenario 1 fails to meet the growing demand for AD confirmatory testing (assumed annual care-seeking rate of 50%), with approximately 0.3% of all amyloid-\u03b2-positive patients receiving a timely and accurate diagnosis with amyloid-PET, and 1.7% with CSF analysis. Scenarios 2 and 4 resulted in the highest proportion of accurate and timely diagnoses for amyloid-\u03b2-positive patients (24.8% and 44.6%, respectively) versus 15.1% of patients in scenario 3.ConclusionsIt is imperative to address capacity issues for AD confirmatory testing to facilitate timely diagnosis and initiation of amyloid-targeting therapies. Increasing CSF analysis utilization has the capacity to meet this growing demand.", "source": "PubMed"}, {"chunk_id": "41555795_2", "pmid": "41555795", "title": "The capacity for Alzheimer's disease confirmatory testing in the United States: The current situation and simulations for future increase.", "authors": "Roth S, Yan J, Patru MM et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, United States, amyloid-\u03b2 peptides, biomarkers, medical economics, positron emission tomography", "chunk": "growing demand.", "source": "PubMed"}, {"chunk_id": "41282061_0", "pmid": "41282061", "title": "APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.", "authors": "Lizi\u0144czyk AM, Pankiewicz JE, Cullina WL et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, apolipoprotein E, astrocytes, microglia, neurodegeneration, neuroinflammation, prion diseases, prion protein", "chunk": "<i>APOE</i> polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer's disease, primary tauopathies, \u03b1-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using <i>APOE</i> targeted replacement (TR) mice, we investigated how <i>APOE</i> genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female <i>\u03b52/\u03b52</i>, <i>\u03b53/\u03b53</i>, and <i>\u03b54/\u03b54 APOE</i>-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. <i>\u03b54/\u03b54</i> <sub>22L</sub> mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. <i>\u03b52/\u03b52</i> <sub>22L</sub> mice performed significantly better than <i>\u03b54/\u03b54</i> <sub>22L</sub> mice but significantly worse than <i>\u03b53/\u03b53</i> <sub>22L</sub> animals. Numerous aspects of PrP proteinopathy were", "source": "PubMed"}, {"chunk_id": "41282061_1", "pmid": "41282061", "title": "APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.", "authors": "Lizi\u0144czyk AM, Pankiewicz JE, Cullina WL et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, apolipoprotein E, astrocytes, microglia, neurodegeneration, neuroinflammation, prion diseases, prion protein", "chunk": "and the highest load of spongiform lesions. <i>\u03b52/\u03b52</i> <sub>22L</sub> mice performed significantly better than <i>\u03b54/\u03b54</i> <sub>22L</sub> mice but significantly worse than <i>\u03b53/\u03b53</i> <sub>22L</sub> animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the <i>\u03b54</i> allele including increased PrP<sup>Sc</sup> accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between <i>\u03b52/\u03b52</i> <sub>22L</sub> and <i>\u03b53/\u03b53</i> <sub>22L</sub> mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in <i>\u03b54/\u03b54</i> <sub>22L</sub> mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in <i>\u03b54/\u03b54</i> <sub>22L</sub> mice. <i>\u03b54/\u03b54</i> <sub>22L</sub> mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by <i>\u03b52/\u03b52</i> <sub>22L</sub>, with <i>\u03b53/\u03b53</i> <sub>22L</sub> having the lowest. Thus, <i>APOE</i> polymorphism differentially regulates the progression of prion pathology attributable to two <i>\u03b54</i>-affected mechanisms: increased conversion and accumulation of PrP<sup>Sc</sup>", "source": "PubMed"}, {"chunk_id": "41282061_2", "pmid": "41282061", "title": "APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.", "authors": "Lizi\u0144czyk AM, Pankiewicz JE, Cullina WL et al.", "year": "2025", "journal": "Research square", "keywords": "Alzheimer\u2019s disease, apolipoprotein E, astrocytes, microglia, neurodegeneration, neuroinflammation, prion diseases, prion protein", "chunk": "by <i>\u03b52/\u03b52</i> <sub>22L</sub>, with <i>\u03b53/\u03b53</i> <sub>22L</sub> having the lowest. Thus, <i>APOE</i> polymorphism differentially regulates the progression of prion pathology attributable to two <i>\u03b54</i>-affected mechanisms: increased conversion and accumulation of PrP<sup>Sc</sup> and worsened prion-associated neuroinflammation. Though less severely than <i>\u03b54</i>, the <i>\u03b52</i> allele also increased the inflammatory response, rendering disease outcome worse relative to the <i>\u03b53</i> allele. Our findings suggest both <i>\u03b54</i> and <i>\u03b52</i> alleles are disadvantageous determinants in prion pathology.", "source": "PubMed"}, {"chunk_id": "39664587_0", "pmid": "39664587", "title": "Inhibition of miR-4763-3p expression activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to ameliorate cognitive decline.", "authors": "Qi W, Ying Y, Wu P et al.", "year": "2024", "journal": "International journal of biological sciences", "keywords": "AD-MCI, apoptosis, autophagy, phosphatidylserine", "chunk": "Cognitive decline and memory impairment are subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs has been implicated in the pathogenesis of Alzheimer's disease (AD) and may play a pivotal role in the early stages of the disease. In this study, we identified the critical role of miR-4763-3p in AD pathogenesis, focusing on early-stage mild cognitive impairment (AD-MCI). Leveraging fluorescence <i>in situ</i> hybridization, we observed miR-4763-3p upregulation in AD hippocampal tissue, colocalizing with A\u03b2 and Tau. Antagomir-mediated inhibition of miR-4763-3p ameliorated cognitive decline in AD-MCI mice. RNA-seq and functional assays revealed that miR-4763-3p targets ATP11A, and antagomir enhancing inward flipping of the \"eat me\" phosphatidylserine signal on the surface of neuronal cells, autophagy, and clearance of A\u03b2/lipofuscin, while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI,", "source": "PubMed"}, {"chunk_id": "39664587_1", "pmid": "39664587", "title": "Inhibition of miR-4763-3p expression activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to ameliorate cognitive decline.", "authors": "Qi W, Ying Y, Wu P et al.", "year": "2024", "journal": "International journal of biological sciences", "keywords": "AD-MCI, apoptosis, autophagy, phosphatidylserine", "chunk": "while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI, offering a novel strategy to enhance neuronal autophagy, alleviate inflammation, and improve cognitive function.", "source": "PubMed"}, {"chunk_id": "36209638_0", "pmid": "36209638", "title": "Associations of sensory and motor function with blood-based biomarkers of neurodegeneration and Alzheimer's disease in midlife.", "authors": "Paulsen AJ, Schubert CR, Pinto AA et al.", "year": "2022", "journal": "Neurobiology of aging", "keywords": "Alzheimer's disease, Biomarker, Dementia, Neurodegeneration", "chunk": "Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (A\u03b2)). Mixed-effects models with baseline sensory and motor function as determinants and 10-year biomarker change as outcome were used. Participants with hearing impairment and worse motor function (among women) showed faster increases in NfL level over time (0.8% per year; 0.3% per year, respectively). There were no significant associations with TTau or A\u03b2. We found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and", "source": "PubMed"}, {"chunk_id": "36209638_1", "pmid": "36209638", "title": "Associations of sensory and motor function with blood-based biomarkers of neurodegeneration and Alzheimer's disease in midlife.", "authors": "Paulsen AJ, Schubert CR, Pinto AA et al.", "year": "2022", "journal": "Neurobiology of aging", "keywords": "Alzheimer's disease, Biomarker, Dementia, Neurodegeneration", "chunk": "found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and motor changes are more reflective of general neurodegeneration than AD-specific pathology and whether sensory and motor tests may be useful screening tools for neurodegeneration risk.", "source": "PubMed"}, {"chunk_id": "41038490_0", "pmid": "41038490", "title": "Bifunctional chitosan-based nanocarriers as promising therapeutic approach for brain disease therapy: A critical review focusing on multiple sclerosis over emerging strategies, technologies and applications.", "authors": "Naghib SM, Khorasani MA, Sharifianjazi F et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Blood-brain barrier, CS nanoparticles, Drug delivery, Immunomodulation, Multiple sclerosis, Neuroprotection", "chunk": "Chitosan (CS) has appeared as a promising candidate in brain disease (BD) (such as Alzheimer's, Parkinson's, and Multiple sclerosis (MS)) therapy due to its anti-inflammatory, antioxidative, and neuroprotective properties. CS's capacity to interact with the blood-brain barrier (BBB) enhances the central nervous system (CNS) drug permeability, offering new avenues for effective treatment strategies aimed at overcoming the limitations of conventional therapies. Furthermore, CS's role in regenerative medicine extends beyond drug delivery, as it fosters neural repair by providing a supportive microenvironment for oligodendrocyte proliferation and neuronal regeneration. Studies have shown that CS-based scaffolds, when combined with neurotrophic factors and stem cells, can enhance remyelination and neuroprotection in BD models. The immunomodulatory effects of CS further contribute to reducing neuroinflammation by shifting immune responses toward an anti-inflammatory phenotype, thereby mitigating the progression of BD-associated damage. This review provides a comprehensive analysis of the latest advancements in CS-based BD therapies, exploring its", "source": "PubMed"}, {"chunk_id": "41038490_1", "pmid": "41038490", "title": "Bifunctional chitosan-based nanocarriers as promising therapeutic approach for brain disease therapy: A critical review focusing on multiple sclerosis over emerging strategies, technologies and applications.", "authors": "Naghib SM, Khorasani MA, Sharifianjazi F et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Blood-brain barrier, CS nanoparticles, Drug delivery, Immunomodulation, Multiple sclerosis, Neuroprotection", "chunk": "shifting immune responses toward an anti-inflammatory phenotype, thereby mitigating the progression of BD-associated damage. This review provides a comprehensive analysis of the latest advancements in CS-based BD therapies, exploring its multifunctional applications in drug delivery, immune modulation, and tissue engineering. The discussion also addresses the current challenges in clinical translation, including variability in CS formulations, regulatory considerations, and potential safety concerns. Future research directions should focus on optimizing CS derivatives, improving its bioavailability, and integrating it with emerging therapeutic approaches such as gene therapy and biomimetic nanocarriers.", "source": "PubMed"}, {"chunk_id": "35068458_0", "pmid": "35068458", "title": "Toward Pre-Diagnostic Detection of Dementia in Primary Care.", "authors": "Levy B, Priest A, Delaney T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, dementia, pre-diagnostic detection, prevention, primary care, screening", "chunk": "Preventing dementia warrants the pragmatic engagement of primary care. This study predicted conversion to dementia 12 months before diagnosis with indicators that primary care can utilize within the practical constraints of routine practice. The study analyzed data from the Alzheimer's Disease Neuroimaging Initiative (Total sample = 645, converting participants = 54). It predicted the conversion from biological (plasma neurofilament light chain), cognitive (Trails Making Test- B), and functional (Functional Activities Questionnaire) measures, in addition to demographic variables (age and education). A Gradient Booster Trees classifier effectively predicted the conversion, based on a Synthetic Minority Oversampling Technique (n = 1,290, F1 Score = 92, AUC = 94, Recall = 87, Precision = 97, Accuracy = 92). Subsequent analysis indicated that the MCI False Positive group (i.e., non-converting participants with cognitive impairment flagged by the model for prospective conversion) scored significantly lower on multiple cognitive tests (Montreal Cognitive Assessment, p < 0.002;", "source": "PubMed"}, {"chunk_id": "35068458_1", "pmid": "35068458", "title": "Toward Pre-Diagnostic Detection of Dementia in Primary Care.", "authors": "Levy B, Priest A, Delaney T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, dementia, pre-diagnostic detection, prevention, primary care, screening", "chunk": "MCI False Positive group (i.e., non-converting participants with cognitive impairment flagged by the model for prospective conversion) scored significantly lower on multiple cognitive tests (Montreal Cognitive Assessment, p < 0.002; ADAS-13, p < 0.0004; Rey Auditory Verbal Learning Test, p < 0.002/0.003) than the MCI True Negative group (i.e., correctly classified non-converting participants with cognitive impairment). These groups also differed in CSF tau levels (p < 0.04), while consistent effect size differences emerged in the all-pairwise comparisons of hippocampal volume and CSF A\u03b21 - 42. The model effectively predicted 12-month conversion to dementia and further identified non-converting participants with MCI, in the False Positive group, at relatively higher neurocognitive risk. Future studies may seek to extend these results to earlier prodromal phases. Detection of dementia before diagnosis may be feasible and practical in primary care settings, pending replication of these findings in diverse clinical samples.", "source": "PubMed"}, {"chunk_id": "35068458_2", "pmid": "35068458", "title": "Toward Pre-Diagnostic Detection of Dementia in Primary Care.", "authors": "Levy B, Priest A, Delaney T et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, dementia, pre-diagnostic detection, prevention, primary care, screening", "chunk": "prodromal phases. Detection of dementia before diagnosis may be feasible and practical in primary care settings, pending replication of these findings in diverse clinical samples.", "source": "PubMed"}, {"chunk_id": "38706284_0", "pmid": "38706284", "title": "24-Hour Blood Pressure Variability Via Ambulatory Monitoring and Risk for Probable Dementia in the SPRINT Trial.", "authors": "Sible IJ, Nation DA", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Blood pressure variability, ambulatory blood pressure monitoring, antihypertensives, dementia", "chunk": "Blood pressure variability is an emerging risk factor for dementia, independent and oftentimes beyond mean blood pressure levels. Recent evidence from interventional cohorts with rigorously controlled mean blood pressure levels suggest blood pressure variability over months to years remains a risk for dementia, but no prior studies have investigated relationships with blood pressure variability over shorter time periods. To investigate the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering. Post hoc analysis of the randomized, controlled, open-label Systolic Blood Pressure Intervention Trial clinical trial. Multisite Systolic Blood Pressure Intervention Trial. 793 participants at increased risk for cardiovascular disease and without history of dementia at study randomization. Standard (<140 mmHg systolic blood pressure target) vs intensive (<120 mmHg systolic blood pressure target) lowering of mean blood pressure. 24-hour ambulatory blood pressure monitoring 27 months after treatment randomization (standard vs", "source": "PubMed"}, {"chunk_id": "38706284_1", "pmid": "38706284", "title": "24-Hour Blood Pressure Variability Via Ambulatory Monitoring and Risk for Probable Dementia in the SPRINT Trial.", "authors": "Sible IJ, Nation DA", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Blood pressure variability, ambulatory blood pressure monitoring, antihypertensives, dementia", "chunk": "mmHg systolic blood pressure target) vs intensive (<120 mmHg systolic blood pressure target) lowering of mean blood pressure. 24-hour ambulatory blood pressure monitoring 27 months after treatment randomization (standard vs intensive) and follow-up cognitive testing. Intraindividual blood pressure variability was calculated as the average real variability over 24-hour, daytime, and nighttime periods. Participants were categorized into 3 adjudicated clinical outcomes: no cognitive impairment, mild cognitive impairment, probable dementia. Cox proportional hazards models examined the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering. Associations with mean blood pressure were also explored. Higher systolic 24-hour blood pressure variability was associated with increased risk for probable dementia in the standard group (adjusted hazard ratio [HR]: 2.56 [95% CI 1.16, 5.62], p = 0.019) but not in the intensive group (HR: 0.54 [95% CI 0.24, 1.23], p = 0.141). Similar findings were", "source": "PubMed"}, {"chunk_id": "38706284_2", "pmid": "38706284", "title": "24-Hour Blood Pressure Variability Via Ambulatory Monitoring and Risk for Probable Dementia in the SPRINT Trial.", "authors": "Sible IJ, Nation DA", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Blood pressure variability, ambulatory blood pressure monitoring, antihypertensives, dementia", "chunk": "(adjusted hazard ratio [HR]: 2.56 [95% CI 1.16, 5.62], p = 0.019) but not in the intensive group (HR: 0.54 [95% CI 0.24, 1.23], p = 0.141). Similar findings were observed with daytime systolic blood pressure variability but not nighttime blood pressure variability. Mean blood pressure was not associated with cognitive outcomes. Higher systolic 24-hour and daytime blood pressure variability via ambulatory monitoring is associated with risk for dementia under standard blood pressure treatment. Findings support prior evidence that blood pressure variability remains a risk for dementia despite strict control of mean blood pressure levels.", "source": "PubMed"}, {"chunk_id": "40495607_0", "pmid": "40495607", "title": "Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline.", "authors": "Shi D, Ye C, Li A et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, GAP\u201043, NfL, axonal degeneration, neurodegeneration, presynaptic loss", "chunk": "Baseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood. We investigated dynamic changes of CSF GAP-43 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years. Individuals with hippocampal atrophy, AD-signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid/tau status. In contrast, none of these N+ imaging indicators correlated with more rapid increases in CSF GAP-43. Furthermore, CSF GAP-43 and plasma NfL synergistically predicted subsequent gray matter atrophy, cortical thinning, hypometabolism of the middle temporal region, and cognition. CSF GAP-43-associated presynaptic loss indicates tau-dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy/hypometabolism-associated fluid neurodegeneration biomarker. Plasma neurofilament light", "source": "PubMed"}, {"chunk_id": "40495607_1", "pmid": "40495607", "title": "Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline.", "authors": "Shi D, Ye C, Li A et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, GAP\u201043, NfL, axonal degeneration, neurodegeneration, presynaptic loss", "chunk": "region, and cognition. CSF GAP-43-associated presynaptic loss indicates tau-dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy/hypometabolism-associated fluid neurodegeneration biomarker. Plasma neurofilament light (NfL) was increased in N+ or cognitively impaired individuals. Increases in tau-dependent cerebrospinal fluid CSF growth-associated protein 43 (GAP-43) before imaging neurodegeneration indicators. CSF GAP-43 and plasma NfL are synergistically related to longitudinal neurodegeneration. CSF GAP-43 and plasma NfL are synergistically related to longitudinal cognitive decline.", "source": "PubMed"}, {"chunk_id": "39821948_0", "pmid": "39821948", "title": "Searching for responders to multidomain dementia prevention in late life: A pooled analysis of individual participant data from the MAPT and preDIVA trials.", "authors": "Coley N, Hoevenaar-Blom MP, Shourick J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "dementia, differential intervention effect, efficacy, multidomain intervention, prevention, risk, subgroup analysis", "chunk": "It is unknown in which, if any, subgroups of older adults multidomain interventions are effective at reducing long-term dementia incidence. We pooled up to 12 years of follow-up data from 5205 participants aged > 70 from the Multidomain Alzheimer Preventive Trial (MAPT) and Prevention of Dementia by Intensive Vascular Care (preDIVA) studies. The primary outcome was incident all-cause dementia. Pre-specified subgroups were defined by dementia risk factors (age, sex, education, apolipoprotein E [APOE] genotype, cognitive status, and cardiovascular risk factors). Four hundred eighty-six participants developed dementia during 37,782 person-years of follow-up. Higher incidence was associated with baseline age, APOE \u03b54 genotype, physical inactivity, Mini-Mental State Examination, and blood pressure. Multidomain intervention had no effect on incident dementia overall (hazard ratio = 0.98, 95% confidence interval 0.80-1.21), or in any pre-specified subgroup. A recursive partitioning algorithm also did not detect any subgroups, defined by single or multiple risk factors, showing a", "source": "PubMed"}, {"chunk_id": "39821948_1", "pmid": "39821948", "title": "Searching for responders to multidomain dementia prevention in late life: A pooled analysis of individual participant data from the MAPT and preDIVA trials.", "authors": "Coley N, Hoevenaar-Blom MP, Shourick J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "dementia, differential intervention effect, efficacy, multidomain intervention, prevention, risk, subgroup analysis", "chunk": "= 0.98, 95% confidence interval 0.80-1.21), or in any pre-specified subgroup. A recursive partitioning algorithm also did not detect any subgroups, defined by single or multiple risk factors, showing a differential intervention effect. We did not identify any subgroups of older adults in whom multidomain interventions significantly reduced incident dementia. MAPT: NCT00672685 (clinicaltrials.gov); PreDIVA: ISRCTN29711771 (ISRCTN registry) HIGHLIGHTS: We pooled up to 12 years of follow-up data from two multidomain prevention trials. Five thousand two hundred five participants aged \u2265 70 were included. Subgroups were pre-defined by modifiable and non-modifiable dementia risk factors. A data-driven recursive partitioning algorithm was also used. Multidomain intervention did not lower incident dementia overall or in any subgroup.", "source": "PubMed"}, {"chunk_id": "26290229_0", "pmid": "26290229", "title": "Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-\u03b2 Clearance.", "authors": "Gontier G, George C, Chaker Z et al.", "year": "2015", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "Alzheimer's disease, amyloid-\u03b2, conditional mutagenesis, insulin-like growth factor, mouse model, neuron", "chunk": "Alzheimer's disease (AD) is a frequent and irreversible age-related neurodegeneration without efficient treatment. Experimental AD in mice responds positively to decreased insulin-like growth factor I (IGF-I) signaling, a pathway also implicated in aging. Here we aimed to protect the aging brain from devastating amyloid pathology by making specifically adult neurons resistant to IGF signaling. To achieve that, we knocked out neuronal IGF-1R during adulthood in APP/PS1 mice. We found that mutants exhibited improved spatial memory and reduced anxiety. Mutant brains displayed fewer amyloid plaques, less amyloid-\u03b2 (A\u03b2), and diminished neuroinflammation. Surprisingly, adult neurons undergoing IGF-1R knock-out reduced their apical soma and developed leaner dendrites, indicative of remarkable structural plasticity entailing condensed forebrain neuroarchitecture. Neurons lacking IGF-1R in AD showed less accumulation of A\u03b2-containing autophagic vacuoles. At the same time, plasma A\u03b2 levels were increased. Our data indicate that neuronal IGF-1R ablation, via preserved autophagic compartment and enhanced systemic elimination, offers", "source": "PubMed"}, {"chunk_id": "26290229_1", "pmid": "26290229", "title": "Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-\u03b2 Clearance.", "authors": "Gontier G, George C, Chaker Z et al.", "year": "2015", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "Alzheimer's disease, amyloid-\u03b2, conditional mutagenesis, insulin-like growth factor, mouse model, neuron", "chunk": "accumulation of A\u03b2-containing autophagic vacuoles. At the same time, plasma A\u03b2 levels were increased. Our data indicate that neuronal IGF-1R ablation, via preserved autophagic compartment and enhanced systemic elimination, offers lifelong protection from AD pathology by clearing toxic A\u03b2. Neuronal IGF-1R, and possibly other cell size-controlling pathways are promising targets for AD treatment. We found compelling evidence in vivo that Alzheimer's disease (AD) progression is significantly delayed when insulin-like growth factor (IGF) signaling is blocked in adult neurons. To show that, we built a novel mouse model, combining inducible neuron-specific IGF-1R knock-out with AD transgenics. Analysis of the experimental AD phenotype revealed less abundant amyloid-\u03b2 (A\u03b2) peptides, fewer plaques, and diminished neuroinflammation in mutants with inactivated IGF signaling, together with clearly preserved behavioral and memory performances. We present for the first time evidence that IGF signaling has profound effects on neuronal proteostasis and maintenance of cell morphology in vivo. Our", "source": "PubMed"}, {"chunk_id": "26290229_2", "pmid": "26290229", "title": "Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-\u03b2 Clearance.", "authors": "Gontier G, George C, Chaker Z et al.", "year": "2015", "journal": "The Journal of neuroscience : the official journal of the Society for Neuroscience", "keywords": "Alzheimer's disease, amyloid-\u03b2, conditional mutagenesis, insulin-like growth factor, mouse model, neuron", "chunk": "clearly preserved behavioral and memory performances. We present for the first time evidence that IGF signaling has profound effects on neuronal proteostasis and maintenance of cell morphology in vivo. Our results indicate in a model highly pertinent to translational research that neuronal IGF resistance may represent a pathophysiologically relevant mechanism of the brain for preventing A\u03b2 accumulation.", "source": "PubMed"}, {"chunk_id": "36370225_0", "pmid": "36370225", "title": "Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice.", "authors": "Shima T, Kawabata-Iwakawa R, Onishi H et al.", "year": "2023", "journal": "Metabolic brain disease", "keywords": "Light-intensity exercise, Memory function, Monocarboxylate transporter, Type 2 diabetes, miR-Seq", "chunk": "Cognitive decline associated with type 2 diabetes mellitus (T2DM) is a risk factor to impair human health. Although light-intensity exercise prevents hippocampal memory dysfunction in pre-symptomatic T2DM animals by altering hippocampal lactate transport and neurotrophic factors, the effects of light-intensity exercise in an advanced stage of T2DM animals remain unclear. Here, ob/ob mice, an animal model of T2DM, were subjected to light-intensity exercise (5.0 m/min) for 30 min/day, five days/week for four weeks. The effects of light-intensity exercise on hippocampal complications, mRNA expressions of monocarboxylate transporter (MCT), and miRNA levels were assessed. The light-intensity exercise improved hippocampal memory retention in ob/ob mice. Downregulated hippocampal Mct2 mRNA levels in T2DM were improved with light-intensity exercise. Hippocampal mRNA levels of Mct1 and Mct4 were unchanged within groups. Based on miRNA sequencing, sedentary ob/ob mice exhibited that 71 miRNAs were upregulated, and 77 miRNAs were downregulated in the hippocampus. In addition, the exercise", "source": "PubMed"}, {"chunk_id": "36370225_1", "pmid": "36370225", "title": "Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice.", "authors": "Shima T, Kawabata-Iwakawa R, Onishi H et al.", "year": "2023", "journal": "Metabolic brain disease", "keywords": "Light-intensity exercise, Memory function, Monocarboxylate transporter, Type 2 diabetes, miR-Seq", "chunk": "Mct4 were unchanged within groups. Based on miRNA sequencing, sedentary ob/ob mice exhibited that 71 miRNAs were upregulated, and 77 miRNAs were downregulated in the hippocampus. In addition, the exercise significantly increased 24 miRNAs and decreased 4 miRNAs in the T2DM hippocampus. The exercise reversed T2DM-induced alterations of hippocampal 9 miRNAs, including miR-200a-3p. Our findings imply that miR-200a-3p/Mct2 in the hippocampus would be a possible clinical target for treating T2DM-induced memory dysfunction.", "source": "PubMed"}, {"chunk_id": "37523918_0", "pmid": "37523918", "title": "Evaluation of MRI-based machine learning approaches for computer-aided diagnosis of dementia in a clinical data warehouse.", "authors": "Bottani S, Burgos N, Maire A et al.", "year": "2023", "journal": "Medical image analysis", "keywords": "Clinical data warehouse, Deep learning, Dementia, MRI, Neuroimaging, Shortcut learning", "chunk": "A variety of algorithms have been proposed for computer-aided diagnosis of dementia from anatomical brain MRI. These approaches achieve high accuracy when applied to research data sets but their performance on real-life clinical routine data has not been evaluated yet. The aim of this work was to study the performance of such approaches on clinical routine data, based on a hospital data warehouse, and to compare the results to those obtained on a research data set. The clinical data set was extracted from the hospital data warehouse of the Greater Paris area, which includes 39 different hospitals. The research set was composed of data from the Alzheimer's Disease Neuroimaging Initiative data set. In the clinical set, the population of interest was identified by exploiting the diagnostic codes from the 10th revision of the International Classification of Diseases that are assigned to each patient. We studied how the imbalance of the", "source": "PubMed"}, {"chunk_id": "37523918_1", "pmid": "37523918", "title": "Evaluation of MRI-based machine learning approaches for computer-aided diagnosis of dementia in a clinical data warehouse.", "authors": "Bottani S, Burgos N, Maire A et al.", "year": "2023", "journal": "Medical image analysis", "keywords": "Clinical data warehouse, Deep learning, Dementia, MRI, Neuroimaging, Shortcut learning", "chunk": "was identified by exploiting the diagnostic codes from the 10th revision of the International Classification of Diseases that are assigned to each patient. We studied how the imbalance of the training sets, in terms of contrast agent injection and image quality, may bias the results. We demonstrated that computer-aided diagnosis performance was strongly biased upwards (over 17 percent points of balanced accuracy) by the confounders of image quality and contrast agent injection, a phenomenon known as the Clever Hans effect or shortcut learning. When these biases were removed, the performance was very poor. In any case, the performance was considerably lower than on the research data set. Our study highlights that there are still considerable challenges for translating dementia computer-aided diagnosis systems to clinical routine.", "source": "PubMed"}, {"chunk_id": "37523918_2", "pmid": "37523918", "title": "Evaluation of MRI-based machine learning approaches for computer-aided diagnosis of dementia in a clinical data warehouse.", "authors": "Bottani S, Burgos N, Maire A et al.", "year": "2023", "journal": "Medical image analysis", "keywords": "Clinical data warehouse, Deep learning, Dementia, MRI, Neuroimaging, Shortcut learning", "chunk": "diagnosis systems to clinical routine.", "source": "PubMed"}, {"chunk_id": "40516772_0", "pmid": "40516772", "title": "Advances in alginate-based nanoformulations: Innovative and effective strategies for targeting and treating brain disorders.", "authors": "Rawat E, Sharma S, Vyas S et al.", "year": "2025", "journal": "International journal of pharmaceutics", "keywords": "Alginate, Blood brain barrier, Nanoformulations, Neurological disorders, Targeted therapy", "chunk": "Brain disorders, encompassing neurodegenerative conditions and intracranial neoplasms, present formidable obstacles in the realm of pharmacological delivery due to the existence of athe blood-brain barrier (BBB) and the restricted bioavailability of therapeutic agents. Alginate-derived nanoformulations have emerged as highly promising systems for drug delivery, offering attributes such as biocompatibility, regulated release, and improved targeting efficacies. This review investigates contemporary advancements in alginate-based nanoformulations, with a particular emphasis on their efficacy in surmounting obstacles to successful pharmacological delivery to the brain. Initially, we furnish a comprehensive overview of alginate, underscoring its pertinent properties, biomedical applications, and inherent limitations. Subsequently, the discourse progresses to strategies for nanoformulation, which encompass lipid-based, polymeric, and inorganic methodologies, with a focus on their benefits in relation to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and", "source": "PubMed"}, {"chunk_id": "40516772_1", "pmid": "40516772", "title": "Advances in alginate-based nanoformulations: Innovative and effective strategies for targeting and treating brain disorders.", "authors": "Rawat E, Sharma S, Vyas S et al.", "year": "2025", "journal": "International journal of pharmaceutics", "keywords": "Alginate, Blood brain barrier, Nanoformulations, Neurological disorders, Targeted therapy", "chunk": "to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis. By amalgamating cutting-edge nanotechnology with the distinctive properties of alginate, these formulations signify a promising pathway for the advancement of efficacious therapies aimed at brain targeting. Additionally, prospective research trajectories and challenges associated with the optimization of alginate-based nanocarriers for clinical applications are also elucidated.", "source": "PubMed"}, {"chunk_id": "30040724_0", "pmid": "30040724", "title": "Quantitative PET and Histology of Brain Biopsy Reveal Lack of Selective Pittsburgh Compound-B Binding to Intracerebral Amyloidoma.", "authors": "Groot C, Tolboom N, Ikonomovic MD et al.", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Amyloid, case study, histology, positron emission tomography", "chunk": "This single case study examines selective Pittsburgh compound-B (PiB) binding to an intracerebral light-chain amyloidoma using a 90-minute dynamic [11C]PiB-PET scan and brain biopsy tissue. Parametric non-displaceable binding potential (BPND) images showed low specific binding in the amyloidoma (BPND = 0.23), while relative tracer delivery was adequate (R1 = 0.44). Histology of the tissue revealed strong coloring with Congo-red, thioflavin-S, and X-34, indicating presence of amyloid. However, immunological staining with 6F/3D revealed absence of amyloid-\u03b2 and histofluorescence of 6-CN-PiB, a highly fluorescent derivative of PiB, was at background levels. Our results suggest that PiB does not detect the atypical amyloid pathology associated with an intracerebral light-chain amyloidoma. These findings are of interest to clinicians and researchers applying [11C]PiB-PET to detect atypical forms of amyloid pathology.", "source": "PubMed"}, {"chunk_id": "30040724_1", "pmid": "30040724", "title": "Quantitative PET and Histology of Brain Biopsy Reveal Lack of Selective Pittsburgh Compound-B Binding to Intracerebral Amyloidoma.", "authors": "Groot C, Tolboom N, Ikonomovic MD et al.", "year": "2018", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Amyloid, case study, histology, positron emission tomography", "chunk": "atypical forms of amyloid pathology.", "source": "PubMed"}, {"chunk_id": "38382645_0", "pmid": "38382645", "title": "Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests.", "authors": "Barth\u00e9lemy NR, Salvad\u00f3 G, Schindler SE et al.", "year": "2024", "journal": "Nature medicine", "keywords": "None", "chunk": "With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-\u03b2 (A\u03b2) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort (n = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for A\u03b242/40 and p-tau181/A\u03b242. The primary and secondary outcomes were detection of brain A\u03b2 or tau pathology, respectively, using positron emission tomography (PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments.", "source": "PubMed"}, {"chunk_id": "38382645_1", "pmid": "38382645", "title": "Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests.", "authors": "Barth\u00e9lemy NR, Salvad\u00f3 G, Schindler SE et al.", "year": "2024", "journal": "Nature medicine", "keywords": "None", "chunk": "(PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying A\u03b2 PET status, with an area under the curve (AUC) for both between 0.95 and 0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired subcohorts (BioFINDER-2: n = 720; Knight ADRC: n = 50), plasma %p-tau217 had an accuracy, a positive predictive value and a negative predictive value of 89-90% for A\u03b2 PET and 87-88% for tau PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two-cutoffs approach. Blood plasma %p-tau217 demonstrated performance that was clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use", "source": "PubMed"}, {"chunk_id": "38382645_2", "pmid": "38382645", "title": "Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests.", "authors": "Barth\u00e9lemy NR, Salvad\u00f3 G, Schindler SE et al.", "year": "2024", "journal": "Nature medicine", "keywords": "None", "chunk": "to 95% using a two-cutoffs approach. Blood plasma %p-tau217 demonstrated performance that was clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high-performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.", "source": "PubMed"}, {"chunk_id": "39387454_0", "pmid": "39387454", "title": "Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.", "authors": "Devanand DP, Lee S, Luchsinger JA et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "amyloid imaging, cognition, cognitive decline, dementia, olfaction, positron emission tomography", "chunk": "We evaluated impaired odor identification and global cognition as simple, cost-effective alternatives to neuroimaging biomarkers to predict cognitive decline and dementia in the Mayo Clinic Study of Aging. Six hundred forty-seven participants (mean 8.1, standard deviation 3.4 years' follow-up) had the following baseline procedures: modified Blessed Information Memory Concentration Test (BIMCT), 12-item Brief Smell Identification Test (BSIT), structural brain magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging with 11C-Pittsburgh compound B (11C-PiB) and fluorodeoxyglucose (FDG; subset). Cognitive decline developed in 102 participants and dementia in 34 participants. In survival analyses, PiB PET showed robust prediction for cognitive decline. Impaired BSIT, impaired BIMCT, MRI, and FDG measures were also significant predictors. The combination of demographics + BSIT + BIMCT showed strong predictive utility (C-index 0.81), similar to demographics + PiB PET (C-index 0.80). Similar but stronger results were obtained for prediction of dementia. Impairment in both odor identification test", "source": "PubMed"}, {"chunk_id": "39387454_1", "pmid": "39387454", "title": "Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.", "authors": "Devanand DP, Lee S, Luchsinger JA et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "amyloid imaging, cognition, cognitive decline, dementia, olfaction, positron emission tomography", "chunk": "showed strong predictive utility (C-index 0.81), similar to demographics + PiB PET (C-index 0.80). Similar but stronger results were obtained for prediction of dementia. Impairment in both odor identification test and global cognition was comparable to PiB PET for predicting cognitive decline and dementia. In 647 participants in the population-based Mayo Clinic Study of Aging, several clinical markers and biomarkers each predicted cognitive decline or dementia during an average 8 years of follow-up. The combination of the demographic variables of age, sex, and education with a brief odor identification test (BSIT) and a global cognitive test (Blessed Information Memory Concentration Test) showed strong predictive utility (C-index 0.81) for cognitive decline that was similar to the demographic variables combined with Pittsburgh Compound B amyloid imaging (C-index 0.80). Combining a brief odor identification test with a brief cognitive test needs consideration as a simple, cost-effective option in the clinical assessment of individuals", "source": "PubMed"}, {"chunk_id": "39387454_2", "pmid": "39387454", "title": "Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.", "authors": "Devanand DP, Lee S, Luchsinger JA et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "amyloid imaging, cognition, cognitive decline, dementia, olfaction, positron emission tomography", "chunk": "Compound B amyloid imaging (C-index 0.80). Combining a brief odor identification test with a brief cognitive test needs consideration as a simple, cost-effective option in the clinical assessment of individuals at risk of cognitive decline and dementia, as well as a potential tool to identify individuals who may benefit from disease-modifying treatments and to screen participants for prevention trials.", "source": "PubMed"}, {"chunk_id": "38718161_0", "pmid": "38718161", "title": "Synthesis and Evaluation of a Novel PET Radioligand for Imaging Glutaminyl Cyclase Activity as a Biomarker for Detecting Alzheimer's Disease.", "authors": "Behof WJ, Haynes JR, Whitmore CA et al.", "year": "2024", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease, PET imaging, [18F]PB0822, glutaminyl cyclase, pyroglutamate Abeta", "chunk": "Several new lines of research have demonstrated that a significant number of amyloid-\u03b2 peptides found in Alzheimer's disease (AD) are truncated and undergo post-translational modification by glutaminyl cyclase (QC) at the N-terminal. Notably, QC's products of Abeta-pE3 and Abeta-pE11 have been active targets for investigational drug development. This work describes the design, synthesis, characterization, and in vivo validation of a novel PET radioligand, [<sup>18</sup>F]PB0822, for targeted imaging of QC. We report herein a simplified and robust chemistry for the synthesis of the standard compound, [<sup>19</sup>F]PB0822, and the corresponding [<sup>18</sup>F]PB0822 radioligand. The PET probe was developed with 99.9% radiochemical purity, a molar activity of 965 Ci.mmol<sup>-1</sup>, and an IC<sub>50</sub> of 56.3 nM, comparable to those of the parent PQ912 inhibitor (62.5 nM). Noninvasive PET imaging showed that the probe is distributed in the brain 5 min after intravenous injection. Further, in vivo PET imaging with [<sup>18</sup>F]PB0822 revealed that AD 5XFAD mice", "source": "PubMed"}, {"chunk_id": "38718161_1", "pmid": "38718161", "title": "Synthesis and Evaluation of a Novel PET Radioligand for Imaging Glutaminyl Cyclase Activity as a Biomarker for Detecting Alzheimer's Disease.", "authors": "Behof WJ, Haynes JR, Whitmore CA et al.", "year": "2024", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease, PET imaging, [18F]PB0822, glutaminyl cyclase, pyroglutamate Abeta", "chunk": "nM). Noninvasive PET imaging showed that the probe is distributed in the brain 5 min after intravenous injection. Further, in vivo PET imaging with [<sup>18</sup>F]PB0822 revealed that AD 5XFAD mice harbor significantly higher QC activity than WT counterparts. The data also suggested that QC activity is found across different brain regions of the tested animals.", "source": "PubMed"}, {"chunk_id": "41554399_0", "pmid": "41554399", "title": "Stable isotope measurement of in vivo nitric oxide production in health and disease: an updated systematic review and meta-analysis.", "authors": "Loftus T, Benjamim J, Vaccarezza M et al.", "year": "2026", "journal": "Nitric oxide : biology and chemistry", "keywords": "Measurement protocols, Nitric oxide, Stable isotope tracers, Systematic review", "chunk": "Nitric oxide (NO) is involved in the regulation of vascular, immune and metabolic functions. Physiological modelling of stable isotope tracers provides an accurate method to measure whole-body NO production in humans. A systematic review and meta-analysis of studies using stable isotope methods was conducted to measure in vivo NO production in healthy individuals and patients with various disease conditions, characterise production rates across different populations and assess methodological factors contributing to measurement variability. PubMed/MEDLINE, Embase, Scopus and Web of Science databases were searched from inception to April 2025. Random-effect models were used to estimate of NO production. Risk of bias was assessed using the BIOCROSS scale for biomarker studies. Publication bias was evaluated by Funnel Plots and Egger's regression test. 58 studies were included in the systematic review, and 42 had valid data to be included in the meta-analysis. Mean NO production in healthy adults was 0.74 (95 %CI 0.47,", "source": "PubMed"}, {"chunk_id": "41554399_1", "pmid": "41554399", "title": "Stable isotope measurement of in vivo nitric oxide production in health and disease: an updated systematic review and meta-analysis.", "authors": "Loftus T, Benjamim J, Vaccarezza M et al.", "year": "2026", "journal": "Nitric oxide : biology and chemistry", "keywords": "Measurement protocols, Nitric oxide, Stable isotope tracers, Systematic review", "chunk": "58 studies were included in the systematic review, and 42 had valid data to be included in the meta-analysis. Mean NO production in healthy adults was 0.74 (95 %CI 0.47, 1.00) \u03bcmol\u00b7kg<sup>-1</sup>\u00b7hour<sup>-1</sup> and ranged from 0.73 to 4.89 \u03bcmol kg<sup>-1</sup>\u00b7hour<sup>-1</sup> depending on methodology and population characteristics. NO production in cardiovascular diseases [0.19 (95 %CI 0.11, 0.28) \u03bcmol\u00b7kg<sup>-1</sup>\u00b7hour<sup>-1</sup>] and metabolic diseases [0.43 (95 %CI 0.21, 0.64) \u03bcmol\u00b7kg<sup>-1</sup>\u00b7hour<sup>-1</sup>] was associated with lower physiological NO production. Conversely, chronic kidney disease [5.42 (95 %CI 2.04, 8.81) \u03bcmol\u00b7kg<sup>-1</sup>\u00b7hour<sup>-1</sup>] and inflammatory conditions [1.35 (95 %CI 0.78, 1.92) \u03bcmol\u00b7kg<sup>-1</sup>\u00b7hour<sup>-1</sup>] were associated with increased NO production. Chronic metabolic and cardiovascular diseases were overall characterised by a lower NO production. Standardisation of stable isotope protocols and reference ranges are needed to improve clinical utility for monitoring and therapy.", "source": "PubMed"}, {"chunk_id": "41554399_2", "pmid": "41554399", "title": "Stable isotope measurement of in vivo nitric oxide production in health and disease: an updated systematic review and meta-analysis.", "authors": "Loftus T, Benjamim J, Vaccarezza M et al.", "year": "2026", "journal": "Nitric oxide : biology and chemistry", "keywords": "Measurement protocols, Nitric oxide, Stable isotope tracers, Systematic review", "chunk": "needed to improve clinical utility for monitoring and therapy.", "source": "PubMed"}, {"chunk_id": "39059466_0", "pmid": "39059466", "title": "Medial Amygdalar Tau Is Associated With Mood Symptoms in Preclinical Alzheimer's Disease.", "authors": "Li JS, Tun SM, Ficek-Tani B et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Amygdala, Anxiety, Default mode network, Depression, Functional networks, Preclinical Alzheimer\u2019s disease", "chunk": "While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms. We examined 598 individuals (347 amyloid positive [58% female], 251 amyloid negative [62% female] subset in tau positron emission tomography and functional magnetic resonance imaging cohorts) from the A4 (Anti-Amyloid Treatment in Asymptomatic AD) Study. In the tau positron emission tomography cohort, we used amygdalar segmentations to examine representative nuclei from 3 functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the functional magnetic resonance imaging cohort.", "source": "PubMed"}, {"chunk_id": "39059466_1", "pmid": "39059466", "title": "Medial Amygdalar Tau Is Associated With Mood Symptoms in Preclinical Alzheimer's Disease.", "authors": "Li JS, Tun SM, Ficek-Tani B et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Amygdala, Anxiety, Default mode network, Depression, Functional networks, Preclinical Alzheimer\u2019s disease", "chunk": "We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the functional magnetic resonance imaging cohort. Finally, we conducted exploratory post hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores. Amyloid-positive individuals demonstrated increased tau binding in the medial and lateral amygdala, and tau binding in these regions was associated with mood symptoms. Across amygdalar divisions, amyloid-positive individuals had relatively higher regional connectivity from the amygdala to other temporal regions, the insula, and the orbitofrontal cortex, but medial amygdala to retrosplenial cortex connectivity was lower. Medial amygdala to retrosplenial connectivity was negatively associated with anxiety symptoms, as was retrosplenial tau. Our findings suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may be related to early mood symptoms in AD.", "source": "PubMed"}, {"chunk_id": "39059466_2", "pmid": "39059466", "title": "Medial Amygdalar Tau Is Associated With Mood Symptoms in Preclinical Alzheimer's Disease.", "authors": "Li JS, Tun SM, Ficek-Tani B et al.", "year": "2024", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Amygdala, Anxiety, Default mode network, Depression, Functional networks, Preclinical Alzheimer\u2019s disease", "chunk": "suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may be related to early mood symptoms in AD.", "source": "PubMed"}, {"chunk_id": "39496415_0", "pmid": "39496415", "title": "[Effects of JAL-TA9 on cognitive deficits in Alzheimer's disease model mouse].", "authors": "Zou S", "year": "2024", "journal": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "keywords": "None", "chunk": "Many studies have been conducted to find an effective drug for Alzheimer's disease (AD) treatment. However, no effective drug applicable for clinical use has been developed. Recently, the FDA approved Lecanemab, an antibody drug that acts as an aggregation inhibitor against Amyloid-beta (A\u03b2), for AD treatment. However, there are still no fundamental drugs for AD. In this study, we present a strategy for AD treatment that removes A\u03b2 by cleavage reaction using one of the Catalytides, JAL-TA9 (YKGSGFRMI). A single dose of JAL-TA9 administered into the CA1 region of the hippocampus and the intraventricular space improved the deficits in short-term memory of APP-knock-in mice. It also improved the memory of A\u03b225-35-induced model mice, as evaluated by the Y-maze and objective recognition tests. These data strongly suggest that JAL-TA9 could be effective in treating AD. However, these administration methods are difficult to apply clinically due to their high invasiveness. Thus, we", "source": "PubMed"}, {"chunk_id": "39496415_1", "pmid": "39496415", "title": "[Effects of JAL-TA9 on cognitive deficits in Alzheimer's disease model mouse].", "authors": "Zou S", "year": "2024", "journal": "Nihon yakurigaku zasshi. Folia pharmacologica Japonica", "keywords": "None", "chunk": "recognition tests. These data strongly suggest that JAL-TA9 could be effective in treating AD. However, these administration methods are difficult to apply clinically due to their high invasiveness. Thus, we tested the improvement effects of dementia by administering JAL-TA9 nasally. It is very interesting and exciting that the dementia of A\u03b225-35 induced AD model mice was improved by four applications once every three days. These results strongly suggest that JAL-TA9 is the best candidate for AD treatment because it is effective even in the late stage of AD.", "source": "PubMed"}, {"chunk_id": "40057456_0", "pmid": "40057456", "title": "Comparing high and low amyloid producers in Alzheimer's disease: An in-depth analysis.", "authors": "Leroy M, Aziz AL, Schraen S et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "A/T/N, Alzheimer's disease, A\u03b2(42/40) ratio, Cerebrospinal fluid biomarkers", "chunk": "The cerebrospinal fluid (CSF) A\u03b2<sub>42/40</sub> ratio has proven to be a more reliable biomarker for amyloid pathology than CSF A\u03b2<sub>42</sub> in Alzheimer's disease (AD), helping to correctly classify patients with positive tau biomarkers (T+) that would otherwise have remained outside of the AD continuum. It was shown that the A\u03b2<sub>42/40</sub> ratio better captures a relative decrease of A\u03b2<sub>42</sub> in patients with high CSF A\u03b2. However, whether patients with high-amyloid (HiA) AD, in whom A+ is defined by the A\u03b2<sub>42/40</sub> ratio, exactly compare with their low-amyloid (LoA) counterparts, in whom A+ is defined by A\u03b2<sub>42</sub> solely, deserves further analysis. We retrospectively included patients with A+T+ AD and evidence of cognitive and neurodegenerative changes (N+). LoA patients were operationally defined as patients with T+N+ and low CSF A\u03b2<sub>42</sub>, while HiA patients were defined as patients with T+N+ and normal CSF A\u03b2<sub>42</sub> but abnormal A\u03b2<sub>42/40</sub> ratio. Tau CSF biomarkers, neuropsychological profile, rates of", "source": "PubMed"}, {"chunk_id": "40057456_1", "pmid": "40057456", "title": "Comparing high and low amyloid producers in Alzheimer's disease: An in-depth analysis.", "authors": "Leroy M, Aziz AL, Schraen S et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "A/T/N, Alzheimer's disease, A\u03b2(42/40) ratio, Cerebrospinal fluid biomarkers", "chunk": "with T+N+ and low CSF A\u03b2<sub>42</sub>, while HiA patients were defined as patients with T+N+ and normal CSF A\u03b2<sub>42</sub> but abnormal A\u03b2<sub>42/40</sub> ratio. Tau CSF biomarkers, neuropsychological profile, rates of cognitive decline, structural and metabolic imaging, ApoE genotype and brain neuropathology were compared between the HiA and LoA groups. At the time of the lumbar puncture, LoA patients were significantly younger than the HiA patients (68.9\u00b18.7years vs. 71.8\u00b19.4; P=0.0015) and had a lower Mini-Mental Status Examination (MMSE) (18.7\u00b16.4 vs. 20.7\u00b16.2; P=0.0005). There was no difference in the neuropsychological profile nor in the annual rates of cognitive decline between the two groups with early AD. No differences were retrieved between groups on CSF Tau and P-Tau biomarkers, atrophy and brain metabolism, distribution of the APOE4 allele and APOE4/E4 genotype, and neuropathology. Overall, our study supports the surrogate use of the A\u03b2<sub>42/40</sub> ratio as an equivalent to A\u03b2<sub>42</sub> to define AD. We", "source": "PubMed"}, {"chunk_id": "40057456_2", "pmid": "40057456", "title": "Comparing high and low amyloid producers in Alzheimer's disease: An in-depth analysis.", "authors": "Leroy M, Aziz AL, Schraen S et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "A/T/N, Alzheimer's disease, A\u03b2(42/40) ratio, Cerebrospinal fluid biomarkers", "chunk": "distribution of the APOE4 allele and APOE4/E4 genotype, and neuropathology. Overall, our study supports the surrogate use of the A\u03b2<sub>42/40</sub> ratio as an equivalent to A\u03b2<sub>42</sub> to define AD. We showed that HiA CSF profiles were not associated with differences in cognition, brain structures and metabolism, APOE genotype tau CSF biomarkers or the rates of cognitive decline, but may be the associated with later-onset and early-stage AD.", "source": "PubMed"}, {"chunk_id": "41565312_0", "pmid": "41565312", "title": "Retinal biomarkers for early Alzheimer's detection: a systematic review of optical coherence tomography (OCT) findings.", "authors": "Lepoittevin M, Greig J, Erol O et al.", "year": "2026", "journal": "BMJ open ophthalmology", "keywords": "Degeneration, Imaging, Retina", "chunk": "Retinal biomarkers accessible via non-invasive optical coherence tomography (OCT) could facilitate early detection of Alzheimer's disease (AD), complementing current invasive or costly diagnostic methods. This review evaluates the evidence for spectral-domain OCT (SD-OCT) and OCT angiography (OCT-A) in identifying retinal changes associated with preclinical and early AD. We conducted a systematic review registered in PROSPERO and aligned with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed/MEDLINE was searched up to April 2025, complemented by reference list screening and citation tracking. Eligible studies assessed SD-OCT and/or OCT-A in biomarker-defined preclinical or early AD, mild cognitive impairment or mild AD. Data were synthesised narratively by disease stage, and methodological quality was appraised with the Newcastle-Ottawa Scale. 22 studies met inclusion criteria. Reported alterations included thinning of the peripapillary retinal nerve fibre layer and retinal ganglion cell layer, macular and choroidal thickness changes and microvascular alterations on OCT-A. However, findings", "source": "PubMed"}, {"chunk_id": "41565312_1", "pmid": "41565312", "title": "Retinal biomarkers for early Alzheimer's detection: a systematic review of optical coherence tomography (OCT) findings.", "authors": "Lepoittevin M, Greig J, Erol O et al.", "year": "2026", "journal": "BMJ open ophthalmology", "keywords": "Degeneration, Imaging, Retina", "chunk": "inclusion criteria. Reported alterations included thinning of the peripapillary retinal nerve fibre layer and retinal ganglion cell layer, macular and choroidal thickness changes and microvascular alterations on OCT-A. However, findings were heterogeneous: some studies observed early thickening or increased vascular density, possibly reflecting inflammatory or compensatory mechanisms, while others reported thinning and rarefaction more consistent with neurodegeneration. Most studies were of moderate quality, limited by small sample sizes, cross-sectional designs and incomplete control for ocular/systemic confounders. SD-OCT and OCT-A hold promise as candidate biomarkers of early AD, but current evidence remains variable, non-specific and methodologically constrained. Further research is needed to standardise imaging protocols, validate findings in biomarker-confirmed longitudinal cohorts and compare OCT-based measures across dementia subtypes. Integration with other biomarkers (eg, plasma or metabolomics) may improve diagnostic specificity and support translation of OCT/OCT-A into clinical practice. CRD42024600456.", "source": "PubMed"}, {"chunk_id": "41565312_2", "pmid": "41565312", "title": "Retinal biomarkers for early Alzheimer's detection: a systematic review of optical coherence tomography (OCT) findings.", "authors": "Lepoittevin M, Greig J, Erol O et al.", "year": "2026", "journal": "BMJ open ophthalmology", "keywords": "Degeneration, Imaging, Retina", "chunk": "biomarkers (eg, plasma or metabolomics) may improve diagnostic specificity and support translation of OCT/OCT-A into clinical practice. CRD42024600456.", "source": "PubMed"}, {"chunk_id": "38804091_0", "pmid": "38804091", "title": "Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders.", "authors": "Zheng J, Zong X, Tang L et al.", "year": "2024", "journal": "Psychological medicine", "keywords": "genetic risks, gray matter volume, maturational subtypes, mood disorders, normative modeling", "chunk": "Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine. We recruited 174 drug-na\u00efve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort. Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for", "source": "PubMed"}, {"chunk_id": "38804091_1", "pmid": "38804091", "title": "Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders.", "authors": "Zheng J, Zong X, Tang L et al.", "year": "2024", "journal": "Psychological medicine", "keywords": "genetic risks, gray matter volume, maturational subtypes, mood disorders, normative modeling", "chunk": "GMV deviations based subtyping analysis in a replication cohort. Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable. Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.", "source": "PubMed"}, {"chunk_id": "41318861_0", "pmid": "41318861", "title": "Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.", "authors": "Yadav JP, Yadav S, Dubey NK et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Clinical management, Immune dysregulation, LCS, Pathophysiology, Persistent symptoms, SARS-CoV-2", "chunk": "Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies,", "source": "PubMed"}, {"chunk_id": "41318861_1", "pmid": "41318861", "title": "Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.", "authors": "Yadav JP, Yadav S, Dubey NK et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Clinical management, Immune dysregulation, LCS, Pathophysiology, Persistent symptoms, SARS-CoV-2", "chunk": "treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.", "source": "PubMed"}, {"chunk_id": "32139775_0", "pmid": "32139775", "title": "Shared Causal Paths underlying Alzheimer's dementia and Type 2 Diabetes.", "authors": "Hu Z, Jiao R, Wang P et al.", "year": "2020", "journal": "Scientific reports", "keywords": "None", "chunk": "Although Alzheimer's disease (AD) is a central nervous system disease and type 2 diabetes MELLITUS (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however such analyses lack power to discover the mechanisms of the diseases. As an alternative, we developed novel causal inference methods for genetic studies of AD and T2DM and pipelines for systematic multi-omic casual analysis to infer multilevel omics causal networks for the discovery of common paths from genetic variants to AD and T2DM. The proposed pipelines were applied to 448 individuals from the ROSMAP Project. We identified 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks.", "source": "PubMed"}, {"chunk_id": "32139775_1", "pmid": "32139775", "title": "Shared Causal Paths underlying Alzheimer's dementia and Type 2 Diabetes.", "authors": "Hu Z, Jiao R, Wang P et al.", "year": "2020", "journal": "Scientific reports", "keywords": "None", "chunk": "genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks.", "source": "PubMed"}, {"chunk_id": "40519469_0", "pmid": "40519469", "title": "The Effect of Chronic Inflammation and Oxidative Stress on Alzheimer's Disease Progression: A Systematic Review.", "authors": "Bornemann EA, Kamma HK, Alabbas M et al.", "year": "2025", "journal": "Cureus", "keywords": "alzheimer's disease, metabolic syndrome, neuroinflammation, oxidative stress, pro-inflammatory state., systemic inflammation", "chunk": "Alzheimer's Disease (AD) is known to be the most common type of dementia among older adults. It is characterized by a gradual decline in cognitive abilities, particularly the deterioration of short-term memory. The hallmark neuropathology of AD is the accumulation of neurofibrillary tau tangles (NFTs), which consist of hyperphosphorylated tau protein, as well as extracellular beta-amyloid plaques in the brain. Evidence suggests that AD is not solely tied to neurological mechanisms, and that other factors, such as inflammation, can affect disease progression, including systemic inflammation seen in metabolic syndrome and oxidative stress. We performed a literature review by searching databases and conducting a manual search of studies regarding the relationship between AD, inflammation, and oxidative stress, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After meticulous scrutiny and the application of inclusion and exclusion criteria to clinically relevant papers, 14 studies were deemed relevant for this", "source": "PubMed"}, {"chunk_id": "40519469_1", "pmid": "40519469", "title": "The Effect of Chronic Inflammation and Oxidative Stress on Alzheimer's Disease Progression: A Systematic Review.", "authors": "Bornemann EA, Kamma HK, Alabbas M et al.", "year": "2025", "journal": "Cureus", "keywords": "alzheimer's disease, metabolic syndrome, neuroinflammation, oxidative stress, pro-inflammatory state., systemic inflammation", "chunk": "Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After meticulous scrutiny and the application of inclusion and exclusion criteria to clinically relevant papers, 14 studies were deemed relevant for this review regarding the effect of inflammation and oxidative stress in relation to AD and its progression. The findings conclude that there is new evidence supporting the theory that chronic inflammation plays a significant role in the progression of the disease, which could allow for future advancements in treatments, diagnostics, and preventive tools for its management. These advancements could include the implementation and use of biomarkers for inflammation, the use of algorithms to stratify the disease's grade, and the use of mineral supplements like zinc. Furthermore, the management of underlying conditions has been shown to be beneficial in slowing the progression of AD.", "source": "PubMed"}, {"chunk_id": "40519469_2", "pmid": "40519469", "title": "The Effect of Chronic Inflammation and Oxidative Stress on Alzheimer's Disease Progression: A Systematic Review.", "authors": "Bornemann EA, Kamma HK, Alabbas M et al.", "year": "2025", "journal": "Cureus", "keywords": "alzheimer's disease, metabolic syndrome, neuroinflammation, oxidative stress, pro-inflammatory state., systemic inflammation", "chunk": "has been shown to be beneficial in slowing the progression of AD.", "source": "PubMed"}, {"chunk_id": "34992526_0", "pmid": "34992526", "title": "Does Chronic Sleep Fragmentation Lead to Alzheimer's Disease in Young Wild-Type Mice?", "authors": "Ba L, Huang L, He Z et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, F-18-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET), amyloid-\u03b2, neuroinflammation, sleep fragmentation, stress, tau", "chunk": "Chronic sleep insufficiency is becoming a common issue in the young population nowadays, mostly due to life habits and work stress. Studies in animal models of neurological diseases reported that it would accelerate neurodegeneration progression and exacerbate interstitial metabolic waste accumulation in the brain. In this paper, we study whether chronic sleep insufficiency leads to neurodegenerative diseases in young wild-type animals without a genetic pre-disposition. To this aim, we modeled chronic sleep fragmentation (SF) in young wild-type mice. We detected pathological hyperphosphorylated-tau (Ser396/Tau5) and gliosis in the SF hippocampus. <sup>18</sup>F-labeled fluorodeoxyglucose positron emission tomography scan (<sup>18</sup>F-FDG-PET) further revealed a significant increase in brain glucose metabolism, especially in the hypothalamus, hippocampus and amygdala. Hippocampal RNAseq indicated that immunological and inflammatory pathways were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease,", "source": "PubMed"}, {"chunk_id": "34992526_1", "pmid": "34992526", "title": "Does Chronic Sleep Fragmentation Lead to Alzheimer's Disease in Young Wild-Type Mice?", "authors": "Ba L, Huang L, He Z et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, F-18-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET), amyloid-\u03b2, neuroinflammation, sleep fragmentation, stress, tau", "chunk": "were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease, normal aging, and APOE\u03b54 mutation mouse models did not exhibit any significant pattern. In summary, 1.5-month sleep fragmentation could generate AD-like pathological changes including tauopathy and gliosis, mainly linked to stress, as the incremented glucose metabolism observed with PET imaging suggested. Further investigation will show whether SF could eventually lead to chronic neurodegeneration if the stress condition is prolonged in time.", "source": "PubMed"}, {"chunk_id": "21307566_0", "pmid": "21307566", "title": "Production of anti-amyloid \u03b2 antibodies in mice fed rice expressing amyloid \u03b2.", "authors": "Nojima J, Ishii-Katsuno R, Futai E et al.", "year": "2011", "journal": "Bioscience, biotechnology, and biochemistry", "keywords": "None", "chunk": "The main signs of Alzheimer's disease (AD) are cognitive impairment and senile plaques composed of amyloid beta (A\u03b2) observed in patients' brains. Therefore, therapy for AD focuses on the removal of A\u03b2. We developed an \"edible vaccine\" that employs intestinal immunity with little to no side effects. Rice was utilized as an edible vaccine. It expressed GFP-A\u03b242. A\u03b2 rice was administered orally to wild-type (WT) mice causing production of anti-A\u03b2 antibodies. Since A\u03b2 rice was mixed with the cholera toxin B subunit (CTB), antibody against the rice seed protein was also produced. Then, mice were caused to develop immune tolerance against the rice seed protein by oral administration of A\u03b2 rice mixed with CTB. The results indicated that only anti-A\u03b2 antibodies were produced.", "source": "PubMed"}, {"chunk_id": "21307566_1", "pmid": "21307566", "title": "Production of anti-amyloid \u03b2 antibodies in mice fed rice expressing amyloid \u03b2.", "authors": "Nojima J, Ishii-Katsuno R, Futai E et al.", "year": "2011", "journal": "Bioscience, biotechnology, and biochemistry", "keywords": "None", "chunk": "antibodies were produced.", "source": "PubMed"}, {"chunk_id": "35721012_0", "pmid": "35721012", "title": "Deep Learning Model for Prediction of Progressive Mild Cognitive Impairment to Alzheimer's Disease Using Structural MRI.", "authors": "Lim BY, Lai KW, Haiskin K et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, deep learning, magnetic resonance imaging, mild cognitive impairment, prediction", "chunk": "Alzheimer's disease (AD) is an irreversible neurological disorder that affects the vast majority of dementia cases, leading patients to experience gradual memory loss and cognitive function decline. Despite the lack of a cure, early detection of Alzheimer's disease permits the provision of preventive medication to slow the disease's progression. The objective of this project is to develop a computer-aided method based on a deep learning model to distinguish Alzheimer's disease (AD) from cognitively normal and its early stage, mild cognitive impairment (MCI), by just using structural MRI (sMRI). To attain this purpose, we proposed a multiclass classification method based on 3D T1-weight brain sMRI images from the ADNI database. Axial brain images were extracted from 3D MRI and fed into the convolutional neural network (CNN) for multiclass classification. Three separate models were tested: a CNN built from scratch, VGG-16, and ResNet-50. As a feature extractor, the VGG-16 and ResNet-50 convolutional", "source": "PubMed"}, {"chunk_id": "35721012_1", "pmid": "35721012", "title": "Deep Learning Model for Prediction of Progressive Mild Cognitive Impairment to Alzheimer's Disease Using Structural MRI.", "authors": "Lim BY, Lai KW, Haiskin K et al.", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, deep learning, magnetic resonance imaging, mild cognitive impairment, prediction", "chunk": "the convolutional neural network (CNN) for multiclass classification. Three separate models were tested: a CNN built from scratch, VGG-16, and ResNet-50. As a feature extractor, the VGG-16 and ResNet-50 convolutional bases trained on the ImageNet dataset were employed. To achieve classification, a new densely connected classifier was implemented on top of the convolutional bases.", "source": "PubMed"}, {"chunk_id": "41229731_0", "pmid": "41229731", "title": "TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.", "authors": "Nasir AR, Delpirou Nouh C", "year": "2025", "journal": "Frontiers in cellular neuroscience", "keywords": "TDP-43, biomarkers, copathology, neuroimaging, tauopathies", "chunk": "Though usually described as isolated models, neurodegenerative diseases exist in a significant proportion of cases as mixed pathologies, particularly in older adults. The presence of co-pathologies may influence phenotypes and progression, and the correct classification <i>in vivo</i> has proven to be challenging, particularly without proper biomarker panels. Recent breakthroughs in biomarkers, enabling earlier detection in Alzheimer's disease and, more recently, in synuclein-related diseases, are promising as a first step toward the wider detection of all other abnormal proteins involved in neurodegenerative diseases. Over the past decade, the growing body of research on TDP-43 pathology has led to considering TDP-43 as a potential major contributor to the neurodegenerative process. TDP-43's normal function is essential for neuronal survival and the regulation of RNA processing and cellular stress response; abnormal TDP-43 protein leads to altered cell function and survival. TDP-43 is notably the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) as well as", "source": "PubMed"}, {"chunk_id": "41229731_1", "pmid": "41229731", "title": "TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.", "authors": "Nasir AR, Delpirou Nouh C", "year": "2025", "journal": "Frontiers in cellular neuroscience", "keywords": "TDP-43, biomarkers, copathology, neuroimaging, tauopathies", "chunk": "RNA processing and cellular stress response; abnormal TDP-43 protein leads to altered cell function and survival. TDP-43 is notably the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) as well as some form of frontotemporolobar degeneration (FTLD). Tauopathies, divided in primary or secondary tauopathies cover other forms of FTLD including Pick disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) but also non-FTLD diseases like Alzheimer's disease (AD) which can be classified as secondary tauopathy. As the importance of copathology is more and more recognized, TDP-43 is also frequently observed in conjunction with other proteinopathies, possibly with a synergistic or additive effect, although the exact mechanism is still unclear. In Alzheimer's disease, the limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) co-occurrence with Alzheimer's disease neuropathologic changes (ADNC) lead to a more rapid course. Although there are currently no approved and validated biomarkers for its early detection, several promising tools, including", "source": "PubMed"}, {"chunk_id": "41229731_2", "pmid": "41229731", "title": "TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.", "authors": "Nasir AR, Delpirou Nouh C", "year": "2025", "journal": "Frontiers in cellular neuroscience", "keywords": "TDP-43, biomarkers, copathology, neuroimaging, tauopathies", "chunk": "co-occurrence with Alzheimer's disease neuropathologic changes (ADNC) lead to a more rapid course. Although there are currently no approved and validated biomarkers for its early detection, several promising tools, including neuroimaging and biofluid biomarkers, are under development, offering hope for the earlier detection of TDP-43 pathology <i>in vivo</i>. Accurate identification of the underlying proteinopathies and pathological processes could lead to better diagnosis and classification, more precise selection of clinical trial candidates, and ultimately, disease-specific tailored treatments.", "source": "PubMed"}, {"chunk_id": "37541842_0", "pmid": "37541842", "title": "Association of Plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> Ratio and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.", "authors": "Johnson EL, Sullivan KJ, Schneider ALC et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "The objective of this study was to determine the relationship between plasma \u03b2-amyloid (A\u03b2), specifically the ratio of 2 A\u03b2 peptides (the A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratio, which correlates with increased accumulation of A\u03b2 in the CNS), and late-onset epilepsy (LOE). We used Medicare fee-for-service claims codes from 1991 to 2018 to identify cases of LOE among 1,424 Black and White men and women enrolled in the Atherosclerosis Risk in Communities (ARIC) study cohort. The A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratio was calculated from plasma samples collected from ARIC participants in 1993-1995 (age 50-71 years) and 2011-2013 (age 67-90 years). We used survival analysis accounting for the competing risk of death to determine the relationship between late-life plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and its change from midlife to late life, and the subsequent development of epilepsy. We adjusted for demographics, the apolipoprotein e4 genotype, and comorbidities, including stroke, dementia, and head injury. A low plasma ratio of 2 A\u03b2 peptides,", "source": "PubMed"}, {"chunk_id": "37541842_1", "pmid": "37541842", "title": "Association of Plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> Ratio and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.", "authors": "Johnson EL, Sullivan KJ, Schneider ALC et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "and the subsequent development of epilepsy. We adjusted for demographics, the apolipoprotein e4 genotype, and comorbidities, including stroke, dementia, and head injury. A low plasma ratio of 2 A\u03b2 peptides, the A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratio, correlates with low CSF A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> and with increased accumulation of A\u03b2 in the CNS. Decrease in plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratio from midlife to late life, but not an isolated measurement of A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, was associated with development of epilepsy in later life. For every 50% reduction in A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, there was a 2-fold increase in risk of epilepsy (adjusted subhazard ratio 2.30, 95% CI 1.27-4.17). A reduction in plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> is associated with an increased risk of subsequent epilepsy. Our observations provide a further validation of the link between A\u03b2, hyperexcitable states, and LOE.", "source": "PubMed"}, {"chunk_id": "37541842_2", "pmid": "37541842", "title": "Association of Plasma A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> Ratio and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.", "authors": "Johnson EL, Sullivan KJ, Schneider ALC et al.", "year": "2023", "journal": "Neurology", "keywords": "None", "chunk": "hyperexcitable states, and LOE.", "source": "PubMed"}, {"chunk_id": "39584780_0", "pmid": "39584780", "title": "Identification and cognitive function prediction of Alzheimer's disease based on multivariate pattern analysis of hippocampal volumes.", "authors": "Gao Z, Zhu W, Li Y et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amnestic mild cognitive impairment, hippocampus, relevance vector regression, structural magnetic resonance image, support vector machine", "chunk": "Alzheimer's disease (AD) is strongly associated with slowly progressive hippocampal atrophy. Elucidating the relationships between local morphometric changes and disease status for early diagnosis could be aided by machine learning algorithms trained on neuroimaging datasets. This study intended to propose machine learning models for the accurate identification and cognitive function prediction across the AD severity spectrum based on structural magnetic resonance imaging (sMRI) of the bilateral hippocampi. The high-resolution sMRI data of 120 AD dementia patients, 232 amnestic mild cognitive impairment (aMCI) patients, and 206 healthy controls (HCs) were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The classification capacity and cognitive predict ability of hippocampal volume was evaluated by multiple pattern analysis using the support vector machine (SVM) and relevance vector regression (RVR) application of the Pattern Recognition for Neuroimaging Toolbox, separately. For validation, the analyses were performed using a biomarker-based regrouping method and another independent local dataset. The", "source": "PubMed"}, {"chunk_id": "39584780_1", "pmid": "39584780", "title": "Identification and cognitive function prediction of Alzheimer's disease based on multivariate pattern analysis of hippocampal volumes.", "authors": "Gao Z, Zhu W, Li Y et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amnestic mild cognitive impairment, hippocampus, relevance vector regression, structural magnetic resonance image, support vector machine", "chunk": "relevance vector regression (RVR) application of the Pattern Recognition for Neuroimaging Toolbox, separately. For validation, the analyses were performed using a biomarker-based regrouping method and another independent local dataset. The SVM application produced a total accuracy of 94.17%, 80.85%, and 70.74% and area under receiver operating characteristic curves of 0.97, 0.87, and 0.72 between HC versus AD dementia, HC versus aMCI, and aMCI versus AD dementia classification, respectively. The RVR application significantly predicted the baseline and mean cognitive function at three years of follow-up. Qualitatively consistent results were obtained using different regrouping method and the local dataset. The machine learning methods based on the bilateral hippocampi distinguished across the AD severity spectrum and predicted the baseline and the longitudinal cognitive function with greater accuracy.", "source": "PubMed"}, {"chunk_id": "39584780_2", "pmid": "39584780", "title": "Identification and cognitive function prediction of Alzheimer's disease based on multivariate pattern analysis of hippocampal volumes.", "authors": "Gao Z, Zhu W, Li Y et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amnestic mild cognitive impairment, hippocampus, relevance vector regression, structural magnetic resonance image, support vector machine", "chunk": "function with greater accuracy.", "source": "PubMed"}, {"chunk_id": "32898682_0", "pmid": "32898682", "title": "Disentangling time series between brain tissues improves fMRI data quality using a time-dependent deep neural network.", "authors": "Yang Z, Zhuang X, Sreenivasan K et al.", "year": "2020", "journal": "NeuroImage", "keywords": "Alzheimer's disease, Artificial intelligence, Deep learning, Deep neural network, fMRI denoising", "chunk": "Functional MRI (fMRI) is a prominent imaging technique to probe brain function, however, a substantial proportion of noise from multiple sources influences the reliability and reproducibility of fMRI data analysis and limits its clinical applications. Extensive effort has been devoted to improving fMRI data quality, but in the last two decades, there is no consensus reached which technique is more effective. In this study, we developed a novel deep neural network for denoising fMRI data, named denoising neural network (DeNN). This deep neural network is 1) applicable without requiring externally recorded data to model noise; 2) spatially and temporally adaptive to the variability of noise in different brain regions at different time points; 3) automated to output denoised data without manual interference; 4) trained and applied on each subject separately and 5) insensitive to the repetition time (TR) of fMRI data. When we compared DeNN with a number of nuisance", "source": "PubMed"}, {"chunk_id": "32898682_1", "pmid": "32898682", "title": "Disentangling time series between brain tissues improves fMRI data quality using a time-dependent deep neural network.", "authors": "Yang Z, Zhuang X, Sreenivasan K et al.", "year": "2020", "journal": "NeuroImage", "keywords": "Alzheimer's disease, Artificial intelligence, Deep learning, Deep neural network, fMRI denoising", "chunk": "manual interference; 4) trained and applied on each subject separately and 5) insensitive to the repetition time (TR) of fMRI data. When we compared DeNN with a number of nuisance regression methods for denoising fMRI data from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, only DeNN had connectivity for functionally uncorrelated regions close to zero and successfully identified unbiased correlations between the posterior cingulate cortex seed and multiple brain regions within the default mode network or task positive network. The whole brain functional connectivity maps computed with DeNN-denoised data are approximately three times as homogeneous as the functional connectivity maps computed with raw data. Furthermore, the improved homogeneity strengthens rather than weakens the statistical power of fMRI in detecting intrinsic functional differences between cognitively normal subjects and subjects with Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "32898682_2", "pmid": "32898682", "title": "Disentangling time series between brain tissues improves fMRI data quality using a time-dependent deep neural network.", "authors": "Yang Z, Zhuang X, Sreenivasan K et al.", "year": "2020", "journal": "NeuroImage", "keywords": "Alzheimer's disease, Artificial intelligence, Deep learning, Deep neural network, fMRI denoising", "chunk": "differences between cognitively normal subjects and subjects with Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41023633_0", "pmid": "41023633", "title": "Convolutional neural network models of structural MRI for discriminating categories of cognitive impairment: a systematic review and meta-analysis.", "authors": "Dong X, Li Y, Hao J et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease, Convolutional neural networks, Diagnostic accuracy, Mild cognitive impairment, Radiomics, Structural magnetic resonance imaging", "chunk": "Alzheimer's disease (AD) and mild cognitive impairment (MCI) pose significant challenges to public health and underscore the need for accurate and early diagnostic tools. Structural magnetic resonance imaging (sMRI) combined with advanced analytical techniques like convolutional neural networks (CNNs) seemed to offer a promising avenue for the diagnosis of these conditions. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of CNN algorithms applied to sMRI data in differentiating between AD, MCI, and normal cognition (NC). Following the PRISMA-DTA guidelines, a comprehensive literature search was carried out in PubMed and Web of Science databases for studies published between 2018 and 2024. Studies were included if they employed CNNs for the diagnostic classification of sMRI data from participants with AD, MCI, or NC. The methodological quality of the included studies was assessed using the QUADAS-2 and METRICS tools. Data extraction and statistical analysis were performed to calculate pooled diagnostic", "source": "PubMed"}, {"chunk_id": "41023633_1", "pmid": "41023633", "title": "Convolutional neural network models of structural MRI for discriminating categories of cognitive impairment: a systematic review and meta-analysis.", "authors": "Dong X, Li Y, Hao J et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease, Convolutional neural networks, Diagnostic accuracy, Mild cognitive impairment, Radiomics, Structural magnetic resonance imaging", "chunk": "AD, MCI, or NC. The methodological quality of the included studies was assessed using the QUADAS-2 and METRICS tools. Data extraction and statistical analysis were performed to calculate pooled diagnostic accuracy metrics. A total of 21 studies were included in the study, comprising 16,139 participants in the analysis. The pooled sensitivity and specificity of CNN algorithms for differentiating AD from NC were 0.92 and 0.91, respectively. For distinguishing MCI from NC, the pooled sensitivity and specificity were 0.74 and 0.79, respectively. The algorithms also showed a moderate ability to differentiate AD from MCI, with a pooled sensitivity and specificity of 0.73 and 0.79, respectively. In the pMCI versus sMCI classification, a pooled sensitivity was 0.69 and a specificity was 0.81. Heterogeneity across studies was significant, as indicated by meta-regression results. CNN algorithms demonstrated promising diagnostic performance in differentiating AD, MCI, and NC using sMRI data. The highest accuracy was observed", "source": "PubMed"}, {"chunk_id": "41023633_2", "pmid": "41023633", "title": "Convolutional neural network models of structural MRI for discriminating categories of cognitive impairment: a systematic review and meta-analysis.", "authors": "Dong X, Li Y, Hao J et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Alzheimer\u2019s disease, Convolutional neural networks, Diagnostic accuracy, Mild cognitive impairment, Radiomics, Structural magnetic resonance imaging", "chunk": "Heterogeneity across studies was significant, as indicated by meta-regression results. CNN algorithms demonstrated promising diagnostic performance in differentiating AD, MCI, and NC using sMRI data. The highest accuracy was observed in distinguishing AD from NC and the lowest accuracy observed in distinguishing pMCI from sMCI. These findings suggest that CNN-based radiomics has the potential to serve as a valuable tool in the diagnostic armamentarium for neurodegenerative diseases. However, the heterogeneity among studies indicates a need for further methodological refinement and validation. This systematic review was registered in PROSPERO (Registration ID: CRD42022295408).", "source": "PubMed"}, {"chunk_id": "41181519_0", "pmid": "41181519", "title": "Generative diffusion model enables quantification of calibration-free arterial spin labeling perfusion magnetic resonance imaging data in an Alzheimer's disease cohort.", "authors": "Shou Q, Cen S, Chen NK et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, arterial spin labeling, diffusion model, quantification", "chunk": "M0 images were missing in Siemens ASL data in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, prohibiting cerebral blood flow (CBF) quantification. A conditional latent diffusion model was trained and evaluated on in-house datasets, then applied to the Siemens data in ADNI-3. Regional CBF differences by Alzheimer's disease (AD) stages, their accuracy for AD classification, and CBF trajectory slopes were compared between generated data (Siemens) and acquired data (General Electric). The diffusion model generated M0 images with high fidelity (SSIM = 0.918 \u00b1 0.023, PSNR = 31.361 \u00b1 2.537) and minimal CBF bias (mean difference is 0.21 \u00b1 1.58 mL/100 g/min). Both generated and acquired CBF showed similar spatial patterns and decreasing trends with AD progression in specific AD-related regions. Generated CBF also improved accuracy in classifying AD stages compared to qualitative perfusion images. This study shows the potential of diffusion models for imputing missing modalities in large-scale studies exploring the", "source": "PubMed"}, {"chunk_id": "41181519_1", "pmid": "41181519", "title": "Generative diffusion model enables quantification of calibration-free arterial spin labeling perfusion magnetic resonance imaging data in an Alzheimer's disease cohort.", "authors": "Shou Q, Cen S, Chen NK et al.", "year": "2025", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, arterial spin labeling, diffusion model, quantification", "chunk": "CBF also improved accuracy in classifying AD stages compared to qualitative perfusion images. This study shows the potential of diffusion models for imputing missing modalities in large-scale studies exploring the use of ASL as a biomarker of AD. Using latent diffusion model, we can generate M0 image from control image in arterial spin labeling (ASL) with high fidelity.The generated M0 can be used for cerebral blood flow (CBF) quantification in Alzheimer's Disease Neuroimaging Initiative dataset.The performance of classification between Alzheimer's disease (AD) patients and cognitive normal people is better when using generated CBF maps than using non-quantitative perfusion images.ASL CBF decreases with AD progression in key AD-related brain regions.", "source": "PubMed"}, {"chunk_id": "40332937_0", "pmid": "40332937", "title": "APOE4, Blood Neurodegenerative Biomarkers, and Cognitive Decline in Community-Dwelling Older Adults.", "authors": "Ng TKS, Beck T, Boyle P et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "Scarce population-based data exist on whether APOE4 modifies associations of blood-based neurodegenerative biomarkers with cognitive decline, particularly in a diverse, biracial population of community-dwelling older adults without dementia. To assess whether APOE4 carrier status is associated with an accelerated rate of cognitive decline in older adults without dementia and with elevated neurodegenerative burden. This 20-year prospective cohort study started in 1993 and was conducted through 2012 on the South Side of Chicago among community-dwelling older adults without dementia from the longitudinal biracial Chicago Health and Aging Project. The interaction of APOE4 carrier status with prospective associations of serum neurodegenerative biomarkers with global cognitive decline was examined using a mixed-effects regression model, adjusting for demographics and chronic health conditions. Statistical analyses were conducted from June 2024 to January 2025. APOE4 carrier status and serum biomarker levels for total tau (t-tau), neurofilament light (NfL) chain, and glial fibrillary acidic protein (GFAP) measured", "source": "PubMed"}, {"chunk_id": "40332937_1", "pmid": "40332937", "title": "APOE4, Blood Neurodegenerative Biomarkers, and Cognitive Decline in Community-Dwelling Older Adults.", "authors": "Ng TKS, Beck T, Boyle P et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "were conducted from June 2024 to January 2025. APOE4 carrier status and serum biomarker levels for total tau (t-tau), neurofilament light (NfL) chain, and glial fibrillary acidic protein (GFAP) measured with a Quanterix Neuroplex kit at baseline. Cognitive decline calculated from composite global cognition scores across study waves. Among 1038 community-dwelling older adults (mean [SD] age, 77.1 [5.9] years; 615 Black [59.2%] and 423 White [40.8%]; 651 female [62.7%]), there was a mean (SD) of 12.8 (3.4) years of education and 343 individuals (33.0%) were APOE4 carriers. Higher levels of blood-based neurodegenerative biomarkers (ie, t-tau, NfL, and GFAP) were associated with a faster rate of cognitive decline among APOE4 carriers than noncarriers. Specifically, compared with noncarriers, APOE4 carriers had annual rates of cognitive decline per 1-log10 unit higher levels in t-tau and GFAP that were accelerated by a \u03b2 (SD) of -0.03 (0.02) (P = .046) and -0.07 (0.03) (P", "source": "PubMed"}, {"chunk_id": "40332937_2", "pmid": "40332937", "title": "APOE4, Blood Neurodegenerative Biomarkers, and Cognitive Decline in Community-Dwelling Older Adults.", "authors": "Ng TKS, Beck T, Boyle P et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "rates of cognitive decline per 1-log10 unit higher levels in t-tau and GFAP that were accelerated by a \u03b2 (SD) of -0.03 (0.02) (P = .046) and -0.07 (0.03) (P = .02), respectively. Similarly, compared with noncarriers and participants in the lower NfL tertile, APOE4 carriers with middle and upper tertiles of NfL levels experienced accelerated cognitive decline, with a \u03b2 (SD) of -0.04 (0.02) (P = .006) and -0.03 (0.02) (P = .07), respectively, although the difference was not significant for upper tertiles. This study found that higher levels of neurodegeneration (t-tau), axonal injury (NfL), and reactive astrocytes and neuroinflammation (GFAP) biomarkers were associated with accelerated cognitive decline in genetically susceptible APOE4 carriers. These findings highlight the association of APOE4 with exacerbation of neurodegenerative processes, with not only significant implications for understanding and tracking the progression of neurodegenerative diseases, but also a call for inclusivity of APOE4 status in", "source": "PubMed"}, {"chunk_id": "40332937_3", "pmid": "40332937", "title": "APOE4, Blood Neurodegenerative Biomarkers, and Cognitive Decline in Community-Dwelling Older Adults.", "authors": "Ng TKS, Beck T, Boyle P et al.", "year": "2025", "journal": "JAMA network open", "keywords": "None", "chunk": "APOE4 with exacerbation of neurodegenerative processes, with not only significant implications for understanding and tracking the progression of neurodegenerative diseases, but also a call for inclusivity of APOE4 status in scientific investigations and clinical trials.", "source": "PubMed"}, {"chunk_id": "41332787_0", "pmid": "41332787", "title": "Degraded neural coding of temporal fine structure with age predicts effortful listening in multi-talker environments.", "authors": "Zhen L, Parida S, McHaney JR et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "Middle age represents a critical window for early detection of neurophysiological decline. Hearing loss is increasingly recognized as both an early marker of neural degeneration and a modifiable risk factor for dementia. Yet many adults report difficulty understanding speech in noise despite normal audiograms, highlighting the limitations of current clinical tests that fail to capture the underlying physiology or effort required for real-world listening. Beyond hearing thresholds, speech comprehension in complex environments depends on precise neural encoding of temporal fine structure (TFS) cues that convey pitch and spatial information. Here, we use a noninvasive EEG-based measure of neural phase-locking (frequency modulation following responses or FMFRs) to quantify TFS encoding in young and middle-aged adults with normal hearing thresholds. Middle-aged listeners exhibited reduced FMFR amplitudes and shallower discriminability slopes, reflecting diminished neural synchrony despite preserved hearing thresholds. Using a multi-talker speech task we further found that pupil-indexed listening effort was significantly", "source": "PubMed"}, {"chunk_id": "41332787_1", "pmid": "41332787", "title": "Degraded neural coding of temporal fine structure with age predicts effortful listening in multi-talker environments.", "authors": "Zhen L, Parida S, McHaney JR et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "exhibited reduced FMFR amplitudes and shallower discriminability slopes, reflecting diminished neural synchrony despite preserved hearing thresholds. Using a multi-talker speech task we further found that pupil-indexed listening effort was significantly greater in middle-aged adults despite matched accuracy across groups. Further, increases in listening effort were predicted by decreases in TFS encoding. Together, these results reveal that degraded neural encoding of TFS underlies subclinical listening difficulties and increased cognitive load, establishing the FMFR as a sensitive biomarker of hidden auditory neural decline.", "source": "PubMed"}, {"chunk_id": "40294669_0", "pmid": "40294669", "title": "Unveiling the therapeutic role of Vibrio alginolyticus GH5 exopolysaccharide in Alzheimer's disease.", "authors": "Abdelrazik M, El Awady ME, Abdel-Razik G et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Alzheimer's disease, Antioxidant, Immunomodulatory, Marine exopolysaccharide, Neurodegenerative disorders, Rats animal model", "chunk": "Vibrio alginolyticus strain GH5 (OR865148.1) was isolated from the Red Sea, Hurghada, Egypt, and classified according to cultural attributes, biochemical properties, and the analysis of genetic relationships using 16S rRNA sequences. A substantial proportion of exopolysaccharides (EPS) in GH5-EPS contained a sulfate level of 19.8 %, uronic acid of 6.7 %, and N-acetylglucosamine of 16.07 %. The composition of monosaccharides in these fractions consists of arabinose, glucose, and galacturonic acid in a proportion of 2:1:2, respectively. GH5-EPS surface appeared as a needle-like shape by SEM. GH5-EPS enhancement of the RAW264.7 macrophage line ATTC number J774 cell proliferation via MTT assay for cell viability. GH5-EPS had a high immunomodulatory effect on releasing TNF-alfa and IL-10. Followed by its effect against cyclooxygenase (COX-2) and lipoxygenase (LOX). Antioxidant activity was evaluated for GPx4, GSS, and MDA with highly significant results for DPPH, ABTS, and iron chelating. AChE was inhibited by a mean of", "source": "PubMed"}, {"chunk_id": "40294669_1", "pmid": "40294669", "title": "Unveiling the therapeutic role of Vibrio alginolyticus GH5 exopolysaccharide in Alzheimer's disease.", "authors": "Abdelrazik M, El Awady ME, Abdel-Razik G et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Alzheimer's disease, Antioxidant, Immunomodulatory, Marine exopolysaccharide, Neurodegenerative disorders, Rats animal model", "chunk": "(COX-2) and lipoxygenase (LOX). Antioxidant activity was evaluated for GPx4, GSS, and MDA with highly significant results for DPPH, ABTS, and iron chelating. AChE was inhibited by a mean of (30.25 \u00b1 1.76 and 52.1 \u00b1 2.77 \u03bcg/mL). GH5-EPS illustrated a good treatment effect for AD in a rat animal model, supporting biochemical studies, histopathology for some brain parts, and toxicity. Bioinformatic investigation for GH5 gene and translated protein structure and function provide insights for future drug-targeting of the EPS production pathway.", "source": "PubMed"}, {"chunk_id": "38876518_0", "pmid": "38876518", "title": "Accurate and highly sensitive detection of Alzheimer's disease-related extracellular vesicles via f\u00f6rster resonance energy transfer.", "authors": "Gu M, Zhang H, Liu Y et al.", "year": "2024", "journal": "Analytica chimica acta", "keywords": "Alzheimer's disease, Biomarker, Extracellular vesicles, FRET, Liquid biopsy", "chunk": "Alzheimer's disease (AD) is the most common neurodegenerative disease in the world and poses a huge challenge to global healthcare. Early and accurate detection of amyloid-\u03b2 (1-42) (A\u03b242), a key biomarker of AD, is crucial for effective diagnosis and intervention of AD. Specific or overexpressed proteins on extracellular vesicles (EVs) describe a close correlation with the occurrence and development of diseases. EVs are a very promising non-invasive biomarker for the diagnosis of AD and other diseases. As a sensitive, simple and rapid analytical method, fluorescence resonance energy transfer (FRET) has been widely applied in the detection of EVs. Herein, we developed a dual labelling strategy for simultaneously detecting EV membrane proteins of A\u03b242 and CD63 based on FRET pair consisting of Au nanoclusters (AuNCs) and polydopamine nanospheres (PDANSs). The constructed nanoprobe, termed EV<sub>MPFAP</sub> assay, could specifically measure the A\u03b242 and CD63 on EVs with excellent sensitivity, high specificity and satisfactory", "source": "PubMed"}, {"chunk_id": "38876518_1", "pmid": "38876518", "title": "Accurate and highly sensitive detection of Alzheimer's disease-related extracellular vesicles via f\u00f6rster resonance energy transfer.", "authors": "Gu M, Zhang H, Liu Y et al.", "year": "2024", "journal": "Analytica chimica acta", "keywords": "Alzheimer's disease, Biomarker, Extracellular vesicles, FRET, Liquid biopsy", "chunk": "of Au nanoclusters (AuNCs) and polydopamine nanospheres (PDANSs). The constructed nanoprobe, termed EV<sub>MPFAP</sub> assay, could specifically measure the A\u03b242 and CD63 on EVs with excellent sensitivity, high specificity and satisfactory accuracy. The limit of detection of EV<sub>MPFAP</sub> assay was 1.4 \u00d7 10<sup>3</sup> particles mL<sup>-1</sup> and the linear range was from 10<sup>4</sup> to 10<sup>8</sup> particles mL<sup>-1</sup>. EV<sub>MPFAP</sub> assay was successfully used to analyze plasma EVs to distinguish AD and healthy mice. We expect that EV<sub>MPFAP</sub> assay can be routinely applied for early diagnosis and development-monitoring of AD, thus facilitating the fight against AD.", "source": "PubMed"}, {"chunk_id": "36741545_0", "pmid": "36741545", "title": "Nanotechnology-based drug delivery for the treatment of CNS disorders.", "authors": "Mittal KR, Pharasi N, Sarna B et al.", "year": "2022", "journal": "Translational neuroscience", "keywords": "blood\u2013brain barrier, central nervous system, nanomedicine, nanotechnology, neurodegeneration, neurodegenerative diseases", "chunk": "Approximately 6.8 million people die annually because of problems related to the central nervous system (CNS), and out of them, approximately 1 million people are affected by neurodegenerative diseases that include Alzheimer's disease, multiple sclerosis, epilepsy, and Parkinson's disease. CNS problems are a primary concern because of the complexity of the brain. There are various drugs available to treat CNS disorders and overcome problems with toxicity, specificity, and delivery. Barriers like the blood-brain barrier (BBB) are a challenge, as they do not allow therapeutic drugs to cross and reach their target. Researchers have been searching for ways to allow drugs to pass through the BBB and reach the target sites. These problems highlight the need of nanotechnology to alter or manipulate various processes at the cellular level to achieve the desired attributes. Due to their nanosize, nanoparticles are able to pass through the BBB and are an effective alternative to", "source": "PubMed"}, {"chunk_id": "36741545_1", "pmid": "36741545", "title": "Nanotechnology-based drug delivery for the treatment of CNS disorders.", "authors": "Mittal KR, Pharasi N, Sarna B et al.", "year": "2022", "journal": "Translational neuroscience", "keywords": "blood\u2013brain barrier, central nervous system, nanomedicine, nanotechnology, neurodegeneration, neurodegenerative diseases", "chunk": "manipulate various processes at the cellular level to achieve the desired attributes. Due to their nanosize, nanoparticles are able to pass through the BBB and are an effective alternative to drug administration and other approaches. Nanotechnology has the potential to improve treatment and diagnostic techniques for CNS disorders and facilitate effective drug transfer. With the aid of nanoengineering, drugs could be modified to perform functions like transference across the BBB, altering signaling pathways, targeting specific cells, effective gene transfer, and promoting regeneration and preservation of nerve cells. The involvement of a nanocarrier framework inside the delivery of several neurotherapeutic agents used in the treatment of neurological diseases is reviewed in this study.", "source": "PubMed"}, {"chunk_id": "18945929_0", "pmid": "18945929", "title": "Metabolic syndrome and risk for incident Alzheimer's disease or vascular dementia: the Three-City Study.", "authors": "Raffaitin C, Gin H, Empana JP et al.", "year": "2009", "journal": "Diabetes care", "keywords": "None", "chunk": "Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent. The 7,087 community-dwelling subjects aged > or =65 years were recruited from the French Three-City (3C) cohort. Hazard ratios (over 4 years) of incident dementia and its subtypes (vascular dementia and Alzheimer's disease) and association with metabolic syndrome (defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria) and its individual components (hypertension, large waist circumference, high triglycerides, low HDL cholesterol, and elevated fasting glycemia) were estimated in separate Cox proportional hazard models. Metabolic syndrome was present in 15.8% of the study participants. The presence of metabolic syndrome increased the risk of incident vascular dementia but not Alzheimer's disease over 4 years, independent of sociodemographic characteristics and the apolipoprotein (apo) Eepsilon4 allele. High triglyceride level was the only component of metabolic syndrome that was significantly associated with the", "source": "PubMed"}, {"chunk_id": "18945929_1", "pmid": "18945929", "title": "Metabolic syndrome and risk for incident Alzheimer's disease or vascular dementia: the Three-City Study.", "authors": "Raffaitin C, Gin H, Empana JP et al.", "year": "2009", "journal": "Diabetes care", "keywords": "None", "chunk": "disease over 4 years, independent of sociodemographic characteristics and the apolipoprotein (apo) Eepsilon4 allele. High triglyceride level was the only component of metabolic syndrome that was significantly associated with the incidence of all-cause (hazard ratio 1.45 [95% CI 1.05-2.00]; P = 0.02) and vascular (2.27 [1.16-4.42]; P = 0.02) dementia, even after adjustment of the apoE genotype. Diabetes, but not impaired fasting glycemia, was significantly associated with all-cause (1.58 [1.05-2.38]; P = 0.03) and vascular (2.53 [1.15-5.66]; P = 0.03) dementia. The observed relation between high triglycerides, diabetes, and vascular dementia emphasizes the need for detection and treatment of vascular risk factors in older individuals in order to prevent the likelihood of clinical dementia.", "source": "PubMed"}, {"chunk_id": "32016694_0", "pmid": "32016694", "title": "The role of epsilon phenotype in brain glucose consumption in Alzheimer's disease.", "authors": "Ricci M, Chiaravalloti A, Martorana A et al.", "year": "2020", "journal": "Annals of nuclear medicine", "keywords": "APOE polymorphism, Alzheimer\u2019s disease, FDG, PET", "chunk": "The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer's disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (\u00b1 7) years; the mean Mini-Mental State Examination was 19(\u00b1 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (\u00b1 149.1), 584.7 (\u00b1 312.1), and 79.2(\u00b1 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered", "source": "PubMed"}, {"chunk_id": "32016694_1", "pmid": "32016694", "title": "The role of epsilon phenotype in brain glucose consumption in Alzheimer's disease.", "authors": "Ricci M, Chiaravalloti A, Martorana A et al.", "year": "2020", "journal": "Annals of nuclear medicine", "keywords": "APOE polymorphism, Alzheimer\u2019s disease, FDG, PET", "chunk": "367.4 (\u00b1 149.1), 584.7 (\u00b1 312.1), and 79.2(\u00b1 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and", "source": "PubMed"}, {"chunk_id": "32016694_2", "pmid": "32016694", "title": "The role of epsilon phenotype in brain glucose consumption in Alzheimer's disease.", "authors": "Ricci M, Chiaravalloti A, Martorana A et al.", "year": "2020", "journal": "Annals of nuclear medicine", "keywords": "APOE polymorphism, Alzheimer\u2019s disease, FDG, PET", "chunk": "glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.", "source": "PubMed"}, {"chunk_id": "37334598_0", "pmid": "37334598", "title": "Refining Risk for Alzheimer's Disease Among Heterozygous APOE\u025b4 Carriers.", "authors": "Patel S, Wei J, Shi Z et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE, Alzheimer\u2019s disease, UK Biobank, genetic counseling, polygenic risk score", "chunk": "In a large population-based cohort, we show not all heterozygous APOE\u025b4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for \u025b3/\u025b4, not \u025b2/\u025b4. Among \u025b3/\u025b4 carriers (24% in the cohort), the AD proportion differed considerably by polygenic risk score (PRS). In particular, the AD proportion was lower than the entire cohort for subjects in the bottom 20-percentile PRS and was higher than that of homozygous \u025b4 carriers for subjects at the top 5th-percentile PRS. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.", "source": "PubMed"}, {"chunk_id": "41007668_0", "pmid": "41007668", "title": "Immersive Technologies Targeting Spatial Memory Decline: A Systematic Review.", "authors": "Solares L, Garc\u00eda-Navarra S, Llana T et al.", "year": "2025", "journal": "Biomedicines", "keywords": "aging, cognitive assessment, immersive technology, mixed reality, navigation, neuropsychology, spatial memory, virtual reality", "chunk": "<b>Background/Objectives</b>: The ability to preserve cognitive health in aging populations increasingly relies on early detection and intervention in neurodegenerative processes. Spatial memory, a fundamental cognitive ability supporting navigation, environmental awareness, and daily independence, often deteriorates in the preclinical stages of neurodegenerative diseases. However, conventional assessment tools frequently lack ecological validity and fail to capture the multifaceted nature of spatial cognition in real-world contexts. This systematic review aims to examine the application of immersive technologies, specifically Immersive Virtual Reality (VR) and Mixed Reality (MR), in the evaluation and rehabilitation of spatial memory. <b>Methods</b>: Following PRISMA guidelines, a total of 42 peer-reviewed studies were selected from SCOPUS, Web of Science, and PubMed databases. We included original, peer-reviewed studies that assessed spatial memory or cognition using VR/MR in adults aged \u226550 or clinical populations at neurodegenerative risk and reported quantitative data or diagnostic validity. A narrative synthesis was performed to examine the most", "source": "PubMed"}, {"chunk_id": "41007668_1", "pmid": "41007668", "title": "Immersive Technologies Targeting Spatial Memory Decline: A Systematic Review.", "authors": "Solares L, Garc\u00eda-Navarra S, Llana T et al.", "year": "2025", "journal": "Biomedicines", "keywords": "aging, cognitive assessment, immersive technology, mixed reality, navigation, neuropsychology, spatial memory, virtual reality", "chunk": "or cognition using VR/MR in adults aged \u226550 or clinical populations at neurodegenerative risk and reported quantitative data or diagnostic validity. A narrative synthesis was performed to examine the most employed immersive tools, assessing their benefits, limitations, and practical challenges. <b>Results</b>: Findings indicate substantial variability in diagnostic sensitivity, ecological validity, and user engagement across platforms. Nevertheless, the evidence supports the potential of immersive environments as effective tools for the early detection of spatial disorientation and cognitive decline, particularly in at-risk populations such as individuals with Mild Cognitive Impairment and Alzheimer's Disease. <b>Conclusions</b>: Immersive and semi-immersive VR technologies represent a promising advancement in spatial memory assessment and rehabilitation, offering scalable solutions for both clinical and home-based interventions in aging populations.", "source": "PubMed"}, {"chunk_id": "40949788_0", "pmid": "40949788", "title": "Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data.", "authors": "Alzenaidi F, Aldoweesh O, Alghofaili S et al.", "year": "2025", "journal": "Metabolism open", "keywords": "Alzheimer's disease, Dementia, Glucose metabolism, Metabolism, Selective serotonin reuptake inhibitors", "chunk": "Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression in Alzheimer's disease (AD), however their effects on glucose metabolism remain poorly understood. We conducted a systematic review and meta-analysis to evaluate SSRI effects on brain glucose metabolism and metabolic adverse events in AD patients. Following PRISMA 2020 guidelines, we searched multiple databases up to July 11, 2025 for studies investigating SSRI effects on glucose-related outcomes in AD patients. Despite significant heterogeneity in study designs and populations, we performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. We performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. Advanced Bayesian hierarchical modeling and Markov simulations projected long-term metabolic outcomes. Twelve studies with total included 7143 participants met our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52-1.22,", "source": "PubMed"}, {"chunk_id": "40949788_1", "pmid": "40949788", "title": "Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data.", "authors": "Alzenaidi F, Aldoweesh O, Alghofaili S et al.", "year": "2025", "journal": "Metabolism open", "keywords": "Alzheimer's disease, Dementia, Glucose metabolism, Metabolism, Selective serotonin reuptake inhibitors", "chunk": "our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52-1.22, P-value = 0.001). Meta-analysis demonstrated increased gastrointestinal adverse events (risk ratio 2.15, 95 % CI: 1.68-2.76, P-value<0.001, with moderate between-study heterogeneity), with sertraline showing highest rates. Citalopram 30 mg provided significant weight loss protection (risk ratio 0.13, 95 % CI: 0.02-0.98, P-value = 0.02), though this exceeds the recommended 20 mg maximum dose for elderly patients due to cardiac safety considerations. Long-term diabetes incidence showed no increased risk (hazard ratio 0.75, 95 % CI: 0.50-1.12, P-value = 0.15). Bayesian modeling revealed 85 % probability of beneficial brain metabolic effects and 89 % probability of citalopram superiority for weight protection. SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients,", "source": "PubMed"}, {"chunk_id": "40949788_2", "pmid": "40949788", "title": "Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data.", "authors": "Alzenaidi F, Aldoweesh O, Alghofaili S et al.", "year": "2025", "journal": "Metabolism open", "keywords": "Alzheimer's disease, Dementia, Glucose metabolism, Metabolism, Selective serotonin reuptake inhibitors", "chunk": "89 % probability of citalopram superiority for weight protection. SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients, while sertraline requires gastrointestinal monitoring. These findings support SSRI safety for metabolic outcomes in AD treatment, however longer-term studies with controlled metabolic outcomes are needed to confirm our findings. The observed citalopram weight protection benefit was documented at 30 mg daily, which exceeds recommended dosing limits for elderly patients due to cardiac safety concerns.", "source": "PubMed"}, {"chunk_id": "37236517_0", "pmid": "37236517", "title": "Apolipoprotein E4 heterologous expression, purification under non-denaturing conditions, and effects on neuronal clonal cell lines.", "authors": "Serrano E, Barrantes FJ, Valdivieso \u00c1G", "year": "2023", "journal": "Protein expression and purification", "keywords": "3C-protease, Apolipoprotein E, Expression, Immobilized metal affinity chromatography, Purification, SEC-FPLC, rApoE4", "chunk": "The \u03b54 allele of the apolipoprotein E gene (APOE4) constitutes the main genetic risk factor for late-onset Alzheimer disease (AD). High amounts of pure apolipoprotein E4 (ApoE4), in a rapid and reproducible fashion, could be of value for studying its pathophysiological roles in AD. The aim of the present work was to optimize a preparative method to obtain highly purified recombinant ApoE4 (rApoE4) with full biological activity. rApoE4 was expressed in the E. Coli BL21(D3) strain and a soluble form of the protein was purified by a combination of affinity and size-exclusion chromatography that precluded a denaturation step. The structural integrity and the biochemical activity of the purified rApoE4 were confirmed by circular dichroism and a lipid-binding assay. Several biological parameters affected by rApoE4, such as mitochondrial morphology, mitochondrial membrane potential and reactive oxygen species production were studied in CNh cells, a neuronal cell line, and neurodifferentiation and dendritogenesis were", "source": "PubMed"}, {"chunk_id": "37236517_1", "pmid": "37236517", "title": "Apolipoprotein E4 heterologous expression, purification under non-denaturing conditions, and effects on neuronal clonal cell lines.", "authors": "Serrano E, Barrantes FJ, Valdivieso \u00c1G", "year": "2023", "journal": "Protein expression and purification", "keywords": "3C-protease, Apolipoprotein E, Expression, Immobilized metal affinity chromatography, Purification, SEC-FPLC, rApoE4", "chunk": "parameters affected by rApoE4, such as mitochondrial morphology, mitochondrial membrane potential and reactive oxygen species production were studied in CNh cells, a neuronal cell line, and neurodifferentiation and dendritogenesis were analyzed in the SH-SY5Y neuroblastoma cell line. The improved rApoE4 purification technique reported here enables the production of highly purified protein that retain the structural properties and functional activity of the native protein, as confirmed by tests in two different neuronal cell lines in culture.", "source": "PubMed"}, {"chunk_id": "39501294_0", "pmid": "39501294", "title": "Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.", "authors": "Wang J, Wen S, Liu W et al.", "year": "2024", "journal": "BioData mining", "keywords": "Alzheimer\u2019s disease, Attention mechanism, Deep joint learning diagnosis, Multimodal feature fusion, ResNet", "chunk": "Alzheimer's disease (AD) is an advanced and incurable neurodegenerative disease. Genetic variations are intrinsic etiological factors contributing to the abnormal expression of brain function and structure in AD patients. A new multimodal feature fusion called \"magnetic resonance imaging (MRI)-p value\" was proposed to construct 3D fusion images by introducing genes as a priori knowledge. Moreover, a new deep joint learning diagnostic model was constructed to fully learn images features. One branch trained a residual network (ResNet) to learn the features of local pathological regions. The other branch learned the position information of brain regions with different changes in the different categories of subjects' brains by introducing attention convolution, and then obtained the discriminative probability information from locations via convolution and global average pooling. The feature and position information of the two branches were linearly interacted to acquire the diagnostic basis for classifying the different categories of subjects. The diagnoses of", "source": "PubMed"}, {"chunk_id": "39501294_1", "pmid": "39501294", "title": "Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.", "authors": "Wang J, Wen S, Liu W et al.", "year": "2024", "journal": "BioData mining", "keywords": "Alzheimer\u2019s disease, Attention mechanism, Deep joint learning diagnosis, Multimodal feature fusion, ResNet", "chunk": "global average pooling. The feature and position information of the two branches were linearly interacted to acquire the diagnostic basis for classifying the different categories of subjects. The diagnoses of AD and health control (HC), AD and mild cognitive impairment (MCI), HC and MCI were performed with data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results showed that the proposed method achieved optimal results in AD-related diagnosis. The classification accuracy (ACC) and area under the curve (AUC) of the three experimental groups were 93.44% and 96.67%, 89.06% and 92%, and 84% and 81.84%, respectively. Moreover, a total of six novel genes were found to be significantly associated with AD, namely NTM, MAML2, NAALADL2, FHIT, TMEM132D and PCSK5, which provided new targets for the potential treatment of neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "39501294_2", "pmid": "39501294", "title": "Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.", "authors": "Wang J, Wen S, Liu W et al.", "year": "2024", "journal": "BioData mining", "keywords": "Alzheimer\u2019s disease, Attention mechanism, Deep joint learning diagnosis, Multimodal feature fusion, ResNet", "chunk": "new targets for the potential treatment of neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "40982080_0", "pmid": "40982080", "title": "Non-coding RNA-mediated gene regulation in Alzheimer's disease pathogenesis: molecular insights and emerging innovations.", "authors": "Alzarea SI", "year": "2025", "journal": "Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society", "keywords": "Alzheimer's disease, Biomarkers, Long non-coding RNAs, MicroRNAs, Non-coding RNAs", "chunk": "The accumulation of pathological markers, such as tau tangles and amyloid-beta (A\u03b2) plaques, and progressive cognitive dysfunction are the markers of Alzheimer's disease (AD). The development of successful therapeutic plans requires exposure to the molecular mechanisms underlying AD development. The importance of non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), microRNAs (miRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), in controlling gene expression and influencing the pathophysiology of disease has been brought to light by recent studies. With a focus on their role in important processes such tau hyperphosphorylation, neuroinflammation, and amyloid-beta formation, this study attempts to give a thorough overview of the several types of ncRNAs and their dysregulation in AD. The genetic variants that are associated with the function of ncRNA including single nucleotide polymorphisms (SNPs) may influence ncRNA expression and activity, thereby impacting the susceptibility of individual towards AD. Furthermore, the impact of biomarkers of ncRNAs for", "source": "PubMed"}, {"chunk_id": "40982080_1", "pmid": "40982080", "title": "Non-coding RNA-mediated gene regulation in Alzheimer's disease pathogenesis: molecular insights and emerging innovations.", "authors": "Alzarea SI", "year": "2025", "journal": "Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society", "keywords": "Alzheimer's disease, Biomarkers, Long non-coding RNAs, MicroRNAs, Non-coding RNAs", "chunk": "function of ncRNA including single nucleotide polymorphisms (SNPs) may influence ncRNA expression and activity, thereby impacting the susceptibility of individual towards AD. Furthermore, the impact of biomarkers of ncRNAs for early diagnosis and therapeutic option for intervention, highlighting most recent advancement in high-throughput technologies and bioinformatics facilitating ncRNA profiling has also being discussed. The integration of multi-omics approaches and artificial intelligence, new advancement for the complex relationship among ncRNAs and AD pathology are also discussed. The enhancement and understanding of ncRNAs could lead to the door for novel therapeutic concepts for the mitigation of AD progression, offering effective interventions in a disease that currently starves the curative treatments.", "source": "PubMed"}, {"chunk_id": "41070364_0", "pmid": "41070364", "title": "Simulation of Alzheimer's diagnostic flows with blood biomarker test options in Japan.", "authors": "Igarashi A, Kimura N, Ataka T et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, blood biomarker tests, diagnostic pathways, diagnostic wait times, dynamic simulation, healthcare access, lecanemab treatment, mild cognitive impairment", "chunk": "This study projected the diagnostic testing landscape for lecanemab treatment in Japan under different workflows. A dynamic simulation estimated wait times and treatment-eligible patient numbers under four scenarios: current diagnostic workflow, blood biomarker (BBM) tests as triage tools, BBM tests for confirmatory diagnostics, and both combined. Willingness-to-pay (WTP) and intangible costs were assessed via an online survey to estimate testing demand. The maximum mean wait time under the current workflow was projected at 6.4 months, decreasing with BBM integration. The number of treatment-eligible patients increased considerably with BBM-based confirmatory diagnostics. BBM triage testing reduced wait times but temporarily increased treatment-eligible patients. Replacing positron emission tomography (PET) or cerebrospinal fluid with BBM-based diagnostics may increase treatment eligibility because of lower costs, driving higher demand for testing. A dynamic simulation models Alzheimer's diagnostic workflows in Japan.Blood biomarker (BBM) tests reduce diagnostic wait times for Alzheimer's in Japan.Implementing BBM tests improves access to", "source": "PubMed"}, {"chunk_id": "41070364_1", "pmid": "41070364", "title": "Simulation of Alzheimer's diagnostic flows with blood biomarker test options in Japan.", "authors": "Igarashi A, Kimura N, Ataka T et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, blood biomarker tests, diagnostic pathways, diagnostic wait times, dynamic simulation, healthcare access, lecanemab treatment, mild cognitive impairment", "chunk": "driving higher demand for testing. A dynamic simulation models Alzheimer's diagnostic workflows in Japan.Blood biomarker (BBM) tests reduce diagnostic wait times for Alzheimer's in Japan.Implementing BBM tests improves access to Alzheimer's diagnostics.Study quantifies demand for diagnostic testing based on costs and accessibility.Testing costs impact the number of treatment-eligible Alzheimer's patients.", "source": "PubMed"}, {"chunk_id": "41012995_0", "pmid": "41012995", "title": "Sympathetic Burden Measured Through a Chest-Worn Sensor Correlates with Spatiotemporal Gait Performances and Global Cognition in Parkinson's Disease.", "authors": "Sergi G, Yekutieli Z, Meloni M et al.", "year": "2025", "journal": "Sensors (Basel, Switzerland)", "keywords": "Baevsky stress index, autonomic dysfunction, cognitive function, gait analysis, heart rate variability", "chunk": "Autonomic dysfunction is a key non-motor feature of Parkinson's disease (PD) and may influence motor performance, particularly gait. While heart rate variability (HRV) has been associated with freezing of gait, its relationship with broader gait parameters remains unclear. The objective was to investigate correlations between resting-state HRV time-domain measures and spatiotemporal gait parameters during comfortable and fast walking in patients with idiopathic PD. Twenty-eight PD patients (mean age 68 \u00b1 9 years) were evaluated at Campus Bio-Medico University Hospital. HRV was recorded at rest using the e-Sense pule\u2122 portable sensor, including the Baevsky's Stress Index a measure increasing with sympathetic burden. Gait parameters were assessed via the 10 m Timed Up and Go (TUG) test using the Mon4t\u2122 smartphone app at comfortable and fast pace. Clinical data included UPDRS III, MoCA, and disease characteristics. Gait metrics significantly changed between walking conditions. HRV parameters clustered separately from gait metrics but intersected", "source": "PubMed"}, {"chunk_id": "41012995_1", "pmid": "41012995", "title": "Sympathetic Burden Measured Through a Chest-Worn Sensor Correlates with Spatiotemporal Gait Performances and Global Cognition in Parkinson's Disease.", "authors": "Sergi G, Yekutieli Z, Meloni M et al.", "year": "2025", "journal": "Sensors (Basel, Switzerland)", "keywords": "Baevsky stress index, autonomic dysfunction, cognitive function, gait analysis, heart rate variability", "chunk": "at comfortable and fast pace. Clinical data included UPDRS III, MoCA, and disease characteristics. Gait metrics significantly changed between walking conditions. HRV parameters clustered separately from gait metrics but intersected with significant correlations. Higher Stress Index values, reflecting sympathetic dominance, were associated with poorer gait performance, including prolonged transition times, shorter steps, and increased variability (<i>p</i> < 0.001, r = 0.57-0.61). MoCA scores inversely correlated with the Stress Index (r = -0.52, <i>p</i> = 0.004), linking cognitive and autonomic status. UPDRS III and MoCA were related to TUG metrics but not HRV. Time-domain HRV measures, particularly the Stress Index, are significantly associated with spatiotemporal gait features in PD, independent of gait speed. These findings suggest that impaired autonomic regulation contributes to functional mobility deficits in PD and supports the role of HRV as a biomarker in motor assessment.", "source": "PubMed"}, {"chunk_id": "41012995_2", "pmid": "41012995", "title": "Sympathetic Burden Measured Through a Chest-Worn Sensor Correlates with Spatiotemporal Gait Performances and Global Cognition in Parkinson's Disease.", "authors": "Sergi G, Yekutieli Z, Meloni M et al.", "year": "2025", "journal": "Sensors (Basel, Switzerland)", "keywords": "Baevsky stress index, autonomic dysfunction, cognitive function, gait analysis, heart rate variability", "chunk": "to functional mobility deficits in PD and supports the role of HRV as a biomarker in motor assessment.", "source": "PubMed"}, {"chunk_id": "39437446_0", "pmid": "39437446", "title": "TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.", "authors": "Lin Y, Cheng L, Chen Y et al.", "year": "2024", "journal": "American journal of physiology. Cell physiology", "keywords": "NLRP3, TFEB, autophagy, diabetic encephalopathy, microglia", "chunk": "Diabetic encephalopathy (DE), a neurological complication of diabetes mellitus, has an unclear etiology. Shreds of evidence show that the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome-induced neuroinflammation and transcription factor EB (TFEB)-mediated autophagy impairment may take part in DE development. The cross talk between these two pathways and their contribution to DE remains to be explored. A mouse model of type 2 diabetes mellitus (T2DM) exhibiting cognitive dysfunction was created, along with high-glucose (HG) cultured BV2 cells. Following, 3-methyladenine (3-MA) and rapamycin were used to modulate autophagy. To evaluate the potential therapeutic benefits of TFEB in DE, we overexpressed and knocked down TFEB in both mice and cells. Autophagy impairment and NLRP3 inflammasome activation were noticed in T2DM mice and HG-cultured BV2 cells. The inflammatory response caused by NLRP3 inflammasome activation was decreased by rapamycin-induced autophagy enhancement, while 3-MA treatment further deteriorated it. Nuclear translocation and expression of", "source": "PubMed"}, {"chunk_id": "39437446_1", "pmid": "39437446", "title": "TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.", "authors": "Lin Y, Cheng L, Chen Y et al.", "year": "2024", "journal": "American journal of physiology. Cell physiology", "keywords": "NLRP3, TFEB, autophagy, diabetic encephalopathy, microglia", "chunk": "mice and HG-cultured BV2 cells. The inflammatory response caused by NLRP3 inflammasome activation was decreased by rapamycin-induced autophagy enhancement, while 3-MA treatment further deteriorated it. Nuclear translocation and expression of TFEB were hampered in HG-cultured BV2 cells and T2DM mice. Exogenous TFEB overexpression boosted NLRP3 degradation via autophagy, which in turn alleviated microglial activation as well as ameliorated cognitive deficits and neuronal damage. In addition, TFEB knockdown exacerbated neuroinflammation by decreasing autophagy-mediated NLRP3 degradation. Our findings have unraveled the pathogenesis of a previously underappreciated disease, implying that the activation of NLRP3 inflammasome and impairment of autophagy in microglia are significant etiological factors in the DE. The TFEB-mediated autophagy pathway can reduce neuroinflammation by enhancing NLRP3 degradation. This could potentially serve as a viable and innovative treatment approach for DE.<b>NEW & NOTEWORTHY</b> This article delves into the intricate connections between inflammation, autophagy, diabetes, and neurodegeneration, with a particular focus on a", "source": "PubMed"}, {"chunk_id": "39437446_2", "pmid": "39437446", "title": "TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.", "authors": "Lin Y, Cheng L, Chen Y et al.", "year": "2024", "journal": "American journal of physiology. Cell physiology", "keywords": "NLRP3, TFEB, autophagy, diabetic encephalopathy, microglia", "chunk": "as a viable and innovative treatment approach for DE.<b>NEW & NOTEWORTHY</b> This article delves into the intricate connections between inflammation, autophagy, diabetes, and neurodegeneration, with a particular focus on a disease that is not yet fully understood-diabetic encephalopathy (DE). TFEB emerges as a pivotal regulator in balancing autophagy and inflammation in DE. Our findings highlight the crucial function of the TFEB-mediated autophagy pathway in mitigating inflammatory damage in DE, suggesting a new treatment strategy.", "source": "PubMed"}, {"chunk_id": "36111130_0", "pmid": "36111130", "title": "Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study).", "authors": "Swann OJ, Turner M, Heslegrave A et al.", "year": "2022", "journal": "BMJ open sport & exercise medicine", "keywords": "Athlete, Brain, Concussion, Horse racing", "chunk": "To investigate the association and utility of blood plasma markers of neurodegeneration in a population of retired athletes self-reporting multiple concussions throughout a sporting career. It is hypothesised that this type of athletic history would cause an increased prevalence of neurodegenerative disease, as detected by biomarkers for neurodegenerative disease processes. One hundred and fifty-nine participants were recruited (90 males, 69 females, mean age 61.3\u00b19.13 years), including 121 participants who had retired from playing professional or semiprofessional sports and self-reported \u22651 concussion during their careers (range 1-74; mean concussions=10.7). The control group included 38 age-matched and sex-matched controls, with no history of concussion. We measured neurofilament light (NfL) and tau (neurodegeneration markers), glial fibrillar acidic protein (GFAP) (astrocytic activation marker) and 40 and 42 amino acid-long amyloid beta (A\u03b240 and A\u03b242) (Alzheimer-associated amyloid pathology markers) concentrations using ultrasensitive single molecule array technology. We found retired athletes reporting one or more concussions", "source": "PubMed"}, {"chunk_id": "36111130_1", "pmid": "36111130", "title": "Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study).", "authors": "Swann OJ, Turner M, Heslegrave A et al.", "year": "2022", "journal": "BMJ open sport & exercise medicine", "keywords": "Athlete, Brain, Concussion, Horse racing", "chunk": "40 and 42 amino acid-long amyloid beta (A\u03b240 and A\u03b242) (Alzheimer-associated amyloid pathology markers) concentrations using ultrasensitive single molecule array technology. We found retired athletes reporting one or more concussions throughout an athletic career showed no significant changes in NfL, tau, GFAP and A\u03b240 and A\u03b242 concentrations in comparison to a control group. No correlations were found between biomarkers and number of concussions (mean=10.7). A moderate correlation was found between NfL concentration and age. No difference in blood concentrations of neurodegeneration markers NfL, tau, GFAP and A\u03b240 and A\u03b242 was found in retired athletes with a history of concussion compared with controls. An increased prevalence of neurodegenerative diseases is not detected by biomarkers in a population self-reporting multiple concussions. ISRCTN 11312093.", "source": "PubMed"}, {"chunk_id": "36111130_2", "pmid": "36111130", "title": "Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study).", "authors": "Swann OJ, Turner M, Heslegrave A et al.", "year": "2022", "journal": "BMJ open sport & exercise medicine", "keywords": "Athlete, Brain, Concussion, Horse racing", "chunk": "11312093.", "source": "PubMed"}, {"chunk_id": "39200877_0", "pmid": "39200877", "title": "Insights from a 7-Year Dementia Cohort (VALCODIS): ApoE Genotype Evaluation.", "authors": "Baquero M, Ferr\u00e9-Gonz\u00e1lez L, \u00c1lvarez-S\u00e1nchez L et al.", "year": "2024", "journal": "Journal of clinical medicine", "keywords": "Alzheimer\u2019s, ApoE, biomarkers, cognitive disease, dementia, neuropsychology", "chunk": "<b>Background:</b> The VALCODIS (Valencian Cognitive Diseases Study) cohort was designed and studied at the Hospital Universitari i Polit\u00e8cnic La Fe (Valencia, Spain) for the research of cognitive diseases, especially in the search for new biomarkers of Alzheimer's disease (AD). <b>Methods:</b> Participants in the VALCODIS cohort had cerebrospinal fluid (CSF) and blood samples, neuroimaging, and neuropsychological tests. The ApoE genotype was evaluated to identify its relationship with CSF biomarkers and neuropsychological tests in AD and non-AD participants. <b>Results:</b> A total of 1249 participants were included. They were mainly AD patients (<i>n</i> = 547) but also patients with other dementias (frontotemporal lobar dementia (<i>n</i> = 61), Lewy body dementia without AD CSF signature (<i>n</i> = 10), vascular dementia (<i>n</i> = 24) and other specific causes of cognitive impairment (<i>n</i> = 442), and patients with subjective memory complaints (<i>n</i> = 165)). In the ApoE genotype evaluation, significant differences were found for A\u03b242 levels", "source": "PubMed"}, {"chunk_id": "39200877_1", "pmid": "39200877", "title": "Insights from a 7-Year Dementia Cohort (VALCODIS): ApoE Genotype Evaluation.", "authors": "Baquero M, Ferr\u00e9-Gonz\u00e1lez L, \u00c1lvarez-S\u00e1nchez L et al.", "year": "2024", "journal": "Journal of clinical medicine", "keywords": "Alzheimer\u2019s, ApoE, biomarkers, cognitive disease, dementia, neuropsychology", "chunk": "other specific causes of cognitive impairment (<i>n</i> = 442), and patients with subjective memory complaints (<i>n</i> = 165)). In the ApoE genotype evaluation, significant differences were found for A\u03b242 levels between genotypes in both AD and non-AD patients, as well as a negative correlation between tau values and a cognitive test in non-carriers and \u03b54 heterozygous. <b>Conclusions:</b> The VALCODIS cohort provides biologically diagnosed patients with demographical, clinical and biochemical data, and biological samples for further studies on early AD diagnosis. Also, the ApoE genotype evaluation showed correlations between CSF biomarkers and neuropsychological tests.", "source": "PubMed"}, {"chunk_id": "31867067_0", "pmid": "31867067", "title": "Physical activity is associated with better global cognition and frontal function in overweight/obese older adults with metabolic syndrome.", "authors": "Coll-Padr\u00f3s N, Le\u00f3n M, Valech N et al.", "year": "2019", "journal": "European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity", "keywords": "Aging, Cognitive function, Metabolic syndrome, Obesity, PREDIMED-PLUS study, Physical activity", "chunk": "There is epidemiological evidence of an association between the metabolic syndrome (MetS), a cluster of cardiovascular risk factors related to central adiposity and insulin resistance, and cognitive impairment and dementia. On the other hand, there is evidence for a beneficial effect of physical activity on cognitive outcomes in older adult populations. In a cross-sectional study, we evaluated the relationship between aerobic physical activity and cognition in a cohort of overweight/obese older adults with MetS at risk for dementia. Cognitive function was assessed in a subsample of 82 subjects (men 55-75 y; women 60-75 y), with MetS and a BMI \u226527 to < 40 kg/m<sup>2</sup> enrolled in the PREDIMED-PLUS study, a trial of diet and exercise in individuals with MetS with outcomes of cardiovascular prevention. Domain Z scores were calculated for the different cognitive domains. Aerobic physical activity was determined with the Rapid Assessment of Physical Activity questionnaire. Adjusted covariance analyses", "source": "PubMed"}, {"chunk_id": "31867067_1", "pmid": "31867067", "title": "Physical activity is associated with better global cognition and frontal function in overweight/obese older adults with metabolic syndrome.", "authors": "Coll-Padr\u00f3s N, Le\u00f3n M, Valech N et al.", "year": "2019", "journal": "European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity", "keywords": "Aging, Cognitive function, Metabolic syndrome, Obesity, PREDIMED-PLUS study, Physical activity", "chunk": "outcomes of cardiovascular prevention. Domain Z scores were calculated for the different cognitive domains. Aerobic physical activity was determined with the Rapid Assessment of Physical Activity questionnaire. Adjusted covariance analyses revealed that, compared to sedentary participants, those physically active obtained higher scores in mean global cognitive scores, with mean adjusted difference 0.254 (95% CI 0.032 to 0.477, <i>p</i> = 0.026) and frontal composites, with mean adjusted difference 0.375 (95% CI 0.110 to 0.639, <i>p</i> = 0.006). Our findings indicate that aerobic physical activity is associated with better global cognition and frontal function in overweight/obese older individuals with MetS, suggesting that physical activity could be a therapeutic strategy to reduce the risk of developing cognitive impairment or dementia in this population.", "source": "PubMed"}, {"chunk_id": "41589495_0", "pmid": "41589495", "title": "Enzymatic Biomarkers for Early Diagnosis of Alzheimer's Disease: Uncovering Key Targets and Mechanisms.", "authors": "Dewangan A, Nandy SK, Das AK et al.", "year": "2026", "journal": "CNS & neurological disorders drug targets", "keywords": "Alzheimer\u2019s disease, Amyloid-c Cascade hypothesis, Tau-c Cascade hypothesis, early diagnosis, enzymatic biomarkers, metalloproteinases.", "chunk": "Alzheimer's Disease (AD) is a neuronal illness that disrupts behavior, cognitive, and functional abilities. The development of AD is progressive, continuous, and irreversible, from preclinical illness to mild cognitive or even behavioral disturbance to dementia (a medical brain condition) triggered by AD. Worldwide accepted hypotheses of AD are called the amyloid-cascade and hyperphosphorylated tau-cascade hypotheses, and enzymes are implicated in the pathophysiology of AD directly or indirectly. There is an implication of enzymes in the pathophysiology of AD. Enzymes include proteases (e.g., neprilysin), kinases (e.g., glycogen synthase kinase-3), cholinergic enzymes (e.g., acetylcholinesterase), metalloproteinases (e.g., matrix metalloproteinases), and oxidative stress-related enzymes (e.g., superoxide dismutase). However, during abnormal or early Alzheimer's Disease (AD) conditions, the activity and expression of these enzymes are altered in biological samples such as blood, urine, and cerebrospinal fluid (CSF) in patients with early AD when examined. These alterations in enzyme activity in early AD demonstrate the potential", "source": "PubMed"}, {"chunk_id": "41589495_1", "pmid": "41589495", "title": "Enzymatic Biomarkers for Early Diagnosis of Alzheimer's Disease: Uncovering Key Targets and Mechanisms.", "authors": "Dewangan A, Nandy SK, Das AK et al.", "year": "2026", "journal": "CNS & neurological disorders drug targets", "keywords": "Alzheimer\u2019s disease, Amyloid-c Cascade hypothesis, Tau-c Cascade hypothesis, early diagnosis, enzymatic biomarkers, metalloproteinases.", "chunk": "altered in biological samples such as blood, urine, and cerebrospinal fluid (CSF) in patients with early AD when examined. These alterations in enzyme activity in early AD demonstrate the potential of these enzymes as biomarkers. Early detection of AD in its early stages is crucial for effective control and treatment of the disease. Existing diagnostic techniques rely mainly on neuroimaging and medical evaluation. Through this technique, we can only diagnose the advanced or late stage of AD. Therefore, there is a crucial need to establish valid biomarkers that might assist in the early detection of AD. Enzymatic targets have come to light as a promising alternative for the development of selective and sensitive diagnostic assays. This review aims to investigate the potential of enzymes as an enzymatic target for early AD diagnosis, emphasizing their diagnostic use and fundamental mechanisms. Here, we summarize the role or implication of 25 enzymes in", "source": "PubMed"}, {"chunk_id": "41589495_2", "pmid": "41589495", "title": "Enzymatic Biomarkers for Early Diagnosis of Alzheimer's Disease: Uncovering Key Targets and Mechanisms.", "authors": "Dewangan A, Nandy SK, Das AK et al.", "year": "2026", "journal": "CNS & neurological disorders drug targets", "keywords": "Alzheimer\u2019s disease, Amyloid-c Cascade hypothesis, Tau-c Cascade hypothesis, early diagnosis, enzymatic biomarkers, metalloproteinases.", "chunk": "the potential of enzymes as an enzymatic target for early AD diagnosis, emphasizing their diagnostic use and fundamental mechanisms. Here, we summarize the role or implication of 25 enzymes in the pathophysiology of AD in the early stage.", "source": "PubMed"}, {"chunk_id": "41612924_0", "pmid": "41612924", "title": "Amyloid-related default mode network hyperconnectivity and longitudinal decline in network distinctiveness in preclinical Alzheimer's disease.", "authors": "Cha WJ, Chumin EJ, Yi D et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, KBASE, amyloid beta, default mode network, functional connectivity, hyperconnectivity", "chunk": "We investigated stage-specific alterations in functional connectivity (FC) of the default mode network (DMN) across the Alzheimer's disease (AD) continuum and tested whether early amyloid beta (A\u03b2)-related changes in within-DMN FC (DMN-FC<sub>within</sub>) predicted longitudinal alterations in DMN between-network connectivity (DMN-FC<sub>between</sub>). Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 396 older adults: A\u03b2-negative cognitively normal (CN-, n = 213), A\u03b2-positive CN (CN+, n = 37), A\u03b2-positive mild cognitive impairment (MCI+, n = 72), and A\u03b2-positive dementia (dementia+, n = 74). Cross-sectional analyses compared DMN-FC across groups and examined associations with continuous A\u03b2 burden at baseline. Longitudinal analyses in 171 CN participants with 2-year follow-up (CN-, n = 147; CN+, n = 24) tested whether baseline DMN-FC<sub>within</sub> predicted changes in DMN-FC<sub>between</sub>. CN+ individuals showed elevated DMN-FC<sub>within</sub> and reduced DMN-FC<sub>between</sub> relative to other groups. In CN, A\u03b2 burden was associated with FC, and baseline DMN-FC<sub>within</sub> predicted longitudinal increases in DMN-FC<sub>between</sub> only", "source": "PubMed"}, {"chunk_id": "41612924_1", "pmid": "41612924", "title": "Amyloid-related default mode network hyperconnectivity and longitudinal decline in network distinctiveness in preclinical Alzheimer's disease.", "authors": "Cha WJ, Chumin EJ, Yi D et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, KBASE, amyloid beta, default mode network, functional connectivity, hyperconnectivity", "chunk": "DMN-FC<sub>between</sub>. CN+ individuals showed elevated DMN-FC<sub>within</sub> and reduced DMN-FC<sub>between</sub> relative to other groups. In CN, A\u03b2 burden was associated with FC, and baseline DMN-FC<sub>within</sub> predicted longitudinal increases in DMN-FC<sub>between</sub> only in CN+. A\u03b2-related hyperconnectivity characterizes preclinical AD and may drive progressive network-level vulnerability. Cognitively normal amyloid beta (A\u03b2)-positive (CN+) individuals showed stronger connectivity within the default mode network (DMN). CN+ individuals also showed weaker links between the DMN and other brain networks. Amyloid was not linked to connectivity changes in cognitively impaired adults. Higher DMN connectivity predicted broader network changes in CN+ individuals.", "source": "PubMed"}, {"chunk_id": "39821434_0", "pmid": "39821434", "title": "Neuropsychiatric symptoms and neuroimaging-based brain age in mild cognitive impairment and early dementia: A multicenter study.", "authors": "Sone D, Beheshti I, Tagai K et al.", "year": "2025", "journal": "Psychiatry and clinical neurosciences", "keywords": "dementia, machine learning, magnetic resonance imaging, mild cognitive impairment, neuropsychiatric symptoms", "chunk": "Despite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging-derived brain-age estimation by machine-learning analysis has shown promise as an individual-level biomarker. We investigated the relationship between NPS and brain-age in amnestic mild cognitive impairment (MCI) and early dementia. In this cross-sectional study, clinical data, including neuropsychiatric inventory (NPI), and structural brain MRI of 499 individuals with clinical diagnoses of amnestic MCI (n = 185), early Alzheimer's disease (AD) (n = 258) or dementia with Lewy bodies (DLB) (n = 56) were analyzed. We established a brain-age prediction model using 694 healthy brain MRIs and a support vector regression model and applied it to the participants' data. Finally, the brain-predicted age difference (brain-PAD: predicted age minus chronological age) was calculated. All groups showed significantly increased brain-PAD, and the median (IQR) brain-PAD was 4.3 (5.4) years in MCI,", "source": "PubMed"}, {"chunk_id": "39821434_1", "pmid": "39821434", "title": "Neuropsychiatric symptoms and neuroimaging-based brain age in mild cognitive impairment and early dementia: A multicenter study.", "authors": "Sone D, Beheshti I, Tagai K et al.", "year": "2025", "journal": "Psychiatry and clinical neurosciences", "keywords": "dementia, machine learning, magnetic resonance imaging, mild cognitive impairment, neuropsychiatric symptoms", "chunk": "Finally, the brain-predicted age difference (brain-PAD: predicted age minus chronological age) was calculated. All groups showed significantly increased brain-PAD, and the median (IQR) brain-PAD was 4.3 (5.4) years in MCI, 6.3 (6.2) years in AD, and 5.0 (6.5) years in DLB. The NPI scores were subdivided into the following four categories: (i) Agitation and Irritability, (ii) Depression and Apathy, (iii) Delusions and Hallucinations, and (iv) Euphoria and Disinhibition. We found a significantly positive correlation between brain-PAD and the depression/apathy factor (Spearman's rs = 0.156, FDR-corrected P = 0.002), whereas no significance was shown for the other NPS factors. Higher brain-age may be associated with depression and apathy symptoms presented in MCI to early dementia stages, and brain-age analysis may be useful as a novel biomarker for the assessment or monitoring of NPS.", "source": "PubMed"}, {"chunk_id": "39821434_2", "pmid": "39821434", "title": "Neuropsychiatric symptoms and neuroimaging-based brain age in mild cognitive impairment and early dementia: A multicenter study.", "authors": "Sone D, Beheshti I, Tagai K et al.", "year": "2025", "journal": "Psychiatry and clinical neurosciences", "keywords": "dementia, machine learning, magnetic resonance imaging, mild cognitive impairment, neuropsychiatric symptoms", "chunk": "useful as a novel biomarker for the assessment or monitoring of NPS.", "source": "PubMed"}, {"chunk_id": "41722088_0", "pmid": "41722088", "title": "Reboxetine Treatment Reduces Hippocampal Gliosis in the P301S Tauopathy Mouse Model.", "authors": "Guti\u00e9rrez IL, Yanes-Castilla C, MacDowell KS et al.", "year": "2026", "journal": "ASN neuro", "keywords": "Alzheimer, P301S, neuroinflammation, reboxetine, tau", "chunk": "The loss of brain noradrenergic neurons is one of the earliest alterations observed in Alzheimer's disease and other neurodegenerative pathologies. The consequent reduction of brain noradrenaline levels facilitates the progression of neuroinflammatory processes that can be fatal for neurons and other brain cells. For this reason, compensating for noradrenaline deficit through different means constitutes an interesting therapeutic strategy. Drugs that inhibit the reuptake of noradrenaline are used to elevate the extracellular concentrations of this neurotransmitter and potentiate this way its effects. These drugs are approved for the treatment of depression or attention deficit hyperactivity disorder, among other indications, but their repurposing and use in Alzheimer's disease could be of interest given the beneficial effects observed for noradrenaline in numerous studies. Based on this, we previously showed the beneficial effects of reboxetine, a noradrenaline reuptake inhibitor, on 5xFAD mice that accumulate amyloid beta in their brains and reproduce some of the", "source": "PubMed"}, {"chunk_id": "41722088_1", "pmid": "41722088", "title": "Reboxetine Treatment Reduces Hippocampal Gliosis in the P301S Tauopathy Mouse Model.", "authors": "Guti\u00e9rrez IL, Yanes-Castilla C, MacDowell KS et al.", "year": "2026", "journal": "ASN neuro", "keywords": "Alzheimer, P301S, neuroinflammation, reboxetine, tau", "chunk": "Based on this, we previously showed the beneficial effects of reboxetine, a noradrenaline reuptake inhibitor, on 5xFAD mice that accumulate amyloid beta in their brains and reproduce some of the typical alterations of Alzheimer's disease. In this study we have analyzed the effects of reboxetine on P301S mice, a different model of Alzheimer's disease based on the expression of mutant forms of human microtubule-associated protein tau. We observed that the administration of reboxetine with osmotic pumps for 28 days to 9-month-old mice reduced the accumulation and activation of microglia and astrocytes in different areas of the hippocampus. These findings indicate that reboxetine treatment prevents the neuroinflammatory response known to cause brain damage in Alzheimer's disease even when the treatment is initiated at an advanced stage of the disease.", "source": "PubMed"}, {"chunk_id": "41722088_2", "pmid": "41722088", "title": "Reboxetine Treatment Reduces Hippocampal Gliosis in the P301S Tauopathy Mouse Model.", "authors": "Guti\u00e9rrez IL, Yanes-Castilla C, MacDowell KS et al.", "year": "2026", "journal": "ASN neuro", "keywords": "Alzheimer, P301S, neuroinflammation, reboxetine, tau", "chunk": "initiated at an advanced stage of the disease.", "source": "PubMed"}, {"chunk_id": "40582243_0", "pmid": "40582243", "title": "How is self-reported sleep-disordered breathing linked with biomarkers of Alzheimer's disease?", "authors": "Akradi M, Farzane-Daghigh T, Ebneabbasi A et al.", "year": "2025", "journal": "Neurobiology of aging", "keywords": "Alzheimer\u2019s disease, Amyloid-beta, Fluorodeoxyglucose imaging, Grey matter volume, Sleep-disordered breathing", "chunk": "Sleep-disordered breathing (SDB) is prevalent in Alzheimer's disease (AD). Here, we assessed how self-reported SDB is linked with AD biomarkers, including amyloid-beta plaque burden (A\u03b2), regional fluorodeoxyglucose uptake (rFDG-PET), grey matter volume (GMV), cognitive scores, and cerebrospinal fluid (CSF) biomarkers. We selected 757 individuals, including AD, mild cognitive impairment (MCI), and cognitively unimpaired (CU) groups, and divided them according to self-reported SDB condition. Using a stratified subsampling approach, we selected 512 matched subsamples, and effect sizes (ES) of the group-SDB interaction were computed for each biomarker and cognitive score across subsamples. Linear regression assessed associations between the ES of A\u03b2, rFDG, and GMV with the ES of cognitive scores and CSF biomarkers. The group-SDB interaction had a medium-sized effect on A\u03b2, rFDG, and GMV biomarkers in several brain areas. Participants with SDB exhibited reduced A\u03b2 burden and increased rFDG uptake in the CU and MCI groups, whereas the AD group", "source": "PubMed"}, {"chunk_id": "40582243_1", "pmid": "40582243", "title": "How is self-reported sleep-disordered breathing linked with biomarkers of Alzheimer's disease?", "authors": "Akradi M, Farzane-Daghigh T, Ebneabbasi A et al.", "year": "2025", "journal": "Neurobiology of aging", "keywords": "Alzheimer\u2019s disease, Amyloid-beta, Fluorodeoxyglucose imaging, Grey matter volume, Sleep-disordered breathing", "chunk": "A\u03b2, rFDG, and GMV biomarkers in several brain areas. Participants with SDB exhibited reduced A\u03b2 burden and increased rFDG uptake in the CU and MCI groups, whereas the AD group showed elevated A\u03b2 burden and decreased rFDG. Additionally, SDB+ individuals demonstrated GMV alterations across all groups. The ES of group-SDB interaction on A\u03b2 in the precuneus, middle temporal gyrus, and fusiform gyrus was associated with the ES of cognitive scores. Taken together, we observed a robust association of SDB with A\u03b2 pathology in PET and CSF relative to rFDG and GMV in the AD group, which was also associated with cognitive decline.", "source": "PubMed"}, {"chunk_id": "40998026_0", "pmid": "40998026", "title": "Mind the gap - Interthalamic adhesions in prodromal and clinical Alzheimer's disease.", "authors": "Forno G, Vidal JP, Rush P et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Alzheimer\u2019s disease, Interthalamic adhesion, Massa intermedia, Thalamus", "chunk": "The interthalamic adhesion (IA) is an anatomical bridge connecting the left and right thalamus. While prior studies have explored its prevalence and function in healthy populations, stroke, hydrocephalus, and schizophrenia, none have examined the IA in the context of Alzheimer's disease (AD). This study aims to analyse the prevalence of the IA in the prodromal to clinical AD continuum and evaluate the association with AD cerebrospinal fluid (CSF) biomarkers and thalamic, hippocampal, and ventricular volumes. IA prevalence was assessed in 542 MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including healthy controls (HC), early mild cognitive impairment (EMCI), late MCI (LMCI), and AD patients. Inter-rater reliability was assessed with Cohen's Kappa, and a chi-squared test (\u03c72) examined rater differences. Binary and multinomial logistic regressions evaluated the effect of CSF biomarkers, volumes, and clinical data on IA prevalence and type. There were no significant differences in IA prevalence or variants across", "source": "PubMed"}, {"chunk_id": "40998026_1", "pmid": "40998026", "title": "Mind the gap - Interthalamic adhesions in prodromal and clinical Alzheimer's disease.", "authors": "Forno G, Vidal JP, Rush P et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Alzheimer\u2019s disease, Interthalamic adhesion, Massa intermedia, Thalamus", "chunk": "and multinomial logistic regressions evaluated the effect of CSF biomarkers, volumes, and clinical data on IA prevalence and type. There were no significant differences in IA prevalence or variants across the four groups. The single IA was the most common type, while bilobar and double variants were less frequent. Post-hoc analysis, however, showed that AD CSF biomarker measures showed positive associations with the broad IA subtype in HC and EMCI. The study found no overall differences in IA prevalence or its variants related to prodromal or clinical AD. Still, elevated A\u03b242, p-Tau levels, and larger thalamic volume were linked to a higher likelihood of a broad IA. These findings suggest that the IA may be involved in prodromal AD pathophysiological processes.", "source": "PubMed"}, {"chunk_id": "40998026_2", "pmid": "40998026", "title": "Mind the gap - Interthalamic adhesions in prodromal and clinical Alzheimer's disease.", "authors": "Forno G, Vidal JP, Rush P et al.", "year": "2025", "journal": "Brain research bulletin", "keywords": "Alzheimer\u2019s disease, Interthalamic adhesion, Massa intermedia, Thalamus", "chunk": "processes.", "source": "PubMed"}, {"chunk_id": "36174865_0", "pmid": "36174865", "title": "An adjustable amyloid-\u03b2 oligomers aptasensor based on the synergistic effect of self-enhanced metal-organic gel luminophore and triple-helix DNA system.", "authors": "Wang X, Chen R, Hu J et al.", "year": "2022", "journal": "International journal of biological macromolecules", "keywords": "Amyloid-\u03b2 oligomers, Electrochemiluminescence aptasensor, Metal-organic gel", "chunk": "Amyloid-\u03b2 oligomers (A\u03b2Os) was the core-biomarker of Alzheimer's disease (AD), and the detection of A\u03b2Os is very important for the early diagnosis of AD. However, existing tests for A\u03b2Os are majorly suffering from complex process and poor sensitivity. Thus, an adjustable A\u03b2Os electrochemiluminescence (ECL) aptasensor based on the synergistic effect of self-enhanced metal-organic gel (AgCNS) and triple-helix DNA system (THS) was successfully constructed. AgCNS was prepared by an extremely simple one-pot method and was an innovative luminophore with excellent ECL performance. The AgCNS-labeled complementary sequence (AgCNS@CP) was interlaced with the unlabeled aptamer (Apt) carrying two short-arms fixed on the gold electrode (GE) to form the THS. Along with the specific-binding of A\u03b2Os and Apt, the THS was disrupted and adjusted flexibly between \"on\" and \"off\", resulting in significant changes in the ECL signals. Thus, ECL detection of A\u03b2Os was sensitively achieved with a detection limit as low as 0.23 fM", "source": "PubMed"}, {"chunk_id": "36174865_1", "pmid": "36174865", "title": "An adjustable amyloid-\u03b2 oligomers aptasensor based on the synergistic effect of self-enhanced metal-organic gel luminophore and triple-helix DNA system.", "authors": "Wang X, Chen R, Hu J et al.", "year": "2022", "journal": "International journal of biological macromolecules", "keywords": "Amyloid-\u03b2 oligomers, Electrochemiluminescence aptasensor, Metal-organic gel", "chunk": "flexibly between \"on\" and \"off\", resulting in significant changes in the ECL signals. Thus, ECL detection of A\u03b2Os was sensitively achieved with a detection limit as low as 0.23 fM and the different forms of A\u03b2 can be specifically distinguished. The aptasensor also exhibited satisfactory selectivity, stability and reproducibility. Moreover, when proposed method and ELISA-kit were simultaneously applied to artificial cerebrospinal fluid (A-CSF) samples, the obtained results were completely consistent, reflecting the potential clinical application value of this work.", "source": "PubMed"}, {"chunk_id": "40426276_0", "pmid": "40426276", "title": "Differences in Glucose Metabolism Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Longitudinal Study From SILCODE.", "authors": "Wei M, Wang L, Yu X et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "Alzheimer's disease, FDG\u2010PET, plasma AD biomarkers, subjective cognitive decline", "chunk": "Glucose metabolism and plasma biomarkers have emerged as important early markers in Alzheimer's disease. Different subtypes (single memory domain, multidomain) of subjective cognitive decline (SCD) may represent distinct stages of disease progression, but the differences in glucose metabolism remain unclear. This study focused on exploring the differences in glucose metabolism between different SCD subtypes and the correlation with plasma biomarkers based on <sup>18</sup>F-FDG PET. In this study, thirty-three normal controls (NCs), thirty-five individuals with single memory domain SCD (sd-SCD), thirty-nine individuals with multidomain SCD (md-SCD), and twenty-one cognitively impaired (CI) individuals were involved. We investigated the standardized uptake value ratio (SUVR) and voxel differences between the sd-SCD and md-SCD groups followed by FDR and GRF corrections, with an average follow-up time of 44.98 \u00b1 16.49 months. Correlation analyses were employed to assess relationships between FDG-PET SUVR and neuropsychological scales as well as plasma biomarkers. Finally, Kaplan-Meier survival analysis was used", "source": "PubMed"}, {"chunk_id": "40426276_1", "pmid": "40426276", "title": "Differences in Glucose Metabolism Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Longitudinal Study From SILCODE.", "authors": "Wei M, Wang L, Yu X et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "Alzheimer's disease, FDG\u2010PET, plasma AD biomarkers, subjective cognitive decline", "chunk": "time of 44.98 \u00b1 16.49 months. Correlation analyses were employed to assess relationships between FDG-PET SUVR and neuropsychological scales as well as plasma biomarkers. Finally, Kaplan-Meier survival analysis was used to investigate the risk of cognitive decline conversion among SCD subgroups. After controlling for the effects of covariates, the following brain regions showed voxel differences and lower SUVR in md-SCD groups, including right anterior cingulate and paracingulate gyri (ACG.R, p = 0.003), left anterior cingulate and paracingulate gyri (ACG.L, p = 0.003), right middle temporal gyrus (MTG.R, p = 0.004), and right inferior temporal gyrus (ITG.R, p = 0.001), compared to the sd-SCD group. SUVR of ACG.R was correlated with plasma A\u03b242/40 (r = 0.435, p = 0.006) and AVLT-N7 score (r = 0.347, p = 0.031) in the md-SCD group while none of the correlations existed in the sd-SCD group. SUVR of MTG.R was also correlated with the AVLT-N7", "source": "PubMed"}, {"chunk_id": "40426276_2", "pmid": "40426276", "title": "Differences in Glucose Metabolism Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Longitudinal Study From SILCODE.", "authors": "Wei M, Wang L, Yu X et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "Alzheimer's disease, FDG\u2010PET, plasma AD biomarkers, subjective cognitive decline", "chunk": "score (r = 0.347, p = 0.031) in the md-SCD group while none of the correlations existed in the sd-SCD group. SUVR of MTG.R was also correlated with the AVLT-N7 score (r = 0.246, p = 0.035) across SCD individuals. The SCD individuals with positive plasma A\u03b242/40, p-tau181, and glucose metabolism in above four regions, or those in the md-SCD group showed an elevated risk of cognitive conversion in comparison to the controls. Differences in glucose metabolism could be observed between the md-SCD and sd-SCD groups. SCD participants in the md-SCD group, or those with positive biomarkers, might represent a higher risk of cognitive decline conversion.", "source": "PubMed"}, {"chunk_id": "32087284_0", "pmid": "32087284", "title": "Beyond the CNS: The many peripheral roles of APOE.", "authors": "Mart\u00ednez-Mart\u00ednez AB, Torres-Perez E, Devanney N et al.", "year": "2020", "journal": "Neurobiology of disease", "keywords": "Diabetes, Fertility, Mechanisms, Obesity, Review", "chunk": "Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (\u03b52, \u03b53, and \u03b54). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and", "source": "PubMed"}, {"chunk_id": "32087284_1", "pmid": "32087284", "title": "Beyond the CNS: The many peripheral roles of APOE.", "authors": "Mart\u00ednez-Mart\u00ednez AB, Torres-Perez E, Devanney N et al.", "year": "2020", "journal": "Neurobiology of disease", "keywords": "Diabetes, Fertility, Mechanisms, Obesity, Review", "chunk": "this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.", "source": "PubMed"}, {"chunk_id": "41460600_0", "pmid": "41460600", "title": "Blood biomarkers for diagnosis and differential diagnosis of Alzheimer's disease in real-world clinical populations: A systematic review.", "authors": "Suresh S, Maffei L, Bauermeister S et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, GFAP, NfL, blood biomarkers, clinical settings, diagnosis, pTau217", "chunk": "BackgroundGold standard diagnosis of Alzheimer's disease (AD) relies on invasive, expensive, and non-scalable methods (cerebrospinal fluid lumbar puncture and amyloid-positron emission tomography). Blood biomarkers present a scalable, accessible, and resource-efficient diagnostic alternative.ObjectiveTo investigate the diagnostic and differential diagnostic performance of three clinically relevant plasma biomarkers: phosphorylated tau-217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) for biologically confirmed AD patients in real-world, clinical settings.MethodsA systematic search was conducted across 5 databases for peer-reviewed studies between January 2019-January 2025. A narrative synthesis was conducted for eligible studies.Results13 studies (n = 4686 participants) were included. All studies were cross-sectional, and investigated populations recruited from memory clinics, neurology departments, or clinical cohorts. Diagnostic performance of pTau217 was consistently high (AUC > 0.90 across all comparisons). GFAP showed stronger and more consistent diagnostic performance as compared to NfL, though both demonstrated moderate and variable accuracy (AUCs ranging from <0.75 to >0.90).", "source": "PubMed"}, {"chunk_id": "41460600_1", "pmid": "41460600", "title": "Blood biomarkers for diagnosis and differential diagnosis of Alzheimer's disease in real-world clinical populations: A systematic review.", "authors": "Suresh S, Maffei L, Bauermeister S et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, GFAP, NfL, blood biomarkers, clinical settings, diagnosis, pTau217", "chunk": "> 0.90 across all comparisons). GFAP showed stronger and more consistent diagnostic performance as compared to NfL, though both demonstrated moderate and variable accuracy (AUCs ranging from <0.75 to >0.90). No studies assessed combinations of all 3 biomarkers. Methodological and assay heterogeneity was common.ConclusionsPlasma pTau217 demonstrated strong diagnostic accuracy and promise for diagnosis of AD. GFAP and NfL displayed inconsistent results, but could provide complementary information, particularly for differential diagnosis. Further standardized studies in underrepresented populations are required to validate and enable blood biomarker implementation in clinical settings.", "source": "PubMed"}, {"chunk_id": "36774227_0", "pmid": "36774227", "title": "Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?", "authors": "Johnson RJ, Tolan DR, Bredesen D et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "Alzheimer\u2019s disease, energy metabolism, fructose, insulin resistance, metabolic syndrome", "chunk": "An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. How this survival mechanism affects brain metabolism, which in a resting human amounts to 20% of the overall energy demand, is only beginning to be understood. Here, we review and extend a previous hypothesis that this survival mechanism has a major role in the development of Alzheimer's disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and", "source": "PubMed"}, {"chunk_id": "36774227_1", "pmid": "36774227", "title": "Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?", "authors": "Johnson RJ, Tolan DR, Bredesen D et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "Alzheimer\u2019s disease, energy metabolism, fructose, insulin resistance, metabolic syndrome", "chunk": "that this survival mechanism has a major role in the development of Alzheimer's disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. We propose that the pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer's disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. Although more studies are needed on the role of fructose metabolism and its metabolite, uric acid, in Alzheimer's disease, we suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.", "source": "PubMed"}, {"chunk_id": "36774227_2", "pmid": "36774227", "title": "Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?", "authors": "Johnson RJ, Tolan DR, Bredesen D et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "Alzheimer\u2019s disease, energy metabolism, fructose, insulin resistance, metabolic syndrome", "chunk": "metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.", "source": "PubMed"}, {"chunk_id": "38724874_0", "pmid": "38724874", "title": "Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.", "authors": "Weijs RWJ, de Roos BM, Thijssen DHJ et al.", "year": "2024", "journal": "GeroScience", "keywords": "Brain blood flow, Frailty, Geriatrics, Longevity, Orthostatic intolerance, Primary health care", "chunk": "This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target \u2264 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 \u00b1 5.2 years; Clinical Frailty Scale 4-7; unattended SBP \u2265 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP \u2264 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean", "source": "PubMed"}, {"chunk_id": "38724874_1", "pmid": "38724874", "title": "Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.", "authors": "Weijs RWJ, de Roos BM, Thijssen DHJ et al.", "year": "2024", "journal": "GeroScience", "keywords": "Brain blood flow, Frailty, Geriatrics, Longevity, Orthostatic intolerance, Primary health care", "chunk": "(margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P \u2265 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).", "source": "PubMed"}, {"chunk_id": "38724874_2", "pmid": "38724874", "title": "Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.", "authors": "Weijs RWJ, de Roos BM, Thijssen DHJ et al.", "year": "2024", "journal": "GeroScience", "keywords": "Brain blood flow, Frailty, Geriatrics, Longevity, Orthostatic intolerance, Primary health care", "chunk": "This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).", "source": "PubMed"}, {"chunk_id": "39302036_0", "pmid": "39302036", "title": "Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease.", "authors": "Zang F, Liu X, Fan D et al.", "year": "2024", "journal": "CNS neuroscience & therapeutics", "keywords": "APOE, Alzheimer's disease, cerebrospinal fluid biomarkers, dynamic functional network connectivity, lipid metabolism", "chunk": "The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid metabolism-related factors across the Alzheimer's disease (AD) spectrum populations. Data from 242 AD spectrum subjects, including biological, neuroimaging, and general cognition, were obtained from the Alzheimer's Disease Neuroimaging Initiative for this cross-sectional study. The study utilized a sliding-window approach to assess whole-brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid-related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance. Significant group difference concerning were observed in relation to APOE-\u03b54 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference", "source": "PubMed"}, {"chunk_id": "39302036_1", "pmid": "39302036", "title": "Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease.", "authors": "Zang F, Liu X, Fan D et al.", "year": "2024", "journal": "CNS neuroscience & therapeutics", "keywords": "APOE, Alzheimer's disease, cerebrospinal fluid biomarkers, dynamic functional network connectivity, lipid metabolism", "chunk": "and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference for spending more time in state-I, whereas AD patients tended remain in state-II for longer periods. Group difference in dFNC was primarily found between AD and non-AD participants within each state. The dFNC of state-I yielded strong power to distinguish AD from other groups compared with state-II. APOE-\u03b54<sup>+</sup>, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state-I, whereas differential connections of state-II mediated the relationships between APOE-\u03b54 genotype and CSF biomarkers, and cognitive indicators. The dysfunction of dFNC temporal-spatial patterns and increased cognition in individuals with APOE-\u03b54, high polygenic score, and", "source": "PubMed"}, {"chunk_id": "39302036_2", "pmid": "39302036", "title": "Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease.", "authors": "Zang F, Liu X, Fan D et al.", "year": "2024", "journal": "CNS neuroscience & therapeutics", "keywords": "APOE, Alzheimer's disease, cerebrospinal fluid biomarkers, dynamic functional network connectivity, lipid metabolism", "chunk": "state-II mediated the relationships between APOE-\u03b54 genotype and CSF biomarkers, and cognitive indicators. The dysfunction of dFNC temporal-spatial patterns and increased cognition in individuals with APOE-\u03b54, high polygenic score, and higher serum lipid levels shed light on the lipid-related mechanisms of dynamic network reorganization in AD.", "source": "PubMed"}, {"chunk_id": "41465535_0", "pmid": "41465535", "title": "Molecular Signatures of Early-Onset Bipolar Disorder and Schizophrenia: Transcriptomic and Machine-Learning Insights into Calcium and cAMP Signaling, Including Sex-Specific Patterns.", "authors": "Afjeh SS, Dey S, Kiss D et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "age of onset, bipolar disorder, calcium signaling, co-Expression networks, machine learning, schizophrenia, transcriptomics", "chunk": "Early age of onset is a major predictor of poor disease course in Bipolar Disorder (BD) and Schizophrenia (SCZ), often associated with greater symptom severity, cognitive decline, and worse outcomes. However, the biological mechanisms that shape age- and sex-specific vulnerability remain unclear, limiting progress toward early identification and intervention. To address this gap, we conducted an integrative transcriptomic study of 369 postmortem dorsolateral prefrontal cortex samples from the CommonMind Consortium. Differential gene expression, Weighted Gene Co-Expression Network Analysis, and gene set enrichment analysis were applied to identify pathways associated with age of onset, complemented by sex-stratified models and cellular deconvolution. To assess predictive signals, we applied a rigorous two-stage machine-learning framework using nested cross-validation, with Lasso feature selection followed by L2-regularized logistic classification. Performance was evaluated solely on held-out test folds. Genes and modules linked to earlier onset showed consistent enrichment for calcium signaling, with downregulation of <i>CACNA1C</i> and multiple", "source": "PubMed"}, {"chunk_id": "41465535_1", "pmid": "41465535", "title": "Molecular Signatures of Early-Onset Bipolar Disorder and Schizophrenia: Transcriptomic and Machine-Learning Insights into Calcium and cAMP Signaling, Including Sex-Specific Patterns.", "authors": "Afjeh SS, Dey S, Kiss D et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "age of onset, bipolar disorder, calcium signaling, co-Expression networks, machine learning, schizophrenia, transcriptomics", "chunk": "L2-regularized logistic classification. Performance was evaluated solely on held-out test folds. Genes and modules linked to earlier onset showed consistent enrichment for calcium signaling, with downregulation of <i>CACNA1C</i> and multiple adenylate-cyclase-related transcripts, while female-specific analyses revealed selective dysregulation of cyclase-associated pathways. Network analysis identified a calcium-enriched module associated with onset and sex, and diagnosis-specific modeling highlighted <i>MAP2K7</i> in early-onset BD. The predictive model achieved an AUC of 0.63, and the top 50 machine-learning features were significantly enriched in calcium signaling pathway. These findings converge on calcium-cAMP signaling networks as key drivers of early psychiatric vulnerability and suggest biomarkers for precision-targeted interventions.", "source": "PubMed"}, {"chunk_id": "41336040_0", "pmid": "41336040", "title": "Exploring Alpha Desynchronization in Alzheimer's Disease Using Coherence Analysis.", "authors": "Lin CW, Chung HW, Wu WC", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "Electroencephalography (EEG) is a promising tool for early diagnosis of dementia. As the most common form of dementia, Alzheimer's disease (AD) is currently incurable, but patients and those at risk can benefit from timely intervention following accurate diagnosis. Previous studies reported decreased energy in the alpha-band of EEG signals during the transition from the eyes-closed condition to the eyes-open condition, and considered energy as a surrogate index of synchronization (or functional connectivity). In this study, we explored alpha desynchronization by using coherence which is a mathematical index of connectivity. Our results showed that the AD group had lower alpha-band energy and coherence, and diminished alpha desynchronization as compared with the normal control group. Coherence and energy have different implications in synchronization/connectivity (long-range vs. local), and when combined, may advance the understanding of AD pathology-related functional connectivity changes.Clinical Relevance- This study highlights diminished alpha desynchronization in patients with Alzheimer's disease, which", "source": "PubMed"}, {"chunk_id": "41336040_1", "pmid": "41336040", "title": "Exploring Alpha Desynchronization in Alzheimer's Disease Using Coherence Analysis.", "authors": "Lin CW, Chung HW, Wu WC", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "synchronization/connectivity (long-range vs. local), and when combined, may advance the understanding of AD pathology-related functional connectivity changes.Clinical Relevance- This study highlights diminished alpha desynchronization in patients with Alzheimer's disease, which may be used as a biomarker for early diagnosis.", "source": "PubMed"}, {"chunk_id": "38506627_0", "pmid": "38506627", "title": "Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium.", "authors": "Larsen FK, Baksh RA, McGlinchey E et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, age of diagnosis, co\u2010occurring conditions", "chunk": "People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries. Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis. Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age. Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. Mean age of AD", "source": "PubMed"}, {"chunk_id": "38506627_1", "pmid": "38506627", "title": "Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium.", "authors": "Larsen FK, Baksh RA, McGlinchey E et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, age of diagnosis, co\u2010occurring conditions", "chunk": "varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE \u03b54 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis.", "source": "PubMed"}, {"chunk_id": "41156316_0", "pmid": "41156316", "title": "Sleep Disturbances Across Dementias and Cognitive Decline: Study Protocol for a Systematic Review and Network Meta-Analysis of Polysomnographic Findings.", "authors": "Antonioni A, Della Valle A, Leitner C et al.", "year": "2025", "journal": "Journal of clinical medicine", "keywords": "dementia, mild cognitive impairment (MCI), neurodegenerative disorders, polysomnography (PSG), sleep, subjective cognitive impairment (SCI)", "chunk": "Sleep disturbances are increasingly recognized as early and clinically meaningful features in the pathophysiology of neurodegenerative diseases. Polysomnography (PSG), i.e., the gold standard for objectively characterizing sleep architecture, may provide non-invasive and scalable biomarkers for both early detection and differential diagnosis of dementia. This systematic review and network meta-analysis aims to synthesize existing evidence on PSG-derived sleep alterations across the neurodegenerative continuum, including subjective cognitive impairment, mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and Parkinson's disease dementia, compared to healthy controls. It will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for reporting systematic reviews that include network meta-analyses, and it has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251114418. We will include peer-reviewed studies with nocturnal PSG data from adult participants, categorized using validated diagnostic criteria, and scored according to the most recent American", "source": "PubMed"}, {"chunk_id": "41156316_1", "pmid": "41156316", "title": "Sleep Disturbances Across Dementias and Cognitive Decline: Study Protocol for a Systematic Review and Network Meta-Analysis of Polysomnographic Findings.", "authors": "Antonioni A, Della Valle A, Leitner C et al.", "year": "2025", "journal": "Journal of clinical medicine", "keywords": "dementia, mild cognitive impairment (MCI), neurodegenerative disorders, polysomnography (PSG), sleep, subjective cognitive impairment (SCI)", "chunk": "(PROSPERO) under registration number CRD420251114418. We will include peer-reviewed studies with nocturnal PSG data from adult participants, categorized using validated diagnostic criteria, and scored according to the most recent American Academy of Sleep Medicine guidelines. Both pairwise and network meta-analyses will be conducted using standardized mean differences to quantify group-level effects. Additional analyses will explore the correlations between PSG parameters, severity of cognitive impairment, behavioral symptoms, treatments, and relevant comorbidities. Longitudinal data, where available, will be analyzed separately to evaluate prognostic value. This study will provide a comprehensive synthesis of PSG alterations across neurodegenerative disorders, offering insights into their diagnostic utility and potential as early markers for stratification in clinical trials of disease-modifying therapies.", "source": "PubMed"}, {"chunk_id": "40110626_0", "pmid": "40110626", "title": "Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits.", "authors": "Sewell KR, Oberlin LE, Karikari TK et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, blood\u2010based biomarkers, cognition, cognitive function", "chunk": "The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. Participants (n = 648, aged 69.9 \u00b1 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (A\u03b2)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/A\u03b21-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). Greater p-tau217 was exclusively associated with poorer episodic memory performance (\u03b2 = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217. Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention", "source": "PubMed"}, {"chunk_id": "40110626_1", "pmid": "40110626", "title": "Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits.", "authors": "Sewell KR, Oberlin LE, Karikari TK et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, blood\u2010based biomarkers, cognition, cognitive function", "chunk": "across a range of cognitive domains and remained so after covarying for p-tau217. Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. There is heterogeneity in the causes of cognitive decline in aging. AD-related blood biomarkers may help characterize these causes. Elevated p-tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.", "source": "PubMed"}, {"chunk_id": "39740225_0", "pmid": "39740225", "title": "MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.", "authors": "Liu X, Maillard P, Barisano G et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "cerebral small vessel disease (cSVD), diffusion tensor image analysis along the perivascular space index (DTI\u2010ALPS), free water (FW), glymphatic system (GS), vascular cognitive impairment and dementia (VCID)", "chunk": "Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID). Four independent cohorts were examined. A composite score of executive function (UDS3-EF) was used to evaluate EF status. The association between the ALPS index and UDS3-EF scores and the mediator effect of free water in white matter (WM-FW) on such association was analyzed. The ALPS index was significantly associated with UDS3-EF scores in all cohorts. Additionally, WM-FW mediates the relationship between the ALPS index and UDS3-EF scores. Lower ALPS index may be a surrogate marker of glymphatic dysfunction, which is associated with impaired EF, and this association is mediated by the interstitial fluid (ISF) drainage ISF in WM, providing a clinical rationale for using ALPS index as a biomarker for cSVD-related VCID. This", "source": "PubMed"}, {"chunk_id": "39740225_1", "pmid": "39740225", "title": "MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.", "authors": "Liu X, Maillard P, Barisano G et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "cerebral small vessel disease (cSVD), diffusion tensor image analysis along the perivascular space index (DTI\u2010ALPS), free water (FW), glymphatic system (GS), vascular cognitive impairment and dementia (VCID)", "chunk": "EF, and this association is mediated by the interstitial fluid (ISF) drainage ISF in WM, providing a clinical rationale for using ALPS index as a biomarker for cSVD-related VCID. This is the first study to investigate the mediation role of interstitial FW fraction (WM-FW) on the relationship between glymphatic clearance (ALPS index) and EF (UDS3-EF scores) in four independent middle to aged cohorts at risk for cSVD. This study identified that ALPS index was independently associated with UDS3-EF scores after adjusting for demographics, VRFs, and WM hyperintensity burden and that WM-FW mediated this association in all middle to aged cohorts. Our findings suggest that in middle to aged individuals, glymphatic dysfunction (reflected by ALPS index) is strongly associated with EF and that this association is mediated by the ISF drainage in WM. This study provides a strong clinical rationale for the use of the ALPS index as a marker of", "source": "PubMed"}, {"chunk_id": "39740225_2", "pmid": "39740225", "title": "MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.", "authors": "Liu X, Maillard P, Barisano G et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "cerebral small vessel disease (cSVD), diffusion tensor image analysis along the perivascular space index (DTI\u2010ALPS), free water (FW), glymphatic system (GS), vascular cognitive impairment and dementia (VCID)", "chunk": "and that this association is mediated by the ISF drainage in WM. This study provides a strong clinical rationale for the use of the ALPS index as a marker of cognitive function in multi-site observational studies and clinical trials to monitor and prevent VCID.", "source": "PubMed"}, {"chunk_id": "36766752_0", "pmid": "36766752", "title": "Opposing Effects of ApoE2 and ApoE4 on Glycolytic Metabolism in Neuronal Aging Supports a Warburg Neuroprotective Cascade against Alzheimer's Disease.", "authors": "Zhang X, Wu L, Swerdlow RH et al.", "year": "2023", "journal": "Cells", "keywords": "ApoE2, ApoE4, Warburg effect, apolipoprotein E, brain resilience, glycolysis, hexokinase, late-onset Alzheimer\u2019s disease (LOAD)", "chunk": "Apolipoprotein E4 (ApoE4) is the most recognized genetic risk factor for late-onset Alzheimer's disease (LOAD), whereas ApoE2 reduces the risk for LOAD. The underlying mechanisms are unclear but may include effects on brain energy metabolism. Here, we used neuro-2a (N2a) cells that stably express human ApoE isoforms (N2a-hApoE), differentiated N2a-hApoE neuronal cells, and humanized ApoE knock-in mouse models to investigate relationships among ApoE isoforms, glycolytic metabolism, and neuronal health and aging. ApoE2-expressing cells retained robust hexokinase (HK) expression and glycolytic activity, whereas these endpoints progressively declined with aging in ApoE4-expressing cells. These divergent ApoE2 and ApoE4 effects on glycolysis directly correlated with markers of cellular wellness. Moreover, ApoE4-expressing cells upregulated phosphofructokinase and pyruvate kinase with the apparent intent of compensating for the HK-dependent glycolysis reduction. The introduction of ApoE2 increased HK levels and glycolysis flux in ApoE4 cells. PI3K/Akt signaling was distinctively regulated by ApoE isoforms but was only partially", "source": "PubMed"}, {"chunk_id": "36766752_1", "pmid": "36766752", "title": "Opposing Effects of ApoE2 and ApoE4 on Glycolytic Metabolism in Neuronal Aging Supports a Warburg Neuroprotective Cascade against Alzheimer's Disease.", "authors": "Zhang X, Wu L, Swerdlow RH et al.", "year": "2023", "journal": "Cells", "keywords": "ApoE2, ApoE4, Warburg effect, apolipoprotein E, brain resilience, glycolysis, hexokinase, late-onset Alzheimer\u2019s disease (LOAD)", "chunk": "for the HK-dependent glycolysis reduction. The introduction of ApoE2 increased HK levels and glycolysis flux in ApoE4 cells. PI3K/Akt signaling was distinctively regulated by ApoE isoforms but was only partially responsible for the ApoE-mediated effects on HK. Collectively, our findings indicate that human ApoE isoforms differentially modulate neuronal glycolysis through HK regulation, with ApoE2 upregulating and ApoE4 downregulating, which markedly impacts neuronal health during aging. These findings lend compelling support to the emerging inverse-Warburg theory of AD and highlight a therapeutic opportunity for bolstering brain glycolytic resilience to prevent and treat AD.", "source": "PubMed"}, {"chunk_id": "36401868_0", "pmid": "36401868", "title": "Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.", "authors": "Carey A, Fossati S", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, cardiovascular risk, cerebrovascular dysfunction, dementia, hyperhomocysteinemia, hypertension, prevention, therapeutic strategies", "chunk": "This review summarizes recent evidence on how mid-life hypertension, hyperhomocysteinemia (HHcy) and blood pressure variability, as well as late-life hypotension, exacerbate Alzheimer's disease (AD) and dementia risk. Intriguingly, HHcy also increases the risk for hypertension, revealing the importance of understanding the relationship between comorbid cardiovascular risk factors. Hypertension-induced dementia presents more evidently in women, highlighting the relevance of sex differences in the impact of cardiovascular risk. We summarize each major antihypertensive drug class's effects on cognitive impairment and AD pathology, revealing how carbonic anhydrase inhibitors, diuretics modulating cerebral blood flow, have recently gained preclinical evidence as promising treatment against AD. We also report novel vascular biomarkers for AD and dementia risk, highlighting those associated with hypertension and HHcy. Importantly, we propose that future studies should consider hypertension and HHcy as potential contributors to cognitive impairment, and that uncovering the underlying molecular mechanisms and biomarkers would aid in the identification of", "source": "PubMed"}, {"chunk_id": "36401868_1", "pmid": "36401868", "title": "Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.", "authors": "Carey A, Fossati S", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, cardiovascular risk, cerebrovascular dysfunction, dementia, hyperhomocysteinemia, hypertension, prevention, therapeutic strategies", "chunk": "propose that future studies should consider hypertension and HHcy as potential contributors to cognitive impairment, and that uncovering the underlying molecular mechanisms and biomarkers would aid in the identification of preventive strategies.", "source": "PubMed"}, {"chunk_id": "41139687_0", "pmid": "41139687", "title": "Lecanemab Therapy Use Patterns for Alzheimer's Disease Among Early Initiators in a Large National Health Plan.", "authors": "Li X, Singh S, DeVries A et al.", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "Medicare Advantage, lecanemab, real\u2010world utilization, safety monitoring, uptake", "chunk": "Lecanemab, an anti-amyloid monoclonal antibody, has been approved for treatment of early Alzheimer's disease. However, real-world data remain limited regarding use. Using data from a large national health plan with primarily Medicare Advantage enrollees, we characterized demographic and clinical characteristics in the 6 months preceding the initial infusion among individuals who initiated lecanemab between 1/1/2023 and 06/30/2024. We also characterized the patterns of infusions and the timing of MRIs for safety monitoring following the initial infusion among initiators who had \u2265 3 months of follow-up. We further assessed trends in lecanemab use between 1/1/2023 and 12/31/2024. Of the 195 lecanemab initiators, the average age was 74.6 (SD = 5.5) years, 62.1% were female, 87.7% were White, 4.1% were Black, 1.5% were Hispanic, and 98.5% were on a Medicare Advantage plan. Almost all initiators resided in nonrural areas (96.4%); 2.6% used anticoagulants, and 1.5% used antiplatelets. Among the 119 initiators who", "source": "PubMed"}, {"chunk_id": "41139687_1", "pmid": "41139687", "title": "Lecanemab Therapy Use Patterns for Alzheimer's Disease Among Early Initiators in a Large National Health Plan.", "authors": "Li X, Singh S, DeVries A et al.", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "Medicare Advantage, lecanemab, real\u2010world utilization, safety monitoring, uptake", "chunk": "were Hispanic, and 98.5% were on a Medicare Advantage plan. Almost all initiators resided in nonrural areas (96.4%); 2.6% used anticoagulants, and 1.5% used antiplatelets. Among the 119 initiators who had \u2265 3 months of follow-up, 40 (33.6%) received 7 total infusions, the expected number of infusions based on the recommended schedule of every 2 weeks. From the initial infusion, the average number of days to the first MRI was 47.1 (SD = 15.8), and to the second MRI scan was 73.4 (SD = 12.0) days, consistent with the recommended schedule. During 2023-2024, there were 526 patients who had ever received lecanemab. The increase in new initiators was modest over 2024, with only 43 more initiators during the final (n = 137) versus the first quarter (n = 94) of 2024. This study demonstrated slow uptake of lecanemab among Medicare Advantage beneficiaries. Adherence to the ideal treatment schedule was less", "source": "PubMed"}, {"chunk_id": "41139687_2", "pmid": "41139687", "title": "Lecanemab Therapy Use Patterns for Alzheimer's Disease Among Early Initiators in a Large National Health Plan.", "authors": "Li X, Singh S, DeVries A et al.", "year": "2025", "journal": "Journal of the American Geriatrics Society", "keywords": "Medicare Advantage, lecanemab, real\u2010world utilization, safety monitoring, uptake", "chunk": "= 137) versus the first quarter (n = 94) of 2024. This study demonstrated slow uptake of lecanemab among Medicare Advantage beneficiaries. Adherence to the ideal treatment schedule was less than recommended. Early lecanemab users were not representative of the population likely eligible for treatment nationally. Further research is warranted to track longer-term trends in utilization, as well as reasons for treatment interruption or discontinuation in real-world populations.", "source": "PubMed"}, {"chunk_id": "39814858_0", "pmid": "39814858", "title": "Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.", "authors": "Li G, Hsu LM, Wu Y et al.", "year": "2025", "journal": "Communications medicine", "keywords": "None", "chunk": "Alzheimer's disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neuronal circuits in AD, precluding precise targeting of E-I imbalance in AD treatment. In this work, we apply a Multiscale Neural Model Inversion (MNMI) framework to the resting-state functional MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify brain regions with disrupted E-I balance in a large network during AD progression. We observe that both intra-regional and inter-regional E-I balance is progressively disrupted from cognitively normal individuals, to mild cognitive impairment (MCI) and to AD. Also, we find that local inhibitory connections are more significantly impaired than excitatory ones and the strengths of most connections are reduced in MCI and AD, leading to gradual", "source": "PubMed"}, {"chunk_id": "39814858_1", "pmid": "39814858", "title": "Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.", "authors": "Li G, Hsu LM, Wu Y et al.", "year": "2025", "journal": "Communications medicine", "keywords": "None", "chunk": "AD. Also, we find that local inhibitory connections are more significantly impaired than excitatory ones and the strengths of most connections are reduced in MCI and AD, leading to gradual decoupling of neural populations. Moreover, we reveal a core AD network comprised mainly of limbic and cingulate regions. These brain regions exhibit consistent E-I alterations across MCI and AD, and thus may represent important AD biomarkers and therapeutic targets. Lastly, the E-I balance of multiple brain regions in the core AD network is found to be significantly correlated with the cognitive test score. Our study constitutes an important attempt to delineate E-I imbalance in large-scale neuronal circuits during AD progression, which may facilitate the development of new treatment paradigms to restore physiological E-I balance in AD.", "source": "PubMed"}, {"chunk_id": "39814858_2", "pmid": "39814858", "title": "Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.", "authors": "Li G, Hsu LM, Wu Y et al.", "year": "2025", "journal": "Communications medicine", "keywords": "None", "chunk": "restore physiological E-I balance in AD.", "source": "PubMed"}, {"chunk_id": "41588887_0", "pmid": "41588887", "title": "Vagus Nerve Stimulation in the Management of Neurodegenerative Diseases: A Systematic Review of Advances in Animal Research and Clinical Applications.", "authors": "Edelbach B, Huang L, Boling W", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease, Parkinson's disease, Vagus nerve stimulation, anti-neuroinflammation., neurodegeneration, systematic review", "chunk": "Vagus Nerve Stimulation (VNS) has been approved by the FDA as a treatment for epilepsy, depression, post-ischemic stroke rehabilitation, and migraine in patients. It is emerging as a potential treatment for neurodegenerative diseases. Herein, we summarize the research on VNS and its application in common neurodegenerative diseases. A literature search was completed in PubMed, ScienceDirect, and Google Scholar using the terms: \"neurodegeneration,\" \"neuromodulation,\" \"Vagus Nerve Stimulation,\" \"Parkinson's Disease (PD),\" \"Alzheimer's Disease (AD),\" \"dementia,\" \"neuroinflammation,\" and \"cognitive dysfunction.\" Animal and clinical studies using VNS as a primary intervention in neurodegenerative diseases were included. The studies of VNS application in Parkinson's and Alzheimer's models were reviewed. In animal studies, VNS was associated with increased locomotion and balance, as well as reduced cognitive impairments. The underlying neuroprotective mechanisms included: increased dopaminergic neurons, reduced \u03b1-synuclein concentration in the brain, preservation of the nigrostriatal dopaminergic pathway, increased \u03b17nAChR expression, reduced apoptotic markers, reduced neuroinflammation, and", "source": "PubMed"}, {"chunk_id": "41588887_1", "pmid": "41588887", "title": "Vagus Nerve Stimulation in the Management of Neurodegenerative Diseases: A Systematic Review of Advances in Animal Research and Clinical Applications.", "authors": "Edelbach B, Huang L, Boling W", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease, Parkinson's disease, Vagus nerve stimulation, anti-neuroinflammation., neurodegeneration, systematic review", "chunk": "impairments. The underlying neuroprotective mechanisms included: increased dopaminergic neurons, reduced \u03b1-synuclein concentration in the brain, preservation of the nigrostriatal dopaminergic pathway, increased \u03b17nAChR expression, reduced apoptotic markers, reduced neuroinflammation, and significant reductions in microglial and astrocytic densities. In clinical studies with small patient populations of PD or AD/mild cognitive impairment, VNS was associated with improved gait parameters and enhanced performance in memory-based tasks. Vagus Nerve Stimulation (VNS) shows neuroprotective and anti-inflammatory effects in animal models of Alzheimer's and Parkinson's disease, but clinical results remain inconsistent due to variability in treatment duration, outcome measures, and reliance on subjective assessments. Emerging physiologic biomarkers such as VSEP, EEG, and magnetoencephalography may provide more objective measures of therapeutic response. The systematic review highlights the potential of VNS as a therapeutic approach for managing neurodegenerative diseases. The efficacy of VNS in animal models of Parkinson's and Alzheimer's diseases involves both neuroprotection and anti-neuroinflammation, while additional", "source": "PubMed"}, {"chunk_id": "41588887_2", "pmid": "41588887", "title": "Vagus Nerve Stimulation in the Management of Neurodegenerative Diseases: A Systematic Review of Advances in Animal Research and Clinical Applications.", "authors": "Edelbach B, Huang L, Boling W", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Alzheimer's disease, Parkinson's disease, Vagus nerve stimulation, anti-neuroinflammation., neurodegeneration, systematic review", "chunk": "potential of VNS as a therapeutic approach for managing neurodegenerative diseases. The efficacy of VNS in animal models of Parkinson's and Alzheimer's diseases involves both neuroprotection and anti-neuroinflammation, while additional protective mechanisms require further exploration.", "source": "PubMed"}, {"chunk_id": "34108859_0", "pmid": "34108859", "title": "Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain.", "authors": "Gaetani L, Parnetti L, Calabresi P et al.", "year": "2021", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, multiple sclerosis, neurofilament light chain, presymptomatic", "chunk": "The identification of neurological diseases in their presymptomatic phase will be a fundamental aim in the coming years. This step is necessary both to optimize early diagnostics and to verify the effectiveness of experimental disease modifying drugs in the early stages of diseases. Among the biomarkers that can detect neurological diseases already in their preclinical phase, neurofilament light chain (NfL) has given the most promising results. Recently, its measurement in serum has enabled the identification of neurodegeneration in diseases such as multiple sclerosis (MS) and Alzheimer's disease (AD) up to 6-10 years before the onset of symptoms. Similar results have been obtained in conditions such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), up to 2 years before clinical onset. Study of the longitudinal dynamics of serum NfL has also revealed interesting aspects of the pathophysiology of these diseases in the preclinical phase. This review sought to discuss these", "source": "PubMed"}, {"chunk_id": "34108859_1", "pmid": "34108859", "title": "Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain.", "authors": "Gaetani L, Parnetti L, Calabresi P et al.", "year": "2021", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, multiple sclerosis, neurofilament light chain, presymptomatic", "chunk": "onset. Study of the longitudinal dynamics of serum NfL has also revealed interesting aspects of the pathophysiology of these diseases in the preclinical phase. This review sought to discuss these very recent findings on serum NfL in the presymptomatic phase of neurological diseases.", "source": "PubMed"}, {"chunk_id": "41511350_0", "pmid": "41511350", "title": "Multiomic Analyses Reveal Brainstem Metabolic Changes in a Mouse Model of Dravet Syndrome.", "authors": "Sri Hari A, Chan AM, Scholl A et al.", "year": "2025", "journal": "Cells", "keywords": "Dravet Syndrome, brainstem, metabolism, sudden unexpected death in epilepsy (SUDEP)", "chunk": "Dravet Syndrome (DS) is a severe genetic epileptic encephalopathy caused by mutations in the <i>SCN1A</i> gene that encodes the voltage-gated sodium channel (Na<sub>V</sub>1.1) subunit alpha. DS is characterized by intractable seizures, progressive developmental delay, cognitive impairment, and high mortality due to sudden unexpected death in epilepsy (SUDEP). SUDEP is mediated by respiratory dysfunction, but the exact molecular underpinnings are unclear. Though hippocampal metabolic alterations have been reported in DS mice, such changes in brain regions controlling breathing have not been studied. We used <i>Scn1a<sup>A1783V</sup></i><sup>/<i>WT</i></sup> DS mice to study temporal alterations in the brain metabolome, including analysis of brainstem and forebrain regions. Glycolytic and pentose phosphate pathway intermediates were significantly elevated in the brainstem of DS mice during the period of enhanced susceptibility to mortality (post-natal days P20-30). In older P40-P50 mice, mitochondrial aconitate and the antioxidant glutathione were significantly elevated in the brainstem. Single-nuclei RNA sequencing (snRNA seq) and proteomic", "source": "PubMed"}, {"chunk_id": "41511350_1", "pmid": "41511350", "title": "Multiomic Analyses Reveal Brainstem Metabolic Changes in a Mouse Model of Dravet Syndrome.", "authors": "Sri Hari A, Chan AM, Scholl A et al.", "year": "2025", "journal": "Cells", "keywords": "Dravet Syndrome, brainstem, metabolism, sudden unexpected death in epilepsy (SUDEP)", "chunk": "enhanced susceptibility to mortality (post-natal days P20-30). In older P40-P50 mice, mitochondrial aconitate and the antioxidant glutathione were significantly elevated in the brainstem. Single-nuclei RNA sequencing (snRNA seq) and proteomic analyses revealed alterations in genes associated with neurotransmission, cellular respiration, and protein translation, as well as reorganization of protein kinase-mediated pathways that are specific to the brainstem. These findings suggest that there are widespread metabolic changes in the brainstem of DS mice.", "source": "PubMed"}, {"chunk_id": "38077566_0", "pmid": "38077566", "title": "Residual block fully connected DCNN with categorical generalized focal dice loss and its application to Alzheimer's disease severity detection.", "authors": "Alhudhaif A, Polat K", "year": "2023", "journal": "PeerJ. Computer science", "keywords": "Alzheimer\u2019s disease, Categorical generalized focal dice loss, Classification, Deep learning, New hybrid models", "chunk": "Alzheimer's disease (AD) is a disease that manifests itself with a deterioration in all mental activities, daily activities, and behaviors, especially memory, due to the constantly increasing damage to some parts of the brain as people age. Detecting AD at an early stage is a significant challenge. Various diagnostic devices are used to diagnose AD. Magnetic Resonance Images (MRI) devices are widely used to analyze and classify the stages of AD. However, the time-consuming process of recording the affected areas of the brain in the images obtained from these devices is another challenge. Therefore, conventional techniques cannot detect the early stage of AD. In this study, we proposed a deep learning model supported by a fusion loss model that includes fully connected layers and residual blocks to solve the above-mentioned challenges. The proposed model has been trained and tested on the publicly available T1-weighted MRI-based KAGGLE dataset. Data augmentation techniques", "source": "PubMed"}, {"chunk_id": "38077566_1", "pmid": "38077566", "title": "Residual block fully connected DCNN with categorical generalized focal dice loss and its application to Alzheimer's disease severity detection.", "authors": "Alhudhaif A, Polat K", "year": "2023", "journal": "PeerJ. Computer science", "keywords": "Alzheimer\u2019s disease, Categorical generalized focal dice loss, Classification, Deep learning, New hybrid models", "chunk": "fully connected layers and residual blocks to solve the above-mentioned challenges. The proposed model has been trained and tested on the publicly available T1-weighted MRI-based KAGGLE dataset. Data augmentation techniques were used after various preliminary operations were applied to the data set. The proposed model effectively classified four AD classes in the KAGGLE dataset. The proposed model reached the test accuracy of 0.973 in binary classification and 0.982 in multi-class classification thanks to experimental studies and provided a superior classification performance than other studies in the literature. The proposed method can be used online to detect AD and has the feature of a system that will help doctors in the decision-making process.", "source": "PubMed"}, {"chunk_id": "36572988_0", "pmid": "36572988", "title": "A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.", "authors": "McEvoy CT, Regan-Moriarty J, Dolan C et al.", "year": "2023", "journal": "Diabetic medicine : a journal of the British Diabetic Association", "keywords": "dementia, intervention development, qualitative research, type 2 diabetes", "chunk": "Type 2 diabetes is a risk factor for late-life dementia, but dementia prevention strategies have yet to be comprehensively evaluated in people with diabetes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated cognitive benefits of a 2-year multidomain lifestyle intervention. However, given the intensive nature of FINGER, there is uncertainty about whether it can be implemented in other high-risk populations. Our aim was to explore attitudes towards dementia risk, and barriers to an intervention based on the FINGER model in older adults with type 2 diabetes living in rural areas of Ireland. Focus groups were conducted with 21 adults (11 men and 10 women) aged 60+ years with type 2 diabetes living in border regions of north and south Ireland. Data were analysed using thematic analysis. There was limited understanding of diabetes as a risk factor for late-life dementia. The main barriers to engagement with", "source": "PubMed"}, {"chunk_id": "36572988_1", "pmid": "36572988", "title": "A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.", "authors": "McEvoy CT, Regan-Moriarty J, Dolan C et al.", "year": "2023", "journal": "Diabetic medicine : a journal of the British Diabetic Association", "keywords": "dementia, intervention development, qualitative research, type 2 diabetes", "chunk": "of north and south Ireland. Data were analysed using thematic analysis. There was limited understanding of diabetes as a risk factor for late-life dementia. The main barriers to engagement with the multidomain intervention were eating foods that were not compatible with cultural norms, time and travel constraints, and perceived lack of self-efficacy and self-motivation for adopting the desired diet, exercise and computerised cognitive training (CCT) behaviours. Facilitators for intervention acceptability included the provision of culturally tailored and personalised education, support from a trusted source, and inclusion of goal setting and self-monitoring behavioural strategies. While there was high acceptability for a brain health intervention, several barriers including cultural food norms and low self-efficacy for adopting the diet, exercise and CCT components would need to be considered in the intervention design. Findings from this study will be used to inform local decisions regarding the adaptation of FINGER for people with type 2", "source": "PubMed"}, {"chunk_id": "36572988_2", "pmid": "36572988", "title": "A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.", "authors": "McEvoy CT, Regan-Moriarty J, Dolan C et al.", "year": "2023", "journal": "Diabetic medicine : a journal of the British Diabetic Association", "keywords": "dementia, intervention development, qualitative research, type 2 diabetes", "chunk": "would need to be considered in the intervention design. Findings from this study will be used to inform local decisions regarding the adaptation of FINGER for people with type 2 diabetes. The feasibility of the adapted multidomain intervention will then be evaluated in a future pilot trial.", "source": "PubMed"}, {"chunk_id": "40597399_0", "pmid": "40597399", "title": "CSF Amyloid-\u03b242 associates with neuropsychiatric and cognitive outcomes via cerebral glucose metabolism.", "authors": "Azargoonjahromi A, Nasiri H,  ", "year": "2025", "journal": "Molecular brain", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b242, Cerebral glucose metabolism, Cognitive performance, Mild cognitive impairment, Neuropsychiatric symptoms", "chunk": "Amyloid-\u03b242 (A\u03b242) regulates synaptic plasticity and memory formation at physiological levels in the brain, but in Alzheimer's disease (AD), it can disrupt brain function and glucose metabolism. This disruption contributes to cognitive decline and neuropsychiatric symptoms, highlighting the need to better understand its complex effects. This study investigated the associations among cerebrospinal fluid (CSF) A\u03b242 levels, cerebral glucose metabolism (assessed via FDG-PET), neuropsychiatric symptoms (evaluated using the NPI), and cognitive performance (measured by ADAS-Cog13 and MoCA) in individuals with AD, mild cognitive impairment (MCI), and cognitively normal (CN) participants. After adjusting for age, gender, education, and ApoE \u025b4 status, a significant positive relationship between CSF A\u03b242 levels and cerebral glucose metabolism was observed in the MCI and AD groups, but not in the CN group. In the MCI group, higher cerebral glucose metabolism was associated with reductions in both neuropsychiatric and depressive symptoms, suggesting that higher glucose metabolism reflect higher", "source": "PubMed"}, {"chunk_id": "40597399_1", "pmid": "40597399", "title": "CSF Amyloid-\u03b242 associates with neuropsychiatric and cognitive outcomes via cerebral glucose metabolism.", "authors": "Azargoonjahromi A, Nasiri H,  ", "year": "2025", "journal": "Molecular brain", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b242, Cerebral glucose metabolism, Cognitive performance, Mild cognitive impairment, Neuropsychiatric symptoms", "chunk": "not in the CN group. In the MCI group, higher cerebral glucose metabolism was associated with reductions in both neuropsychiatric and depressive symptoms, suggesting that higher glucose metabolism reflect higher activation state of investigated brain regions. In contrast, in the CN group, elevated CSF A\u03b242 levels were directly linked to increased depressive symptoms, indicating that higher CSF A\u03b242 may contribute to depression even in the absence of cognitive decline. Further analysis revealed that CSF A\u03b242 levels were indirectly associated with reduced neuropsychiatric and depressive symptoms through enhanced cerebral glucose metabolism as mediator solely in the MCI group. Regarding cognitive performance, cerebral glucose metabolism showed a strong relationship with cognition in both the MCI and AD groups. Furthermore, higher CSF A\u03b242 levels were positively associated with better cognitive performance in the MCI and AD groups, with cerebral glucose metabolism potentially mediating this relationship, while no effect was seen in the CN", "source": "PubMed"}, {"chunk_id": "40597399_2", "pmid": "40597399", "title": "CSF Amyloid-\u03b242 associates with neuropsychiatric and cognitive outcomes via cerebral glucose metabolism.", "authors": "Azargoonjahromi A, Nasiri H,  ", "year": "2025", "journal": "Molecular brain", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b242, Cerebral glucose metabolism, Cognitive performance, Mild cognitive impairment, Neuropsychiatric symptoms", "chunk": "levels were positively associated with better cognitive performance in the MCI and AD groups, with cerebral glucose metabolism potentially mediating this relationship, while no effect was seen in the CN group. In short, CSF A\u03b242 positively influenced cerebral glucose metabolism, which was linked to reduced neuropsychiatric and depressive symptoms as well as improved cognitive performance in MCI and AD groups.", "source": "PubMed"}, {"chunk_id": "37824728_0", "pmid": "37824728", "title": "Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.", "authors": "Rebelos E, Latva-Rasku A, Koskensalo K et al.", "year": "2024", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "N-acetyl-aspartate, Positron emission tomography, insulin resistance, magnetic resonance spectroscopy, myo-inositol, obesity", "chunk": "The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (<sup>1</sup>H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG-PET)) was also performed in a subset of subjects during clamp. In <i>dataset A,</i> 48 participants were studied during fasting with brain <sup>1</sup>H-MRS, while in <i>dataset B</i> 21 participants underwent paired brain <sup>1</sup>H-MRS acquisitions under fasting and clamp conditions. In <i>dataset C</i> 16 subjects underwent brain <sup>18</sup>F-FDG-PET and <sup>1</sup>H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with", "source": "PubMed"}, {"chunk_id": "37824728_1", "pmid": "37824728", "title": "Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.", "authors": "Rebelos E, Latva-Rasku A, Koskensalo K et al.", "year": "2024", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "N-acetyl-aspartate, Positron emission tomography, insulin resistance, magnetic resonance spectroscopy, myo-inositol, obesity", "chunk": "N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.", "source": "PubMed"}, {"chunk_id": "41790564_0", "pmid": "41790564", "title": "Association between spirochaetal infection and neurodegenerative diseases: a systematic review and quantitative synthesis of observational studies.", "authors": "Horton M, Whiley DJ, Mayhew M et al.", "year": "2026", "journal": "Journal of medical microbiology", "keywords": "Borrelia burgdorferi, Leptospira spp., Treponema pallidum, neurodegenerative disease, spirochaete, systematic review", "chunk": "<b>Introduction.</b> Neurodegenerative diseases, including Alzheimer's and Parkinson's, are a growing global health concern. While age remains the primary risk factor, infectious agents have been proposed as potential contributors to disease onset or progression.<b>Gap statement.</b> Spirochaetal bacteria, such as <i>Treponema pallidum</i>, <i>Borrelia burgdorferi</i> and <i>Leptospira</i> spp., can invade the central nervous system, yet the extent to which these infections influence neurodegenerative outcomes remains unclear.<b>Aim.</b> This systematic review aimed to evaluate observational evidence on the association between spirochaetal infections and neurodegenerative diseases and to identify gaps in the literature to inform future research.<b>Methodology.</b> A systematic search of SCOPUS, EMBASE, PubMed/MEDLINE, Web of Science and CINAHL was conducted for studies published between January 2000 and May 2025. Eligible studies were observational, involved adult human populations and reported both spirochaetal infection and cognitive or neurodegenerative outcomes using standardized methods. Data were extracted using a standardized form. Owing to heterogeneity in study design, diagnostic approaches,", "source": "PubMed"}, {"chunk_id": "41790564_1", "pmid": "41790564", "title": "Association between spirochaetal infection and neurodegenerative diseases: a systematic review and quantitative synthesis of observational studies.", "authors": "Horton M, Whiley DJ, Mayhew M et al.", "year": "2026", "journal": "Journal of medical microbiology", "keywords": "Borrelia burgdorferi, Leptospira spp., Treponema pallidum, neurodegenerative disease, spirochaete, systematic review", "chunk": "human populations and reported both spirochaetal infection and cognitive or neurodegenerative outcomes using standardized methods. Data were extracted using a standardized form. Owing to heterogeneity in study design, diagnostic approaches, outcome measures and reporting formats, an overall pooled meta-analysis was not feasible; however, a quantitative synthesis using meta-analytic methods was conducted for studies reporting mini-mental state examination data. Risk of bias was assessed using the Newcastle-Ottawa Scale.<b>Results.</b> Twenty-seven studies met the inclusion criteria: 13 on <i>T. pallidum</i>, 13 on <i>B. burgdorferi</i> and one on <i>Leptospira</i> spp. No eligible studies were found for <i>Brachyspira</i> spp., and studies involving <i>Treponema denticola</i> were excluded due to confounding by periodontitis. Studies investigating syphilis and leptospirosis consistently reported cognitive impairment and increased dementia risk. In contrast, findings for Lyme disease were heterogeneous, with some studies reporting persistent symptoms or increased Alzheimer's risk, while others found no long-term cognitive effects.<b>Conclusion.</b> This review highlights a potential link", "source": "PubMed"}, {"chunk_id": "41790564_2", "pmid": "41790564", "title": "Association between spirochaetal infection and neurodegenerative diseases: a systematic review and quantitative synthesis of observational studies.", "authors": "Horton M, Whiley DJ, Mayhew M et al.", "year": "2026", "journal": "Journal of medical microbiology", "keywords": "Borrelia burgdorferi, Leptospira spp., Treponema pallidum, neurodegenerative disease, spirochaete, systematic review", "chunk": "contrast, findings for Lyme disease were heterogeneous, with some studies reporting persistent symptoms or increased Alzheimer's risk, while others found no long-term cognitive effects.<b>Conclusion.</b> This review highlights a potential link between spirochaetal infections and neurodegenerative outcomes, particularly for syphilis and leptospirosis. Evidence for Lyme disease remains inconclusive. Future research should prioritize longitudinal studies with standardized diagnostic criteria, integration of neuroimaging and biomarker data and improved diagnostic accuracy for spirochaetal infections.", "source": "PubMed"}, {"chunk_id": "41428981_0", "pmid": "41428981", "title": "Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic.", "authors": "Roveta F, Pizzini FB, Natale V et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative condition often overlapping clinically with Alzheimer disease (AD). No established in vivo biomarkers exist for LATE. The amygdalar atrophy scale (AAS) is a visual MRI rating tool scoring the amygdala as AAS<sub>0</sub> (no atrophy), AAS<sub>1</sub> (mild-to-moderate atrophy), or AAS<sub>2</sub> (severe atrophy) and is associated with TDP-43 neuropathology in limbic regions. This study describes the clinical, neuroimaging, and longitudinal cognitive profiles of individuals classified using a proposed framework that combines the AAS with established AD biomarkers. This retrospective study included individuals attending the Geneva Memory Center (2014-2022) who underwent T1-weighted MRI, as well as clinical and neuropsychological assessments. Participants were categorized with an etiologic grouping defined as No-AD/No-LATE (AAS<sub>0</sub>, negative AD biomarkers), AD (AAS<sub>0</sub>, positive AD biomarkers), LATE (AAS<sub>1-2</sub>, negative AD biomarkers), or AD/LATE (AAS<sub>1-2</sub>, positive AD biomarkers). Group differences were compared using Kruskal-Wallis or \u03c7<sup>2</sup> tests. Differences in MRI brain volumes and", "source": "PubMed"}, {"chunk_id": "41428981_1", "pmid": "41428981", "title": "Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic.", "authors": "Roveta F, Pizzini FB, Natale V et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "(AAS<sub>0</sub>, positive AD biomarkers), LATE (AAS<sub>1-2</sub>, negative AD biomarkers), or AD/LATE (AAS<sub>1-2</sub>, positive AD biomarkers). Group differences were compared using Kruskal-Wallis or \u03c7<sup>2</sup> tests. Differences in MRI brain volumes and cortical thickness between groups were examined with analysis of covariance. Cognitive trajectories using Mini-Mental State Examination (MMSE) scores over 30 months were estimated with linear mixed-effects models accounting for baseline age and education. The analytic sample included 469 participants (mean age 71.2 \u00b1 8.5 years, 53% female). The No-AD/No-LATE group exhibited the highest MMSE scores (N = 181, 27.9 \u00b1 2.2), outperforming AD (N = 146, 24.2 \u00b1 4.9), LATE (N = 36, 26.2 \u00b1 3.2), and AD/LATE (N = 106, 22.5 \u00b1 5.3) groups (<i>p</i> < 0.001). On the Free and Cued Selective Reminding Test, the No-AD/No-LATE group showed the highest scores (15.1 \u00b1 1.8); the LATE and AD groups performed similarly (13.3 \u00b1 3.5 and 12.5 \u00b1 4.0),", "source": "PubMed"}, {"chunk_id": "41428981_2", "pmid": "41428981", "title": "Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic.", "authors": "Roveta F, Pizzini FB, Natale V et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "Free and Cued Selective Reminding Test, the No-AD/No-LATE group showed the highest scores (15.1 \u00b1 1.8); the LATE and AD groups performed similarly (13.3 \u00b1 3.5 and 12.5 \u00b1 4.0), both exceeding the AD/LATE group (10.6 \u00b1 4.1) (<i>p</i> < 0.001). LATE and AD/LATE groups showed lower volumes/thicknesses in TDP-43-related regions compared with AD and No-AD/No-LATE groups. Longitudinally, the LATE group maintained cognitive stability as the No-AD/No-LATE group (\u03b2 = -0.010, 95% CI -0.096 to 0.075, <i>p</i> = 0.813), whereas both AD (\u03b2 = -0.136, 95% CI -0.184 to -0.088, <i>p</i> < 0.001) and AD/LATE (\u03b2 = -0.139, 95% CI -0.196 to -0.082, <i>p</i> < 0.001) groups showed faster decline over time. Patients identified as LATE by the integration of AAS with AD biomarkers had generally mild amnestic cognitive impairment, significant limbic atrophy, and slow decline over time, all features consistent with previous autopsy series. Moreover, AD/LATE cases were more", "source": "PubMed"}, {"chunk_id": "41428981_3", "pmid": "41428981", "title": "Utility of the Amygdalar Atrophy Scale to Identify Patients With Limbic-Predominant Age-Related TDP-43 Encephalopathy in a Memory Clinic.", "authors": "Roveta F, Pizzini FB, Natale V et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "AAS with AD biomarkers had generally mild amnestic cognitive impairment, significant limbic atrophy, and slow decline over time, all features consistent with previous autopsy series. Moreover, AD/LATE cases were more impaired than those with LATE or AD alone. Prospective and neuropathologic validation is warranted.", "source": "PubMed"}, {"chunk_id": "41186808_0", "pmid": "41186808", "title": "Synergistic neuroprotective effects of Vitexin and Thymol against Okadaic acid-induced neurotoxicity: Computational and In vitro evaluation.", "authors": "Jafni S, Nagakanni M, Indhirakumar B et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer\u2019s disease, Gene expression, Neuroprotection, Okadaic acid, Synergism, Thymol, Vitexin", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia and inexorable loss of neurons. Despite extensive research, the currently approved drugs offer only limited efficacy which highlights the need for exploring novel synergistic natural compounds capable of mitigating multiple targets of AD. This study evaluated the neuroprotective potential of the synergistic combination of Vitexin and Thymol using computational and in vitro model systems in N2a cells. Computational pharmacokinetic screening revealed the blood-brain barrier (BBB) permeability of thymol and 0.55 bioavailability score for Vitexin. Molecular docking studies showed higher binding affinity of Vitexin with JNK and Thymol with COX-1 and CAMK-II and 100 ns molecular dynamics simulation exhibited stable binding with sustained hydrogen bond and hydrophobic interactions. Based on the IC<sub>50</sub> values [Vitexin (135.24 \u00b5g/ml, 312.9 \u00b5M) and Thymol (36.91 \u00b5g/ml, 245.7 \u00b5M)] and combination index (CI < 1) determined by the acetylcholinesterase (AChE) inhibition assay and checkerboard assay (performed", "source": "PubMed"}, {"chunk_id": "41186808_1", "pmid": "41186808", "title": "Synergistic neuroprotective effects of Vitexin and Thymol against Okadaic acid-induced neurotoxicity: Computational and In vitro evaluation.", "authors": "Jafni S, Nagakanni M, Indhirakumar B et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer\u2019s disease, Gene expression, Neuroprotection, Okadaic acid, Synergism, Thymol, Vitexin", "chunk": "IC<sub>50</sub> values [Vitexin (135.24 \u00b5g/ml, 312.9 \u00b5M) and Thymol (36.91 \u00b5g/ml, 245.7 \u00b5M)] and combination index (CI < 1) determined by the acetylcholinesterase (AChE) inhibition assay and checkerboard assay (performed with 15 different combinations) respectively, the effective combination (Vitexin 45.08 \u00b5g/ml; Thymol 7.382 \u00b5g/ml; CI = 0.53) was fixed for further studies. In okadaic acid (OA) induced neurotoxicity model, pre-treatment with the combination significantly increased the cell viability (88.36 \u00b1 3.73%) (n = 3). Real-time PCR results revealed the upregulation of PP1 gene expression and modulation of MAPK family (MEK1/2, ERK1/2 and JNK), and other tau related kinases (GSK3\u03b2, CAMKII and P70 s6). The above findings demonstrate that the combination of Vitexin and Thymol effectively protect the neuronal cells from OA induced cytotoxicity and modulate the hyperactivation of kinases, suggesting its potential in preventing tau hyperphosphorylation in AD conditions.", "source": "PubMed"}, {"chunk_id": "41186808_2", "pmid": "41186808", "title": "Synergistic neuroprotective effects of Vitexin and Thymol against Okadaic acid-induced neurotoxicity: Computational and In vitro evaluation.", "authors": "Jafni S, Nagakanni M, Indhirakumar B et al.", "year": "2025", "journal": "Molecular biology reports", "keywords": "Alzheimer\u2019s disease, Gene expression, Neuroprotection, Okadaic acid, Synergism, Thymol, Vitexin", "chunk": "OA induced cytotoxicity and modulate the hyperactivation of kinases, suggesting its potential in preventing tau hyperphosphorylation in AD conditions.", "source": "PubMed"}, {"chunk_id": "41239797_0", "pmid": "41239797", "title": "Role of Liposomes in the Treatment of Neurodegenerative Disorders: A Comprehensive Review.", "authors": "Garg N, Dhankhar S, Dhariya A et al.", "year": "2025", "journal": "Central nervous system agents in medicinal chemistry", "keywords": "Alzheimer's, Liposomes, amyotrophic lateral sclerosis., disorders, huntington, neurodegeneration, parkinson's", "chunk": "The complex etiology and limited therapy options of neurodegenerative illnesses pose daunting challenges to modern medicine. Nonetheless, novel treatment approaches have exciting new possibilities because of developments in nanotechnology. Liposomes have garnered a lot of interest as a potential treatment for neurological illnesses due to the fact that they are able to adapt to their role as nanocarriers. This review article discusses various uses of liposomes, including their ability to help treat neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, as well as their diagnostic and neuroprotective uses. Liposomes allow for the targeted delivery of medicines to specific brain areas with minimal systemic side effects since they encapsulate and carry therapeutic molecules across the blood-brain barrier. Due to the fact that they are biocompatible, have surface features that can be adjusted, and have the ability to co-deliver many drugs, liposomes are excellent candidates for combination therapy and personalized medicine", "source": "PubMed"}, {"chunk_id": "41239797_1", "pmid": "41239797", "title": "Role of Liposomes in the Treatment of Neurodegenerative Disorders: A Comprehensive Review.", "authors": "Garg N, Dhankhar S, Dhariya A et al.", "year": "2025", "journal": "Central nervous system agents in medicinal chemistry", "keywords": "Alzheimer's, Liposomes, amyotrophic lateral sclerosis., disorders, huntington, neurodegeneration, parkinson's", "chunk": "fact that they are biocompatible, have surface features that can be adjusted, and have the ability to co-deliver many drugs, liposomes are excellent candidates for combination therapy and personalized medicine procedures. In spite of this, there is a growing body of research that suggests liposomes could serve as a versatile platform for the improvement of neurodegenerative disease treatment. This is a positive sign for the future results of patients and their quality of life.", "source": "PubMed"}, {"chunk_id": "36120776_0", "pmid": "36120776", "title": "A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.", "authors": "Bolsewig K, Hok-A-Hin YS, Sepe FN et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Biomarker, NPTX2, NPTXR, differential diagnosis, frontotemporal dementia, glial fibrillary acidic protein, neurofilament light", "chunk": "The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of biofluid-based biomarkers. To investigate the diagnostic potential of a combination of novel biomarkers in cerebrospinal fluid (CSF) and blood. We included 135 patients from the Center for Memory Disturbances, University of Perugia, with the diagnoses FTD (n = 37), mild cognitive impairment due to Alzheimer's disease (MCI-AD, n = 47), Lewy body dementia (PDD/DLB, n = 22), and cognitively unimpaired patients as controls (OND, n = 29). Biomarker levels of neuronal pentraxin-2 (NPTX2), neuronal pentraxin receptor, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured in CSF, as well as NfL and GFAP in serum. We assessed biomarker differences by analysis of covariance and generalized linear models (GLM). We performed receiver operating characteristics analyses and Spearman correlation to determine biomarker associations. CSF NPTX2", "source": "PubMed"}, {"chunk_id": "36120776_1", "pmid": "36120776", "title": "A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.", "authors": "Bolsewig K, Hok-A-Hin YS, Sepe FN et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Biomarker, NPTX2, NPTXR, differential diagnosis, frontotemporal dementia, glial fibrillary acidic protein, neurofilament light", "chunk": "in serum. We assessed biomarker differences by analysis of covariance and generalized linear models (GLM). We performed receiver operating characteristics analyses and Spearman correlation to determine biomarker associations. CSF NPTX2 and serum GFAP levels varied most between diagnostic groups. The combination of CSF NPTX2, serum NfL and serum GFAP differentiated FTD from the other groups with good accuracy (FTD versus MCI-AD: area under the curve (AUC) [95% CI] = 0.89 [0.81-0.96]; FTD versus PDD/DLB: AUC = 0.82 [0.71-0.93]; FTD versus OND: AUC = 0.80 [0.70-0.91]). CSF NPTX2 and serum GFAP correlated positively only in PDD/DLB (\u03c1= 0.56, p < 0.05). NPTX2 and serum NfL did not correlate in any of the diagnostic groups. Serum GFAP and serum NfL correlated positively in all groups (\u03c1= 0.47-0.74, p < 0.05). We show the combined potential of CSF NPTX2, serum NfL, and serum GFAP to differentiate FTD from other neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "36120776_2", "pmid": "36120776", "title": "A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.", "authors": "Bolsewig K, Hok-A-Hin YS, Sepe FN et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Biomarker, NPTX2, NPTXR, differential diagnosis, frontotemporal dementia, glial fibrillary acidic protein, neurofilament light", "chunk": "in all groups (\u03c1= 0.47-0.74, p < 0.05). We show the combined potential of CSF NPTX2, serum NfL, and serum GFAP to differentiate FTD from other neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "41428473_0", "pmid": "41428473", "title": "A hemochromatosis allele that protects against Alzheimer's disease injury: A role for H-ferritin.", "authors": "Rogers JT, Tsurumi A, Arai K et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "5\u2032untranslated region, Alzheimer's disease, diffusion tensor imaging, ferritin mRNA, hemochromatosis, iron homeostasis, iron-regulatory protein, iron-responsive element, white matter", "chunk": "Recent epidemiological evidence showed that mutations to the HFE-63 allele of this hemochromatosis-associated iron-assimilation protein improve chances of avoiding Alzheimer's disease (AD). This is unexpected since increased brain ferroptosis in gray-matter increases the risk for vascular dementia and AD. However, diffusion tensor imaging from a key Alzheimer's Disease Neuroimaging Initiative biomarker study showed that the hemochromatosis H63D allele protected white matter tracts and improved cognitive performance in individuals when <i>APOE4</i> accelerates AD. H63D-carrying individuals exhibit elevated serum ferritin levels. We suggest coordinate increased levels of H-ferritin in iron-rich oligodendrocytes in H63D carriers generates sufficient neuroprotection to enhance myelin sheath integrity in white matter axons.", "source": "PubMed"}, {"chunk_id": "41381319_0", "pmid": "41381319", "title": "The Independent Effect of Depression on Financial Decision-Making in Older Adults.", "authors": "Manning KJ, Mackin RS, Wu R et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Depression, IADL, aging, cognition, decision-making, financial capacity", "chunk": "To determine the association between clinically significant depressive symptoms in late life or late-life depression (LLD) and financial and healthcare-related decision-making in older adults. 821 older adults from the Rush Memory and Aging Program underwent a cross-sectional evaluation of depressive symptoms, cognitive functioning, and a performance-based measured of financial and healthcare decision-making. Participant data on financial and health literacy were also obtained. Rush clinicians assigned a diagnosis of mild cognitive impairment (MCI) or normal cognition (NC) based upon review of the clinical data, and participants were assigned to one of three groups based on the presence of clinically significant depression and antidepressant medication use: active depressive symptoms, remitted depressive symptoms, or no-depression. Patients with dementia were excluded from the current analyses. Depression status was not associated with the total decision-making score. However, active depression, MCI status, financial literacy, and demographics were statistically significant independent predictors of financial decision-making. MCI status,", "source": "PubMed"}, {"chunk_id": "41381319_1", "pmid": "41381319", "title": "The Independent Effect of Depression on Financial Decision-Making in Older Adults.", "authors": "Manning KJ, Mackin RS, Wu R et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Depression, IADL, aging, cognition, decision-making, financial capacity", "chunk": "analyses. Depression status was not associated with the total decision-making score. However, active depression, MCI status, financial literacy, and demographics were statistically significant independent predictors of financial decision-making. MCI status, but not depression status, was a significant predictor of healthcare decision-making. Older depressed adults may be at risk for impaired financial decision-making. Evaluation of financial decision-making should be considered in research and clinical management of depression in older adults and could lead to the early identification of seniors at risk for financial exploitation.", "source": "PubMed"}, {"chunk_id": "37980789_0", "pmid": "37980789", "title": "A comparison of measles-rubella-zoster reaction, oligoclonal IgG bands, oligoclonal kappa free light chains and kappa index in multiple sclerosis.", "authors": "Zondra Revendova K, Svub K, Bunganic R et al.", "year": "2024", "journal": "Multiple sclerosis and related disorders", "keywords": "Kappa index, MRZ reaction, Multiple sclerosis, Oligoclonal IgG bands, Oligoclonal kappa free light chains", "chunk": "To evaluate the diagnostic performance of the measles-rubella-zoster reaction (MRZR) in a large real-world multiple sclerosis (MS) cohort. Second, to compare MRZR with the determination of oligoclonal IgG bands (OCB), oligoclonal kappa free light chain bands (oKFLC), and the KFLC index. A single-center retrospective study was conducted at the University Hospital Ostrava (Czech Republic). Patients were eligible if aged \u226518 years with a determined clinical diagnosis. IgG antibodies against measles (M), rubella (R), and varicella zoster (Z) viruses were determined in paired CSF and serum using ELISA and MRZR indicated as positive if at least two components had an antibody index >1.4. OCB and oKFLC were detected by means of isoelectric focusing, and KFLC CSF and serum concentrations for calculation of the KFLC index were determined immunochemically. A total of 1,751 patients were included in the analyzed data set, which comprised 379 MS patients and 1,372 non-MS controls. The frequency", "source": "PubMed"}, {"chunk_id": "37980789_1", "pmid": "37980789", "title": "A comparison of measles-rubella-zoster reaction, oligoclonal IgG bands, oligoclonal kappa free light chains and kappa index in multiple sclerosis.", "authors": "Zondra Revendova K, Svub K, Bunganic R et al.", "year": "2024", "journal": "Multiple sclerosis and related disorders", "keywords": "Kappa index, MRZ reaction, Multiple sclerosis, Oligoclonal IgG bands, Oligoclonal kappa free light chains", "chunk": "of the KFLC index were determined immunochemically. A total of 1,751 patients were included in the analyzed data set, which comprised 379 MS patients and 1,372 non-MS controls. The frequency of positive MRZR was higher in MS than in non-MS cases (MS 32.2 % vs non-MS 2.8 %; p < 0.001). This corresponded to a specificity of 97.2 % (95 % CI 96.1-98.0) and sensitivity of 32.2 % (95 % CI 27.5-37.2) and overall accuracy of 83.1 % (95 % CI 81.3-84.8). In comparison, the highest sensitivity of 95.6% (95 % CI 93.0-97.5) was for OCB with specificity of 86.9 % (95 % CI 84.9-88.7), followed by oKFLC with sensitivity and specificity of 94.7 % (95 % CI 91.5-96.9) and 78.4% (95 % CI 75.7-80.8), respectively, and the KFLC index with sensitivity of 92.5 % (95 % CI 86.6-96.3) and specificity of 93.5 % (95 % CI 90.5-95.9). MRZR remains", "source": "PubMed"}, {"chunk_id": "37980789_2", "pmid": "37980789", "title": "A comparison of measles-rubella-zoster reaction, oligoclonal IgG bands, oligoclonal kappa free light chains and kappa index in multiple sclerosis.", "authors": "Zondra Revendova K, Svub K, Bunganic R et al.", "year": "2024", "journal": "Multiple sclerosis and related disorders", "keywords": "Kappa index, MRZ reaction, Multiple sclerosis, Oligoclonal IgG bands, Oligoclonal kappa free light chains", "chunk": "78.4% (95 % CI 75.7-80.8), respectively, and the KFLC index with sensitivity of 92.5 % (95 % CI 86.6-96.3) and specificity of 93.5 % (95 % CI 90.5-95.9). MRZR remains a very specific test for the diagnosis of MS but has low sensitivity, which disallows its independent use. In contrast, OCB showed the highest sensitivity and thus remains the gold standard for the diagnosis of MS.", "source": "PubMed"}, {"chunk_id": "41086805_0", "pmid": "41086805", "title": "Tuning insulin receptor signaling using de novo-designed agonists.", "authors": "Wang X, Cardoso S, Cai K et al.", "year": "2025", "journal": "Molecular cell", "keywords": "cancer, computational protein design, diabetes, insulin, insulin receptor, metabolism, receptor tyrosine kinase, severe insulin-resistance syndromes, signaling, trafficking", "chunk": "Insulin binding induces conformational changes in the insulin receptor (IR) that activate the intracellular kinase domain and the protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways, regulating metabolism and proliferation. We reasoned that designed agonists inducing different IR conformational changes might induce different downstream responses. We used de novo protein design to generate binders for individual IR extracellular domains and fused them in different orientations with different conformational flexibility. We obtained a series of synthetic IR agonists that elicit a wide range of receptor autophosphorylation, MAPK activation, trafficking, and proliferation responses. We identified designs more potent than insulin, causing longer-lasting glucose lowering in vivo and retaining activity on disease-causing IR mutants, while largely avoiding the cancer cell proliferation induced by insulin. Our findings shed light on how changes in IR conformation and dynamics translate into downstream signaling, and with further development, our synthetic agonists could have therapeutic utility", "source": "PubMed"}, {"chunk_id": "41086805_1", "pmid": "41086805", "title": "Tuning insulin receptor signaling using de novo-designed agonists.", "authors": "Wang X, Cardoso S, Cai K et al.", "year": "2025", "journal": "Molecular cell", "keywords": "cancer, computational protein design, diabetes, insulin, insulin receptor, metabolism, receptor tyrosine kinase, severe insulin-resistance syndromes, signaling, trafficking", "chunk": "induced by insulin. Our findings shed light on how changes in IR conformation and dynamics translate into downstream signaling, and with further development, our synthetic agonists could have therapeutic utility for metabolic and proliferative diseases.", "source": "PubMed"}, {"chunk_id": "41573343_0", "pmid": "41573343", "title": "Neurobiological correlates of longitudinal grey matter volume changes in preclinical Alzheimer's disease.", "authors": "Pelkmans W, Cacciaglia R, Kassinopoulos M et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Amyloid-\u03b2, Astrocytic reactivity, Biomarkers, Cerebrospinal fluid, Cognitive decline, Grey matter volume, Microglial reactivity, Non-negative matrix factorization (NMF), Preclinical Alzheimer\u2019s disease, Tau, Voxel-based morphometry (VBM)", "chunk": "Structural brain changes during the earliest asymptomatic stages of Alzheimer's disease (AD) remain poorly understood. Previous research in preclinical AD shows heterogeneous findings, reporting both subtle neuronal loss and paradoxical increases in grey matter (GM) volume. This study applies an extensive cerebrospinal fluid (CSF) biomarker panel to better understand the biological processes underlying longitudinal GM changes in cognitively unimpaired (CU) adults, spanning the amyloid/tau (AT) continuum. We analysed data from 627 CU individuals from three longitudinal cohorts (ALFA+, Wisconsin ADRC, WRAP), with repeated MRI (3.5\u00b10.9 years) and baseline CSF biomarkers from the NeuroToolKit panel (Roche Diagnostics). Using non-negative matrix factorization, we decomposed the CSF biomarker levels into six latent components, reflecting amyloid-\u03b2 (A\u03b2) pathology, tau-related pathophysiology with synaptic injury, neuroaxonal injury, microglial reactivity, astrocytic reactivity, and cytokine signalling. We tested associations between component weights and voxel-wise longitudinal GM volume changes using single-component and a joint-all components model. Analyses were performed", "source": "PubMed"}, {"chunk_id": "41573343_1", "pmid": "41573343", "title": "Neurobiological correlates of longitudinal grey matter volume changes in preclinical Alzheimer's disease.", "authors": "Pelkmans W, Cacciaglia R, Kassinopoulos M et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Amyloid-\u03b2, Astrocytic reactivity, Biomarkers, Cerebrospinal fluid, Cognitive decline, Grey matter volume, Microglial reactivity, Non-negative matrix factorization (NMF), Preclinical Alzheimer\u2019s disease, Tau, Voxel-based morphometry (VBM)", "chunk": "injury, microglial reactivity, astrocytic reactivity, and cytokine signalling. We tested associations between component weights and voxel-wise longitudinal GM volume changes using single-component and a joint-all components model. Analyses were performed across the full sample and stratified by AT status. Associations with longitudinal cognitive performance (PACC) were assessed using linear mixed-effects models. The A\u03b2 pathology component was the strongest and most widespread predictor of longitudinal GM atrophy, predominantly in temporal and frontal regions, also when controlling for tau pathophysiology, neuroaxonal injury, or neuroinflammatory components. Higher A\u03b2 pathology scores were also associated with cognitive decline. The component capturing tau-related pathophysiology and synaptic injury initially associated with GM loss but lost significance after accounting for other biomarker components. In contrast, components reflecting microglial reactivity, astrocytic reactivity, and cytokine signalling were associated with longitudinal GM volume increases, with effects varying by AT stage. In this large longitudinal sample of asymptomatic individuals, A\u03b2 pathology emerged", "source": "PubMed"}, {"chunk_id": "41573343_2", "pmid": "41573343", "title": "Neurobiological correlates of longitudinal grey matter volume changes in preclinical Alzheimer's disease.", "authors": "Pelkmans W, Cacciaglia R, Kassinopoulos M et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Amyloid-\u03b2, Astrocytic reactivity, Biomarkers, Cerebrospinal fluid, Cognitive decline, Grey matter volume, Microglial reactivity, Non-negative matrix factorization (NMF), Preclinical Alzheimer\u2019s disease, Tau, Voxel-based morphometry (VBM)", "chunk": "reactivity, astrocytic reactivity, and cytokine signalling were associated with longitudinal GM volume increases, with effects varying by AT stage. In this large longitudinal sample of asymptomatic individuals, A\u03b2 pathology emerged as the primary contributor to early neurodegeneration and cognitive decline, beyond the effects of tau pathophysiology and neuroaxonal injury. While glial and inflammatory processes may underlie transient GM increases in preclinical AD. A better understanding of these dynamic relationships between structural brain changes and diverse biological pathways at the earliest stages of AD is crucial to inform the development of interventions before irreversible neurodegeneration occurs.", "source": "PubMed"}, {"chunk_id": "39986614_0", "pmid": "39986614", "title": "Sigma-1 receptor agonist PRE-084 increases BDNF by activating the ERK/CREB pathway to rescue learning and memory impairment caused by type II diabetes.", "authors": "Shi L, Wang M, Yu R et al.", "year": "2025", "journal": "Behavioural brain research", "keywords": "BDNF, Diabetes-induced cognitive impairment, ERK/CREB pathway, Sig-1R, T2DM", "chunk": "Sigma-1 receptor (Sig-1R) agonists has therapeutic effects in neurological disorders and possesses properties that can reverse cognitive dysfunction. This study investigated the therapeutic efficacy of Sig-1R activation on cognitive dysfunction in streptozotocin (STZ) combined with high fat and high sugar diet (HFD)-induced type 2 diabetic rats. By employing morris water maze (MWM) testing and computed tomography (CT) imaging, we observed that activation of Sig-1R effectively mitigated brain atrophy and cognitive impairment in diabetes-induced cognitive impairment (DCI) rats. Given the fundamental role of intact hippocampal synaptic plasticity in maintaining cognitive function, we investigated the correlation between Sig-1R and Brain-Derived Neurotrophic Factor (BDNF), a well-established neurotrophic factor. And we also analyzed the expression of Postsynaptic density protein-95 (PSD95) protein. Golgi staining, Haematoxylin-eosin (HE) staining, Nissl staining, and immunofluorescence results show that activating Sig-1R can upregulate BDNF expression and reducing synaptic damage in hippocampal neurons. To elucidate the mechanism by which Sig-1R activation", "source": "PubMed"}, {"chunk_id": "39986614_1", "pmid": "39986614", "title": "Sigma-1 receptor agonist PRE-084 increases BDNF by activating the ERK/CREB pathway to rescue learning and memory impairment caused by type II diabetes.", "authors": "Shi L, Wang M, Yu R et al.", "year": "2025", "journal": "Behavioural brain research", "keywords": "BDNF, Diabetes-induced cognitive impairment, ERK/CREB pathway, Sig-1R, T2DM", "chunk": "(HE) staining, Nissl staining, and immunofluorescence results show that activating Sig-1R can upregulate BDNF expression and reducing synaptic damage in hippocampal neurons. To elucidate the mechanism by which Sig-1R activation leads to increased BDNF levels, we investigated the Extracellular Signal-Regulated Kinase/Cyclic AMP Response Element-Binding Protein(ERK/CREB) protein pathway. In vitro and in vivo, we observed that Sig-1R activates the ERK/CREB signaling pathway, thereby stimulating BDNF release and increased PSD95 expression. Further intervention with BD1047 antagonist and Tropomyosin-Related Kinase B (TrkB) antagonist ANA-12 confirmed our conclusion that Sig-1R activation upregulated p-ERK and p-CREB protein expression, promoted BDNF transcription, the expression of PSD95 protein was up-regulated, reduces synaptic damage in damaged hippocampal neurons, and rescued cognitive impairment in DCI rats.", "source": "PubMed"}, {"chunk_id": "36804020_0", "pmid": "36804020", "title": "Effect of unsaturated fat and protein intake on liver fat in people at risk of unhealthy aging: 1-year results of a randomized controlled trial.", "authors": "Wernicke C, Pohrt A, Pletsch-Borba L et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "MUFA, PUFA, diet, dietary proteins, healthy aging, magnetic resonance spectroscopy, non-Mediterranean population, nonalcoholic fatty liver disease", "chunk": "Short-term trials indicate improvement of intrahepatic lipids (IHLs) and metabolism by dietary protein or unsaturated fatty acids (UFAs) beyond weight loss. We aimed to assess the effect of a dietary intervention high in protein and UFAs on IHLs and metabolic outcome after 12 mo, as long-term effects of such a combined intervention are unknown. Within a 36-mo randomized controlled trial, eligible subjects (aged 50 to 80 y, \u22651 risk factor for unhealthy aging) were randomly assigned to either intervention group (IG) with high intake of mono-/poly-UFAs [15-20 percent of total energy (%E)/10%-15%E, respectively], plant protein (15%-25%E), and fiber (\u226530 g/d), or control group [CG, usual care, dietary recommendations of the German Nutrition Society (fat 30%E/carbohydrates 55%E/protein 15%E)]. Stratification criteria were sex, known cardiovascular disease, heart failure, arterial hypertension, type 2 diabetes, and cognitive or physical impairment. Nutritional counseling and supplementation of foods mirroring the intended dietary pattern were performed in", "source": "PubMed"}, {"chunk_id": "36804020_1", "pmid": "36804020", "title": "Effect of unsaturated fat and protein intake on liver fat in people at risk of unhealthy aging: 1-year results of a randomized controlled trial.", "authors": "Wernicke C, Pohrt A, Pletsch-Borba L et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "MUFA, PUFA, diet, dietary proteins, healthy aging, magnetic resonance spectroscopy, non-Mediterranean population, nonalcoholic fatty liver disease", "chunk": "sex, known cardiovascular disease, heart failure, arterial hypertension, type 2 diabetes, and cognitive or physical impairment. Nutritional counseling and supplementation of foods mirroring the intended dietary pattern were performed in the IG. Diet-induced effects on IHLs, analyzed by magnetic resonance spectroscopy, as well as on lipid and glucose metabolism were predefined secondary endpoints. IHL content was analyzed in 346 subjects without significant alcohol consumption at baseline and in 258 subjects after 12 mo. Adjusted for weight loss, sex, and age, we observed a comparable decline of IHLs in IG and CG (-33.3%; 95% CI: -49.3, -12.3%; n = 128 compared with -21.8%; 95% CI: -39.7, 1.5%; n = 130; P = 0.179), an effect that became significant by comparing adherent IG subjects to adherent CG subjects (-42.1%; 95% CI: -58.1, -20.1%; n = 88 compared with -22.2%; 95% CI: -40.7, 2.0%; n = 121; P = 0.013). Compared with the", "source": "PubMed"}, {"chunk_id": "36804020_2", "pmid": "36804020", "title": "Effect of unsaturated fat and protein intake on liver fat in people at risk of unhealthy aging: 1-year results of a randomized controlled trial.", "authors": "Wernicke C, Pohrt A, Pletsch-Borba L et al.", "year": "2023", "journal": "The American journal of clinical nutrition", "keywords": "MUFA, PUFA, diet, dietary proteins, healthy aging, magnetic resonance spectroscopy, non-Mediterranean population, nonalcoholic fatty liver disease", "chunk": "IG subjects to adherent CG subjects (-42.1%; 95% CI: -58.1, -20.1%; n = 88 compared with -22.2%; 95% CI: -40.7, 2.0%; n = 121; P = 0.013). Compared with the CG, decline of LDL cholesterol (LDL-C) and total cholesterol (TC) was stronger in the IG (for LDL-C P = 0.019, for TC P = 0.010). Both groups decreased in triglycerides and insulin resistance (P for difference between groups P = 0.799 and P = 0.124, respectively). Diets enriched with protein and UFAs have beneficial long-term effects on liver fat and lipid metabolism in adherent older subjects. This study was registered at the German Clinical Trials Register, https://www.drks.de/drks_web/setLocale_EN.do, DRKS00010049. Am J Clin Nutr 20XX;xx:xx-xx.", "source": "PubMed"}, {"chunk_id": "40496670_0", "pmid": "40496670", "title": "Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.", "authors": "Bell TR, Franz CE, Lerman IR et al.", "year": "2025", "journal": "Brain communications", "keywords": "APOE \u025b4, Alzheimer\u2019s risk, chronic pain, cognitive decline, older adults", "chunk": "Multisite chronic pain is a risk factor for Alzheimer's disease, but its relationship with Alzheimer's pathology remains unclear. This study examines the association between multisite chronic pain and single-site chronic pain with cognitive decline and post-mortem Alzheimer's biomarkers in older adults. We conducted a longitudinal and prospective observational study using data from 3459 participants without dementia at baseline in the Religious Orders Study and Rush Memory and Aging Project. Participants (mean age = 77.94, SD = 7.93 years) were followed for an average of 8.53 years (SD = 5.74), with cognitive assessments and post-mortem biomarker analyses in a subset of brain donors (<i>n</i> range from 863 to 987 based on assay quality and tissue preservation). Cognitive function was measured using repeated assessments of five cognitive domains and a global composite score. Chronic pain was classified based on self-reported pain, determined by the number of joint sites affected during the first", "source": "PubMed"}, {"chunk_id": "40496670_1", "pmid": "40496670", "title": "Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.", "authors": "Bell TR, Franz CE, Lerman IR et al.", "year": "2025", "journal": "Brain communications", "keywords": "APOE \u025b4, Alzheimer\u2019s risk, chronic pain, cognitive decline, older adults", "chunk": "repeated assessments of five cognitive domains and a global composite score. Chronic pain was classified based on self-reported pain, determined by the number of joint sites affected during the first two assessments: Multisite chronic pain was defined as chronic pain in more than one site, single-site chronic pain as chronic pain in one site, and no chronic pain as no chronic pain sites. Brain beta-amyloid (A\u03b2) load and tau tangle density were assessed post-mortem, \u223c10 months after the last clinical evaluation. This was assessed as a global measure across eight Alzheimer's-affected brain regions, as well as specifically in the entorhinal cortex and hippocampus. <i>Apolipoprotein</i>-\u025b4 genotype was determined from blood and tissue samples. Compared to individuals with single-site (<i>n</i> = 506) or no chronic pain (<i>n</i> = 2599), participants with multisite chronic pain (<i>n</i> = 354) showed steeper declines in global cognition, episodic memory and working memory-especially among those with higher", "source": "PubMed"}, {"chunk_id": "40496670_2", "pmid": "40496670", "title": "Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.", "authors": "Bell TR, Franz CE, Lerman IR et al.", "year": "2025", "journal": "Brain communications", "keywords": "APOE \u025b4, Alzheimer\u2019s risk, chronic pain, cognitive decline, older adults", "chunk": "or no chronic pain (<i>n</i> = 2599), participants with multisite chronic pain (<i>n</i> = 354) showed steeper declines in global cognition, episodic memory and working memory-especially among those with higher <i>apolipoprotein</i>-\u025b4 load-and were more likely to develop Alzheimer's dementia. Multisite chronic pain was also linked to increased A\u03b2 deposition in the entorhinal cortex and hippocampus, particularly in <i>apolipoprotein</i>-\u025b4 carriers. Compared to people with no chronic pain, single-site chronic pain did not differ on rate of cognitive decline, Alzheimer's dementia risk or post-mortem Alzheimer's biomarkers. Multisite, but not single-site, chronic pain is linked to steeper cognitive decline and increased A\u03b2 deposition, particularly in individuals with elevated Alzheimer's genetic risk. These findings suggest that reducing pain may mitigate the risk of cognitive decline and dementia.", "source": "PubMed"}, {"chunk_id": "40496670_3", "pmid": "40496670", "title": "Multisite chronic pain: association with cognitive decline and post-mortem Alzheimer's biomarkers.", "authors": "Bell TR, Franz CE, Lerman IR et al.", "year": "2025", "journal": "Brain communications", "keywords": "APOE \u025b4, Alzheimer\u2019s risk, chronic pain, cognitive decline, older adults", "chunk": "decline and dementia.", "source": "PubMed"}, {"chunk_id": "41664997_0", "pmid": "41664997", "title": "N-Truncated Superoxide Dismutase-1 in Cerebrospinal Fluid Is Folded and Active.", "authors": "Leykam L, Forsberg KME, Andersen PM et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "amyotrophic lateral sclerosis, cerebrospinal fluid, posttranslational modification, superoxide dismutase\u20101", "chunk": "Mutations in the antioxidant enzyme superoxide dismutase-1 (SOD1) are a well-established cause of amyotrophic lateral sclerosis (ALS). The mutations promote SOD1 misfolding, resulting in protein aggregation and motor neuron degeneration. SOD1 is normally a structurally stable enzyme, and the mechanisms underlying SOD1 misfolding remain poorly understood. Approximately one third of SOD1 in cerebrospinal fluid (CSF) exhibits an N-terminal truncation, the biological significance of which remains unclear. This is remarkable given the dramatic effects ALS-linked C-terminal truncations have on the enzyme. In this study, we identified the truncation site and investigated its impact on SOD1 stability and enzymatic activity. Edman degradation revealed the cleavage site between Asn-26 and Gly-27, generating a 26-residue peptide that was confirmed by mass spectrometry. We analyzed postmortem tissues from different parts of the central nervous system (CNS), including the choroid plexus, and found only trace amounts of N-terminally truncated SOD1. Biochemical characterization of the SOD1 in", "source": "PubMed"}, {"chunk_id": "41664997_1", "pmid": "41664997", "title": "N-Truncated Superoxide Dismutase-1 in Cerebrospinal Fluid Is Folded and Active.", "authors": "Leykam L, Forsberg KME, Andersen PM et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "amyotrophic lateral sclerosis, cerebrospinal fluid, posttranslational modification, superoxide dismutase\u20101", "chunk": "postmortem tissues from different parts of the central nervous system (CNS), including the choroid plexus, and found only trace amounts of N-terminally truncated SOD1. Biochemical characterization of the SOD1 in CSF was done by size exclusion chromatography, ion exchange chromatography, and mass spectrometry. Our findings demonstrate that SOD1 in CSF retains full enzymatic activity, that the N-terminally truncated variant is mainly present in heterodimers with native SOD1 subunits, and that the dimer remains folded and active, with both fragments of the truncated SOD1 fixed after proteolysis. Truncated SOD1 was absent in human plasma. In mice, only transgenically expressed human SOD1 underwent truncation in CSF, whereas endogenous murine SOD1 remained intact. Lastly, the N-terminal truncation does not induce misfolding, unlike the destabilizing effects observed with C-terminal truncations. The location where the truncation takes place and the underlying mechanism could not be identified. Whether the N-truncated SOD1 variant contributes to ALS pathogenesis", "source": "PubMed"}, {"chunk_id": "41664997_2", "pmid": "41664997", "title": "N-Truncated Superoxide Dismutase-1 in Cerebrospinal Fluid Is Folded and Active.", "authors": "Leykam L, Forsberg KME, Andersen PM et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "amyotrophic lateral sclerosis, cerebrospinal fluid, posttranslational modification, superoxide dismutase\u20101", "chunk": "destabilizing effects observed with C-terminal truncations. The location where the truncation takes place and the underlying mechanism could not be identified. Whether the N-truncated SOD1 variant contributes to ALS pathogenesis remains to be determined.", "source": "PubMed"}, {"chunk_id": "38676489_0", "pmid": "38676489", "title": "Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.", "authors": "Vishwas S, Bashir B, Birla D et al.", "year": "2024", "journal": "Current topics in medicinal chemistry", "keywords": "Alzheimer\u2019s disease, Bioavailability, Nanoemulsion, Neurofibrillary tangles., Neuroprotective effects, Phytoconstituents", "chunk": "Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (A\u03b2), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of A\u03b2 and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and", "source": "PubMed"}, {"chunk_id": "38676489_1", "pmid": "38676489", "title": "Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.", "authors": "Vishwas S, Bashir B, Birla D et al.", "year": "2024", "journal": "Current topics in medicinal chemistry", "keywords": "Alzheimer\u2019s disease, Bioavailability, Nanoemulsion, Neurofibrillary tangles., Neuroprotective effects, Phytoconstituents", "chunk": "factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the", "source": "PubMed"}, {"chunk_id": "38676489_2", "pmid": "38676489", "title": "Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.", "authors": "Vishwas S, Bashir B, Birla D et al.", "year": "2024", "journal": "Current topics in medicinal chemistry", "keywords": "Alzheimer\u2019s disease, Bioavailability, Nanoemulsion, Neurofibrillary tangles., Neuroprotective effects, Phytoconstituents", "chunk": "Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of A\u03b2. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.", "source": "PubMed"}, {"chunk_id": "38497046_0", "pmid": "38497046", "title": "Which neuroimaging and fluid biomarkers method is better in theranostic of Alzheimer's disease? An umbrella review.", "authors": "Mohammadi H, Ariaei A, Ghobadi Z et al.", "year": "2024", "journal": "IBRO neuroscience reports", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Diagnosis, Magnetic resonance imaging, Neuroimaging, Plasma", "chunk": "Biomarkers are measured to evaluate physiological and pathological processes as well as responses to a therapeutic intervention. Biomarkers can be classified as diagnostic, prognostic, predictor, clinical, and therapeutic. In Alzheimer's disease (AD), multiple biomarkers have been reported so far. Nevertheless, finding a specific biomarker in AD remains a major challenge. Three databases, including PubMed, Web of Science, and Scopus were selected with the keywords of Alzheimer's disease, neuroimaging, biomarker, and blood. The results were finalized with 49 potential CSF/blood and 35 neuroimaging biomarkers. To distinguish normal from AD patients, amyloid-beta<sub>42</sub> (A\u03b2<sub>42</sub>), plasma glial fibrillary acidic protein (GFAP), and neurofilament light (NFL) as potential biomarkers in cerebrospinal fluid (CSF) as well as the serum could be detected. Nevertheless, most of the biomarkers fairly change in the CSF during AD, listed as kallikrein 6, virus-like particles (VLP-1), galectin-3 (Gal-3), and synaptotagmin-1 (Syt-1). From the neuroimaging aspect, atrophy is an accepted biomarker for", "source": "PubMed"}, {"chunk_id": "38497046_1", "pmid": "38497046", "title": "Which neuroimaging and fluid biomarkers method is better in theranostic of Alzheimer's disease? An umbrella review.", "authors": "Mohammadi H, Ariaei A, Ghobadi Z et al.", "year": "2024", "journal": "IBRO neuroscience reports", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cerebrospinal fluid, Diagnosis, Magnetic resonance imaging, Neuroimaging, Plasma", "chunk": "biomarkers fairly change in the CSF during AD, listed as kallikrein 6, virus-like particles (VLP-1), galectin-3 (Gal-3), and synaptotagmin-1 (Syt-1). From the neuroimaging aspect, atrophy is an accepted biomarker for the neuropathologic progression of AD. In addition, Magnetic resonance spectroscopy (MRS), diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), tractography (DTT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), can be used to detect AD. Using neuroimaging and CSF/blood biomarkers, in combination with artificial intelligence, it is possible to obtain information on prognosis and follow-up on the different stages of AD. Hence physicians could select the suitable therapy to attenuate disease symptoms and follow up on the efficiency of the prescribed drug.", "source": "PubMed"}, {"chunk_id": "41657474_0", "pmid": "41657474", "title": "A Protocol of Korean JOint RegistrY for ALZheimer's Treatment and Diagnostics (JOY-ALZ).", "authors": "Kim GH, Pyun JM, Kang D et al.", "year": "2026", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer Disease, Biomarkers, Dataset, Diagnosis, Monoclonal Antibody, Treatment", "chunk": "To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer's disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer's Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended", "source": "PubMed"}, {"chunk_id": "41657474_1", "pmid": "41657474", "title": "A Protocol of Korean JOint RegistrY for ALZheimer's Treatment and Diagnostics (JOY-ALZ).", "authors": "Kim GH, Pyun JM, Kang D et al.", "year": "2026", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer Disease, Biomarkers, Dataset, Diagnosis, Monoclonal Antibody, Treatment", "chunk": "essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety. Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis. ClinicalTrials.gov Identifier: NCT06889818.", "source": "PubMed"}, {"chunk_id": "41657474_2", "pmid": "41657474", "title": "A Protocol of Korean JOint RegistrY for ALZheimer's Treatment and Diagnostics (JOY-ALZ).", "authors": "Kim GH, Pyun JM, Kang D et al.", "year": "2026", "journal": "Dementia and neurocognitive disorders", "keywords": "Alzheimer Disease, Biomarkers, Dataset, Diagnosis, Monoclonal Antibody, Treatment", "chunk": "care and diagnosis. ClinicalTrials.gov Identifier: NCT06889818.", "source": "PubMed"}, {"chunk_id": "34593971_0", "pmid": "34593971", "title": "Alzheimer's disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline.", "authors": "Bucci M, Chiotis K, Nordberg A et al.", "year": "2021", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "For early detection of Alzheimer's disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status for A\u03b242 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category and to assess their ability to predict longitudinal cognitive decline. A subset of 282 patients, who had had at the same time PET investigations with amyloid-\u03b2 and tau tracers, CSF sampling, and structural MRI (18% within 13 months), was selected from the ADNI dataset. The participants were grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-\u03b2-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-\u03b2 PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume", "source": "PubMed"}, {"chunk_id": "34593971_1", "pmid": "34593971", "title": "Alzheimer's disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline.", "authors": "Bucci M, Chiotis K, Nordberg A et al.", "year": "2021", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-\u03b2-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-\u03b2 PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume (MRI)(N)) positivity in ATN was assessed with Cohen's Kappa. Linear mixed-effects models were used to predict decline in the episodic memory. There was moderate agreement between PET and CSF for A biomarkers (Kappa = 0.39-0.71), while only fair agreement for T biomarkers (Kappa \u2264 0.40, except AD) and discordance for N biomarkers across all groups (Kappa \u2264 0.14) was found. Baseline PET tau predicted longitudinal decline in episodic memory irrespective of CSF p-Tau181 positivity (p \u2264 0.02). Baseline PET tau and amyloid-\u03b2 predicted decline in episodic memory (p \u2264 0.0001), but isolated PET amyloid-\u03b2 did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-\u03b2 were similar using CSF or imaging,", "source": "PubMed"}, {"chunk_id": "34593971_2", "pmid": "34593971", "title": "Alzheimer's disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline.", "authors": "Bucci M, Chiotis K, Nordberg A et al.", "year": "2021", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "but isolated PET amyloid-\u03b2 did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-\u03b2 were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not interchangeable. PET tau positivity was superior to CSF p-Tau181 and PET amyloid-\u03b2 in predicting cognitive decline in the AD continuum within 3 years of follow-up.", "source": "PubMed"}, {"chunk_id": "41709596_0", "pmid": "41709596", "title": "Mixed primary progressive aphasia and alcohol use disorder: a case of detailed clinical phenotyping outperforming molecular imaging.", "authors": "Okoye O, Aguzzoli CS, Battista P et al.", "year": "2026", "journal": "Neurocase", "keywords": "Alzheimer\u2019s disease neuropathology, Primary progressive aphasia (PPA), alcohol use disorder, logopenic variant PPA, semantic variant PPA, \u03b2-amyloid PET imaging", "chunk": "Primary progressive aphasia (PPA) refers to a group of clinically and pathologically heterogeneous syndromes characterized by progressive and relatively selective impairment in speech and language as the main cognitive domain in the early disease stage. The main clinical variants of PPA based on current diagnostic criteria include logopenic variant PPA (lvPPA), nonfluent variant PPA (nfvPPA), and semantic variant PPA (svPPA). Identification of speech/language and non-language abilities and <i>in vivo</i> biomarkers (such as neuroimaging, genetic, and biofluid studies) facilitates the correct classification of the main variants. PPA variants clinical presentation may overlap leading to a diagnosis of mixed or unclassified PPA. We report the case of a trilingual patient with a 10-year history of word-finding difficulties initially attributed to chronic alcohol abuse. Her clinical presentation was evocative of lvPPA with features of svPPA, while her neuropsychological testing and MRI data were suggestive of a diagnosis of svPPA. While \u03b2-amyloid PET brain", "source": "PubMed"}, {"chunk_id": "41709596_1", "pmid": "41709596", "title": "Mixed primary progressive aphasia and alcohol use disorder: a case of detailed clinical phenotyping outperforming molecular imaging.", "authors": "Okoye O, Aguzzoli CS, Battista P et al.", "year": "2026", "journal": "Neurocase", "keywords": "Alzheimer\u2019s disease neuropathology, Primary progressive aphasia (PPA), alcohol use disorder, logopenic variant PPA, semantic variant PPA, \u03b2-amyloid PET imaging", "chunk": "abuse. Her clinical presentation was evocative of lvPPA with features of svPPA, while her neuropsychological testing and MRI data were suggestive of a diagnosis of svPPA. While \u03b2-amyloid PET brain imaging was negative, postmortem immunohistochemical analysis of the brain showed unequivocal evidence of Alzheimer's disease. We describe this case of complex PPA for which clinical data outperformed imaging biomarkers in predicting the underlying neuropathology and discuss chronic alcohol abuse as a potential risk factor for neurodegeneration.", "source": "PubMed"}, {"chunk_id": "41445670_0", "pmid": "41445670", "title": "Association between 24-h time-use composition and brain age: The IGNITE study.", "authors": "Collins AM, Mellow ML, Wan L et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "brain age, compositional data analysis, physical activity, sedentary behavior, sleep", "chunk": "The relationships between 24-h time-use composition (i.e., sleep, sedentary behavior, light physical activity, and moderate-to-vigorous physical activity [MVPA]) and brain morphology in older adulthood remain poorly understood. We examined associations between 24-h time-use composition and brain age using compositional data analysis, predicting that 24-h time use would be associated with brain age and that a greater amount of time engaged in MVPA would drive associations with younger brain age. Baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE; <i>n</i> = 648) were analyzed. Brain age was estimated using T1-weighted magnetic resonance imaging data. Time-use composition was derived from wrist-worn triaxial accelerometers. Regression models examined associations between 24-h time-use composition (expressed as isometric log ratios) and brain age, adjusting for age, sex, apolipoprotein E4 (<i>APOE4</i>) carriage, education, body mass index, image quality, and site. Compositional isotemporal substitution evaluated how hypothetical reallocations of time between behaviors", "source": "PubMed"}, {"chunk_id": "41445670_1", "pmid": "41445670", "title": "Association between 24-h time-use composition and brain age: The IGNITE study.", "authors": "Collins AM, Mellow ML, Wan L et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "brain age, compositional data analysis, physical activity, sedentary behavior, sleep", "chunk": "and brain age, adjusting for age, sex, apolipoprotein E4 (<i>APOE4</i>) carriage, education, body mass index, image quality, and site. Compositional isotemporal substitution evaluated how hypothetical reallocations of time between behaviors related to brain age. The final sample included 573 adults (69.8\u00b13.7 years, 407 females). It was found that 24-h time-use composition was associated with brain age (F = 2.72, <i>p</i> = 0.004). Post hoc modeling indicated that time spent in MVPA primarily drove these associations, such that less MVPA was associated with greater brain age, irrespective of whether time was taken from sleep, sedentary behavior, or light physical activity. These results suggest that 24-h time use, especially time spent in MVPA, relates to structural brain age in late adulthood. Maintaining or increasing MVPA may help preserve younger brain age, irrespective of which behaviors this time was reallocated from. Future research should examine whether systematically shifting 24-h time use toward MVPA", "source": "PubMed"}, {"chunk_id": "41445670_2", "pmid": "41445670", "title": "Association between 24-h time-use composition and brain age: The IGNITE study.", "authors": "Collins AM, Mellow ML, Wan L et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "brain age, compositional data analysis, physical activity, sedentary behavior, sleep", "chunk": "or increasing MVPA may help preserve younger brain age, irrespective of which behaviors this time was reallocated from. Future research should examine whether systematically shifting 24-h time use toward MVPA alters brain aging trajectories.Clinical Trial Registration Number and Name of Trial Registry: ClinicalTrial.gov: NCT02875301. Time use relates to brain age in older adults.More time spent in MVPA may contribute to younger brain age.Associations between time use and brain age are independent of demographic variation or genetic risk for AD.", "source": "PubMed"}, {"chunk_id": "40806521_0", "pmid": "40806521", "title": "Human Glucose Transporters in Health and Selected Neurodegenerative Diseases.", "authors": "Szablewski L", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, GLUT proteins, GLUT1-deficiency syndrome, Huntington\u2019s disease, Parkinson\u2019s disease, SGLT proteins, SWEET proteins, neurodegenerative diseases, stroke, therapies, traumatic brain injury", "chunk": "Glucose is the main source of energy and the source of carbon for the biosynthesis of several molecules, such as neurotransmitters, for most mammalian cells. Therefore, the transport of glucose into cells is very important. There are described three distinct families of glucose transporters: facilitative glucose transporters (GLUTs), sodium-dependent glucose cotransporters (SGLTs), and a uniporter, the SWEET protein. Impaired function and/or expression of these transporters due to, for example, mutations in their genes, may cause severe diseases. Associations with the impaired function of glucose transporters have been described in the case of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, GLUT1-deficiency syndrome, stroke, and traumatic brain injury. Changes in the presence of glucose transporters may be a cause of NDs, and they may be the effect of NDs. On the other hand, in many cases of neurodegenerative diseases, changes in the expression of glucose transporters may be", "source": "PubMed"}, {"chunk_id": "40806521_1", "pmid": "40806521", "title": "Human Glucose Transporters in Health and Selected Neurodegenerative Diseases.", "authors": "Szablewski L", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, GLUT proteins, GLUT1-deficiency syndrome, Huntington\u2019s disease, Parkinson\u2019s disease, SGLT proteins, SWEET proteins, neurodegenerative diseases, stroke, therapies, traumatic brain injury", "chunk": "cause of NDs, and they may be the effect of NDs. On the other hand, in many cases of neurodegenerative diseases, changes in the expression of glucose transporters may be a targeted therapy in the treatment of patients with these diseases.", "source": "PubMed"}, {"chunk_id": "38217040_0", "pmid": "38217040", "title": "Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [<sup>18</sup>F]PSS232 PET/MRI study.", "authors": "Wang J, He Y, Chen X et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid deposition, Cognitive performance, Glucose metabolism, Metabotropic glutamate receptor 5, Plasma biomarkers", "chunk": "Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate the association between mGluR5 availability and AD's biomarkers and cognitive function. We examined 35 individuals with mGluR5 tracer [<sup>18</sup>F]PSS232 to assess mGluR5 availability, and with [<sup>18</sup>F]Florbetapir PET to assess global amyloid deposition, and [<sup>18</sup>F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. The mGluR5 availability was significantly reduced in AD patients' hippocampus and parahippocampal gyrus compared to NCs.", "source": "PubMed"}, {"chunk_id": "38217040_1", "pmid": "38217040", "title": "Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [<sup>18</sup>F]PSS232 PET/MRI study.", "authors": "Wang J, He Y, Chen X et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid deposition, Cognitive performance, Glucose metabolism, Metabotropic glutamate receptor 5, Plasma biomarkers", "chunk": "glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. The mGluR5 availability was significantly reduced in AD patients' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance. [<sup>18</sup>F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be", "source": "PubMed"}, {"chunk_id": "38217040_2", "pmid": "38217040", "title": "Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [<sup>18</sup>F]PSS232 PET/MRI study.", "authors": "Wang J, He Y, Chen X et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Amyloid deposition, Cognitive performance, Glucose metabolism, Metabotropic glutamate receptor 5, Plasma biomarkers", "chunk": "AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.", "source": "PubMed"}, {"chunk_id": "40870510_0", "pmid": "40870510", "title": "From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.", "authors": "Bougea A, Debasa-Mouce M, Gulkarov S et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "APOE, Alzheimer\u2019s disease (AD), BBB, amyloid hypothesis, biomarkers", "chunk": "<i>Background and Objectives</i>: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer's disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. <i>Materials and Methods</i>: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. <i>Results</i>: Genome-wide association studies (GWASs) discovered 37 loci", "source": "PubMed"}, {"chunk_id": "40870510_1", "pmid": "40870510", "title": "From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.", "authors": "Bougea A, Debasa-Mouce M, Gulkarov S et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "APOE, Alzheimer\u2019s disease (AD), BBB, amyloid hypothesis, biomarkers", "chunk": "in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. <i>Results</i>: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (\u03b1-amyloid A\u03b242, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of A\u03b2-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal", "source": "PubMed"}, {"chunk_id": "40870510_2", "pmid": "40870510", "title": "From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.", "authors": "Bougea A, Debasa-Mouce M, Gulkarov S et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "APOE, Alzheimer\u2019s disease (AD), BBB, amyloid hypothesis, biomarkers", "chunk": "T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. <i>Conclusions</i>: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments.", "source": "PubMed"}, {"chunk_id": "37662267_0", "pmid": "37662267", "title": "A Cross-Modal Mutual Knowledge Distillation Framework for Alzheimer's Disease Diagnosis: Addressing Incomplete Modalities.", "authors": "Kwak MG, Mao L, Zheng Z et al.", "year": "2024", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, incomplete multimodal datasets, knowledge distillation, mild cognitive impairment, representation disentanglement", "chunk": "Early detection of Alzheimer's Disease (AD) is crucial for timely interventions and optimizing treatment outcomes. Despite the promise of integrating multimodal neuroimages such as MRI and PET, handling datasets with incomplete modalities remains under-researched. This phenomenon, however, is common in real-world scenarios as not every patient has all modalities due to practical constraints such as cost, access, and safety concerns. We propose a deep learning framework employing cross-modal Mutual Knowledge Distillation (MKD) to model different sub-cohorts of patients based on their available modalities. In MKD, the multimodal model (e.g., MRI and PET) serves as a teacher, while the single-modality model (e.g., MRI only) is the student. Our MKD framework features three components: a Modality-Disentangling Teacher (MDT) model designed through information disentanglement, a student model that learns from classification errors and MDT's knowledge, and the teacher model enhanced via distilling the student's single-modal feature extraction capabilities. Moreover, we show the effectiveness", "source": "PubMed"}, {"chunk_id": "37662267_1", "pmid": "37662267", "title": "A Cross-Modal Mutual Knowledge Distillation Framework for Alzheimer's Disease Diagnosis: Addressing Incomplete Modalities.", "authors": "Kwak MG, Mao L, Zheng Z et al.", "year": "2024", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, incomplete multimodal datasets, knowledge distillation, mild cognitive impairment, representation disentanglement", "chunk": "disentanglement, a student model that learns from classification errors and MDT's knowledge, and the teacher model enhanced via distilling the student's single-modal feature extraction capabilities. Moreover, we show the effectiveness of the proposed method through theoretical analysis and validate its performance with simulation studies. In addition, our method is demonstrated through a case study with Alzheimer's Disease Neuroimaging Initiative (ADNI) datasets, underscoring the potential of artificial intelligence in addressing incomplete multimodal neuroimaging datasets and advancing early AD detection. This paper was motivated by the challenge of early AD diagnosis, particularly in scenarios when clinicians encounter varied availability of patient imaging data, such as MRI and PET scans, often constrained by cost or accessibility issues. We propose an incomplete multimodal learning framework that produces tailored models for patients with only MRI and patients with both MRI and PET. This approach improves the accuracy and effectiveness of early AD diagnosis, especially when", "source": "PubMed"}, {"chunk_id": "37662267_2", "pmid": "37662267", "title": "A Cross-Modal Mutual Knowledge Distillation Framework for Alzheimer's Disease Diagnosis: Addressing Incomplete Modalities.", "authors": "Kwak MG, Mao L, Zheng Z et al.", "year": "2024", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, incomplete multimodal datasets, knowledge distillation, mild cognitive impairment, representation disentanglement", "chunk": "framework that produces tailored models for patients with only MRI and patients with both MRI and PET. This approach improves the accuracy and effectiveness of early AD diagnosis, especially when imaging resources are limited, via bi-directional knowledge transfer. We introduced a teacher model that prioritizes extracting common information between different modalities, significantly enhancing the student model's learning process. This paper includes theoretical analysis, simulation study, and real-world case study to illustrate the method's promising potential in early AD detection. However, practitioners should be mindful of the complexities involved in model tuning. Future work will focus on improving model interpretability and expanding its application. This includes developing methods to discover the key brain regions for predictions, enhancing clinical trust, and extending the framework to incorporate a broader range of imaging modalities, demographic information, and clinical data. These advancements aim to provide a more comprehensive view of patient health and improve diagnostic", "source": "PubMed"}, {"chunk_id": "37662267_3", "pmid": "37662267", "title": "A Cross-Modal Mutual Knowledge Distillation Framework for Alzheimer's Disease Diagnosis: Addressing Incomplete Modalities.", "authors": "Kwak MG, Mao L, Zheng Z et al.", "year": "2024", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, incomplete multimodal datasets, knowledge distillation, mild cognitive impairment, representation disentanglement", "chunk": "the framework to incorporate a broader range of imaging modalities, demographic information, and clinical data. These advancements aim to provide a more comprehensive view of patient health and improve diagnostic accuracy across various neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "36090283_0", "pmid": "36090283", "title": "A new classification network for diagnosing Alzheimer's disease in class-imbalance MRI datasets.", "authors": "Chen Z, Wang Z, Zhao M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer's disease diagnosis, class-imbalance problem, classification network, global contextual information, gradient density, lightweight blocks", "chunk": "Automatic identification of Alzheimer's Disease (AD) through magnetic resonance imaging (MRI) data can effectively assist to doctors diagnose and treat Alzheimer's. Current methods improve the accuracy of AD recognition, but they are insufficient to address the challenge of small interclass and large intraclass differences. Some studies attempt to embed patch-level structure in neural networks which enhance pathologic details, but the enormous size and time complexity render these methods unfavorable. Furthermore, several self-attention mechanisms fail to provide contextual information to represent discriminative regions, which limits the performance of these classifiers. In addition, the current loss function is adversely affected by outliers of class imbalance and may fall into local optimal values. Therefore, we propose a 3D Residual RepVGG Attention network (ResRepANet) stacked with several lightweight blocks to identify the MRI of brain disease, which can also trade off accuracy and flexibility. Specifically, we propose a Non-local Context Spatial Attention block (NCSA)", "source": "PubMed"}, {"chunk_id": "36090283_1", "pmid": "36090283", "title": "A new classification network for diagnosing Alzheimer's disease in class-imbalance MRI datasets.", "authors": "Chen Z, Wang Z, Zhao M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer's disease diagnosis, class-imbalance problem, classification network, global contextual information, gradient density, lightweight blocks", "chunk": "stacked with several lightweight blocks to identify the MRI of brain disease, which can also trade off accuracy and flexibility. Specifically, we propose a Non-local Context Spatial Attention block (NCSA) and embed it in our proposed ResRepANet, which aggregates global contextual information in spatial features to improve semantic relevance in discriminative regions. In addition, in order to reduce the influence of outliers, we propose a Gradient Density Multiple-weighting Mechanism (GDMM) to automatically adjust the weights of each MRI image <i>via</i> a normalizing gradient norm. Experiments are conducted on datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarker and Lifestyle Flagship Study of Aging (AIBL). Experiments on both datasets show that the accuracy, sensitivity, specificity, and Area Under the Curve are consistently better than for state-of-the-art methods.", "source": "PubMed"}, {"chunk_id": "36090283_2", "pmid": "36090283", "title": "A new classification network for diagnosing Alzheimer's disease in class-imbalance MRI datasets.", "authors": "Chen Z, Wang Z, Zhao M et al.", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer's disease diagnosis, class-imbalance problem, classification network, global contextual information, gradient density, lightweight blocks", "chunk": "the Curve are consistently better than for state-of-the-art methods.", "source": "PubMed"}, {"chunk_id": "35697501_0", "pmid": "35697501", "title": "Neuropathology and emerging biomarkers in corticobasal syndrome.", "authors": "Koga S, Josephs KA, Aiba I et al.", "year": "2022", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "alzheimer's disease, corticobasal degeneration, genetics, neuropathology, supranuclear palsy", "chunk": "Corticobasal syndrome (CBS) is a clinical syndrome characterised by progressive asymmetric limb rigidity and apraxia with dystonia, myoclonus, cortical sensory loss and alien limb phenomenon. Corticobasal degeneration (CBD) is one of the most common underlying pathologies of CBS, but other disorders, such as progressive supranuclear palsy (PSP), Alzheimer's disease (AD) and frontotemporal lobar degeneration with TDP-43 inclusions, are also associated with this syndrome.In this review, we describe common and rare neuropathological findings in CBS, including tauopathies, synucleinopathies, TDP-43 proteinopathies, fused in sarcoma proteinopathy, prion disease (Creutzfeldt-Jakob disease) and cerebrovascular disease, based on a narrative review of the literature and clinicopathological studies from two brain banks. Genetic mutations associated with CBS, including <i>GRN</i> and <i>MAPT</i>, are also reviewed. Clinicopathological studies on neurodegenerative disorders associated with CBS have shown that regardless of the underlying pathology, frontoparietal, as well as motor and premotor pathology is associated with CBS. Clinical features that can predict", "source": "PubMed"}, {"chunk_id": "35697501_1", "pmid": "35697501", "title": "Neuropathology and emerging biomarkers in corticobasal syndrome.", "authors": "Koga S, Josephs KA, Aiba I et al.", "year": "2022", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "alzheimer's disease, corticobasal degeneration, genetics, neuropathology, supranuclear palsy", "chunk": "neurodegenerative disorders associated with CBS have shown that regardless of the underlying pathology, frontoparietal, as well as motor and premotor pathology is associated with CBS. Clinical features that can predict the underlying pathology of CBS remain unclear. Using AD-related biomarkers (ie, amyloid and tau positron emission tomography (PET) and fluid biomarkers), CBS caused by AD often can be differentiated from other causes of CBS. Tau PET may help distinguish AD from other tauopathies and non-tauopathies, but it remains challenging to differentiate non-AD tauopathies, especially PSP and CBD. Although the current clinical diagnostic criteria for CBS have suboptimal sensitivity and specificity, emerging biomarkers hold promise for future improvements in the diagnosis of underlying pathology in patients with CBS.", "source": "PubMed"}, {"chunk_id": "41839611_0", "pmid": "41839611", "title": "[Application and research progress of fMRI in acupuncture treatment for ischemic stroke].", "authors": "Huang S, Fan B, Nie D et al.", "year": "2026", "journal": "Zhongguo zhen jiu = Chinese acupuncture & moxibustion", "keywords": "acupuncture, functional magnetic resonance imaging, ischemic stroke, review", "chunk": "Focusing on functional magnetic resonance imaging (fMRI) technology, the paper systematically reviews fMRI research on brain functional activity and structural abnormalities after ischemic stroke (IS), and summarizes the regulatory effects of acupuncture on abnormal brain function and structure after IS. Studies have demonstrated that IS can induce the dysregulation of functional activity and microstructural damage in brain regions. Acupuncture, through bidirectional modulation of motor and related brain activities, can ameliorate abnormal brain functional patterns, promote the restoration of functional network coordination and balance, facilitate the remodeling of white matter microstructure and enhance neural pathway connectivity. Additionally, it exerts the positive effect on cerebral blood flow and metabolic status. Furthermore, fMRI demonstrates the potential value in identifying populations with specific responses, guiding acupoint selection and optimizing acupuncture parameters. However, existing researche has predominantly focus on motor dysfunction, with the insufficient attention to the other symptoms related to cognitive and swallowing functions.", "source": "PubMed"}, {"chunk_id": "41839611_1", "pmid": "41839611", "title": "[Application and research progress of fMRI in acupuncture treatment for ischemic stroke].", "authors": "Huang S, Fan B, Nie D et al.", "year": "2026", "journal": "Zhongguo zhen jiu = Chinese acupuncture & moxibustion", "keywords": "acupuncture, functional magnetic resonance imaging, ischemic stroke, review", "chunk": "guiding acupoint selection and optimizing acupuncture parameters. However, existing researche has predominantly focus on motor dysfunction, with the insufficient attention to the other symptoms related to cognitive and swallowing functions. Besides, the methodological limitations are presented in the single analytical method and the lack of high-quality randomized controlled trials. Future research should advance large-sample, multicenter, sham-acupuncture controlled trials, integrate multimodal indexes and interdisciplinary approaches and deepen the mechanistic exploration of acupuncture effect on different symptoms and among subgroups in patients, so as to provide more robust scientific evidence for the clinical application and standardization of acupuncture in treatment of IS.", "source": "PubMed"}, {"chunk_id": "41384401_0", "pmid": "41384401", "title": "[Malnutrition in older adults].", "authors": " ", "year": "2025", "journal": "Assistenza infermieristica e ricerca : AIR", "keywords": "None", "chunk": ". Malnutrition in older adults. Malnutrition in older adults is a multifactorial condition with serious health and social consequences. Physiological changes such as reduced appetite, impaired taste and smell, and slower gastrointestinal signaling contribute to the \"anorexia of aging.\" Physical impairments, including poor oral health, chewing and swallowing difficulties, and mobility limitations, further reduce food intake. Cognitive decline, dementia, depression, and delirium also compromise nutrition, while chronic diseases, inflammation, and polypharmacy increase nutritional needs or interfere with absorption. Social isolation, poverty, and inadequate institutional care exacerbate the problem. Prevalence varies by setting: about 3% in community dwelling elders, 22% in hospitalized patients, and up to 50% in those with cancer, heart failure, or in long term care. Malnutrition leads to frailty, falls, infections, longer hospital stays, disability, and higher costs. Diagnosis relies on validated tools such as the Mini Nutritional Assessment and the GLIM criteria, which combine phenotypic markers (weight", "source": "PubMed"}, {"chunk_id": "41384401_1", "pmid": "41384401", "title": "[Malnutrition in older adults].", "authors": " ", "year": "2025", "journal": "Assistenza infermieristica e ricerca : AIR", "keywords": "None", "chunk": "frailty, falls, infections, longer hospital stays, disability, and higher costs. Diagnosis relies on validated tools such as the Mini Nutritional Assessment and the GLIM criteria, which combine phenotypic markers (weight loss, low BMI, reduced muscle mass) with etiologic factors (low intake, malabsorption, inflammation). Prevention and treatment require routine screening, individualized nutrition plans, and multidisciplinary approaches. Strategies include enriched diets, oral supplements, assistance during meals, social support, and, when necessary, enteral or parenteral nutrition. Early, personalized, and comprehensive interventions improve outcomes, reduce mortality, and enhance quality of life in older adults.", "source": "PubMed"}, {"chunk_id": "36046332_0", "pmid": "36046332", "title": "Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid.", "authors": "Kasuga K, Kikuchi M, Tsukie T et al.", "year": "2022", "journal": "BMJ neurology open", "keywords": "ALZHEIMER'S DISEASE, AMYLOID, BIOCHEMISTRY, CSF", "chunk": "The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population. We stratified 177 individuals who participated in the Japanese Alzheimer's Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)<sub>tau</sub> and AT(N)<sub>NfL</sub>). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles. We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer's disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)<sub>tau</sub> and AT(N)<sub>NfL</sub> classifications. When we used t-tau as the N marker (AT(N)<sub>tau</sub>), those who had T- were more frequently assigned to (N)-,", "source": "PubMed"}, {"chunk_id": "36046332_1", "pmid": "36046332", "title": "Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid.", "authors": "Kasuga K, Kikuchi M, Tsukie T et al.", "year": "2022", "journal": "BMJ neurology open", "keywords": "ALZHEIMER'S DISEASE, AMYLOID, BIOCHEMISTRY, CSF", "chunk": "of AT(N) profiles substantially differed between the AT(N)<sub>tau</sub> and AT(N)<sub>NfL</sub> classifications. When we used t-tau as the N marker (AT(N)<sub>tau</sub>), those who had T- were more frequently assigned to (N)-, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)<sub>NfL</sub>). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)<sub>tau</sub> and AT(N)<sub>NfL</sub> classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)<sub>tau</sub> classification, but not in the AT(N)<sub>NfL</sub> classification. AT(N)<sub>tau</sub> and AT(N)<sub>NfL</sub> in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.", "source": "PubMed"}, {"chunk_id": "36046332_2", "pmid": "36046332", "title": "Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid.", "authors": "Kasuga K, Kikuchi M, Tsukie T et al.", "year": "2022", "journal": "BMJ neurology open", "keywords": "ALZHEIMER'S DISEASE, AMYLOID, BIOCHEMISTRY, CSF", "chunk": "the AD continuum biology in various populations.", "source": "PubMed"}, {"chunk_id": "41554757_0", "pmid": "41554757", "title": "Moderating effect of the domains of the cognitive reserve index questionnaire (CRIq) on longitudinal change slopes in episodic memory across the cognitive aging continuum.", "authors": "Arora S, Lojo-Seoane C, Leiva D et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Cognitive complaints, Cognitive reserve index questionnaire, Episodic memory, Longitudinal design, MCI, Older adults, Socio-behavioral CR proxies", "chunk": "Cognitive reserve (CR) hypothesis predicts reduced impact of aging and neurodegeneration on cognition in adults who have lived in cognitively stimulating environments. Our study tested the moderating role of socio-behavioral CR proxies on longitudinal episodic memory (EM) decline, one of the cognitive domains that has been suggested to be most sensitive to early deterioration in presymptomatic stages of dementia. 323 participants (\u2265 50 years old) from CompAS study were classified into four groups based on baseline diagnosis and progression at 18-24 (T1) and 48-70 months (T2): Subjective cognitive complaints (SCC) who remain stable (SCC-stable), Mild cognitive impairment (MCI) who remain stable (MCI-stable), SCC who progressed to MCI (Prog-to-MCI), and SCC or MCI who progressed to dementia (Prog-to-Dem). Mixed models analyzed changes across EM measures of immediate and long delay with and without cued recall from the Spanish CVLT to account for the EM processes of encoding and consolidation in the", "source": "PubMed"}, {"chunk_id": "41554757_1", "pmid": "41554757", "title": "Moderating effect of the domains of the cognitive reserve index questionnaire (CRIq) on longitudinal change slopes in episodic memory across the cognitive aging continuum.", "authors": "Arora S, Lojo-Seoane C, Leiva D et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Cognitive complaints, Cognitive reserve index questionnaire, Episodic memory, Longitudinal design, MCI, Older adults, Socio-behavioral CR proxies", "chunk": "changes across EM measures of immediate and long delay with and without cued recall from the Spanish CVLT to account for the EM processes of encoding and consolidation in the short and long term. Domains from Cognitive Reserve Index Questionnaire (School, Work and Leisure) were tested as moderators of longitudinal EM trends in progression groups across two nested models. Our results confirm the CR hypothesis:1) steeper memory decline observed in all progression groups compared to SCC-stable, especially at T2 relative to baseline; 2) Higher CRIq-School and CRIq-Work scores moderated changes in EM measures in participants who progress to MCI and who progress to dementia compared to SCC-stable group; 3) CR moderation effect was stronger at T2. Our findings support the validity of CR proxies of Education and Occupation in attenuating memory decline along the continuum of subjective and objective cognitive decline.", "source": "PubMed"}, {"chunk_id": "41554757_2", "pmid": "41554757", "title": "Moderating effect of the domains of the cognitive reserve index questionnaire (CRIq) on longitudinal change slopes in episodic memory across the cognitive aging continuum.", "authors": "Arora S, Lojo-Seoane C, Leiva D et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Cognitive complaints, Cognitive reserve index questionnaire, Episodic memory, Longitudinal design, MCI, Older adults, Socio-behavioral CR proxies", "chunk": "validity of CR proxies of Education and Occupation in attenuating memory decline along the continuum of subjective and objective cognitive decline.", "source": "PubMed"}, {"chunk_id": "37990900_0", "pmid": "37990900", "title": "Based on Bioinformatics to Explore the Mechanism of \"Tangzhiqing\" Decoction Alleviating Type 2 Diabetes-associated Cognitive Dysfunction in Mice by Regulating Hippocampal Neuron Apoptosis and Autophagy.", "authors": "Shi Y, Sheng P, Zhao Y et al.", "year": "2024", "journal": "Combinatorial chemistry & high throughput screening", "keywords": "Diabetic cognitive dysfunction, TZQ., apoptosis, autophagy, biological information analysis, traditional chinese medicine", "chunk": "Diabetic cognitive dysfunction (DCD) is emerging as a chronic complication of diabetes that is gaining increasing international recognition. The traditional Chinese medicine (TCM) formulation, Tangzhiqing decoction (TZQ), has shown the capacity to modulate the memory function of mice with DCD by ameliorating insulin resistance. Nevertheless, the precise mechanism underlying the effects of TZQ remains elusive. The chemical constituents of TZQ were screened using TCMSP databases, and DCDassociated disease targets were retrieved from various databases. Subsequently, core targets were identified through network topology analysis. The core targets underwent analysis using Gene Ontology (GO) functional annotations and enrichment in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Models were established through high-fat and high-glucose diet feeding along with intraperitoneal injection of streptozotocin (STZ). TZQ and metformin were administered at varying doses over 8 weeks. The Morris water maze was employed to evaluate the cognitive capabilities of each rat group, while indicators", "source": "PubMed"}, {"chunk_id": "37990900_1", "pmid": "37990900", "title": "Based on Bioinformatics to Explore the Mechanism of \"Tangzhiqing\" Decoction Alleviating Type 2 Diabetes-associated Cognitive Dysfunction in Mice by Regulating Hippocampal Neuron Apoptosis and Autophagy.", "authors": "Shi Y, Sheng P, Zhao Y et al.", "year": "2024", "journal": "Combinatorial chemistry & high throughput screening", "keywords": "Diabetic cognitive dysfunction, TZQ., apoptosis, autophagy, biological information analysis, traditional chinese medicine", "chunk": "streptozotocin (STZ). TZQ and metformin were administered at varying doses over 8 weeks. The Morris water maze was employed to evaluate the cognitive capabilities of each rat group, while indicators of oxidative stress and insulin were assessed in mice. Neuronal apoptosis in distinct groups of mice's hippocampi was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL), and western blot (WB) analysis was conducted to assess the expression of apoptosis- and autophagy-related proteins, including Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, LC3, p62, and Lamp2, within the hippocampus. TZQ exhibited the capacity to modulate neuronal autophagy, ameliorate endoplasmic reticulum stress, apoptosis, inflammation, and oxidative stress, as well as to regulate synaptic plasticity and conduction. TZQ mitigated cognitive dysfunction in mice, while also regulating hippocampal inflammation and apoptosis. Additionally, it influenced the protein expression of autophagy-related factors such as Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, and LC3. Notably, this modulation significantly reduced neuronal apoptosis", "source": "PubMed"}, {"chunk_id": "37990900_2", "pmid": "37990900", "title": "Based on Bioinformatics to Explore the Mechanism of \"Tangzhiqing\" Decoction Alleviating Type 2 Diabetes-associated Cognitive Dysfunction in Mice by Regulating Hippocampal Neuron Apoptosis and Autophagy.", "authors": "Shi Y, Sheng P, Zhao Y et al.", "year": "2024", "journal": "Combinatorial chemistry & high throughput screening", "keywords": "Diabetic cognitive dysfunction, TZQ., apoptosis, autophagy, biological information analysis, traditional chinese medicine", "chunk": "hippocampal inflammation and apoptosis. Additionally, it influenced the protein expression of autophagy-related factors such as Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, and LC3. Notably, this modulation significantly reduced neuronal apoptosis in the hippocampus and curbed excessive autophagy. TZQ demonstrated a substantial reduction in neuronal apoptosis within the hippocampus and effectively suppressed excessive autophagy.", "source": "PubMed"}, {"chunk_id": "25057411_0", "pmid": "25057411", "title": "Duration of type 2 diabetes and very low density lipoprotein levels are associated with cognitive dysfunction in metabolic syndrome.", "authors": "Yogi-Morren D, Galioto R, Strandjord SE et al.", "year": "2014", "journal": "Cardiovascular psychiatry and neurology", "keywords": "None", "chunk": "Type 2 diabetes (T2D) is now recognized as an independent risk factor for accelerated cognitive decline and neurological conditions like Alzheimer's disease. Less is known about the neurocognitive function of T2D patients with comorbid metabolic syndrome, despite their elevated risk for impairment. Computerized testing in 47 adults with T2D that met criteria for NCEP metabolic syndrome revealed that cognitive impairment was prevalent, including 13% in tests of memory, 50% in attention, and 35% in executive function. Partial correlations showed that longer duration of diabetes was associated with poorer performance on tests of basic attention (r = -0.43), working memory (r = 0.43), and executive function (r = 0.42). Strong associations between very low density lipoprotein and poor cognitive function also emerged, including tests of set shifting (r = 0.47) and cognitive inhibition (r = -0.51). Findings suggest that patients with T2D that meet criteria for metabolic syndrome are at high", "source": "PubMed"}, {"chunk_id": "25057411_1", "pmid": "25057411", "title": "Duration of type 2 diabetes and very low density lipoprotein levels are associated with cognitive dysfunction in metabolic syndrome.", "authors": "Yogi-Morren D, Galioto R, Strandjord SE et al.", "year": "2014", "journal": "Cardiovascular psychiatry and neurology", "keywords": "None", "chunk": "emerged, including tests of set shifting (r = 0.47) and cognitive inhibition (r = -0.51). Findings suggest that patients with T2D that meet criteria for metabolic syndrome are at high risk for cognitive impairment. Prospective studies should look to replicate these findings and examine the possible neuroprotective effects of lipid-lowering medication in this population.", "source": "PubMed"}, {"chunk_id": "39143583_0", "pmid": "39143583", "title": "Plasma lipidomics in early APP/PS1 female mouse model and its relationship with brain: Is it affected by the estrous cycle?", "authors": "Ferr\u00e9-Gonz\u00e1lez L, Balaguer \u00c1, Roca M et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer, Brain, Early, Estrous cycle, Lipid, Mouse model, Plasma", "chunk": "Alzheimer's disease (AD) is the most prevalent dementia, showing higher incidence in women. Besides, lipids play an essential role in brain, and they could be dysregulated in neurodegeneration. Specifically, impaired plasma lipid levels could predict early AD diagnosis. This work aims to identify the main plasma lipids altered in early AD female mouse model and evaluate their relationship with brain lipidome. Also, the possible involvement of the estrous cycle in lipid metabolism has been evaluated. Plasma samples of wild-type (n = 10) and APP/PS1 (n = 10) female mice of 5 months of age were collected, processed, and analysed using a lipidomic mass spectrometry-based method. A statistical analysis involving univariate and multivariate approaches was performed to identify significant lipid differences related to AD between groups. Also, cytology tests were conducted to confirm estrous cycle phases. Three hundred thirty lipids were detected in plasma, 18 of them showed significant differences between", "source": "PubMed"}, {"chunk_id": "39143583_1", "pmid": "39143583", "title": "Plasma lipidomics in early APP/PS1 female mouse model and its relationship with brain: Is it affected by the estrous cycle?", "authors": "Ferr\u00e9-Gonz\u00e1lez L, Balaguer \u00c1, Roca M et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer, Brain, Early, Estrous cycle, Lipid, Mouse model, Plasma", "chunk": "related to AD between groups. Also, cytology tests were conducted to confirm estrous cycle phases. Three hundred thirty lipids were detected in plasma, 18 of them showed significant differences between groups; specifically, some triacylglycerols, cholesteryl esters, lysophosphatidylcholines, phosphatidylcholines, and ether-linked phosphatidylcholines, increased in early AD; while other phosphatidylcholines, phosphatidylethanolamines, ceramides, and ether-linked phosphatidylethanolamines decreased in early AD. A multivariate approach was developed from some lipid variables, showing high diagnostic indexes (70% sensitivity, 90% specificity, 80% accuracy). From brain and plasma lipidome, some significant correlations were observed, mainly in the glycerophospholipid family. Also, some differences were found in both plasma and brain lipids, according to the estrous cycle phase. Therefore, lipid alterations can be identified in plasma at early AD stages in mice females, with a relationship with brain lipid metabolism for most of the lipid subfamilies, suggesting some lipids as potential AD biomarkers. In addition, the estrous cycle monitoring could", "source": "PubMed"}, {"chunk_id": "39143583_2", "pmid": "39143583", "title": "Plasma lipidomics in early APP/PS1 female mouse model and its relationship with brain: Is it affected by the estrous cycle?", "authors": "Ferr\u00e9-Gonz\u00e1lez L, Balaguer \u00c1, Roca M et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer, Brain, Early, Estrous cycle, Lipid, Mouse model, Plasma", "chunk": "in mice females, with a relationship with brain lipid metabolism for most of the lipid subfamilies, suggesting some lipids as potential AD biomarkers. In addition, the estrous cycle monitoring could be relevant in female studies.", "source": "PubMed"}, {"chunk_id": "37932910_0", "pmid": "37932910", "title": "Vascular risk, gait, behavioral, and plasma indicators of VCID.", "authors": "Raghavan S, Przybelski SA, Lesnick TG et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "diffusion magnetic resonance imaging (MRI), vascular contributions to cognitive impairment and dementia, white matter, white matter hyperintensities", "chunk": "Cost-effective screening tools for vascular contributions to cognitive impairment and dementia (VCID) has significant implications. We evaluated non-imaging indicators of VCID using magnetic resonance imaging (MRI)-measured white matter (WM) damage and hypothesized that these indicators differ based on age. In 745 participants from the Mayo Clinic Study of Aging (\u226550 years of age) with serial WM assessments from diffusion MRI and fluid-attenuated inversion recovery (FLAIR)-MRI, we examined associations between baseline non-imaging indicators (demographics, vascular risk factors [VRFs], gait, behavioral, plasma glial fibrillary acidic protein [GFAP], and plasma neurofilament light chain [NfL]) and WM damage across three age tertiles. VRFs and gait were associated with diffusion changes even in low age strata. All measures (VRFs, gait, behavioral, plasma GFAP, plasma NfL) were associated with white matter hyperintensities (WMHs) but mainly in intermediate and high age strata. Non-imaging indicators of VCID were related to WM damage and may aid in screening participants", "source": "PubMed"}, {"chunk_id": "37932910_1", "pmid": "37932910", "title": "Vascular risk, gait, behavioral, and plasma indicators of VCID.", "authors": "Raghavan S, Przybelski SA, Lesnick TG et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "diffusion magnetic resonance imaging (MRI), vascular contributions to cognitive impairment and dementia, white matter, white matter hyperintensities", "chunk": "were associated with white matter hyperintensities (WMHs) but mainly in intermediate and high age strata. Non-imaging indicators of VCID were related to WM damage and may aid in screening participants and assessing outcomes for VCID. Non-imaging indicators of VCID can aid in prediction of MRI-measured WM damage but their importance differed by age. Vascular risk and gait measures were associated with early VCID changes measured using diffusion MRI. Plasma markers explained variability in WMH across age strata. Most non-imaging measures explained variability in WMH and vascular WM scores in intermediate and older age groups. The framework developed here can be used to evaluate new non-imaging VCID indicators proposed in the future.", "source": "PubMed"}, {"chunk_id": "40255041_0", "pmid": "40255041", "title": "Key biomarkers in Alzheimer's disease: Insights for diagnosis and treatment strategies.", "authors": "Jamal R, Shaikh MA, Taleuzzaman M et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amyloid-\u03b2, biomarkers, neuroimaging, precision medicine, tau proteins", "chunk": "Alzheimer's disease (AD) remains a significant global health challenge, characterized by its progressive neurodegeneration and cognitive decline. The urgent need for early diagnosis and effective treatment necessitates the identification of reliable biomarkers that can illuminate the underlying pathophysiology of AD. This review provides a comprehensive overview of the latest advancements in biomarker research, focusing on their applications in diagnosis, prognosis, and therapeutic development. We delve into the multifaceted landscape of AD biomarkers, encompassing molecular, imaging, and fluid-based markers. The integration of these biomarkers, including amyloid-\u03b2 and tau proteins, neuroimaging modalities, cerebrospinal fluid analysis, and genetic risk factors, offers a more nuanced understanding of AD's complex etiology. By leveraging the power of precision medicine, biomarker-driven approaches can enable personalized treatment strategies and enhance diagnostic accuracy. Moreover, this review highlights the potential of biomarker research to accelerate drug discovery and development. By identifying novel therapeutic targets and monitoring disease progression, biomarkers can", "source": "PubMed"}, {"chunk_id": "40255041_1", "pmid": "40255041", "title": "Key biomarkers in Alzheimer's disease: Insights for diagnosis and treatment strategies.", "authors": "Jamal R, Shaikh MA, Taleuzzaman M et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, amyloid-\u03b2, biomarkers, neuroimaging, precision medicine, tau proteins", "chunk": "and enhance diagnostic accuracy. Moreover, this review highlights the potential of biomarker research to accelerate drug discovery and development. By identifying novel therapeutic targets and monitoring disease progression, biomarkers can facilitate the evaluation of experimental treatments and ultimately improve patient outcomes. In conclusion, this review underscores the critical role of biomarkers in advancing our comprehension of AD and driving the development of effective interventions. By providing a comprehensive overview of the current state-of-the-art, this work aims to inspire future research and contribute to the goal of conquering AD.", "source": "PubMed"}, {"chunk_id": "41813037_0", "pmid": "41813037", "title": "Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology.", "authors": "Ribeiro IC, Gon\u00e7alves BC, Aventurato \u00cdK et al.", "year": "2026", "journal": "Arquivos de neuro-psiquiatria", "keywords": "None", "chunk": "The diagnosis of predementia stages indicates an increased risk of progression to dementia. The Amyloid, Tau, and Neurodegeneration AT(N) classification considers measurements of altered proteins and the presence of neurodegeneration to classify the risk groups regarding the pathophysiology of Alzheimer's disease (AD). The cognitive and anatomical characteristics of the patients in the predementia stage according to the AT(N) classification are not fully understood.To investigate whether there are differences in the clinical and anatomical profiles among older adults in the predementia stage according to the ATN classification, and to investigate the associations involving cognition and cortical thickness and subcortical volume in the AT(N) groups.In total, 72 older adults with subjective cognitive decline and mild cognitive impairment were allocated to groups according to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging", "source": "PubMed"}, {"chunk_id": "41813037_1", "pmid": "41813037", "title": "Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology.", "authors": "Ribeiro IC, Gon\u00e7alves BC, Aventurato \u00cdK et al.", "year": "2026", "journal": "Arquivos de neuro-psiquiatria", "keywords": "None", "chunk": "to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging scans, and cerebrospinal fluid analyses. We used multivariate and univariate analyses with post-hoc testing to verify differences among groups. In addition, linear regressions were performed to verify the interactions involving cognition and gray matter metrics.The suspected non-AD pathophysiology group showed worse performance in attention/executive function than the AD continuum and normal biomarkers groups (<i>p</i> = 0.04). However, the ATN classification groups did not differ in terms of cortical thickness (<i>p</i> > 0.05). In addition, in the AD continuum group, memory was associated with left fusiform gyrus thickness (<i>p</i> = 0.000 uncorrected; r = 0.238).Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).", "source": "PubMed"}, {"chunk_id": "41813037_2", "pmid": "41813037", "title": "Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology.", "authors": "Ribeiro IC, Gon\u00e7alves BC, Aventurato \u00cdK et al.", "year": "2026", "journal": "Arquivos de neuro-psiquiatria", "keywords": "None", "chunk": "uncorrected; r = 0.238).Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).", "source": "PubMed"}, {"chunk_id": "39174535_0", "pmid": "39174535", "title": "Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.", "authors": "Zhang J, Zhang Y, Wang J et al.", "year": "2024", "journal": "Signal transduction and targeted therapy", "keywords": "None", "chunk": "Alzheimer's disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate and diverse, stemming from a combination of factors such as aging, genetics, and environment. Our current understanding of AD pathologies involves various hypotheses, such as the cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, and abnormal autophagy. Nonetheless, unraveling the interplay among these pathological aspects and pinpointing the primary initiators of AD require further elucidation and validation. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available drugs primarily offer symptomatic relief and often accompanied by undesirable side effects. However, recent approvals of aducanumab (1) and lecanemab (2) by the Food and Drug Administration (FDA) present the potential in disrease-modifying effects. Nevertheless, the long-term efficacy and safety of these drugs need further validation. Consequently, the quest", "source": "PubMed"}, {"chunk_id": "39174535_1", "pmid": "39174535", "title": "Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.", "authors": "Zhang J, Zhang Y, Wang J et al.", "year": "2024", "journal": "Signal transduction and targeted therapy", "keywords": "None", "chunk": "lecanemab (2) by the Food and Drug Administration (FDA) present the potential in disrease-modifying effects. Nevertheless, the long-term efficacy and safety of these drugs need further validation. Consequently, the quest for safer and more effective AD drugs persists as a formidable and pressing task. This review discusses the current understanding of AD pathogenesis, advances in diagnostic biomarkers, the latest updates of clinical trials, and emerging technologies for AD drug development. We highlight recent progress in the discovery of selective inhibitors, dual-target inhibitors, allosteric modulators, covalent inhibitors, proteolysis-targeting chimeras (PROTACs), and protein-protein interaction (PPI) modulators. Our goal is to provide insights into the prospective development and clinical application of novel AD drugs.", "source": "PubMed"}, {"chunk_id": "38740448_0", "pmid": "38740448", "title": "Automatic offline-capable smartphone paper-based microfluidic device for efficient biomarker detection of Alzheimer's disease.", "authors": "Duan S, Cai T, Liu F et al.", "year": "2024", "journal": "Analytica chimica acta", "keywords": "Alzheimer's disease, Colorimetric enzyme-linked immunoassay (c-ELISA), Deep learning, Microfluidic paper analysis devices (\u03bcPADs), Offline, Smartphone", "chunk": "Alzheimer's disease (AD) is a prevalent neurodegenerative disease with no effective treatment. Efficient and rapid detection plays a crucial role in mitigating and managing AD progression. Deep learning-assisted smartphone-based microfluidic paper analysis devices (\u03bcPADs) offer the advantages of low cost, good sensitivity, and rapid detection, providing a strategic pathway to address large-scale disease screening in resource-limited areas. However, existing smartphone-based detection platforms usually rely on large devices or cloud servers for data transfer and processing. Additionally, the implementation of automated colorimetric enzyme-linked immunoassay (c-ELISA) on \u03bcPADs can further facilitate the realization of smartphone \u03bcPADs platforms for efficient disease detection. This paper introduces a new deep learning-assisted offline smartphone platform for early AD screening, offering rapid disease detection in low-resource areas. The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on \u03bcPADs. Our platform successfully applied sandwich c-ELISA for detecting the \u03b2-amyloid peptide", "source": "PubMed"}, {"chunk_id": "38740448_1", "pmid": "38740448", "title": "Automatic offline-capable smartphone paper-based microfluidic device for efficient biomarker detection of Alzheimer's disease.", "authors": "Duan S, Cai T, Liu F et al.", "year": "2024", "journal": "Analytica chimica acta", "keywords": "Alzheimer's disease, Colorimetric enzyme-linked immunoassay (c-ELISA), Deep learning, Microfluidic paper analysis devices (\u03bcPADs), Offline, Smartphone", "chunk": "The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on \u03bcPADs. Our platform successfully applied sandwich c-ELISA for detecting the \u03b2-amyloid peptide 1-42 (A\u03b2 1-42, a crucial AD biomarker) and demonstrated its efficacy in 38 artificial plasma samples (healthy: 19, unhealthy: 19, N = 6). Moreover, we employed the YOLOv5 deep learning model and achieved an impressive 97 % accuracy on a dataset of 1824 images, which is 10.16 % higher than the traditional method of curve-fitting results. The trained YOLOv5 model was seamlessly integrated into the smartphone using the NCNN (Tencent's Neural Network Inference Framework), enabling deep learning-assisted offline detection. A user-friendly smartphone application was developed to control the entire process, realizing a streamlined \"samples in, answers out\" approach. This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT).", "source": "PubMed"}, {"chunk_id": "38740448_2", "pmid": "38740448", "title": "Automatic offline-capable smartphone paper-based microfluidic device for efficient biomarker detection of Alzheimer's disease.", "authors": "Duan S, Cai T, Liu F et al.", "year": "2024", "journal": "Analytica chimica acta", "keywords": "Alzheimer's disease, Colorimetric enzyme-linked immunoassay (c-ELISA), Deep learning, Microfluidic paper analysis devices (\u03bcPADs), Offline, Smartphone", "chunk": "realizing a streamlined \"samples in, answers out\" approach. This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT). Moreover, our platform provides a feasible approach for efficient AD detection by examining the level of A\u03b2 1-42, particularly in areas with low resources and limited communication infrastructure.", "source": "PubMed"}, {"chunk_id": "39059565_0", "pmid": "39059565", "title": "Exploratory Dual PET imaging of [<sup>18</sup>F] fluorodeoxyglucose and [<sup>11</sup>C]acetoacetate in type 2 diabetic nonhuman primates.", "authors": "Krizan I, Solingapuram Sai KK, Damuka N et al.", "year": "2024", "journal": "Bioorganic & medicinal chemistry letters", "keywords": "Alzheimer\u2019s, Central nervous system, Diabetes, Metabolism, Positron emission tomography", "chunk": "Despite recent advancements in imaging (amyloid-PET & tau-PET) and fluid (A\u03b242/A\u03b240 & A\u03b242/ptau) biomarkers, the current standard for in vivo assessment of AD, diagnosis and prediction of Alzheimer's disease (AD) remains challenging. We demonstrated in nonhuman primates (NHP) that increased plasma and cerebrospinal fluid (CSF) glucose correlated with decreased CSF A\u03b242 and CSF A\u03b240, a hallmark of plaque promoting pathogenesis. Together, our findings demonstrate that altered glucose homeostasis and insulin resistance are associated with A\u03b2 and amyloid in rodent and NHP models. This warranted further exploration into the dynamics of altered brain metabolism in the NHP model of T2D, cross referenced with CSF and blood-based AD markers. Preliminary dual PET ([<sup>11</sup>C]acetoacetate ([<sup>11</sup>C]AcAc) and [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG) imaging studies were conducted in an aged cohort of NHPs classified as T2D (n = 5) and pre-diabetic (n = 1) along with corresponding plasma and CSF samples for metabolite analysis. [<sup>11</sup>C]AcAc and [<sup>18</sup>F]FDG PET", "source": "PubMed"}, {"chunk_id": "39059565_1", "pmid": "39059565", "title": "Exploratory Dual PET imaging of [<sup>18</sup>F] fluorodeoxyglucose and [<sup>11</sup>C]acetoacetate in type 2 diabetic nonhuman primates.", "authors": "Krizan I, Solingapuram Sai KK, Damuka N et al.", "year": "2024", "journal": "Bioorganic & medicinal chemistry letters", "keywords": "Alzheimer\u2019s, Central nervous system, Diabetes, Metabolism, Positron emission tomography", "chunk": "an aged cohort of NHPs classified as T2D (n = 5) and pre-diabetic (n = 1) along with corresponding plasma and CSF samples for metabolite analysis. [<sup>11</sup>C]AcAc and [<sup>18</sup>F]FDG PET brain standard uptake values (SUV) were highly positively associated (r = 0.88, p = 0.02) in the T2D and pre-diabetic NHPs. Age was not significantly associated with brain SUV (age range 16.5-23.5 years old). Metabolic measures were positively correlated with brain [<sup>18</sup>F]FDG and CSF A\u03b242:40 was positively correlated to fasting glucose values. Although our findings suggest moderate correlations, this study further elucidates that peripheral insulin resistance and poor glycemia control alter AD-related pathology, illustrating how T2D is a risk factor for AD.", "source": "PubMed"}, {"chunk_id": "38735056_0", "pmid": "38735056", "title": "Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.", "authors": "Kotredes KP, Pandey RS, Persohn S et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "APOE4, Alzheimer's disease, LOAD, MODEL\u2010AD, TREM2, genetics, high\u2010fat diet, late\u2010onset Alzheimer's disease", "chunk": "MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately. We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (A\u03b2). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, A\u03b2, neurodegeneration, neuroimaging, and multi-omics. By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain A\u03b242, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen-based cognitive tasks were observed. The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of", "source": "PubMed"}, {"chunk_id": "38735056_1", "pmid": "38735056", "title": "Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.", "authors": "Kotredes KP, Pandey RS, Persohn S et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "APOE4, Alzheimer's disease, LOAD, MODEL\u2010AD, TREM2, genetics, high\u2010fat diet, late\u2010onset Alzheimer's disease", "chunk": "in acquiring touchscreen-based cognitive tasks were observed. The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL). Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease-relevant processes including lipid metabolism and synaptic function. In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT). LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.", "source": "PubMed"}, {"chunk_id": "38735056_2", "pmid": "38735056", "title": "Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.", "authors": "Kotredes KP, Pandey RS, Persohn S et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "APOE4, Alzheimer's disease, LOAD, MODEL\u2010AD, TREM2, genetics, high\u2010fat diet, late\u2010onset Alzheimer's disease", "chunk": "also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.", "source": "PubMed"}, {"chunk_id": "41685496_0", "pmid": "41685496", "title": "Empowering Alzheimer's and Related Dementia Prevention Through Primary Care Using Responsible AI: A Pilot Walk-in Memory Sync Booth.", "authors": "Datta SC, Banerjee S, Roy UB et al.", "year": "2026", "journal": "Studies in health technology and informatics", "keywords": "Alzheimer\u2019s disease, Cognitive Screening, Dementia, Early Detection, Responsible AI", "chunk": "Alzheimer's disease and related dementias (ADRD) remain underdiagnosed early due to reliance on costly, invasive, and time-intensive assessments, prompting development of the Memory Sync Booth, an AI-assisted walk-in screening tool for older adults. The booth delivers accessible, automated, and secure tablet-based evaluations which include orientation, attention, naming, picture description, voice analysis, and clock drawing, then processed using NLP, speech recognition, and computer vision for consistent scoring. Grounded in Responsible AI and Digital Health Innovation, it enables equitable deployment across senior community spaces and long-term care settings, with optional direct result-sharing to family doctors and automated alerts for cognitive decline. Tested with 20 volunteers aged 60+, the pilot demonstrated feasibility and potential for earlier MCI detection, reduced clinical wait times, and more proactive dementia management.", "source": "PubMed"}, {"chunk_id": "41685496_1", "pmid": "41685496", "title": "Empowering Alzheimer's and Related Dementia Prevention Through Primary Care Using Responsible AI: A Pilot Walk-in Memory Sync Booth.", "authors": "Datta SC, Banerjee S, Roy UB et al.", "year": "2026", "journal": "Studies in health technology and informatics", "keywords": "Alzheimer\u2019s disease, Cognitive Screening, Dementia, Early Detection, Responsible AI", "chunk": "more proactive dementia management.", "source": "PubMed"}, {"chunk_id": "35527737_0", "pmid": "35527737", "title": "Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer's Disease and Other Tauopathies.", "authors": "Maschio C, Ni R", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, Amyloid-beta, affinities, binding sites, biomarker, positron emission tomography, tau", "chunk": "The detection and staging of Alzheimer's disease (AD) using non-invasive imaging biomarkers is of substantial clinical importance. Positron emission tomography (PET) provides readouts to uncover molecular alterations in the brains of AD patients with high sensitivity and specificity. A variety of amyloid-\u03b2 (A\u03b2) and tau PET tracers are already available for the clinical diagnosis of AD, but there is still a lack of imaging biomarkers with high affinity and selectivity for tau inclusions in primary tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease (PiD). This review aims to provide an overview of the existing A\u03b2 and tau PET imaging biomarkers and their binding properties from <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> assessment. Imaging biomarkers for pathologic proteins are vital for clinical diagnosis, disease staging and monitoring of the potential therapeutic approaches of AD. Off-target binding of radiolabeled tracers to white matter or other neural", "source": "PubMed"}, {"chunk_id": "35527737_1", "pmid": "35527737", "title": "Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer's Disease and Other Tauopathies.", "authors": "Maschio C, Ni R", "year": "2022", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, Amyloid-beta, affinities, binding sites, biomarker, positron emission tomography, tau", "chunk": "for pathologic proteins are vital for clinical diagnosis, disease staging and monitoring of the potential therapeutic approaches of AD. Off-target binding of radiolabeled tracers to white matter or other neural structures is one confounding factor when interpreting images. To improve binding properties such as binding affinity and to eliminate off-target binding, second generation of tau PET tracers have been developed. To conclude, we further provide an outlook for imaging tauopathies and other pathological features of AD and primary tauopathies.", "source": "PubMed"}, {"chunk_id": "40480806_0", "pmid": "40480806", "title": "Retinal imaging and tissue analysis for frontotemporal degeneration: recent advances and challenges for biomarker development.", "authors": "Zhao AT, Nair RM, Lee EB et al.", "year": "2025", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "ALZHEIMER'S DISEASE, FRONTOTEMPORAL DEMENTIA, OPHTHALMOLOGY", "chunk": "Frontotemporal degeneration (FTD) is a group of neurodegenerative disorders affecting behaviour, language and executive functions. FTD is a common cause of early-onset dementia, but there are no FDA-approved treatments or established biomarkers for diagnosing and tracking these conditions, making early and accurate diagnosis challenging during life. Recent advances in retinal imaging, particularly through technologies like optical coherence tomography (OCT), have emerged as promising tools for identifying potential biomarkers for FTD and related neurodegenerative diseases. The retina, being an accessible extension of the central nervous system, has shown abnormalities that might serve as indicators of forms of FTD. Retinal imaging has revealed changes such as thinning of specific retinal layers that could correlate with molecular forms of FTD, Alzheimer's disease and other neurodegenerative diseases. These advances highlight the potential of retinal imaging to not only aid in diagnosis but also differentiate between various neurodegenerative conditions. Emerging data on retinal tissue analysis", "source": "PubMed"}, {"chunk_id": "40480806_1", "pmid": "40480806", "title": "Retinal imaging and tissue analysis for frontotemporal degeneration: recent advances and challenges for biomarker development.", "authors": "Zhao AT, Nair RM, Lee EB et al.", "year": "2025", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "ALZHEIMER'S DISEASE, FRONTOTEMPORAL DEMENTIA, OPHTHALMOLOGY", "chunk": "other neurodegenerative diseases. These advances highlight the potential of retinal imaging to not only aid in diagnosis but also differentiate between various neurodegenerative conditions. Emerging data on retinal tissue analysis with immunohistochemistry and other techniques further support the potential of retinal biomarkers, though further studies are required to validate and refine these findings. Future advancements in retinal imaging technologies, along with longitudinal and autopsy-validated studies, are crucial for enhancing diagnostic capabilities and understanding FTD-related pathologies within the retina.", "source": "PubMed"}, {"chunk_id": "40861782_0", "pmid": "40861782", "title": "S-9-PAHSA ameliorates cognitive decline in a type 2 diabetes mouse model by inhibiting oxidative stress and apoptosis via CAIII modulation.", "authors": "Wang XR, Huang SS, Wang M et al.", "year": "2025", "journal": "Frontiers in molecular neuroscience", "keywords": "CAIII, S-9-PAHSA, diabetes-associated cognitive disorder, mitochondrial dysfunction, oxidative stress", "chunk": "S-palmitic acid-9-hydroxy stearic acid (SP), a newly characterized endogenous lipid with multifaceted biological activities, is poised to shed light on its potential in diabetes-related cognitive disorder (DRCD). This study aims to uncover the effects of SP on DRCD and the underlying mechanisms. C57BL/6 mice were fed with high-fat diet for 5 months to induce type 2 diabetes mellitus (T2DM). Subsequently, they received bilateral hippocampal injections of adeno-associated virus (AAV) carrying carbonic anhydrase III (CAIII) shRNA or control shRNA. Following one-month treatment with SP or vehicle, cognitive function was assessed using the Morris water maze and Y-maze tests. Oxidative stress and apoptosis were measured by Enzyme-linked Immunosorbent Assay (ELISA), and hippocampal neuronal morphology was examined through HE, Nissl, or NeuN staining. RNA sequencing (RNA seq), cell viability, tetramethylrhodamine ethyl ester (TMRE) staining, and mitoSOX assays were also performed in cultured PC12 cells. Our findings demonstrated that CAIII played a pivotal role", "source": "PubMed"}, {"chunk_id": "40861782_1", "pmid": "40861782", "title": "S-9-PAHSA ameliorates cognitive decline in a type 2 diabetes mouse model by inhibiting oxidative stress and apoptosis via CAIII modulation.", "authors": "Wang XR, Huang SS, Wang M et al.", "year": "2025", "journal": "Frontiers in molecular neuroscience", "keywords": "CAIII, S-9-PAHSA, diabetes-associated cognitive disorder, mitochondrial dysfunction, oxidative stress", "chunk": "RNA sequencing (RNA seq), cell viability, tetramethylrhodamine ethyl ester (TMRE) staining, and mitoSOX assays were also performed in cultured PC12 cells. Our findings demonstrated that CAIII played a pivotal role in enhancing cognitive function in T2DM mice by improving spatial memory. SP ameliorated hippocampal injury by CAIII-mediated AMPK/Sirt1/PGC1\u03b1 pathway, Bcl-2/Bax ratio elevation, and cleaved-Caspase 3 reduction. CAIII participated in various biological processes in the effects of SP on PC12 cells, including cell viability, lactate dehydrogenase (LDH) release, antioxidant enzymes, the maintenance of mitochondrial membrane potential, and the reduction of mitochondrial reactive oxygen species (ROS). Our study revealed that CAIII was integral to the effects of SP on DRCD, suggesting its potential as a therapeutic target for DRCD.", "source": "PubMed"}, {"chunk_id": "38839623_0", "pmid": "38839623", "title": "[<sup>18</sup>F]FDG PET integrated with structural MRI for accurate brain age prediction.", "authors": "Xue L, Fu Y, Gao X et al.", "year": "2024", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Brain age, Brain aging, Deep learning, Magnetic resonance imaging, Positron emission tomography", "chunk": "Brain aging is a complex and heterogeneous process characterized by both structural and functional decline. This study aimed to establish a novel deep learning (DL) method for predicting brain age by utilizing structural and metabolic imaging data. The dataset comprised participants from both the Universal Medical Imaging Diagnostic Center (UMIDC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The former recruited 395 normal control (NC) subjects, while the latter included 438 NC subjects, 51 mild cognitive impairment (MCI) subjects, and 56 Alzheimer's disease (AD) subjects. We developed a novel dual-pathway, 3D simple fully convolutional network (Dual-SFCNeXt) to estimate brain age using [<sup>18</sup>F]fluorodeoxyglucose positron emission tomography ([<sup>18</sup>F]FDG PET) and structural magnetic resonance imaging (sMRI) images of NC subjects as input. Several prevailing DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age", "source": "PubMed"}, {"chunk_id": "38839623_1", "pmid": "38839623", "title": "[<sup>18</sup>F]FDG PET integrated with structural MRI for accurate brain age prediction.", "authors": "Xue L, Fu Y, Gao X et al.", "year": "2024", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Brain age, Brain aging, Deep learning, Magnetic resonance imaging, Positron emission tomography", "chunk": "DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age gap (BAG), deviations of brain age from chronologic age, was correlated with cognitive assessments in MCI and AD subjects. Both PET- and MRI-based models achieved high prediction accuracy. The leading model was the SFCNeXt (the single-pathway version) for PET (MAE = 2.92, r = 0.96) and MRI (MAE = 3.23, r = 0.95) on all samples. By integrating both PET and MRI images, the Dual-SFCNeXt demonstrated significantly improved accuracy (MAE = 2.37, r = 0.97) compared to all single-modality models. Significantly higher BAG was observed in both the AD (P < 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the", "source": "PubMed"}, {"chunk_id": "38839623_2", "pmid": "38839623", "title": "[<sup>18</sup>F]FDG PET integrated with structural MRI for accurate brain age prediction.", "authors": "Xue L, Fu Y, Gao X et al.", "year": "2024", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Brain age, Brain aging, Deep learning, Magnetic resonance imaging, Positron emission tomography", "chunk": "< 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores (r = 0.333 for AD, r = 0.372 for MCI). The integration of [<sup>18</sup>F]FDG PET with structural MRI enhances the accuracy of brain age prediction, potentially introducing a new avenue for related multimodal brain age prediction studies.", "source": "PubMed"}, {"chunk_id": "41105718_0", "pmid": "41105718", "title": "Multiscale networks in Alzheimer's disease identify brain hypometabolism as central across biological scales.", "authors": "Lara-Simon E, Gispert JD, Garcia-Ojalvo J et al.", "year": "2025", "journal": "PLoS computational biology", "keywords": "None", "chunk": "Alzheimer's disease encompasses multiple biological scales, spanning molecular factors, cells, tissues, and behavioral manifestations. The interplay among these scales in shaping the clinical phenotype is not yet fully comprehended. In particular, there is great interest in understanding the heterogeneity of the clinical aspects of AD in order to improve treatment and prevention, by targeting those aspects most susceptible to the disease. Here we employed a systems biology approach to address this issue, utilizing multilayer network analysis and deep phenotyping. This integrative analysis incorporated genomics, cerebrospinal fluid biomarkers, tau and amyloid beta (A\u03b2) PET imaging, brain MRI data, risk factors, and clinical information (cognitive tests scores, Clinical Dementia Rating and clinical diagnosis) obtained through the ADNI collaboration. Multilayer networks were built based on mutual information between the elements of each layer and between layers. Boolean simulations allowed us to identify paths that transmit dynamic information across layers. The most prominent path", "source": "PubMed"}, {"chunk_id": "41105718_1", "pmid": "41105718", "title": "Multiscale networks in Alzheimer's disease identify brain hypometabolism as central across biological scales.", "authors": "Lara-Simon E, Gispert JD, Garcia-Ojalvo J et al.", "year": "2025", "journal": "PLoS computational biology", "keywords": "None", "chunk": "based on mutual information between the elements of each layer and between layers. Boolean simulations allowed us to identify paths that transmit dynamic information across layers. The most prominent path for predicting variables in the cognitive phenotype layer included the PET radiotracer fluorodeoxyglucose (FDG) in the posterior cingulate. Combinations of different symptomatic variables, mainly related to mental health (depression, mood swings, drowsiness) and vascular features (hypertension, cardiovascular history), were also part of the paths explaining the average phenotype. Our results show that integrating the flow of information across biological scales reveals relevant paths for AD, which can be subsequently explored as potential biomarkers or therapeutic targets. In particular, our results point for paths related with brain hypometabolism as a key feature in AD.", "source": "PubMed"}, {"chunk_id": "41105718_2", "pmid": "41105718", "title": "Multiscale networks in Alzheimer's disease identify brain hypometabolism as central across biological scales.", "authors": "Lara-Simon E, Gispert JD, Garcia-Ojalvo J et al.", "year": "2025", "journal": "PLoS computational biology", "keywords": "None", "chunk": "feature in AD.", "source": "PubMed"}, {"chunk_id": "39826774_0", "pmid": "39826774", "title": "Adapting to evolving MRI data: A transfer learning approach for Alzheimer's disease prediction.", "authors": "Turrisi R, Pati S, Pioggia G et al.", "year": "2025", "journal": "NeuroImage", "keywords": "ACS convolutions, Alzheimer\u2019s disease, Domain adaptation, Evolving MRI, Transfer learning", "chunk": "Integrating 3D magnetic resonance imaging (MRI) with machine learning has shown promising results in healthcare, especially in detecting Alzheimer's Disease (AD). However, changes in MRI technologies and acquisition protocols often yield limited data, leading to potential overfitting. This study explores Transfer Learning (TL) approaches to enhance AD diagnosis using a Baseline model consisting of a 3D-Convolutional Neural Network trained on 80 3T MRI scans. Two scenarios are explored: (A) utilizing historical data to address changes in MRI acquisitions (from 1.5T to 3T MRI), and (B) adapting 2D models pre-trained on ImageNet (ResNet18, ResNet50, ResNet101) for 3D image processing when historical data is unavailable. In both scenarios, two modeling approaches are tested. The General Approach involves distinct feature extraction and classification steps, using Radiomic features and TL-based features evaluated with six classifiers. The Deep Approach integrates these steps by fine-tuning the pre-trained models for AD diagnosis. In scenario (A), TL significantly", "source": "PubMed"}, {"chunk_id": "39826774_1", "pmid": "39826774", "title": "Adapting to evolving MRI data: A transfer learning approach for Alzheimer's disease prediction.", "authors": "Turrisi R, Pati S, Pioggia G et al.", "year": "2025", "journal": "NeuroImage", "keywords": "ACS convolutions, Alzheimer\u2019s disease, Domain adaptation, Evolving MRI, Transfer learning", "chunk": "steps, using Radiomic features and TL-based features evaluated with six classifiers. The Deep Approach integrates these steps by fine-tuning the pre-trained models for AD diagnosis. In scenario (A), TL significantly boosts the Baseline's accuracy from 63% to 99%. In scenario (B), Radiomic features better represents 3D MRI than TL-features in the General Approach. Nonetheless, fine-tuning models pre-trained on natural images can increase the Baseline's accuracy by up to 12 percentage points, achieving an overall accuracy of 83%.", "source": "PubMed"}, {"chunk_id": "41110552_0", "pmid": "41110552", "title": "Locus Coeruleus Microstructure and Connectivity as Novel Markers of Depression and Cognitive Dysfunction in Older Adults.", "authors": "Vald\u00e9s Cabrera D, Calarco N, Cassidy CM et al.", "year": "2026", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Cognitive dysfunction, Depression, Diffusion magnetic resonance imaging, Locus coeruleus, Neuromelanin, Tractography", "chunk": "Late-life depression (LLD) is a risk factor for age-related cognitive decline. Postmortem studies have highlighted pathological changes in the locus coeruleus (LC) and its projections as potential early cognitive vulnerability markers. Here, we used a novel individualized multimodal magnetic resonance imaging (MRI) approach to characterize the cognitive correlates of LC microstructure and connectivity in participants with LLD and age-matched never-depressed (ND) control participants. Diffusion-weighted and LC-sensitive MRI were acquired for 52 participants (LLD: n = 26, 19 female, age 67.8 \u00b1 5.48 years; ND: n = 26, 12 female, age 69.8 \u00b1 7.62 years). Using LC-sensitive MRI to localize the LC in each participant's native space, we computed diffusion metrics (fractional anisotropy [FA] and mean diffusivity [MD]) for the LC and its projections to the hippocampus (Hp), reconstructed with constrained spherical deconvolution tractography. Associations of FA and MD with diagnosis and cognitive performance were evaluated with analyses of covariance and", "source": "PubMed"}, {"chunk_id": "41110552_1", "pmid": "41110552", "title": "Locus Coeruleus Microstructure and Connectivity as Novel Markers of Depression and Cognitive Dysfunction in Older Adults.", "authors": "Vald\u00e9s Cabrera D, Calarco N, Cassidy CM et al.", "year": "2026", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Cognitive dysfunction, Depression, Diffusion magnetic resonance imaging, Locus coeruleus, Neuromelanin, Tractography", "chunk": "and its projections to the hippocampus (Hp), reconstructed with constrained spherical deconvolution tractography. Associations of FA and MD with diagnosis and cognitive performance were evaluated with analyses of covariance and Pearson correlations, respectively, adjusted for demographic/disease covariates and multiple testing (Bonferroni-corrected p < .05). Higher MD (F<sub>1,45</sub> = 10.07, p = .003) was observed in the LC of individuals with LLD relative to ND control participants. Conversely, no group differences emerged in the LC-Hp pathway. In the combined LLD-ND sample, accounting for LLD diagnosis, lower FA in the LC and its hippocampal projections were associated with worse processing speed (LC: word reading r = -0.47; LC-medial temporal lobe [MTL]: word reading r = -0.46, color naming r = -0.49; all ps \u2264 .0007) and executive functions (LC-MTL: inhibition r = -0.50, inhibition/switching r = -0.45, number/letter sequencing r = -0.40; all ps \u2264 .0033). Neuronal injury of the LC may", "source": "PubMed"}, {"chunk_id": "41110552_2", "pmid": "41110552", "title": "Locus Coeruleus Microstructure and Connectivity as Novel Markers of Depression and Cognitive Dysfunction in Older Adults.", "authors": "Vald\u00e9s Cabrera D, Calarco N, Cassidy CM et al.", "year": "2026", "journal": "Biological psychiatry. Cognitive neuroscience and neuroimaging", "keywords": "Cognitive dysfunction, Depression, Diffusion magnetic resonance imaging, Locus coeruleus, Neuromelanin, Tractography", "chunk": "ps \u2264 .0007) and executive functions (LC-MTL: inhibition r = -0.50, inhibition/switching r = -0.45, number/letter sequencing r = -0.40; all ps \u2264 .0033). Neuronal injury of the LC may be a marker for LLD. Alternatively, the microstructural status of LC-Hp projections may be a biomarker more specific to age-related cognitive deterioration, irrespective of depression diagnosis.", "source": "PubMed"}, {"chunk_id": "37606627_0", "pmid": "37606627", "title": "Artificial intelligence for dementia genetics and omics.", "authors": "Bettencourt C, Skene N, Bandres-Ciga S et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "artificial intelligence, biomarkers, pathology, causality, dementia, disease pathways, etiology, genetics, machine learning, omics, risk factors", "chunk": "Genetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible omics signatures that differentiate between dementia subtypes? Can high-dimensional omics data identify improved biomarkers? How can genetics inform our understanding of causal status of dementia risk factors? And which biological processes are altered by dementia-related genetic variation? Artificial intelligence (AI) and machine learning approaches give us powerful new tools in helping us to tackle these challenges, and we review possible solutions and examples of best practice. However, their limitations also need to be considered, as well as the need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine. HIGHLIGHTS: We have identified", "source": "PubMed"}, {"chunk_id": "37606627_1", "pmid": "37606627", "title": "Artificial intelligence for dementia genetics and omics.", "authors": "Bettencourt C, Skene N, Bandres-Ciga S et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "artificial intelligence, biomarkers, pathology, causality, dementia, disease pathways, etiology, genetics, machine learning, omics, risk factors", "chunk": "need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine. HIGHLIGHTS: We have identified five key challenges in dementia genetics and omics studies. AI can enable detection of undiscovered patterns in dementia genetics and omics data. Enhanced and more diverse genetics and omics datasets are still needed. Multidisciplinary collaborative efforts using AI can boost dementia research.", "source": "PubMed"}, {"chunk_id": "36775284_0", "pmid": "36775284", "title": "Aducanumab for the treatment of Alzheimer's disease: a systematic review.", "authors": "Rahman A, Hossen MA, Chowdhury MFI et al.", "year": "2023", "journal": "Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society", "keywords": "Alzheimer disease, aducanumab, aged, drug safety profile, efficacy", "chunk": "Aducanumab is a novel disease-modifying anti-amyloid-beta (A\u03b2) human monoclonal antibody specifically targeted to the pathophysiology of Alzheimer's disease (AD). It was granted for treating AD in June 2021 by the United States Food and Drug Administration. We systematically analyzed available trials to evaluate the efficacy and safety of aducanumab treating AD. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We conducted an extensive literature search using the electronic databases MEDLINE through PubMed, EMBASE, Cochrane, Web of Science, and Scopus for suitable studies on aducanumab. We considered human clinical trials of aducanumab, assessing its efficacy and adverse effects in treating AD, excluding any experimental animal studies. We included three randomised controlled trials. Studies reported that aducanumab reduced brain amyloid-beta plaques in a time- and dose-dependent manner (dose-response, P < 0.05) and a slowed decline in cognition (22% reduction) in the high-dose treated group, difference of -0.39", "source": "PubMed"}, {"chunk_id": "36775284_1", "pmid": "36775284", "title": "Aducanumab for the treatment of Alzheimer's disease: a systematic review.", "authors": "Rahman A, Hossen MA, Chowdhury MFI et al.", "year": "2023", "journal": "Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society", "keywords": "Alzheimer disease, aducanumab, aged, drug safety profile, efficacy", "chunk": "reduced brain amyloid-beta plaques in a time- and dose-dependent manner (dose-response, P < 0.05) and a slowed decline in cognition (22% reduction) in the high-dose treated group, difference of -0.39 versus placebo in Clinical Dementia Rating Scale Sum Boxes (95% CI, -0.69 to -0.09; P = 0.012) along with a reduced amyloid positron emission tomography standard uptake value ratio score (P < 0.001) and plasma p181-tau (phosphorylated tau) level. Amyloid-related imaging abnormality was reported as a serious adverse event and was profound in high-dose treated group (425/1029 in 10 mg/kg). Aducanumab has been reported to affect two main pathophysiologic hallmarks (A\u03b2 and tau) of AD. We suggest future studies addressing aducanumab's efficacy and safety to confirm that the benefit of this drug outweighs the risk.", "source": "PubMed"}, {"chunk_id": "36775284_2", "pmid": "36775284", "title": "Aducanumab for the treatment of Alzheimer's disease: a systematic review.", "authors": "Rahman A, Hossen MA, Chowdhury MFI et al.", "year": "2023", "journal": "Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society", "keywords": "Alzheimer disease, aducanumab, aged, drug safety profile, efficacy", "chunk": "this drug outweighs the risk.", "source": "PubMed"}, {"chunk_id": "36086465_0", "pmid": "36086465", "title": "Probing the link between the APOE-\u03b54 allele and whole-brain gray matter using deep learning.", "authors": "Abrol A, Hajjar I, Calhoun V", "year": "2022", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "The APOE-\u03b54 allele is a known genetic risk for Alzheimer's disease (AD). Thus, it can be reasoned that the APOE-\u03b54 allele would also impact neurodegeneration-associated structural brain changes. Here we probe if the APOE-\u03b54 genotype directly modulates the human brain's gray matter using a neural network trained on the whole-brain gray matter images from the cognitively normally aging (CN) and AD individuals. To investigate the linkage between the APOE-\u03b54 allele and whole-brain (voxel-wise) gray matter, we systematically profile our investigation in multiple classification tasks, including diagnostic classification and APOE-\u03b54 classification conjointly as well as independently. Results suggest that although the MRI data can reliably track and reflect neurodegenerative changes in the brain cross-sectionally, the APOE-\u03b54 status may not be distinguishable correspondingly. The nonexistence of a direct and convincing modulative effect of APOE-\u03b54 on the whole-brain gray matter indicates that the gray matter changes may be independent of the APOE-\u03b54 status,", "source": "PubMed"}, {"chunk_id": "36086465_1", "pmid": "36086465", "title": "Probing the link between the APOE-\u03b54 allele and whole-brain gray matter using deep learning.", "authors": "Abrol A, Hajjar I, Calhoun V", "year": "2022", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "correspondingly. The nonexistence of a direct and convincing modulative effect of APOE-\u03b54 on the whole-brain gray matter indicates that the gray matter changes may be independent of the APOE-\u03b54 status, and instead characterize a non-APOE, comorbid mechanism in AD.", "source": "PubMed"}, {"chunk_id": "36804285_0", "pmid": "36804285", "title": "Role of lipocalin 2 in stroke.", "authors": "Zhao RY, Wei PJ, Sun X et al.", "year": "2023", "journal": "Neurobiology of disease", "keywords": "Glial activation, Intracerebral hemorrhage, Ischemic stroke, Lipocalin 2, Neuroinflammation, Subarachnoid hemorrhage, White matter injury", "chunk": "Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates,", "source": "PubMed"}, {"chunk_id": "36804285_1", "pmid": "36804285", "title": "Role of lipocalin 2 in stroke.", "authors": "Zhao RY, Wei PJ, Sun X et al.", "year": "2023", "journal": "Neurobiology of disease", "keywords": "Glial activation, Intracerebral hemorrhage, Ischemic stroke, Lipocalin 2, Neuroinflammation, Subarachnoid hemorrhage, White matter injury", "chunk": "microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.", "source": "PubMed"}, {"chunk_id": "38406610_0", "pmid": "38406610", "title": "Clinical classification of memory and cognitive impairment with multimodal digital biomarkers.", "authors": "Banks R, Higgins C, Greene BR et al.", "year": "2024", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "amnestic MCI, automatic speech recognition, digital clock drawing, mild cognitive impairment, non\u2010amnestic MCI, speech, verbal memory, voice", "chunk": "Early detection of Alzheimer's disease and cognitive impairment is critical to improving the healthcare trajectories of aging adults, enabling early intervention and potential prevention of decline. To evaluate multi-modal feature sets for assessing memory and cognitive impairment, feature selection and subsequent logistic regressions were used to identify the most salient features in classifying Rey Auditory Verbal Learning Test-determined memory impairment. Multimodal models incorporating graphomotor, memory, and speech and voice features provided the stronger classification performance (area under the curve = 0.83; sensitivity = 0.81, specificity = 0.80). Multimodal models were superior to all other single modality and demographics models. The current research contributes to the prevailing multimodal profile of those with cognitive impairment, suggesting that it is associated with slower speech with a particular effect on the duration, frequency, and percentage of pauses compared to normal healthy speech.", "source": "PubMed"}, {"chunk_id": "38406610_1", "pmid": "38406610", "title": "Clinical classification of memory and cognitive impairment with multimodal digital biomarkers.", "authors": "Banks R, Higgins C, Greene BR et al.", "year": "2024", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "amnestic MCI, automatic speech recognition, digital clock drawing, mild cognitive impairment, non\u2010amnestic MCI, speech, verbal memory, voice", "chunk": "speech with a particular effect on the duration, frequency, and percentage of pauses compared to normal healthy speech.", "source": "PubMed"}, {"chunk_id": "36970897_0", "pmid": "36970897", "title": "Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype.", "authors": "Franz CE, Gustavson DE, Elman JA et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "PM2.5, APOE genotype, Aging, air pollution, cognition, midlife, nitrogen dioxide", "chunk": "Fine particulate matter (PM2.5) and nitrogen dioxide (NO2) measures of ambient air pollution are associated with accelerated age-related cognitive impairment, and Alzheimer's disease and related dementias (ADRD). We examined associations between air pollution, four cognitive factors, and the moderating role of apolipoprotein E (APOE) genotype in the understudied period of midlife. Participants were \u223c1,100 men in the Vietnam Era Twin Study of Aging. Baseline cognitive assessments were from 2003 to 2007. Measures included past (1993-1999) and recent (3 years prior to baseline assessment) PM2.5 and NO2 exposure, in-person assessment of episodic memory, executive function, verbal fluency, and processing speed, and APOE genotype. Average baseline age was 56 years with a 12-year follow-up. Analyses adjusted for health and lifestyle covariates. Performance in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains:", "source": "PubMed"}, {"chunk_id": "36970897_1", "pmid": "36970897", "title": "Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype.", "authors": "Franz CE, Gustavson DE, Elman JA et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "PM2.5, APOE genotype, Aging, air pollution, cognition, midlife, nitrogen dioxide", "chunk": "in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains: PM2.5 with executive function and NO2 with episodic memory. Higher PM2.5 exposure was related to worse executive function in APOE \u025b4 carriers, but not in non-carriers. There were no associations with processing speed. These results indicate negative effects of ambient air pollution exposure on fluency alongside intriguing differential modifications of cognitive performance by APOE genotype. APOE \u025b4 carriers appeared more sensitive to environmental differences. The process by which air pollution and its interaction with genetic risk for ADRD affects risk for later life cognitive decline or progression to dementia may begin in midlife.", "source": "PubMed"}, {"chunk_id": "36970897_2", "pmid": "36970897", "title": "Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype.", "authors": "Franz CE, Gustavson DE, Elman JA et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "PM2.5, APOE genotype, Aging, air pollution, cognition, midlife, nitrogen dioxide", "chunk": "begin in midlife.", "source": "PubMed"}, {"chunk_id": "40164764_0", "pmid": "40164764", "title": "Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models.", "authors": "Feng X, Jiang BW, Zhai SN et al.", "year": "2026", "journal": "Nature biotechnology", "keywords": "None", "chunk": "Alzheimer disease (AD) therapy may benefit from optimized approaches to inhibit neuroinflammation. Small-molecule inhibitors of the proinflammatory molecule double-stranded RNA (dsRNA)-activated protein kinase R (PKR) have efficacy in AD models but their utility is compromised by adverse side effects. Here, we target PKR in two mouse models of AD using circular RNAs containing short double-stranded regions (ds-cRNAs), which are structurally similar to what we used previously to target PKR in psoriasis models. We show that the intrahippocampal injection of ds-cRNAs to neurons and microglia by adeno-associated virus (AAV) effectively dampens excessive PKR activity with minimal toxicity, accompanied by reduced neuroinflammation and amyloid-\u03b2 plaques. We also deliver ds-cRNAs to the whole brain through intravenous injection of AAV-PHP.eB, which crosses the blood-brain barrier, resulting in neuroprotection and enhanced capability of spatial learning and memory in AD mouse models. The delivery of ds-cRNAs at different progressive stages of AD alleviates disease phenotypes, with", "source": "PubMed"}, {"chunk_id": "40164764_1", "pmid": "40164764", "title": "Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models.", "authors": "Feng X, Jiang BW, Zhai SN et al.", "year": "2026", "journal": "Nature biotechnology", "keywords": "None", "chunk": "barrier, resulting in neuroprotection and enhanced capability of spatial learning and memory in AD mouse models. The delivery of ds-cRNAs at different progressive stages of AD alleviates disease phenotypes, with therapeutic effects sustained for at least 6 months after a single administration.", "source": "PubMed"}, {"chunk_id": "38190615_0", "pmid": "38190615", "title": "First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT<sub>6</sub> Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.", "authors": "Pyka P, Haberek W, Wi\u0119cek M et al.", "year": "2024", "journal": "Journal of medicinal chemistry", "keywords": "None", "chunk": "Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT<sub>6</sub> emerged as a promising target for AD treatment; thus, here a new series of 5-HT<sub>6</sub>R ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HT<sub>6</sub>R affinity and selectivity over 5-HT<sub>1A</sub>R (<b>13</b>-<b>15</b>), 5-HT<sub>7</sub>R (<b>14</b> and <b>15</b>), and 5-HT<sub>2A</sub>R (<b>13</b>). Compound <b>15</b> displayed high selectivity for 5-HT<sub>6</sub>R over other central nervous system receptors and exhibited low risk of cardio-, hepato-, and nephrotoxicity and no mutagenicity, indicating its \"drug-like\" potential. Compound <b>15</b> also demonstrated neuroprotection against rotenone-induced neurotoxicity as well as antioxidant and glutathione peroxidase (GPx)-like activity and regulated antioxidant and pro-inflammatory genes and NRF2 nuclear translocation. In rats, <b>15</b> showed satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. <b>15</b>'s neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the", "source": "PubMed"}, {"chunk_id": "38190615_1", "pmid": "38190615", "title": "First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT<sub>6</sub> Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.", "authors": "Pyka P, Haberek W, Wi\u0119cek M et al.", "year": "2024", "journal": "Journal of medicinal chemistry", "keywords": "None", "chunk": "satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. <b>15</b>'s neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the way for the use of selenotriazines to inhibit both causes and symptoms in AD therapy.", "source": "PubMed"}, {"chunk_id": "41338456_0", "pmid": "41338456", "title": "A humanized transferrin receptor 1-transferrin model supports functional iron homeostasis and therapeutic delivery across the blood-brain barrier.", "authors": "Yesiltepe M, Metkar S, Yin T et al.", "year": "2026", "journal": "The Journal of biological chemistry", "keywords": "NewroBus, TfR1-mediated transcytosis, blood\u2013brain barrier, brain delivery, humanized animal models, iron homeostasis, knock-in rats, nanobodies, transferrin, transferrin receptor 1", "chunk": "The transferrin receptor 1 (TfR1)-transferrin (TF) axis is central to iron homeostasis and represents a validated route for delivering biologics across the blood-brain barrier (BBB). We developed human-specific anti-TfR1 nanobodies (NewroBus) that exploit this pathway, but their lack of cross-reactivity with rodent TfR1 limits conventional preclinical testing. To overcome this, we generated knock-in rats in which the coding sequences of the endogenous Tfrc and Tf genes were replaced with their human counterparts, producing animals that express human TfR1 and/or human TF under physiological control. Rats homozygous for both humanized alleles were viable and fertile, indicating functional replacement of their rodent orthologs but exhibited erythropoietic abnormalities and altered iron distribution-reduced splenic and increased hepatic iron-suggesting incomplete compensation. In contrast, heterozygous rats displayed only mild, subclinical microcytosis and hypochromia while maintaining normal BBB integrity and near-physiological iron homeostasis. Using these heterozygous humanized Tfrc rats, we demonstrated that a biologic engineered to engage", "source": "PubMed"}, {"chunk_id": "41338456_1", "pmid": "41338456", "title": "A humanized transferrin receptor 1-transferrin model supports functional iron homeostasis and therapeutic delivery across the blood-brain barrier.", "authors": "Yesiltepe M, Metkar S, Yin T et al.", "year": "2026", "journal": "The Journal of biological chemistry", "keywords": "NewroBus, TfR1-mediated transcytosis, blood\u2013brain barrier, brain delivery, humanized animal models, iron homeostasis, knock-in rats, nanobodies, transferrin, transferrin receptor 1", "chunk": "displayed only mild, subclinical microcytosis and hypochromia while maintaining normal BBB integrity and near-physiological iron homeostasis. Using these heterozygous humanized Tfrc rats, we demonstrated that a biologic engineered to engage human TfR1, NewroBus, fused to a therapeutic payload such as TNF\u03b1-neutralizing nanobodies, achieved significant BBB penetration and central nervous system exposure. These results validate the translational relevance of this model for studying TfR1-mediated drug delivery. Overall, the humanized TfR1-TF axis is compatible with life and systemic iron regulation, albeit with gene dosage-dependent effects on compensation. These knock-in rats provide a unique, translationally relevant platform for evaluating the pharmacokinetics, central nervous system penetration, efficacy, and safety of human-specific biologics engineered to access the brain via human TfR1-mediated transcytosis.", "source": "PubMed"}, {"chunk_id": "38735950_0", "pmid": "38735950", "title": "Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.", "authors": "Wang X, Shi Z, Qiu Y et al.", "year": "2024", "journal": "BMC medicine", "keywords": "Biomarker, Cognitive function, Genetic risk, Predictive value", "chunk": "Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer's disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts. This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates. A", "source": "PubMed"}, {"chunk_id": "38735950_1", "pmid": "38735950", "title": "Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.", "authors": "Wang X, Shi Z, Qiu Y et al.", "year": "2024", "journal": "BMC medicine", "keywords": "Biomarker, Cognitive function, Genetic risk, Predictive value", "chunk": "NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates. A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 \u00b1 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia", "source": "PubMed"}, {"chunk_id": "38735950_2", "pmid": "38735950", "title": "Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.", "authors": "Wang X, Shi Z, Qiu Y et al.", "year": "2024", "journal": "BMC medicine", "keywords": "Biomarker, Cognitive function, Genetic risk, Predictive value", "chunk": "from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels. These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.", "source": "PubMed"}, {"chunk_id": "36549843_0", "pmid": "36549843", "title": "Apolipoprotein E \u03b54 disrupts oligodendrocyte differentiation by interfering with astrocyte-derived lipid transport.", "authors": "Mok KK, Yeung SH, Cheng GW et al.", "year": "2023", "journal": "Journal of neurochemistry", "keywords": "APOE4, Alzheimer's disease, astrocyte, lipid transport, myelin, oligodendrocyte", "chunk": "Carriers of the APOE4 (apolipoprotein E \u03b54) variant of the APOE gene are subject to several age-related health risks, including Alzheimer's disease (AD). The deficient lipid and cholesterol transport capabilities of the APOE4 protein are one reason for the altered risk profile. In particular, APOE4 carriers are at elevated risk for sporadic AD. While deposits o misfolded proteins are present in the AD brain, white matter (WM) myelin is also disturbed. As myelin is a lipid- and cholesterol-rich structure, the connection to APOE makes considerable biological sense. To explore the APOE-WM connection, we have analyzed the impact of human APOE4 on oligodendrocytes (OLs) of the mouse both in vivo and in vitro. We find that APOE proteins is enriched in astrocytes but sparse in OL. In human APOE4 (hAPOE4) knock-in mice, myelin lipid content is increased but the density of major myelin proteins (MBP, MAG, and PLP) is largely unchanged.", "source": "PubMed"}, {"chunk_id": "36549843_1", "pmid": "36549843", "title": "Apolipoprotein E \u03b54 disrupts oligodendrocyte differentiation by interfering with astrocyte-derived lipid transport.", "authors": "Mok KK, Yeung SH, Cheng GW et al.", "year": "2023", "journal": "Journal of neurochemistry", "keywords": "APOE4, Alzheimer's disease, astrocyte, lipid transport, myelin, oligodendrocyte", "chunk": "astrocytes but sparse in OL. In human APOE4 (hAPOE4) knock-in mice, myelin lipid content is increased but the density of major myelin proteins (MBP, MAG, and PLP) is largely unchanged. We also find an unexpected but significant reduction of cell density of the OL lineage (Olig2<sup>+</sup> ) and an abnormal accumulation of OL precursors (Nkx 2.2<sup>+</sup> ), suggesting a disruption of OL differentiation. Gene ontology analysis of an existing RNA-seq dataset confirms a robust transcriptional response to the altered chemistry of the hAPOE4 mouse brain. In culture, the uptake of astrocyte-derived APOE during Lovastatin-mediated depletion of cholesterol synthesis is sufficient to sustain OL differentiation. While endogenous hAPOE protein isoforms have no effects on OL development, exogenous hAPOE4 abolishes the ability of very low-density lipoprotein to restore myelination in Apoe-deficient, cholesterol-depleted OL. Our data suggest that APOE4 impairs myelination in the aging brain by interrupting the delivery of astrocyte-derived lipids to", "source": "PubMed"}, {"chunk_id": "36549843_2", "pmid": "36549843", "title": "Apolipoprotein E \u03b54 disrupts oligodendrocyte differentiation by interfering with astrocyte-derived lipid transport.", "authors": "Mok KK, Yeung SH, Cheng GW et al.", "year": "2023", "journal": "Journal of neurochemistry", "keywords": "APOE4, Alzheimer's disease, astrocyte, lipid transport, myelin, oligodendrocyte", "chunk": "of very low-density lipoprotein to restore myelination in Apoe-deficient, cholesterol-depleted OL. Our data suggest that APOE4 impairs myelination in the aging brain by interrupting the delivery of astrocyte-derived lipids to the oligodendrocytes. We propose that high myelin turnover and OL exhaustion found in APOE4 carriers is a likely explanation for the APOE-dependent myelin phenotypes of the AD brain.", "source": "PubMed"}, {"chunk_id": "33252084_0", "pmid": "33252084", "title": "Blood TDP-43 Combined with Demographics Information Predicts Dementia Occurrence in Community Non-Dementia Elderly.", "authors": "Sun L, Li W, Yue L et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Dementia, TDP-43, follow-up, mild cognitive impairment, neurofilament light chain", "chunk": "TAR DNA-binding protein-43 (TDP-43) and neurofilament light chain (NfL) are promising fluid biomarkers of disease progression for various dementia. We would explore whether blood levels of NfL and TDP-43 could predict the long-term progression to dementia, and the relationship of TDP-43 levels between cerebrospinal fluid (CSF) and blood. A total of 86 non-dementia elderly received 7-year follow-up, and were divided into 49 stable normal control (NC)/mild cognitive impairment (MCI) subjects, 19 subjects progressing from NC to MCI, and 18 subjects progressing from NC/MCI to dementia. Blood TDP-43 and NfL levels, and cognitive functions were measured in all subjects. Furthermore, another cohort of 23 dementia patients, including 13 AD and 10 non-AD patients received blood and CSF measurements of TDP-43. In cohort 1, compared to stable NC/MCI group, there were higher levels of blood TDP-43 at baseline in subjects progressing from NC/MCI to dementia. The combination of baseline blood TDP-43 levels", "source": "PubMed"}, {"chunk_id": "33252084_1", "pmid": "33252084", "title": "Blood TDP-43 Combined with Demographics Information Predicts Dementia Occurrence in Community Non-Dementia Elderly.", "authors": "Sun L, Li W, Yue L et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Dementia, TDP-43, follow-up, mild cognitive impairment, neurofilament light chain", "chunk": "cohort 1, compared to stable NC/MCI group, there were higher levels of blood TDP-43 at baseline in subjects progressing from NC/MCI to dementia. The combination of baseline blood TDP-43 levels with demographics including age, education, and diabetes had the detection for dementia occurrence. Baseline blood levels of NfL are negatively associated with cognitive function at 7-year follow-up. In cohort 2, we found there were no relationship between CSF and blood levels of TDP-43. Moreover, the levels of TDP-43 in CSF was positively associated with the age of patients, especially in AD group. Single blood TDP-43 could not estimate dementia occurrence; however, TDP-43 combined with demographics has the predictive effect for dementia occurrence and NfL level is associated with a decrease of cognitive function.", "source": "PubMed"}, {"chunk_id": "33252084_2", "pmid": "33252084", "title": "Blood TDP-43 Combined with Demographics Information Predicts Dementia Occurrence in Community Non-Dementia Elderly.", "authors": "Sun L, Li W, Yue L et al.", "year": "2021", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Dementia, TDP-43, follow-up, mild cognitive impairment, neurofilament light chain", "chunk": "of cognitive function.", "source": "PubMed"}, {"chunk_id": "35061824_0", "pmid": "35061824", "title": "Automated analysis of facial emotions in subjects with cognitive impairment.", "authors": "Jiang Z, Seyedi S, Haque RU et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "Differences in expressing facial emotions are broadly observed in people with cognitive impairment. However, these differences have been difficult to objectively quantify and systematically evaluate among people with cognitive impairment across disease etiologies and severity. Therefore, a computer vision-based deep learning model for facial emotion recognition trained on 400.000 faces was utilized to analyze facial emotions expressed during a passive viewing memory test. In addition, this study was conducted on a large number of individuals (n = 493), including healthy controls and individuals with cognitive impairment due to diverse underlying etiologies and across different disease stages. Diagnoses included subjective cognitive impairment, Mild Cognitive Impairment (MCI) due to AD, MCI due to other etiologies, dementia due to Alzheimer's diseases (AD), and dementia due to other etiologies (e.g., Vascular Dementia, Frontotemporal Dementia, Lewy Body Dementia, etc.). The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance across all participants. A participant", "source": "PubMed"}, {"chunk_id": "35061824_1", "pmid": "35061824", "title": "Automated analysis of facial emotions in subjects with cognitive impairment.", "authors": "Jiang Z, Seyedi S, Haque RU et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "dementia due to other etiologies (e.g., Vascular Dementia, Frontotemporal Dementia, Lewy Body Dementia, etc.). The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance across all participants. A participant with a score of less than or equal to 24 was considered cognitively impaired (CI). Compared to cognitively unimpaired (CU) participants, CI participants expressed significantly less positive emotions, more negative emotions, and higher facial expressiveness during the test. In addition, classification analysis revealed that facial emotions expressed during the test allowed effective differentiation of CI from CU participants, largely independent of sex, race, age, education level, mood, and eye movements (derived from an eye-tracking-based digital biomarker for cognitive impairment). No screening methods reliably differentiated the underlying etiology of the cognitive impairment. The findings provide quantitative and comprehensive evidence that the expression of facial emotions is significantly different in people with cognitive impairment, and suggests this may be a useful tool", "source": "PubMed"}, {"chunk_id": "35061824_2", "pmid": "35061824", "title": "Automated analysis of facial emotions in subjects with cognitive impairment.", "authors": "Jiang Z, Seyedi S, Haque RU et al.", "year": "2022", "journal": "PloS one", "keywords": "None", "chunk": "impairment. The findings provide quantitative and comprehensive evidence that the expression of facial emotions is significantly different in people with cognitive impairment, and suggests this may be a useful tool for passive screening of cognitive impairment.", "source": "PubMed"}, {"chunk_id": "37470232_0", "pmid": "37470232", "title": "Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms.", "authors": "Naval\u00f3n-Monllor V, Soriano-Roman\u00ed L, Silva M et al.", "year": "2023", "journal": "Food & function", "keywords": "None", "chunk": "Microbiota dysbiosis and metabolic syndrome, consequences of a non-adequate diet, generate a feedback pathogenic state implicated in Alzheimer's disease development. The lower production of short chain fatty acids (SCFAs) under dysbiosis status leads to lipid homeostasis deregulation and decreases Angptl4 release and AMPK activation in the adipose tissue, promoting higher lipid storage (adipocyte hypertrophy) and cholesterol levels. Also, low SCFA generation reduces GPR41 and GPR43 receptor activation at the adipose tissue (increasing leptin release and leptin receptor resistance) and intestinal levels, reducing the release of GLP-1 and YPP. Therefore, lower satiety sensation and energy expenditure occur, promoting a weight gaining environment mediated by higher food intake and lipid storage, developing dyslipemia. In this context, higher glucose levels, together with higher free fatty acids in the bloodstream, promote glycolipotoxicity, provoking a reduction in insulin released, insulin receptor resistance, advanced glycation products (AGEs) and type 2 diabetes. Intestinal dysbiosis and low SCFAs", "source": "PubMed"}, {"chunk_id": "37470232_1", "pmid": "37470232", "title": "Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms.", "authors": "Naval\u00f3n-Monllor V, Soriano-Roman\u00ed L, Silva M et al.", "year": "2023", "journal": "Food & function", "keywords": "None", "chunk": "free fatty acids in the bloodstream, promote glycolipotoxicity, provoking a reduction in insulin released, insulin receptor resistance, advanced glycation products (AGEs) and type 2 diabetes. Intestinal dysbiosis and low SCFAs reduce bacterial biodiversity, increasing lipopolysaccharide (LPS)-producing bacteria and intestinal barrier permeability. Higher amounts of LPS pass to the bloodstream (endotoxemia), causing a low-grade chronic inflammatory state characterized by higher levels of leptin, IL-1\u03b2, IL-6 and TNF-\u03b1, together with a reduced release of adiponectin and IL-10. At the brain and neuronal levels, the generated insulin resistance, low-grade chronic inflammation, leptin resistance, AGE production and LPS increase directly impact the secretase enzymes and tau hyperphosphorylation, creating an enabling environment for \u03b2-amyloid senile plaque and tau tangled formations and, as a consequence, Alzheimer's initiation, development and maintenance.", "source": "PubMed"}, {"chunk_id": "37470232_2", "pmid": "37470232", "title": "Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms.", "authors": "Naval\u00f3n-Monllor V, Soriano-Roman\u00ed L, Silva M et al.", "year": "2023", "journal": "Food & function", "keywords": "None", "chunk": "initiation, development and maintenance.", "source": "PubMed"}, {"chunk_id": "35286856_0", "pmid": "35286856", "title": "A\u03b2-responsive metformin-based supramolecular synergistic nanodrugs for Alzheimer's disease via enhancing microglial A\u03b2 clearance.", "authors": "Fan Z, Ren T, Wang Y et al.", "year": "2022", "journal": "Biomaterials", "keywords": "Alzheimer's disease, Drug delivery, On-demand drug release, Supramolecular nanodrugs, Synergistic therapy", "chunk": "Here, inspired by the concept of supramolecular inclusion complex, we successfully fabricate metformin (Met)-based supramolecular nanodrugs with the A\u03b2-responsive on-demand drug release for synergistic Alzheimer's disease (AD) therapy via enhancing microglial A\u03b2 clearance. Interestingly, the introduction of low-dosage Met (1.1 mg/kg) can not only significantly improve the structural stability of nanodrugs but also exert a synergistic anti-dementia effect with donepezil (Don). Besides, such nanodrugs with outstanding physiological stability can selectively penetrate the blood-brain barrier (BBB), target brain, increase efficient uptake of microglia and neurons, and then achieve simultaneous spatiotemporal on-demand drug release under stimuli of the overexpressed amyloid-beta (A\u03b2). Furthermore, Met and Don released from nanodrugs exhibit a superior synergistic anti-dementia effect by enhancing microglial phagocytosis and A\u03b2 clearance through the lysosomal pathway. Taken together, we report a synergistic strategy based on A\u03b2-responsive supramolecular nanodrugs for AD therapy, which can be expected to provide a novel clinical therapeutic idea for", "source": "PubMed"}, {"chunk_id": "35286856_1", "pmid": "35286856", "title": "A\u03b2-responsive metformin-based supramolecular synergistic nanodrugs for Alzheimer's disease via enhancing microglial A\u03b2 clearance.", "authors": "Fan Z, Ren T, Wang Y et al.", "year": "2022", "journal": "Biomaterials", "keywords": "Alzheimer's disease, Drug delivery, On-demand drug release, Supramolecular nanodrugs, Synergistic therapy", "chunk": "the lysosomal pathway. Taken together, we report a synergistic strategy based on A\u03b2-responsive supramolecular nanodrugs for AD therapy, which can be expected to provide a novel clinical therapeutic idea for ameliorating central nervous system disease.", "source": "PubMed"}, {"chunk_id": "39434871_0", "pmid": "39434871", "title": "Higher amyloid is associated with greater loneliness among cognitively normal older adults during the COVID-19 pandemic.", "authors": "Kehrer-Dunlap A, Bollinger R, Chen SW et al.", "year": "2022", "journal": "F1000Research", "keywords": "Alzheimer disease, COVID-19, loneliness, preclinical Alzheimer disease", "chunk": "Loneliness has been associated with several consequences, including increased risk of developing Alzheimer disease (AD). Loneliness may arise during the preclinical phase of AD, but little is known about the relationship between loneliness and amyloid accumulation consistent with preclinical AD. Therefore, the purpose of this study was to examine the relationship between amyloid accumulation and subjective experiences of loneliness among cognitively normal older adults during the COVID-19 pandemic. A global Clinical Dementia Rating <sup><sup>\u00ae</sup></sup> Scale score of 0 was required for enrollment. Cortical amyloid burden was measured using [11C] Pittsburgh compound B or [18F]-Florbetapir PET tracers. Centiloids were used to synchronize measures. Demographic characteristics and measures of loneliness, anxiety, and depression were collected via self-report. Multiple linear regression was used to examine the relationship between loneliness and amyloid accumulation. The 108 participants had a mean age of 75.0 and an average amyloid accumulation of 22.2 \u00b1 31.9. Mean UCLA Loneliness", "source": "PubMed"}, {"chunk_id": "39434871_1", "pmid": "39434871", "title": "Higher amyloid is associated with greater loneliness among cognitively normal older adults during the COVID-19 pandemic.", "authors": "Kehrer-Dunlap A, Bollinger R, Chen SW et al.", "year": "2022", "journal": "F1000Research", "keywords": "Alzheimer disease, COVID-19, loneliness, preclinical Alzheimer disease", "chunk": "to examine the relationship between loneliness and amyloid accumulation. The 108 participants had a mean age of 75.0 and an average amyloid accumulation of 22.2 \u00b1 31.9. Mean UCLA Loneliness Scale scores were 31.6 \u00b1 10.8. A significant positive association was detected between loneliness and amyloid accumulation (\u03b2 = 0.064, SE = 0.027, 95% CI = [0.011, 0.118], p = 0.018). These findings highlight the relationship between higher amyloid accumulation and greater loneliness during the COVID-19 pandemic. Healthcare professionals should include routine assessments for characteristics of loneliness in routine clinical evaluations and integrate loneliness reduction and prevention treatments among older adults experiencing loneliness. Additional research is needed with a larger, more diverse sample to examine the relationship between loneliness and amyloid accumulation.", "source": "PubMed"}, {"chunk_id": "39434871_2", "pmid": "39434871", "title": "Higher amyloid is associated with greater loneliness among cognitively normal older adults during the COVID-19 pandemic.", "authors": "Kehrer-Dunlap A, Bollinger R, Chen SW et al.", "year": "2022", "journal": "F1000Research", "keywords": "Alzheimer disease, COVID-19, loneliness, preclinical Alzheimer disease", "chunk": "amyloid accumulation.", "source": "PubMed"}, {"chunk_id": "39010871_0", "pmid": "39010871", "title": "Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers.", "authors": "Kumar S, Earnest T, Yang B et al.", "year": "2024", "journal": "ArXiv", "keywords": "ATN biomarkers, AV1451 tau PET, AV45 amyloid PET, Alzheimer\u2019s disease, Disease Severity Index (DSI), MRI, abnormal deviations, heterogeneity, multimodal, normative modeling", "chunk": "Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers. We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET. Normative modeling estimated individual-level abnormal deviations in amyloid-positive individuals compared to amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels to assess intra-group heterogeneity. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN. Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression. Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.", "source": "PubMed"}, {"chunk_id": "39010871_1", "pmid": "39010871", "title": "Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers.", "authors": "Kumar S, Earnest T, Yang B et al.", "year": "2024", "journal": "ArXiv", "keywords": "ATN biomarkers, AV1451 tau PET, AV45 amyloid PET, Alzheimer\u2019s disease, Disease Severity Index (DSI), MRI, abnormal deviations, heterogeneity, multimodal, normative modeling", "chunk": "was associated with worse cognitive function and increased risk of disease progression. Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.", "source": "PubMed"}, {"chunk_id": "40034778_0", "pmid": "40034778", "title": "Clinical Progression on CDR-SB<sup>\u00a9</sup>: Progression Free Time at Each 0.5-unit Level in Dominantly Inherited and Sporadic Alzheimer's Disease Populations.", "authors": "Wang G, Li Y, McDade E et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer disease, CDR-SB, Progression-free time, clinically meaningful interpretation, disease progression model", "chunk": "CDR-SB is a reliable and clinically meaningful composite for assessing treatment effects in Alzheimer's disease (AD) clinical trials. Small CDR-SB differences at the end of a trial often lead to controversy in deriving clinically meaningful interpretations. We estimated progression-free time participants remained at each 0.5-unit CDR-SB increment in dominantly inherited AD (DIAD) and sporadic AD populations, evaluating its potential as an alternative measure of treatment effects. Progression-free time is longer at CDR-SB \u2264 2.0 (1-2 years) and shorter at CDR-SB \u2265 5 (0.33 or less) in the ADNI cohort. The DIAD cohort showed similar but shorter times. Using progression-free time, continuous lecanemab treatment for three years is estimated to delay disease progression by 0.7 years in the sporadic population. Progression-free time provides a benchmark for expressing clinical progression and treatment effects and can be applied particularly during open-label extensions and single-arm trials without placebo comparisons.", "source": "PubMed"}, {"chunk_id": "40034778_1", "pmid": "40034778", "title": "Clinical Progression on CDR-SB<sup>\u00a9</sup>: Progression Free Time at Each 0.5-unit Level in Dominantly Inherited and Sporadic Alzheimer's Disease Populations.", "authors": "Wang G, Li Y, McDade E et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer disease, CDR-SB, Progression-free time, clinically meaningful interpretation, disease progression model", "chunk": "time provides a benchmark for expressing clinical progression and treatment effects and can be applied particularly during open-label extensions and single-arm trials without placebo comparisons.", "source": "PubMed"}, {"chunk_id": "41038390_0", "pmid": "41038390", "title": "MUSASHI1 promotes tau phosphorylation by activating the p38 MAPK pathway.", "authors": "Li W, Ma B, Tian X et al.", "year": "2025", "journal": "Neurochemistry international", "keywords": "Alzheimer's disease (AD), Phosphorylation, RNA-Binding protein MUSASHI1 (MSI1), Tau, p38 MAPK", "chunk": "Aberrant phosphorylation of the Tau protein represents a critical event in the pathogenesis of Alzheimer's disease (AD); however, therapeutic interventions specifically targeting this modification remain limited. Therefore, a thorough understanding of the molecular mechanisms underlying Tau hyperphosphorylation is essential for the development of effective preventive and therapeutic strategies against AD. The RNA-binding protein MUSASHI1 (MSI1) is recognized for its significant role in neurodevelopment, and previous studies have reported its dysregulated overexpression in the brains of AD patients. In the current investigation, we demonstrate that MSI1 expression progressively increases in parallel with the advancement of Tau pathology in P301S transgenic mouse models. Furthermore, our findings suggest that MSI1 activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway, thereby promoting Tau phosphorylation. Additionally, we have identified two microtubule-associated proteins as novel potential interaction partners of MSI1 within neuronal cells. Collectively, these results reveal a previously uncharacterized mechanism that may contribute to aberrant", "source": "PubMed"}, {"chunk_id": "41038390_1", "pmid": "41038390", "title": "MUSASHI1 promotes tau phosphorylation by activating the p38 MAPK pathway.", "authors": "Li W, Ma B, Tian X et al.", "year": "2025", "journal": "Neurochemistry international", "keywords": "Alzheimer's disease (AD), Phosphorylation, RNA-Binding protein MUSASHI1 (MSI1), Tau, p38 MAPK", "chunk": "Additionally, we have identified two microtubule-associated proteins as novel potential interaction partners of MSI1 within neuronal cells. Collectively, these results reveal a previously uncharacterized mechanism that may contribute to aberrant Tau phosphorylation in AD, offering new directions for future research in this field.", "source": "PubMed"}, {"chunk_id": "35616643_0", "pmid": "35616643", "title": "Deep transfer learning-based fully automated detection and classification of Alzheimer's disease on brain MRI.", "authors": "Ghaffari H, Tavakoli H, Pirzad Jahromi G", "year": "2022", "journal": "The British journal of radiology", "keywords": "None", "chunk": "To employ different automated convolutional neural network (CNN)-based transfer learning (TL) methods for both binary and multiclass classification of Alzheimer's disease (AD) using brain MRI. Herein, we applied three popular pre-trained CNN models (ResNet101, Xception, and InceptionV3) using a fine-tuned approach of TL on 3D <i>T</i><sub>1</sub>-weighted brain MRI from a subset of ADNI dataset (<i>n</i> = 305 subjects). To evaluate power of TL, the aforementioned networks were also trained from scratch for performance comparison. Initially, Unet network segmentedthe MRI scans into characteristic components of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The proposed networks were trained and tested over the pre-processed and augmented segmented and whole images for both binary (NC/AD + progressive mild cognitive impairment (pMCI)+stable MCI (sMCI)) and 4-class (AD/pMCI/sMCI/NC) classification. Also, two independent test sets from the OASIS (<i>n</i> = 30) and AIBL (<i>n</i> = 60) datasets were used to externally assess the performance", "source": "PubMed"}, {"chunk_id": "35616643_1", "pmid": "35616643", "title": "Deep transfer learning-based fully automated detection and classification of Alzheimer's disease on brain MRI.", "authors": "Ghaffari H, Tavakoli H, Pirzad Jahromi G", "year": "2022", "journal": "The British journal of radiology", "keywords": "None", "chunk": "MCI (sMCI)) and 4-class (AD/pMCI/sMCI/NC) classification. Also, two independent test sets from the OASIS (<i>n</i> = 30) and AIBL (<i>n</i> = 60) datasets were used to externally assess the performance of the proposed algorithms. The proposed TL-based CNN models achieved better performance compared to the training CNN models from scratch. On the ADNI test set, InceptionV3-TL achieved the highest accuracy of 93.75% and AUC of 92.0% for binary classification, as well as the highest accuracy of 93.75% and AUC of 96.0% for multiclass classification of AD on the whole images. On the OASIS test set, InceptionV3-TL outperformed two other models by achieving 93.33% accuracy with 93.0% AUC in binary classification of AD on the whole images. On the AIBL test set, InceptionV3-TL also outperformed two other models in both binary and multiclass classification tasks on the whole MR images and achieved accuracy/AUC of 93.33%/95.0% and 90.0%/93.0%, respectively. The GM segment", "source": "PubMed"}, {"chunk_id": "35616643_2", "pmid": "35616643", "title": "Deep transfer learning-based fully automated detection and classification of Alzheimer's disease on brain MRI.", "authors": "Ghaffari H, Tavakoli H, Pirzad Jahromi G", "year": "2022", "journal": "The British journal of radiology", "keywords": "None", "chunk": "set, InceptionV3-TL also outperformed two other models in both binary and multiclass classification tasks on the whole MR images and achieved accuracy/AUC of 93.33%/95.0% and 90.0%/93.0%, respectively. The GM segment as input provided the highest performance in both binary and multiclass classification of AD, as compared to the WM and CSF segments. This study demonstrates the potential of applying deep TL approach for automated detection and classification of AD using brain MRI with high accuracy and robustness across internal and external test data, suggesting that these models can possibly be used as a supportive tool to assist clinicians in creating objective opinion and correct diagnosis. We used CNN-based TL approaches and the augmentation techniques to overcome the insufficient data problem. Our study provides evidence that deep TL algorithms can be used for both binary and multiclass classification of AD with high accuracy.", "source": "PubMed"}, {"chunk_id": "35616643_3", "pmid": "35616643", "title": "Deep transfer learning-based fully automated detection and classification of Alzheimer's disease on brain MRI.", "authors": "Ghaffari H, Tavakoli H, Pirzad Jahromi G", "year": "2022", "journal": "The British journal of radiology", "keywords": "None", "chunk": "Our study provides evidence that deep TL algorithms can be used for both binary and multiclass classification of AD with high accuracy.", "source": "PubMed"}, {"chunk_id": "41361485_0", "pmid": "41361485", "title": "Respiratory complex I deficiency caused by a novel multi-exonic PUS1 deletion.", "authors": "Yuan JH, Higuchi Y, Ando M et al.", "year": "2025", "journal": "Journal of human genetics", "keywords": "None", "chunk": "Myopathy, lactic acidosis, and sideroblastic anemia type 1 (MLASA1) is an extremely rare mitochondrial disorder caused by biallelic pathogenic variants in PUS1, which encodes a mitochondrial tRNA pseudouridine synthase essential for mitochondrial protein synthesis. We describe two affected siblings presenting with progressive myopathy, lactic acidosis, sideroblastic anemia, short stature, developmental delay, and mild cognitive impairment. Depth-based copy number variation analysis of whole-exome sequencing data revealed a novel homozygous multi-exonic deletion in PUS1. The deletion breakpoints were defined by Sanger sequencing as a 9964 bp deletion spanning part of intron 3 through exons 4-6 and extending into the 3' untranslated region, resulting in complete loss of the C-terminal coding region. Skeletal muscle histology demonstrated ragged red fibers, whereas immunohistochemistry showed a selective and near-complete loss of NDUFB8, indicating impaired assembly of respiratory chain complex I. A systematic review of previously reported MLASA1 cases revealed marked clinical heterogeneity, including frequent developmental delay,", "source": "PubMed"}, {"chunk_id": "41361485_1", "pmid": "41361485", "title": "Respiratory complex I deficiency caused by a novel multi-exonic PUS1 deletion.", "authors": "Yuan JH, Higuchi Y, Ando M et al.", "year": "2025", "journal": "Journal of human genetics", "keywords": "None", "chunk": "selective and near-complete loss of NDUFB8, indicating impaired assembly of respiratory chain complex I. A systematic review of previously reported MLASA1 cases revealed marked clinical heterogeneity, including frequent developmental delay, dysmorphic features, and multi-organ involvement. These findings expand the genotypic and phenotypic landscape of MLASA1 and highlight the diagnostic value of copy number variation analysis in unresolved mitochondrial disorders. The impairment of complex I underscores the particular vulnerability of translation-dependent respiratory chain components in PUS1-related diseases.", "source": "PubMed"}, {"chunk_id": "40374237_0", "pmid": "40374237", "title": "A fully automated paper-based smartphone-assisted microfluidic chemiluminescence sample to result immunoassay platform.", "authors": "Sun J, Duan S, Xu W et al.", "year": "2025", "journal": "Analytica chimica acta", "keywords": "Automation, Chemiluminescence, Microfluidic paper-based analytical device, POCT, Smartphone", "chunk": "In recent years, adapting immunoassay technologies for point-of-care testing (POCT) to enable low-cost, on-site diagnostics has gained great attention. Among the various approaches to achieving this goal, microfluidic paper-based analytical devices (\u03bcPADs) have emerged as a promising platform. These devices are particularly appealing due to their low cost, simple procedures, and minimal sample consumption. Among the detection methods used in \u03bcPADs, chemiluminescence (CL) has attracted widespread attention for its high sensitivity. However, existing CL immunoassays often require expensive detection equipment and extensive manual operation, which limits their use in resource-poor areas or where trained personnel are lacking. In this study, we developed a newly designed \u03bcPAD for CL immunoassays, leveraging smartphone-based image capture, valve-regulated reaction process, and app-driven result analysis to enable fully automated detection. Each element of the device was highly integrated and designed for programmable operation, enhancing reliability and stability. An app was developed to manage the entire", "source": "PubMed"}, {"chunk_id": "40374237_1", "pmid": "40374237", "title": "A fully automated paper-based smartphone-assisted microfluidic chemiluminescence sample to result immunoassay platform.", "authors": "Sun J, Duan S, Xu W et al.", "year": "2025", "journal": "Analytica chimica acta", "keywords": "Automation, Chemiluminescence, Microfluidic paper-based analytical device, POCT, Smartphone", "chunk": "to enable fully automated detection. Each element of the device was highly integrated and designed for programmable operation, enhancing reliability and stability. An app was developed to manage the entire process, maximizing the convenience of smartphones. The device's effectiveness was calibrated using rabbit IgG as a model, achieving a limit of detection (LOD) of 62.4 pg/mL, which represents an improvement compared to the colorimetric ELISA method with a LOD of 3 ng/mL (20pM). We then applied the device to detect tau protein, a biomarker associated with Alzheimer's disease and achieved a detection limit of 26.1 pg/mL, which is lower than the clinical cut-off value. Our device achieves complete automation and integrates the versatility of \u03bcPADs with the precision of CL immunoassays, offering an effective and accessible solution for POCT. By incorporating a user-friendly smartphone interface, it simplifies operation while maintain detection sensitivity, providing a practical and valuable improvement in the", "source": "PubMed"}, {"chunk_id": "40374237_2", "pmid": "40374237", "title": "A fully automated paper-based smartphone-assisted microfluidic chemiluminescence sample to result immunoassay platform.", "authors": "Sun J, Duan S, Xu W et al.", "year": "2025", "journal": "Analytica chimica acta", "keywords": "Automation, Chemiluminescence, Microfluidic paper-based analytical device, POCT, Smartphone", "chunk": "immunoassays, offering an effective and accessible solution for POCT. By incorporating a user-friendly smartphone interface, it simplifies operation while maintain detection sensitivity, providing a practical and valuable improvement in the development of POCT technologies.", "source": "PubMed"}, {"chunk_id": "35581440_0", "pmid": "35581440", "title": "Alzheimer disease neuropathology in a patient previously treated with aducanumab.", "authors": "Plowey ED, Bussiere T, Rajagovindan R et al.", "year": "2022", "journal": "Acta neuropathologica", "keywords": "Alzheimer disease, Amyloid PET, Amyloid beta, Case report, Immunotherapy, Neuropathology", "chunk": "Amyloid beta (A\u03b2) plaque is a defining pathologic feature of Alzheimer disease (AD). Aducanumab, a monoclonal IgG1 that selectively binds aggregated species of A\u03b2, has been shown by amyloid positron emission tomography (Amyloid PET) to reduce A\u03b2 plaques in patients with prodromal and mild AD. This is the first autopsy report of the AD neuropathology in a patient previously treated with aducanumab. The patient was an 84-year-old woman who was randomized to the placebo arm of the PRIME Phase 1b study (221AD103). The patient progressed to moderate dementia (MMSE = 14/30), beyond the targeted early AD treatment stage, before receiving aducanumab in the long-term extension (LTE). The patient then received 32 monthly doses of aducanumab, titrated up to 6 mg/kg, for a cumulative dose of 186 mg/kg. In the LTE, Amyloid PET scans demonstrated robust A\u03b2 plaque reduction, from a composite standard uptake value ratio (SUVR) of 1.5 at screening", "source": "PubMed"}, {"chunk_id": "35581440_1", "pmid": "35581440", "title": "Alzheimer disease neuropathology in a patient previously treated with aducanumab.", "authors": "Plowey ED, Bussiere T, Rajagovindan R et al.", "year": "2022", "journal": "Acta neuropathologica", "keywords": "Alzheimer disease, Amyloid PET, Amyloid beta, Case report, Immunotherapy, Neuropathology", "chunk": "for a cumulative dose of 186 mg/kg. In the LTE, Amyloid PET scans demonstrated robust A\u03b2 plaque reduction, from a composite standard uptake value ratio (SUVR) of 1.5 at screening to < 1.1 at 56 weeks post-aducanumab dosing. MRI examinations were negative for amyloid-related imaging abnormalities (ARIA). She passed away in hospice care 4 months after her last dose of aducanumab. The postmortem neuropathologic examination confirmed AD neuropathologic changes. A\u03b2 and IBA1 immunohistochemistry assays demonstrated sparse residual A\u03b2 plaque engaged by amoeboid reactive microglia. Phospho-Tau (pTau) immunohistochemistry demonstrated neocortical neurofibrillary degeneration (Braak stage V, NIA/AA Stage B3). However, the density of pTau neuropathology, including neuritic plaque pTau (NP-Tau), appeared lower in the PRIME LTE Patient compared to a reference cohort of untreated Braak stage V-VI, NIA/AA Stage B3 AD cases. Taken together, this case report is the first to provide Amyloid PET and neuropathologic evidence substantiating the impact of aducanumab", "source": "PubMed"}, {"chunk_id": "35581440_2", "pmid": "35581440", "title": "Alzheimer disease neuropathology in a patient previously treated with aducanumab.", "authors": "Plowey ED, Bussiere T, Rajagovindan R et al.", "year": "2022", "journal": "Acta neuropathologica", "keywords": "Alzheimer disease, Amyloid PET, Amyloid beta, Case report, Immunotherapy, Neuropathology", "chunk": "of untreated Braak stage V-VI, NIA/AA Stage B3 AD cases. Taken together, this case report is the first to provide Amyloid PET and neuropathologic evidence substantiating the impact of aducanumab to reduce A\u03b2 plaque neuropathology in a patient with AD. Furthermore, this report underscores the critical importance of autopsy neuropathology studies to augment our understanding of aducanumab's mechanism of action and impact on AD biomarkers.", "source": "PubMed"}, {"chunk_id": "41622456_0", "pmid": "41622456", "title": "Brain organoids as models of extracellular vesicle-mediated human neural communication.", "authors": "La Rosa G, Pascale E, Iazzetta MR et al.", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyloid-\u03b2, brain organoid, cell-cell communication, extracellular vesicle, neurodegeneration, neurodevelopment, pluripotent stem cell, \u03b1-synuclein", "chunk": "Cellular communication orchestrates human brain development through complex interactions involving adhesion molecules, signaling ligands, extracellular matrix, and extracellular vesicles. While intrinsic genetic programs governing neural differentiation are well characterized, the roles of extrinsic, non-cell-autonomous signaling, particularly extracellularmediated communication, remain poorly understood. Here, we review recent advances in three-dimensional brain organoids derived from human pluripotent stem cells as physiologically relevant models that recapitulate key aspects of human neurodevelopment, enabling detailed study of extracellular vesicle-mediated intracellular signaling. We highlight how organoid systems facilitate the investigation of extracellular vesicle cargo dynamics and their influence on neural cell fate, migration, and circuit assembly, as well as their involvement in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. These insights show the potential of brain organoids to unravel complex cellular interactions and inform biomarkers discovery and therapeutic strategies for neurological diseases.", "source": "PubMed"}, {"chunk_id": "41622456_1", "pmid": "41622456", "title": "Brain organoids as models of extracellular vesicle-mediated human neural communication.", "authors": "La Rosa G, Pascale E, Iazzetta MR et al.", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, Parkinson\u2019s disease, amyloid-\u03b2, brain organoid, cell-cell communication, extracellular vesicle, neurodegeneration, neurodevelopment, pluripotent stem cell, \u03b1-synuclein", "chunk": "organoids to unravel complex cellular interactions and inform biomarkers discovery and therapeutic strategies for neurological diseases.", "source": "PubMed"}, {"chunk_id": "32206776_0", "pmid": "32206776", "title": "Plasma tau, neurofilament light chain and amyloid-\u03b2 levels and risk of dementia; a population-based cohort study.", "authors": "de Wolf F, Ghanbari M, Licher S et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, A\u03b242, NfL, dementia, plasma biomarkers", "chunk": "CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-\u03b2, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-\u03b240 and amyloid-\u03b242 were measured using the Simoa NF-light\u00ae and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE \u03b54 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects.", "source": "PubMed"}, {"chunk_id": "32206776_1", "pmid": "32206776", "title": "Plasma tau, neurofilament light chain and amyloid-\u03b2 levels and risk of dementia; a population-based cohort study.", "authors": "de Wolf F, Ghanbari M, Licher S et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, A\u03b242, NfL, dementia, plasma biomarkers", "chunk": "\u03b54 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-\u03b242 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P < 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P < 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P < 0.0001]. Combining the lowest quartile group of amyloid-\u03b242 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5", "source": "PubMed"}, {"chunk_id": "32206776_2", "pmid": "32206776", "title": "Plasma tau, neurofilament light chain and amyloid-\u03b2 levels and risk of dementia; a population-based cohort study.", "authors": "de Wolf F, Ghanbari M, Licher S et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, A\u03b242, NfL, dementia, plasma biomarkers", "chunk": "1.50 (95% CI, 1.26-1.78); P < 0.0001]. Combining the lowest quartile group of amyloid-\u03b242 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P < 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P < 0.0001], compared to the highest quartile group of amyloid-\u03b242 and lowest of NfL. Total-tau and amyloid-\u03b240 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P < 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-\u03b242 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-\u03b242", "source": "PubMed"}, {"chunk_id": "32206776_3", "pmid": "32206776", "title": "Plasma tau, neurofilament light chain and amyloid-\u03b2 levels and risk of dementia; a population-based cohort study.", "authors": "de Wolf F, Ghanbari M, Licher S et al.", "year": "2020", "journal": "Brain : a journal of neurology", "keywords": "Alzheimer\u2019s disease, A\u03b242, NfL, dementia, plasma biomarkers", "chunk": "to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-\u03b242 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-\u03b242 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.", "source": "PubMed"}, {"chunk_id": "41462694_0", "pmid": "41462694", "title": "Luteolin in Safflower Leaves Suppresses Microglial Inflammation Through FOXO3-Mediated <i>Trem2</i> Transcription.", "authors": "Zhang T, Zhang S, Ma J et al.", "year": "2025", "journal": "Antioxidants (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, luteolin, microglia, safflower leaves, triggering receptor expressed on myeloid cells 2", "chunk": "Neuroinflammation driven by microglial activation is a hallmark of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial inflammation, yet strategies to modulate its expression remain limited. Safflower leaves, a vegetable rich in flavonoids-particularly luteolin-were previously shown to attenuate neuroinflammation, reduce oxidative stress, and ameliorate cognitive impairment in APP/PS1 mice. Here, we demonstrated that safflower leaves inhibit microglial inflammation and upregulate TREM2 in APP/PS1 mice. Luteolin, the major active flavonoid in safflower leaves, exerted anti-inflammatory effects in lipopolysaccharides (LPS)-activated microglia. Mechanistically, luteolin enhanced <i>Trem2</i> transcription by activating forkhead box protein O3 (FOXO3), a novel transcriptional regulator of <i>Trem2</i> identified through promoter analysis. FOXO3 binding to the <i>Trem2</i> promoter was essential for this regulation, and luteolin further promoted FOXO3 nuclear translocation. Crucially, <i>Trem2</i> knockdown attenuated luteolin's anti-inflammatory effects, confirming TREM2 as a key mediator. Overall, our study reveals the FOXO3-TREM2 axis as a", "source": "PubMed"}, {"chunk_id": "41462694_1", "pmid": "41462694", "title": "Luteolin in Safflower Leaves Suppresses Microglial Inflammation Through FOXO3-Mediated <i>Trem2</i> Transcription.", "authors": "Zhang T, Zhang S, Ma J et al.", "year": "2025", "journal": "Antioxidants (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, luteolin, microglia, safflower leaves, triggering receptor expressed on myeloid cells 2", "chunk": "regulation, and luteolin further promoted FOXO3 nuclear translocation. Crucially, <i>Trem2</i> knockdown attenuated luteolin's anti-inflammatory effects, confirming TREM2 as a key mediator. Overall, our study reveals the FOXO3-TREM2 axis as a potential therapeutic target for neuroinflammation and highlights luteolin present in safflower leaves as a candidate dietary intervention for AD, providing new mechanistic insights into the anti-inflammatory activity of this natural antioxidant.", "source": "PubMed"}, {"chunk_id": "41701723_0", "pmid": "41701723", "title": "Early diagnosis of Alzheimer's Disease: Graph theoretical analysis of cerebellar network features based on 18F-AV45 PET.", "authors": "Li R, Jiang S, Pi Z et al.", "year": "2026", "journal": "PloS one", "keywords": "None", "chunk": "Pathological and neuroimaging changes in the cerebellum of Alzheimer's disease (AD) patients have been well documented. However, the changes in cerebellar amyloid plaque deposition connectivity networks during AD progression based on positron emission tomography (PET) imaging remain unclear. We selected 18F-florbetapir PET (18F-AV45 PET) imaging data from the Alzheimer's disease neuroimaging initiative (ADNI) dataset (n = 612) and employed graph theoretical analysis to examine amyloid plaque deposition connectivity, comparing the connectivity differences across cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD groups. In addition, we combined graph theoretical features with the standardized uptake value ratio (SUVR) of regions of interest and applied them to machine learning models for the early diagnosis of AD. As cognitive decline progressed, significant changes in cerebellar network connectivity were observed across groups. Regarding local connectivity, changes in betweenness centrality were evident in multiple cerebellar regions at different cognitive", "source": "PubMed"}, {"chunk_id": "41701723_1", "pmid": "41701723", "title": "Early diagnosis of Alzheimer's Disease: Graph theoretical analysis of cerebellar network features based on 18F-AV45 PET.", "authors": "Li R, Jiang S, Pi Z et al.", "year": "2026", "journal": "PloS one", "keywords": "None", "chunk": "As cognitive decline progressed, significant changes in cerebellar network connectivity were observed across groups. Regarding local connectivity, changes in betweenness centrality were evident in multiple cerebellar regions at different cognitive stages. Cerebellar amyloid networks revealed early changes in amyloid plaque deposition connectivity. The machine learning model achieved an area under the curve (AUC) of 0.950 for distinguishing AD from CN, 0.995 for CN vs. EMCI, 0.964 for EMCI vs. LMCI and 0.632 for LMCI vs. AD. These findings provide new insights into the cerebellar pathological features of AD and highlight the potential of this approach for early identification and prediction of AD progression.", "source": "PubMed"}, {"chunk_id": "41306975_0", "pmid": "41306975", "title": "Genetic knockdown of DYRK1A attenuates cognitive impairment, A\u03b2 pathology, tauopathy and neuroinflammatory responses in mouse models of AD.", "authors": "Lee HJ, Kang S, Lee YJ et al.", "year": "2025", "journal": "Frontiers in immunology", "keywords": "Alzheimer\u2019s disease, DYRK1A, amyloid beta, cognitive function, neuroinflammation, tauopathy", "chunk": "Dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is associated with the pathoprogression of neurodevelopmental and neurodegenerative disorders. However, the effects of direct genetic manipulation of DYRK1A in the brain on cognitive function, neuroinflammation and Alzheimer's disease (AD) pathology and underlying molecular mechanisms have not been fully investigated. To determine whether overexpressing or knocking down DYRK1A expression directly in the brain affects cognitive function, neuroinflammation and AD pathology, adeno-associated viruses (AAVs) were injected into the hippocampus of wild-type (WT), 5xFAD, and PS19 mice. Then, cognitive function was assessed via Y-maze and novel object recognition (NOR) tests, and neuroinflammatory responses and AD pathologies were analyzed by real-time PCR, Western blotting, immunofluorescence staining, AD-associated protein activity assays and ELISA. In WT mice, hippocampal DYRK1A overexpression significantly reduced short-term spatial/recognition memory and SynGAP expression while increasing p-P38 levels. Conversely, in amyloid-beta (A\u03b2)-overexpressing 5xFAD mice, hippocampal DYRK1A knockdown improved short-term spatial/recognition memory and significantly increased", "source": "PubMed"}, {"chunk_id": "41306975_1", "pmid": "41306975", "title": "Genetic knockdown of DYRK1A attenuates cognitive impairment, A\u03b2 pathology, tauopathy and neuroinflammatory responses in mouse models of AD.", "authors": "Lee HJ, Kang S, Lee YJ et al.", "year": "2025", "journal": "Frontiers in immunology", "keywords": "Alzheimer\u2019s disease, DYRK1A, amyloid beta, cognitive function, neuroinflammation, tauopathy", "chunk": "DYRK1A overexpression significantly reduced short-term spatial/recognition memory and SynGAP expression while increasing p-P38 levels. Conversely, in amyloid-beta (A\u03b2)-overexpressing 5xFAD mice, hippocampal DYRK1A knockdown improved short-term spatial/recognition memory and significantly increased CaMKII\u03b1 and CREB phosphorylation. Moreover, hippocampal DYRK1A knockdown in 5xFAD mice significantly suppressed mRNA levels of proinflammatory cytokines and markers of AD-associated reactive astrocytes (RAs), disease-associated microglia (DAMs), and RA-DAM interactions. However, hippocampal DYRK1A overexpression in 5xFAD mice increased mRNA levels of the proinflammatory cytokine IL-1\u03b2, RA markers and the microglial marker Iba-1. Interestingly, hippocampal DYRK1A knockdown in 5xFAD mice significantly increased levels of the anti-oxidative/inflammatory molecule HO-1 without altering p-STAT3/p-NF-\u03baB levels. By contrast, hippocampal DYRK1A overexpression in 5xFAD mice enhanced STAT3/NF-\u03baB phosphorylation but did not affect ROS levels. Importantly, hippocampal DYRK1A knockdown in 5xFAD mice significantly reduced A\u03b2 plaque number, soluble A\u03b240 levels, and soluble/insoluble A\u03b242 levels by suppressing \u03b2-secretase BACE1 activity but not tau hyperphosphorylation. Finally, hippocampal DYRK1A", "source": "PubMed"}, {"chunk_id": "41306975_2", "pmid": "41306975", "title": "Genetic knockdown of DYRK1A attenuates cognitive impairment, A\u03b2 pathology, tauopathy and neuroinflammatory responses in mouse models of AD.", "authors": "Lee HJ, Kang S, Lee YJ et al.", "year": "2025", "journal": "Frontiers in immunology", "keywords": "Alzheimer\u2019s disease, DYRK1A, amyloid beta, cognitive function, neuroinflammation, tauopathy", "chunk": "hippocampal DYRK1A knockdown in 5xFAD mice significantly reduced A\u03b2 plaque number, soluble A\u03b240 levels, and soluble/insoluble A\u03b242 levels by suppressing \u03b2-secretase BACE1 activity but not tau hyperphosphorylation. Finally, hippocampal DYRK1A knockdown in PS19 mice [a model of AD that overexpresses human mutant tau (P301S)] selectively decreased insoluble tau hyperphosphorylation at Ser396 and Ser404 and alleviated proinflammatory responses/glial-associated neuroinflammatory dynamics. Taken together, our data indicate that DYRK1A modulates cognitive function, neuroinflammation, and AD pathology (A\u03b2 and tauopathy) in mouse models of AD and/or WT mice and support DYRK1A as a potential therapeutic target for AD.", "source": "PubMed"}, {"chunk_id": "39544642_0", "pmid": "39544642", "title": "Understanding the Association Between Type 2 Diabetes Mellitus and Cognitive Impairment: A Single-centre Experience.", "authors": "Suvvari TK, Kali CS", "year": "2026", "journal": "Annals of neurosciences", "keywords": "Diabetes mellitus, HbA1c, Montreal Cognitive Assessment (MoCA) test, cognitive function, cognitive impairment", "chunk": "The global prevalence of diabetes mellitus has been increasing, leading to a rise in morbidity associated with the disease. While diabetic nephropathy, retinopathy and neuropathy are routinely screened in diabetic patients, the cognitive decline associated with diabetes is often overlooked. The purpose of this study is to investigate the prevalence of cognitive impairment and its associated risk factors among patients with type 2 diabetes mellitus (T2DM). An observational cross-sectional study was conducted for two months. The Montreal Cognitive Assessment (MoCA) test, which consists of 30 questions, was used to assess cognitive function. In-depth clinical history along with glycaemic parameters were collected. The chi-square test was used to find out the association between categorical variables and cognitive impairment. Pearson's correlation test was performed to determine the correlation between glycaemic parameters and cognitive impairment. A total of 96 patients participated in the study. The mean HbA1c (%) was 9.08 \u00b1 1.73, and", "source": "PubMed"}, {"chunk_id": "39544642_1", "pmid": "39544642", "title": "Understanding the Association Between Type 2 Diabetes Mellitus and Cognitive Impairment: A Single-centre Experience.", "authors": "Suvvari TK, Kali CS", "year": "2026", "journal": "Annals of neurosciences", "keywords": "Diabetes mellitus, HbA1c, Montreal Cognitive Assessment (MoCA) test, cognitive function, cognitive impairment", "chunk": "was performed to determine the correlation between glycaemic parameters and cognitive impairment. A total of 96 patients participated in the study. The mean HbA1c (%) was 9.08 \u00b1 1.73, and the mean MoCA score was 25.14 \u00b1 1.63. Mild cognitive impairment (MCI) was noted in 56% patients. Attention was the most common cognitive domain defect found in all MCI patients-100%. Delayed recall and memory were the second most common cognitive domain defect found-92.5%. Higher HbA1c, high FBS and higher PPBS were found to be statistically associated with MCI. A negative correlation was found between glycaemic parameters (HbA1c, FBS and PPBS levels) and MoCA scores. More than half of our study participants reported mild cognitive impairment. It highlights the need for the implementation of routine cognitive testing for diabetes patients. There is a strong negative correlation between MoCA scores and parameters of glycaemic control; higher levels of HbA1c, FBS, and PPBS", "source": "PubMed"}, {"chunk_id": "39544642_2", "pmid": "39544642", "title": "Understanding the Association Between Type 2 Diabetes Mellitus and Cognitive Impairment: A Single-centre Experience.", "authors": "Suvvari TK, Kali CS", "year": "2026", "journal": "Annals of neurosciences", "keywords": "Diabetes mellitus, HbA1c, Montreal Cognitive Assessment (MoCA) test, cognitive function, cognitive impairment", "chunk": "the implementation of routine cognitive testing for diabetes patients. There is a strong negative correlation between MoCA scores and parameters of glycaemic control; higher levels of HbA1c, FBS, and PPBS are seen in people with a lower MoCA score, indicating mild cognitive impairment. Further studies are needed to evaluate whether improving glucose levels helps in improving cognition or not.", "source": "PubMed"}, {"chunk_id": "41499937_0", "pmid": "41499937", "title": "Herba Patriniae with probiotics targets Escherichia fergusonii and the 5-hydroxytryptophan-trimethylamine N-oxide axis in Parkinson's disease.", "authors": "Wu X, Zhang T, Feng J et al.", "year": "2026", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "keywords": "Butyrate, Enterotype, Escherichia fergusonii, Faecalibacterium prausnitzii, Lactiplantibacillus plantarum, TMAO", "chunk": "Parkinson's disease (PD) exhibits a distinct gut microbiota and microbial metabolites, with specific enterotypes potentially influencing disease susceptibility. Current research lacks systematic comparisons of different enterotypes in PD susceptibility and targeted intervention efficacy. This study identifies their gut microbiota-metabolite biomarkers and validates a \"probiotic plus herbal medicine\" intervention in vitro to explore enterotype-stratified precision strategies for PD prevention and treatment. This study aimed to identify a high-risk enterotype for PD and its associated microbial and metabolic signatures using public metagenomic data. Furthermore, we evaluated the therapeutic efficacy of a combination therapy, comprising Patrinia scabiosaefolia Fisch (Herba Patriniae; HP) extract and the probiotics, Faecalibacterium prausnitzii and Lactiplantibacillus plantarum (F.l-HP), in a PD-relevant in vitro model. Public metagenomic data from PD patients and healthy controls (HC) were analyzed to characterize enterotypes. An in vitro gut-brain axis (GBA) model was established by co-culturing PC12 neuronal cells and Caco-2 intestinal epithelial cells to validate", "source": "PubMed"}, {"chunk_id": "41499937_1", "pmid": "41499937", "title": "Herba Patriniae with probiotics targets Escherichia fergusonii and the 5-hydroxytryptophan-trimethylamine N-oxide axis in Parkinson's disease.", "authors": "Wu X, Zhang T, Feng J et al.", "year": "2026", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "keywords": "Butyrate, Enterotype, Escherichia fergusonii, Faecalibacterium prausnitzii, Lactiplantibacillus plantarum, TMAO", "chunk": "and healthy controls (HC) were analyzed to characterize enterotypes. An in vitro gut-brain axis (GBA) model was established by co-culturing PC12 neuronal cells and Caco-2 intestinal epithelial cells to validate the pathogenic role of Escherichia fergusonii. The effects of the F.l-HP combination therapy were then assessed on bacterial growth, key metabolites (5-hydroxytryptophan (5-HTP), trimethylamine N-oxide (TMAO), butyrate), neuroinflammation, oxidative stress, mitochondrial function, and gut barrier integrity, with a focus on the underlying p-Akt and p-AMPK\u03b1 signaling pathways. The Bacteroidaceae enterotype (ET-B) was identified as a high-risk enterotype for PD, characterized by an enrichment of E. fergusonii. This bacterium was associated with the consumption of neuroprotective 5-HTP and the production of pro-inflammatory TMAO. The F.l-HP combination therapy significantly suppressed the growth of E. fergusonii while promoting the proliferation of beneficial probiotics. This intervention restored metabolic balance by reducing 5-HTP consumption and TMAO production and increasing butyrate levels. Consequently, F.l-HP treatment alleviated", "source": "PubMed"}, {"chunk_id": "41499937_2", "pmid": "41499937", "title": "Herba Patriniae with probiotics targets Escherichia fergusonii and the 5-hydroxytryptophan-trimethylamine N-oxide axis in Parkinson's disease.", "authors": "Wu X, Zhang T, Feng J et al.", "year": "2026", "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology", "keywords": "Butyrate, Enterotype, Escherichia fergusonii, Faecalibacterium prausnitzii, Lactiplantibacillus plantarum, TMAO", "chunk": "of E. fergusonii while promoting the proliferation of beneficial probiotics. This intervention restored metabolic balance by reducing 5-HTP consumption and TMAO production and increasing butyrate levels. Consequently, F.l-HP treatment alleviated neuroinflammation and oxidative stress in neuronal cells, restoring mitochondrial function via the p-Akt pathway. In intestinal cells, it enhanced gut barrier integrity by upregulating zonula occludens-1 expression and activating p-AMPK\u03b1 signaling. E. fergusonii may participate in a 5-HTP-TMAO metabolic axis potentially linked to PD risk. F.l-HP intervention suppressed E. fergusonii activity, reduced 5-HTP consumption and TMAO production, modulated Akt and AMPK\u03b1 signaling pathway, and alleviated neuroinflammation while enhancing intestinal barrier integrity.", "source": "PubMed"}, {"chunk_id": "41168263_0", "pmid": "41168263", "title": "Liver dysfunction triggers early Alzheimer's pathology in an adult rat model of chronic liver disease.", "authors": "Braissant O, McLin VA, Sessa D et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Chronic liver disease, Neurodegeneration, Neurofilaments, Neurometabolism, Tau-bodies", "chunk": "Emerging evidence links liver dysfunction to Alzheimer's disease (AD), though few studies have investigated this connection. While cirrhosis is associated with cognitive impairment, its underlying mechanisms remain poorly understood. This study aimed to assess the presence of central nervous system (CNS) markers of Alzheimer's disease in a rat model of chronic liver disease. Standard histochemical techniques were employed, including Congo red staining for amyloid-\u03b2 (A\u03b2) and Gallyas silver staining for tau pathology. Immunohistochemistry was used to evaluate changes in aquaporin (Aqp1, Aqp4, Aqp9) expression and astrocytic glial fibrillary acidic protein (GFAP) levels. Furthermore, blood concentrations of neurodegeneration markers, neurofilament light chain (NfL), A\u03b2, phosphorylated tau (p-tau), total tau (t-tau), GFAP, and myelin oligodendrocyte glycoprotein (MOG), along with bile acids, were quantified and compared between BDL and SHAM control groups to investigate potential systemic correlates of CNS pathology. CNS analysis revealed the presence of intracellular amyloid-\u03b2 (iA\u03b2) and abnormal tau aggregates", "source": "PubMed"}, {"chunk_id": "41168263_1", "pmid": "41168263", "title": "Liver dysfunction triggers early Alzheimer's pathology in an adult rat model of chronic liver disease.", "authors": "Braissant O, McLin VA, Sessa D et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Chronic liver disease, Neurodegeneration, Neurofilaments, Neurometabolism, Tau-bodies", "chunk": "quantified and compared between BDL and SHAM control groups to investigate potential systemic correlates of CNS pathology. CNS analysis revealed the presence of intracellular amyloid-\u03b2 (iA\u03b2) and abnormal tau aggregates (pre-tangle/tangle stages), consistent with early AD pathology. Additionally, alterations in aquaporin water channels and astrocytic GFAP expression were observed. Peripheral blood analysis showed significant changes in neurodegeneration markers (NfL, A\u03b2, p-tau, t-tau, GFAP, MOG) and bile acid profiles, reinforcing the systemic nature of neuroinflammatory processes in liver disease. Our findings emphasize liver failure as a significant factor in cognitive decline and increased AD risk. The study advocates for incorporating liver function screening into the diagnostic workup of patients with dementia.", "source": "PubMed"}, {"chunk_id": "41823065_0", "pmid": "41823065", "title": "Estimating cognitive function score from mild cognitive impairment to moderate dementia using a hybrid model combining plasma biomarkers with electroencephalogram signal.", "authors": "Chen GW, Liu YH, Pan CC et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cognitive function, dementia, electroencephalography, machine learning, plasma biomarker", "chunk": "BackgroundPredicting cognitive function across dementia stages remains challenging. Plasma biomarkers and electroencephalogram (EEG) features may provide complementary information, but their combined predictive value requires further study.ObjectiveTo evaluate the feasibility of integrating plasma biomarkers and EEG features to predict cognitive function in dementia and examine their correlations.MethodsFrom September 2023 to October 2024, 75 patients from two medical centers with mild cognitive impairment, mild dementia, or moderate dementia were enrolled. Resting-state 19-channel EEG data yielded 2737 time-frequency and connectivity features. Plasma biomarkers included tau, p-Tau181, A\u03b2<sub>1-42</sub>, neurofilament light chain (NfL), brain-derived neurotrophic factor, apolipoprotein E genotype, and glial fibrillary acidic protein. Cognitive function was assessed using Cognitive Abilities Screening Instrument (CASI), Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Sum of Boxes. Machine learning models were developed using plasma-only, EEG-only, and hybrid approaches.ResultsNfL was negatively correlated with CASI (t = -2.059, p < 0.05). Several EEG features showed moderate", "source": "PubMed"}, {"chunk_id": "41823065_1", "pmid": "41823065", "title": "Estimating cognitive function score from mild cognitive impairment to moderate dementia using a hybrid model combining plasma biomarkers with electroencephalogram signal.", "authors": "Chen GW, Liu YH, Pan CC et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cognitive function, dementia, electroencephalography, machine learning, plasma biomarker", "chunk": "Sum of Boxes. Machine learning models were developed using plasma-only, EEG-only, and hybrid approaches.ResultsNfL was negatively correlated with CASI (t = -2.059, p < 0.05). Several EEG features showed moderate correlations with cognitive measures and plasma biomarkers, with delta-band relative power between left frontal and temporal regions (F7-FT7) showing the strongest correlation with MoCA. The hybrid model achieved the best performance, with R<sup>2</sup> > 0.74 across all cognitive measures, outperforming plasma-only and EEG-only models.ConclusionsIntegrating EEG features with plasma biomarkers improves prediction of cognitive function from mild cognitive impairment to moderate dementia, pending external validation.", "source": "PubMed"}, {"chunk_id": "41582250_0", "pmid": "41582250", "title": "Discriminating vascular parkinsonism from early-stage postural instability gait difficulty subtype dominant Parkinson's disease: a dual-task gait analysis using wearable sensors.", "authors": "Li J, Li Y, Aftab K et al.", "year": "2026", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dual task, Gait analysis, Parkinson\u2019s disease, Postural instability gait difficulty subtype, Vascular parkinsonism, Wearable sensors", "chunk": "Vascular parkinsonism (VP) and the postural instability and gait difficulty (PIGD) subtype of Parkinson's disease (PD) exhibit similar gait characteristics. However, most research emphasizes lower-limb gait parameters, often neglecting the role of cognitive function in gait regulation. Therefore, this study investigates differences in cognitive-motor interactions between VP and PIGD to identifying specific gait biomarkers and develop a diagnostic model. We recruited 37 PIGD patients and 37 VP patients between year 2022 to 2024 and used wearable devices to record gait parameters during single-task and dual-task paradigms. Demographic and clinical data were collected from all participants. Statistical analysis was conducted using R software with P < 0.05 as statistically significance. Multiple gait parameters significantly difference between VP and PIGD groups under both single-task and dual-task paradigms. In both single-task and dual-task gait comparisons, significant differences were observed between VP and PIGD in walk speed, shank swing speed, gait speed, phase coordination", "source": "PubMed"}, {"chunk_id": "41582250_1", "pmid": "41582250", "title": "Discriminating vascular parkinsonism from early-stage postural instability gait difficulty subtype dominant Parkinson's disease: a dual-task gait analysis using wearable sensors.", "authors": "Li J, Li Y, Aftab K et al.", "year": "2026", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dual task, Gait analysis, Parkinson\u2019s disease, Postural instability gait difficulty subtype, Vascular parkinsonism, Wearable sensors", "chunk": "both single-task and dual-task paradigms. In both single-task and dual-task gait comparisons, significant differences were observed between VP and PIGD in walk speed, shank swing speed, gait speed, phase coordination index (PCI), and trunk sway maximum (P < 0.05). Corresponding dual-task costs (DTC) also showed significant differences (P < 0.05). ROC curve analysis indicated a good diagnostic performance when combining multiple gait parameters and their DTC with MoCA scores (AUC 0.838, 95% CI 0.745-0.931; AUC 0.880, 95% CI 0.803-0.957). Correlation analysis revealed that several gait and DTC metrics were highly associated with cognitive performance in VP patients. Our study demonstrates that gait parameters provide reliable diagnostic discrimination between VP and PIGD. Moreover, gait parameters were significantly associated with cognitive function in VP patients.", "source": "PubMed"}, {"chunk_id": "41582250_2", "pmid": "41582250", "title": "Discriminating vascular parkinsonism from early-stage postural instability gait difficulty subtype dominant Parkinson's disease: a dual-task gait analysis using wearable sensors.", "authors": "Li J, Li Y, Aftab K et al.", "year": "2026", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Dual task, Gait analysis, Parkinson\u2019s disease, Postural instability gait difficulty subtype, Vascular parkinsonism, Wearable sensors", "chunk": "in VP patients.", "source": "PubMed"}, {"chunk_id": "34161209_0", "pmid": "34161209", "title": "A Review on Chitosan in Drug Delivery for Treatment of Neurological and Psychiatric Disorders.", "authors": "Shayganfard M", "year": "2022", "journal": "Current pharmaceutical biotechnology", "keywords": "Alzheimer\u2019s disease, Chitosan, Parkinson\u2019s disease, blood-brain barrier, depression, epilepsy., hypoxic ischemia injury, neurodegenerative diseases, neurological disease, spinal cord injury", "chunk": "Neurological diseases are known as global health problems with a growing number of patients annually. Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease as well as spinal cord injury, hypoxic ischemia injury, epilepsy, depression and etc., are some examples of neurological diseases. One of the main problems in the treatment of these diseases is the delivery of drugs across the blood-brain barrier (BBB). These days, researchers have tended to find non-invasive and non-toxic strategies for solving this problem. As a non-toxic, safe, and potential agent, chitosan has attracted attention for use in drug delivery systems. Recently, numerous studies have been designed to develop drug delivery systems by using chitosan to treat various neurological diseases. In this paper, the latest developments of chitosan and its derivatives utilization in the drug delivery systems for the treatment of different neurological and psychiatric diseases were reviewed.", "source": "PubMed"}, {"chunk_id": "34161209_1", "pmid": "34161209", "title": "A Review on Chitosan in Drug Delivery for Treatment of Neurological and Psychiatric Disorders.", "authors": "Shayganfard M", "year": "2022", "journal": "Current pharmaceutical biotechnology", "keywords": "Alzheimer\u2019s disease, Chitosan, Parkinson\u2019s disease, blood-brain barrier, depression, epilepsy., hypoxic ischemia injury, neurodegenerative diseases, neurological disease, spinal cord injury", "chunk": "developments of chitosan and its derivatives utilization in the drug delivery systems for the treatment of different neurological and psychiatric diseases were reviewed.", "source": "PubMed"}, {"chunk_id": "22214391_0", "pmid": "22214391", "title": "The growing burden of Alzheimer's disease.", "authors": "Lopez OL", "year": "2011", "journal": "The American journal of managed care", "keywords": "None", "chunk": "Most dementias in people at least 65 years of age are attributable to Alzheimer's disease (AD). While approximately 5.4 million Americans are now believed to have AD, the AD population is expected to nearly triple over the next 40 years, reaching approximately 14.5 million. Presently, there is no cure for AD, but a 2-year delay in AD onset would reduce the expected prevalence by 1.94 million within 50 years. The most important risk factor for AD is age, followed by presence of the apolipoprotein E-4 allele. Other risk factors for AD include sex (female), history of head trauma, family history of Down syndrome or dementia, and cerebrovascular risk factors. The initial neurodegenerative process that causes AD is unknown. However, it is accepted that the presence of amyloid plaques, neurofibrillary tangles, neuronal loss (and synapses), and cerebral amyloid angiopathy are the central pathogenic events. There is selective vulnerability of the limbic", "source": "PubMed"}, {"chunk_id": "22214391_1", "pmid": "22214391", "title": "The growing burden of Alzheimer's disease.", "authors": "Lopez OL", "year": "2011", "journal": "The American journal of managed care", "keywords": "None", "chunk": "is accepted that the presence of amyloid plaques, neurofibrillary tangles, neuronal loss (and synapses), and cerebral amyloid angiopathy are the central pathogenic events. There is selective vulnerability of the limbic system and heteromodal association areas in AD pathology. The most affected neurotransmitter in AD is acetylcholine, as enzymes that are part of its metabolic pathway are depleted. The clinical presentation of AD is heterogeneous and insidious, and the psychological and financial effects of AD on caregivers and family members are significant.", "source": "PubMed"}, {"chunk_id": "41023650_0", "pmid": "41023650", "title": "Association between mitochondrial DNA copy number and the risk of Parkinson's disease: a meta-analysis and Mendelian randomization study.", "authors": "Zheng H, Zhang D, Gan Y et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Copy number, Mendelian randomization, Meta-analysis, Mitochondrial DNA, Parkinson's disease", "chunk": "Parkinson\u2019s disease (PD) is a common neurodegenerative disorder characterized by both motor and non-motor symptoms, with mitochondrial dysfunction being a key pathological feature. Alterations in mitochondrial DNA copy number (mtDNA-CN) have been implicated in PD, but the relationship remains controversial. This study aimed to investigate the association between mtDNA-CN and PD through a meta-analysis and Mendelian randomization (MR) analysis to assess the potential causality. To investigate the relationship between mtDNA-CN and PD, a comprehensive literature search was conducted across PubMed, Scopus, Web of Science, CNKI, and Wan Fang databases. Studies meeting predefined inclusion and exclusion criteria were selected, and a meta-analysis was performed to quantitatively synthesize the effect sizes. To further evaluate the potential causal association between mtDNA-CN and PD risk, MR analysis was conducted using genetic variants associated with mtDNA-CN as instrumental variables. Summary-level data were obtained from publicly available genome-wide association study (GWAS) datasets, including the IEU Open", "source": "PubMed"}, {"chunk_id": "41023650_1", "pmid": "41023650", "title": "Association between mitochondrial DNA copy number and the risk of Parkinson's disease: a meta-analysis and Mendelian randomization study.", "authors": "Zheng H, Zhang D, Gan Y et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Copy number, Mendelian randomization, Meta-analysis, Mitochondrial DNA, Parkinson's disease", "chunk": "risk, MR analysis was conducted using genetic variants associated with mtDNA-CN as instrumental variables. Summary-level data were obtained from publicly available genome-wide association study (GWAS) datasets, including the IEU Open GWAS and FinnGen consortia. These analyses aimed to provide robust evidence regarding the potential causal role of mtDNA-CN in the pathophysiology of PD. Thirteen studies meeting the inclusion criteria were included in the meta-analysis. A significant association was identified between reduced mtDNA-CN in cerebrospinal fluid and an increased risk of PD. However, no significant association was observed between mtDNA-CN levels in blood and PD risk. Additionally, although mtDNA deletion levels were slightly elevated in PD patients compared to controls, this difference did not reach statistical significance. MR analysis, based on aggregated data from the IEU Open GWAS and FinnGen datasets, did not support a causal relationship between mtDNA-CN and PD risk (<i>p</i> = 0.78). The robustness and consistency of the", "source": "PubMed"}, {"chunk_id": "41023650_2", "pmid": "41023650", "title": "Association between mitochondrial DNA copy number and the risk of Parkinson's disease: a meta-analysis and Mendelian randomization study.", "authors": "Zheng H, Zhang D, Gan Y et al.", "year": "2025", "journal": "BMC neurology", "keywords": "Copy number, Mendelian randomization, Meta-analysis, Mitochondrial DNA, Parkinson's disease", "chunk": "aggregated data from the IEU Open GWAS and FinnGen datasets, did not support a causal relationship between mtDNA-CN and PD risk (<i>p</i> = 0.78). The robustness and consistency of the MR results were confirmed by Egger\u2019s test and sensitivity analyses. This study suggests that mtDNA-CN in cerebrospinal fluid holds potential clinical utility as a biomarker for PD. While further validation is needed, these findings contribute to a growing understanding of mitochondrial dysfunction in neurodegeneration and may offer new avenues for improving the diagnosis and management of PD. The online version contains supplementary material available at 10.1186/s12883-025-04400-4.", "source": "PubMed"}, {"chunk_id": "31744447_0", "pmid": "31744447", "title": "Alzheimer's Disease Targeted Nano-Based Drug Delivery Systems.", "authors": "Altinoglu G, Adali T", "year": "2020", "journal": "Current drug targets", "keywords": "Alzheimer's disease, drug delivery, nanoparticles, nanotechnology, physiochemical, targeted delivery.", "chunk": "Alzheimer's disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the", "source": "PubMed"}, {"chunk_id": "31744447_1", "pmid": "31744447", "title": "Alzheimer's Disease Targeted Nano-Based Drug Delivery Systems.", "authors": "Altinoglu G, Adali T", "year": "2020", "journal": "Current drug targets", "keywords": "Alzheimer's disease, drug delivery, nanoparticles, nanotechnology, physiochemical, targeted delivery.", "chunk": "to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer's disease and their implications in therapy is discussed.", "source": "PubMed"}, {"chunk_id": "41756762_0", "pmid": "41756762", "title": "The 2024 NIA-AA biological definition of Alzheimer's disease: linking biomarkers to clinical practice.", "authors": "Kobayashi G, Hirata K, Ono M et al.", "year": "2026", "journal": "Frontiers in dementia", "keywords": "A/T/N framework, Alzheimer\u2019s disease, NIA-AA 2024 diagnostic criteria, amyloid PET, co-pathologies, fluid biomarkers, resilience, tau PET", "chunk": "The 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria establish a biological definition of Alzheimer's disease (AD), marking a pivotal step toward linking research biomarkers with clinical practice. This review traces the evolution of AD diagnostic frameworks from the 1984 NINCDS-ADRDA clinical criteria, through biomarker-informed updates in 2011, to the 2024 biology-based criteria that bridge research and clinical care. The 2024 framework defines AD by its underlying pathology rather than clinical symptoms, recognizing that biomarker evidence alone can establish diagnosis. It expands the traditional AT (N) model into a multimodal profile (AT<sub>1</sub>T<sub>2</sub>NISV), in which Core-1 biomarkers (A and T<sub>1</sub>) are diagnostic, while Core-2 biomarkers (T<sub>2</sub>) support biological staging. Non-specific but mechanistically important processes (N, neurodegeneration; I, inflammation) and common co-pathologies (S, <i>\u03b1</i>-synuclein; V, vascular injury) are also incorporated to better capture the complexity of late-life dementia. Recent advances in plasma and PET biomarkers, including p-tau217, mid-region p-tau, and <i>\u03b1</i>-synuclein imaging,", "source": "PubMed"}, {"chunk_id": "41756762_1", "pmid": "41756762", "title": "The 2024 NIA-AA biological definition of Alzheimer's disease: linking biomarkers to clinical practice.", "authors": "Kobayashi G, Hirata K, Ono M et al.", "year": "2026", "journal": "Frontiers in dementia", "keywords": "A/T/N framework, Alzheimer\u2019s disease, NIA-AA 2024 diagnostic criteria, amyloid PET, co-pathologies, fluid biomarkers, resilience, tau PET", "chunk": "(S, <i>\u03b1</i>-synuclein; V, vascular injury) are also incorporated to better capture the complexity of late-life dementia. Recent advances in plasma and PET biomarkers, including p-tau217, mid-region p-tau, and <i>\u03b1</i>-synuclein imaging, are redefining biological diagnosis and expanding its reach. Moreover, co-pathologies involving TDP-43, glial dysfunction, and vascular factors contribute to disease heterogeneity and variable therapeutic response. While the 2024 criteria represent a major conceptual step forward, they should be regarded as a dynamic framework open to future integration of emerging biomarkers. Bridging molecular pathology, neuroimaging, and clinical presentation will be essential to realize the goal of patient-centered precision medicine in AD. In this review, we synthesize recent advances in biomarker-based frameworks for AD and discuss co-pathologies, resilience-related modifiers, and emerging evidence challenging traditional interpretations of structural neurodegeneration markers. We also address implications for clinical implementation, including PET standardization and disease-modifying therapies.", "source": "PubMed"}, {"chunk_id": "41756762_2", "pmid": "41756762", "title": "The 2024 NIA-AA biological definition of Alzheimer's disease: linking biomarkers to clinical practice.", "authors": "Kobayashi G, Hirata K, Ono M et al.", "year": "2026", "journal": "Frontiers in dementia", "keywords": "A/T/N framework, Alzheimer\u2019s disease, NIA-AA 2024 diagnostic criteria, amyloid PET, co-pathologies, fluid biomarkers, resilience, tau PET", "chunk": "challenging traditional interpretations of structural neurodegeneration markers. We also address implications for clinical implementation, including PET standardization and disease-modifying therapies.", "source": "PubMed"}, {"chunk_id": "38791145_0", "pmid": "38791145", "title": "Diagnostic and Prognostic Value of Plasma GFAP in Sporadic Creutzfeldt-Jakob Disease in the Clinical Setting of Rapidly Progressive Dementia.", "authors": "Bentivenga GM, Baiardi S, Mastrangelo A et al.", "year": "2024", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Creutzfeldt\u2013Jakob disease, GFAP, biomarker, co-pathology, neurodegeneration, neuroinflammation, prion", "chunk": "The diagnostic and prognostic value of plasma glial fibrillary acidic protein (pl-GFAP) in sporadic Creutzfeldt-Jakob disease (sCJD) has never been assessed in the clinical setting of rapidly progressive dementia (RPD). Using commercially available immunoassays, we assayed the plasma levels of GFAP, tau (pl-tau), and neurofilament light chain (pl-NfL) and the CSF total tau (t-tau), 14-3-3, NfL, phospho-tau181 (p-tau), and amyloid-beta isoforms 42 (A\u03b2<sub>42</sub>) and 40 (A\u03b2<sub>40</sub>) in sCJD (<i>n</i> = 132) and non-prion RPD (np-RPD) (<i>n</i> = 94) patients, and healthy controls (HC) (<i>n</i> = 54). We also measured the CSF GFAP in 67 sCJD patients. Pl-GFAP was significantly elevated in the sCJD compared to the np-RPD and HC groups and affected by the sCJD subtype. Its diagnostic accuracy (area under the curve (AUC) 0.760) in discriminating sCJD from np-RPD was higher than the plasma and CSF NfL (AUCs of 0.596 and 0.663) but inferior to the 14-3-3, t-tau, and", "source": "PubMed"}, {"chunk_id": "38791145_1", "pmid": "38791145", "title": "Diagnostic and Prognostic Value of Plasma GFAP in Sporadic Creutzfeldt-Jakob Disease in the Clinical Setting of Rapidly Progressive Dementia.", "authors": "Bentivenga GM, Baiardi S, Mastrangelo A et al.", "year": "2024", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, Creutzfeldt\u2013Jakob disease, GFAP, biomarker, co-pathology, neurodegeneration, neuroinflammation, prion", "chunk": "under the curve (AUC) 0.760) in discriminating sCJD from np-RPD was higher than the plasma and CSF NfL (AUCs of 0.596 and 0.663) but inferior to the 14-3-3, t-tau, and pl-tau (AUCs of 0.875, 0.918, and 0.805). Pl-GFAP showed no association with sCJD survival after adjusting for known prognostic factors. Additionally, pl-GFAP levels were associated with 14-3-3, pl-tau, and pl-NfL but not with CSF GFAP, A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub>, and p-tau. The diagnostic and prognostic value of pl-GFAP is inferior to established neurodegeneration biomarkers. Nonetheless, pl-GFAP noninvasively detects neuroinflammation and neurodegeneration in sCJD, warranting potential applications in disease monitoring.", "source": "PubMed"}, {"chunk_id": "38578889_0", "pmid": "38578889", "title": "Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.", "authors": "Chen Y, Su Y, Wu J et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "A\u03b2 positivity, MRI, amyloid PET, blood-based biomarkers, image features", "chunk": "Amyloid-\u03b2 (A\u03b2) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing A\u03b2 plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of A\u03b2 plaques. To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma A\u03b242/40 ratio. We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma A\u03b242/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results from ADNI (mean age 72.6, A\u03b2+ rate 49.5%) and BAI (mean", "source": "PubMed"}, {"chunk_id": "38578889_1", "pmid": "38578889", "title": "Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.", "authors": "Chen Y, Su Y, Wu J et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "A\u03b2 positivity, MRI, amyloid PET, blood-based biomarkers, image features", "chunk": "other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results from ADNI (mean age 72.6, A\u03b2+ rate 49.5%) and BAI (mean age 66.2, A\u03b2+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma A\u03b242/40 (0.73 and 0.81) predictors. Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to A\u03b2 plaques and structural MRI.", "source": "PubMed"}, {"chunk_id": "38578889_2", "pmid": "38578889", "title": "Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.", "authors": "Chen Y, Su Y, Wu J et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "A\u03b2 positivity, MRI, amyloid PET, blood-based biomarkers, image features", "chunk": "A\u03b2 plaques and structural MRI.", "source": "PubMed"}, {"chunk_id": "41509252_0", "pmid": "41509252", "title": "Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.", "authors": "Jesudason CD, Rangel-Barajas C, Beach CJ et al.", "year": "2026", "journal": "bioRxiv : the preprint server for biology", "keywords": "AKT signaling, Alzheimer\u2019s disease, INPP5D, Phosphoinositide signaling, SHIP1, SHIP2", "chunk": "Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1), encoded by the gene INPP5D, is a lipid phosphatase that negatively regulates immune receptor signaling in hematopoietic cells and microglia. Here, we describe a pyridyl-pyrazole-piperidine scaffold and the lead compound 3-((2-chlorobenzyl)oxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridine (<b>32</b>), which demonstrates SHIP1 target engagement, brain exposure, and evidence of a central pharmacodynamic response <i>in vivo</i>. Structure-activity relationship studies, guided by biochemical and cellular assays using multiple human and murine protein constructs and cells, identified SHIP1-active ligands. A thermal shift assay using full-length SHIP1 was used to assess compounds for cellular target engagement, while studies in IL-4 conditioned THP-1 cells was used to demonstrate changes in downstream AKT signaling. Targeted lipidomics revealed changes in the overall phosphoinositide pool consistent with SHIP1 target engagement and reduction of phospho-AKT levels. In a protein-lipid overlay assay, compound <b>32</b> induced changes in the relative association of SHIP1 with multiple phosphatidylinositols on a membrane surface.", "source": "PubMed"}, {"chunk_id": "41509252_1", "pmid": "41509252", "title": "Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.", "authors": "Jesudason CD, Rangel-Barajas C, Beach CJ et al.", "year": "2026", "journal": "bioRxiv : the preprint server for biology", "keywords": "AKT signaling, Alzheimer\u2019s disease, INPP5D, Phosphoinositide signaling, SHIP1, SHIP2", "chunk": "SHIP1 target engagement and reduction of phospho-AKT levels. In a protein-lipid overlay assay, compound <b>32</b> induced changes in the relative association of SHIP1 with multiple phosphatidylinositols on a membrane surface. In high-content cellular imaging assays, compound <b>32</b> enhanced the uptake of myelin/membrane debris and fibrillar amyloid by primary murine microglia, phenocopying a genetic model with reduced SHIP1 expression. Finally, oral administration of compound <b>32</b> resulted in brain exposure sufficient to alter gene expression and reduce IL-1\u03b2 levels as pharmacodynamic markers of microglial activation and neuroinflammation in an amyloidosis mouse model of Alzheimer's disease. Collectively, these results define a scaffold with SHIP1 target engagement, CNS exposure, and <i>in vivo</i> activity, providing a foundation for the optimization of brain-penetrant SHIP1 ligands suitable for further mechanistic studies and therapeutic development for the treatment of Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41509252_2", "pmid": "41509252", "title": "Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.", "authors": "Jesudason CD, Rangel-Barajas C, Beach CJ et al.", "year": "2026", "journal": "bioRxiv : the preprint server for biology", "keywords": "AKT signaling, Alzheimer\u2019s disease, INPP5D, Phosphoinositide signaling, SHIP1, SHIP2", "chunk": "for further mechanistic studies and therapeutic development for the treatment of Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41724572_0", "pmid": "41724572", "title": "Monitoring neuronal mitophagy and locomotion deficits in a C. elegans model of Alzheimer's disease.", "authors": "Niforos GG, Tsakiri E, Palikaras K", "year": "2026", "journal": "Methods in cell biology", "keywords": "Alzheimer\u2019s disease, Caenorhabditis elegans, Mitochondria, Mitophagy, Motility, Neurodegeneration, Neurons", "chunk": "Neurodegenerative diseases, such as Alzheimer's disease (AD), pose significant socioeconomic and personal burdens due to progressive cognitive and motor decline. AD is characterized by the accumulation of amyloid-beta (A\u03b2) plaques and tau tangles, alongside with emerging evidence linking metabolic dysfunction to its early disease pathogenesis. Impaired mitochondrial selective autophagy (known as mitophagy) and excessive mitochondrial dysfunction have been implicated as key contributors to disease progression. To uncover the mechanistic underpinnings of AD, Caenorhabditis elegans offers a powerful model system providing a fully mapped nervous system, transparency for live imaging, and evolutionary conserved pathways mirroring human pathophysiology. Here, we employ a pan-neuronal A\u03b2<sub>1-42</sub> -expressing C. elegans strain to phenocopy early metabolic disturbances characteristic of AD. Our methodology integrates automated motility tracking with confocal microscopy, utilizing the mitochondria-targeted Rosella biosensor to assess mitophagy dynamics in vivo. This platform enables quantitative assessment of locomotion deficits and spatiotemporal monitoring of mitophagy alterations driven by", "source": "PubMed"}, {"chunk_id": "41724572_1", "pmid": "41724572", "title": "Monitoring neuronal mitophagy and locomotion deficits in a C. elegans model of Alzheimer's disease.", "authors": "Niforos GG, Tsakiri E, Palikaras K", "year": "2026", "journal": "Methods in cell biology", "keywords": "Alzheimer\u2019s disease, Caenorhabditis elegans, Mitochondria, Mitophagy, Motility, Neurodegeneration, Neurons", "chunk": "with confocal microscopy, utilizing the mitochondria-targeted Rosella biosensor to assess mitophagy dynamics in vivo. This platform enables quantitative assessment of locomotion deficits and spatiotemporal monitoring of mitophagy alterations driven by A\u03b2<sub>1-42</sub>-induced toxicity. Our method provides a robust tool for screening genetic and pharmacological interventions aimed at mitigating AD-associated mitochondrial dysfunction and neurodegeneration.", "source": "PubMed"}, {"chunk_id": "35741660_0", "pmid": "35741660", "title": "Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer's Mouse Models.", "authors": "Balbi M, Blackmore DG, Padmanabhan P et al.", "year": "2022", "journal": "Brain sciences", "keywords": "NMDA receptor (NR), Tau, amyloid, long-term potentiation, low-intensity ultrasound, mechanosensory receptor, neurogenesis, neuromodulation, senescence", "chunk": "Ultrasound is routinely used for a wide range of diagnostic imaging applications. However, given that ultrasound can operate over a wide range of parameters that can all be modulated, its applicability extends far beyond the bioimaging field. In fact, the modality has emerged as a hybrid technology that effectively assists drug delivery by transiently opening the blood-brain barrier (BBB) when combined with intravenously injected microbubbles, and facilitates neuromodulation. Studies in aged mice contributed to an insight into how low-intensity ultrasound brings about its neuromodulatory effects, including increased synaptic plasticity and improved cognitive functions, with a potential role for neurogenesis and the modulation of NMDA receptor-mediated neuronal signalling. This work is complemented by studies in mouse models of Alzheimer's disease (AD), a form of pathological ageing. Here, ultrasound was mainly employed as a BBB-opening tool that clears protein aggregates via microglial activation and neuronal autophagy, thereby restoring cognition. We discuss the", "source": "PubMed"}, {"chunk_id": "35741660_1", "pmid": "35741660", "title": "Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer's Mouse Models.", "authors": "Balbi M, Blackmore DG, Padmanabhan P et al.", "year": "2022", "journal": "Brain sciences", "keywords": "NMDA receptor (NR), Tau, amyloid, long-term potentiation, low-intensity ultrasound, mechanosensory receptor, neurogenesis, neuromodulation, senescence", "chunk": "a form of pathological ageing. Here, ultrasound was mainly employed as a BBB-opening tool that clears protein aggregates via microglial activation and neuronal autophagy, thereby restoring cognition. We discuss the currently available ultrasound approaches and how studies in senescent mice are relevant for AD and can accelerate the application of low-intensity ultrasound in the clinic.", "source": "PubMed"}, {"chunk_id": "40717441_0", "pmid": "40717441", "title": "The differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition and mild cognitive impairment.", "authors": "Kim D, Yoon S, Hughes TM et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, magnetic resonance imaging, mild cognitive impairment, neuroimaging, perfusion imaging, white matter", "chunk": "BackgroundMild cognitive impairment (MCI) has been related to impairment in cerebrovascular perfusion and microstructural magnetic resonance imaging (MRI) parameters. However, the relationship between cerebrovascular perfusion and microstructure remains understudied, especially within normal-appearing white matter (NAWM).ObjectiveThis study aimed to investigate the differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition (NC) and MCI using multiple MRI measurements within NAWM.MethodsWe examined differences between 24 MCI and 55 NC participants in NAWM for cerebrovascular perfusion and microstructural measures, including cerebrovascular reactivity (CVR), cerebral blood flow, arterial transit time (ATT), and intracellular volume fraction (ICVF), isotropic volume fraction, and orientation dispersion index in models adjusted for vascular risk factors including hypertension, glycemic status, and the presence of <i>APOE</i> \u03b54 allele.ResultsIn the voxel-wise analyses within NAWM, participants with MCI exhibited lower CVR, prolonged ATT, and lower ICVF. Additionally, ATT and ICVF demonstrated a negative interrelationship in voxel clusters affected by MCI.ConclusionsImpaired ATT", "source": "PubMed"}, {"chunk_id": "40717441_1", "pmid": "40717441", "title": "The differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition and mild cognitive impairment.", "authors": "Kim D, Yoon S, Hughes TM et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, magnetic resonance imaging, mild cognitive impairment, neuroimaging, perfusion imaging, white matter", "chunk": "voxel-wise analyses within NAWM, participants with MCI exhibited lower CVR, prolonged ATT, and lower ICVF. Additionally, ATT and ICVF demonstrated a negative interrelationship in voxel clusters affected by MCI.ConclusionsImpaired ATT and ICVF in NAWM appeared to be closely interlinked in MCI, while CVR served as an independent imaging biomarker. Further investigation into the intrinsic link between ATT and ICVF in NAWM is warranted.", "source": "PubMed"}, {"chunk_id": "41696149_0", "pmid": "41696149", "title": "An anti-inflammatory neuroenhancer mitigates amyloid-\u03b2 pathology to improve Alzheimer's disease therapy.", "authors": "Fang W, Zhao J, Li L et al.", "year": "2026", "journal": "Materials today. Bio", "keywords": "Alzheimer's disease, Lipid-coated calcium phosphate nanoparticles, Natural compounds, Neuroinflammation, siRNA, \u03b2-amyloid", "chunk": "\u03b2-amyloid (A\u03b2) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both A\u03b2 aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block A\u03b2 production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the A\u03b2 aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates A\u03b2-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of A\u03b2 reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR", "source": "PubMed"}, {"chunk_id": "41696149_1", "pmid": "41696149", "title": "An anti-inflammatory neuroenhancer mitigates amyloid-\u03b2 pathology to improve Alzheimer's disease therapy.", "authors": "Fang W, Zhao J, Li L et al.", "year": "2026", "journal": "Materials today. Bio", "keywords": "Alzheimer's disease, Lipid-coated calcium phosphate nanoparticles, Natural compounds, Neuroinflammation, siRNA, \u03b2-amyloid", "chunk": "neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of A\u03b2 reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of A\u03b2 and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.", "source": "PubMed"}, {"chunk_id": "41436906_0", "pmid": "41436906", "title": "Proteasome Dysregulation in Parkinson's Disease: Insights from Blood-Based Analyses.", "authors": "Di Costanzo A, Fusco C, Camerlingo R et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "APEH, PSMB5, Parkinson\u2019s disease, Peripheral blood biomarkers, Proteasome activity", "chunk": "Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by \u03b1-synuclein aggregation, mitochondrial dysfunction, and impaired proteostasis. The peripheral biomarkers that reflect these cellular perturbations remain incompletely defined. This study aimed to evaluate the enzymatic activity and gene expression of two key protein degradation enzymes, Acyl PEptide Hydrolase (APEH) and Proteasome Subunit Beta Type-5 (PSMB5), in the peripheral blood of PD patients and to relate these findings to the severity of the disease. Thirteen PD patients and 13 age-matched healthy controls (HLT) were recruited. APEH and PSMB5 chymotrypsin-like (CT-like) activity were measured in whole blood, erythrocytes and immune cell fractions. Gene expression analysis was performed for APEH and PSMB5 and their related genes, plus other genes typical of parkinsonism or indicative of metabolic alterations: N(alpha)-acetyltransferase (NAA10) Aminoacylase 1 (ACY1), Ubiquitin-activating enzyme 1 (UBA1), Ubiquitin conjugating enzyme E2 I (UBE2I), Parkin RBR E3 ubiquitin protein ligase (PRKN), Alpha-synuclein (SNCA), Parkinsonism", "source": "PubMed"}, {"chunk_id": "41436906_1", "pmid": "41436906", "title": "Proteasome Dysregulation in Parkinson's Disease: Insights from Blood-Based Analyses.", "authors": "Di Costanzo A, Fusco C, Camerlingo R et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "APEH, PSMB5, Parkinson\u2019s disease, Peripheral blood biomarkers, Proteasome activity", "chunk": "or indicative of metabolic alterations: N(alpha)-acetyltransferase (NAA10) Aminoacylase 1 (ACY1), Ubiquitin-activating enzyme 1 (UBA1), Ubiquitin conjugating enzyme E2 I (UBE2I), Parkin RBR E3 ubiquitin protein ligase (PRKN), Alpha-synuclein (SNCA), Parkinsonism associated deglycase DJ-1 (PARK7), and mitochondrial Mn-SOD (SOD2). APEH activity did not differ significantly between PD and HLT in whole blood cells or cellular fractions. Conversely, PSMB5 CT-like activity was reduced in lymphocytes from PD patients, whereas erythrocytes and whole blood exhibited elevated activity. No changes in APEH and PSMB5 expression were observed, while PARK7 significantly decreased in patients with PD. Correlation analysis showed that proteasomal changes correlated with disease severity, and cognitive impairment. Our findings revealed compartment-specific proteasomal dysregulation in the peripheral blood of PD patients, suggesting systemic proteostasis imbalance. These alterations appeared more pronounced in patients with more severe clinical progression. This study supports the potential of peripheral proteasomal activity profiles as biomarkers linked to PD progression, warranting", "source": "PubMed"}, {"chunk_id": "41436906_2", "pmid": "41436906", "title": "Proteasome Dysregulation in Parkinson's Disease: Insights from Blood-Based Analyses.", "authors": "Di Costanzo A, Fusco C, Camerlingo R et al.", "year": "2025", "journal": "Molecular neurobiology", "keywords": "APEH, PSMB5, Parkinson\u2019s disease, Peripheral blood biomarkers, Proteasome activity", "chunk": "imbalance. These alterations appeared more pronounced in patients with more severe clinical progression. This study supports the potential of peripheral proteasomal activity profiles as biomarkers linked to PD progression, warranting further investigation in larger cohorts.", "source": "PubMed"}, {"chunk_id": "37045847_0", "pmid": "37045847", "title": "Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders.", "authors": "Eide PK, Lashkarivand A, Pripp A et al.", "year": "2023", "journal": "Nature communications", "keywords": "None", "chunk": "Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-\u03b2 (A\u03b240 and A\u03b242), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.", "source": "PubMed"}, {"chunk_id": "37045847_1", "pmid": "37045847", "title": "Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders.", "authors": "Eide PK, Lashkarivand A, Pripp A et al.", "year": "2023", "journal": "Nature communications", "keywords": "None", "chunk": "and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.", "source": "PubMed"}, {"chunk_id": "41315874_0", "pmid": "41315874", "title": "Immune dysfunction in Alzheimer disease.", "authors": "Butovsky O, Rosenzweig N, Kleemann KL et al.", "year": "2026", "journal": "Nature reviews. Neuroscience", "keywords": "None", "chunk": "Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can modulate the hallmark features of AD, including amyloid plaque accumulation, tau pathology and chronic neuroinflammation. Mechanistic insights suggest that chronic peripheral inflammation, immune exhaustion, metabolic dysfunction and epigenetic reprogramming exacerbate neurodegeneration in AD by promoting toxic inflammation and impairing protein clearance in the brain. These findings may catalyse the development of novel immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge", "source": "PubMed"}, {"chunk_id": "41315874_1", "pmid": "41315874", "title": "Immune dysfunction in Alzheimer disease.", "authors": "Butovsky O, Rosenzweig N, Kleemann KL et al.", "year": "2026", "journal": "Nature reviews. Neuroscience", "keywords": "None", "chunk": "immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge gaps, particularly the need for human-derived data to advance translational progress. Future research should prioritize personalized approaches that integrate genetic risk, immune profiling and ageing to inform next-generation therapies for AD.", "source": "PubMed"}, {"chunk_id": "37831127_0", "pmid": "37831127", "title": "High intake of ultra-processed food is associated with dementia in adults: a systematic review and meta-analysis of observational studies.", "authors": "Henney AE, Gillespie CS, Alam U et al.", "year": "2024", "journal": "Journal of neurology", "keywords": "Alzheimer\u2019s dementia, Dementia, Metabolic syndrome, Mild cognitive impairment, NOVA, Ultra-processed food", "chunk": "Poor cardiometabolic health is associated with dementia. Considering previous meta-analyses have confirmed associations between ultra-processed foods (UPFs) and cardiometabolic disease, we were interested in the contribution of UPF consumption to the risk of developing dementia. We performed a systematic review and meta-analysis of all records registered on Ovid Medline and Web of Science from inception until December 2022 [PROSPERO (CRD42023388363)]. Studies that assessed UPF consumption in adults, determined according to NOVA, and that reported dementia (Alzheimer's disease, vascular dementia and mild cognitive impairment) determined by clearly stated diagnostic criteria (including formal assessment of dementia or use of diagnostic codes) were included. The association between UPF consumption and dementia was assessed using random-effects meta-analysis, controlling for confounding variables. Study quality was assessed using the Newcastle Ottawa Scale and evidence credibility evaluated using the NutriGrade system. Seven thousand ten records were screened, and 122 records underwent full text review. From these, 10", "source": "PubMed"}, {"chunk_id": "37831127_1", "pmid": "37831127", "title": "High intake of ultra-processed food is associated with dementia in adults: a systematic review and meta-analysis of observational studies.", "authors": "Henney AE, Gillespie CS, Alam U et al.", "year": "2024", "journal": "Journal of neurology", "keywords": "Alzheimer\u2019s dementia, Dementia, Metabolic syndrome, Mild cognitive impairment, NOVA, Ultra-processed food", "chunk": "assessed using the Newcastle Ottawa Scale and evidence credibility evaluated using the NutriGrade system. Seven thousand ten records were screened, and 122 records underwent full text review. From these, 10 observational (8 longitudinal) studies, analysing 867,316 individuals, were included. Included studies adjusted for age, socioeconomic status and co-morbidity, alongside other confounders. High (vs. low) intake of UPF was associated with increased risk of dementia (pooled relative risk 1.44 (95% confidence interval 1.09-1.90) (p = 0.02)) (I<sup>2</sup> = 97.0%), although moderate (vs. low) intake of UPF was not (1.12 (0.96-1.31) (0.13)) (85.0%). Funnel plots demonstrate low risk of publication bias. High UPF consumption is associated with dementia. Public health measures to reduce overconsumption of UPFs are imperative to reduce the burden of dementia.", "source": "PubMed"}, {"chunk_id": "37831127_2", "pmid": "37831127", "title": "High intake of ultra-processed food is associated with dementia in adults: a systematic review and meta-analysis of observational studies.", "authors": "Henney AE, Gillespie CS, Alam U et al.", "year": "2024", "journal": "Journal of neurology", "keywords": "Alzheimer\u2019s dementia, Dementia, Metabolic syndrome, Mild cognitive impairment, NOVA, Ultra-processed food", "chunk": "of dementia.", "source": "PubMed"}, {"chunk_id": "41587788_0", "pmid": "41587788", "title": "Optical-Antenna-Enhanced LED Biochips for Femtomolar Detection of Protein Biomarkers.", "authors": "Wang M, Hu Y, Zhang T et al.", "year": "2026", "journal": "Analytical chemistry", "keywords": "None", "chunk": "The ability to detect protein biomarkers at the single-molecule level represents the ultimate sensitivity in disease diagnostics and has profound societal benefits, including the early detection of cancer and Alzheimer's disease. Typical digital immunosensing assays rely on bulky laser or halogen light sources, which hinder the development of miniaturized and low-cost point-of-care testing devices. This study demonstrates a novel single-molecule biosensing platform that integrates plasmonic optical antennas, comprising gold nanoparticles coupled to a gold film, with an inexpensive LED chip. The concept of enhancing the platform's limit of detection (LOD) was realized by improving the signal-to-noise ratio (SNR) between the scattering light of the plasmonic antenna and the background emission from the working LED chip, resulting in an optimized SNR of 2.67 dB. Consequently, the quantification detection of human IL-6 was achieved with an LOD of 2.01 fg/mL, showing performance similar to that of a current single-molecule detection platform. These", "source": "PubMed"}, {"chunk_id": "41587788_1", "pmid": "41587788", "title": "Optical-Antenna-Enhanced LED Biochips for Femtomolar Detection of Protein Biomarkers.", "authors": "Wang M, Hu Y, Zhang T et al.", "year": "2026", "journal": "Analytical chemistry", "keywords": "None", "chunk": "of 2.67 dB. Consequently, the quantification detection of human IL-6 was achieved with an LOD of 2.01 fg/mL, showing performance similar to that of a current single-molecule detection platform. These findings demonstrate a portable and low-cost single-molecule detection platform that may drive further advances in the field.", "source": "PubMed"}, {"chunk_id": "39686614_0", "pmid": "39686614", "title": "Comparison of visit-to-visit blood pressure variability and time in target range in predicting risk for cognitive outcomes in the SPRINT trial.", "authors": "Sible IJ, Nation DA", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood pressure variability, dementia, mild cognitive impairment, time in target range", "chunk": "Blood pressure (BP) variability (BPV) and time in target range (TTR) are emerging vascular risk factors for dementia, independent of traditionally targeted mean BP. Determine whether BPV or TTR is most strongly associated with cognitive risk. In this post hoc analysis of the SPRINT trial, 8034 participants underwent repeated BP measurement and cognitive testing at baseline and follow-up. Visit-to-visit BPV was calculated as average real variability. TTR was the percent of time in desired treatment arm target range (standard: 120-140 mmHg systolic BP; intensive: 110-130 mmHg systolic BP). Adjudicated clinical outcomes were no cognitive impairment, mild cognitive impairment (MCI), and probable dementia. We investigated a direct comparison of BPV and TTR in predicting cognitive risk, stratified by BP treatment group. Elevated BPV was associated with increased risk for MCI (adjusted HR: 1.21 [95% CI 1.10, 1.33], <i>p </i>< 0.001) and MCI/dementia (HR: 1.17 [95% CI 1.07, 1.27], <i>p </i>< 0.001)", "source": "PubMed"}, {"chunk_id": "39686614_1", "pmid": "39686614", "title": "Comparison of visit-to-visit blood pressure variability and time in target range in predicting risk for cognitive outcomes in the SPRINT trial.", "authors": "Sible IJ, Nation DA", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood pressure variability, dementia, mild cognitive impairment, time in target range", "chunk": "Elevated BPV was associated with increased risk for MCI (adjusted HR: 1.21 [95% CI 1.10, 1.33], <i>p </i>< 0.001) and MCI/dementia (HR: 1.17 [95% CI 1.07, 1.27], <i>p </i>< 0.001) in the standard group, and dementia (HR: 1.17 [95% CI 1.01, 1.36], <i>p </i>= 0.039) in the intensive group. Higher TTR was related to lower dementia risk (HR: 0.72 [95% CI 0.60, 0.86], <i>p </i>< 0.001) in the intensive group only. Visit-to-visit BPV outperformed TTR in predicting risk for MCI and MCI/dementia. TTR was more strongly associated with dementia risk under intensive treatment. Findings were independent of mean BP in a cohort with rigorously controlled BP and suggest newer aspects of BP control may be harnessed to further reduce cognitive risk. ClinicalTrials.gov; NCT01206062.", "source": "PubMed"}, {"chunk_id": "39686614_2", "pmid": "39686614", "title": "Comparison of visit-to-visit blood pressure variability and time in target range in predicting risk for cognitive outcomes in the SPRINT trial.", "authors": "Sible IJ, Nation DA", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, blood pressure variability, dementia, mild cognitive impairment, time in target range", "chunk": "risk. ClinicalTrials.gov; NCT01206062.", "source": "PubMed"}, {"chunk_id": "31853655_0", "pmid": "31853655", "title": "A Deep Learning Approach for Automated Diagnosis and Multi-Class Classification of Alzheimer's Disease Stages Using Resting-State fMRI and Residual Neural Networks.", "authors": "Ramzan F, Khan MUG, Rehmat A et al.", "year": "2019", "journal": "Journal of medical systems", "keywords": "Alzheimer\u2019s disease, Classification, Deep learning, Diagnosis, Functional magnetic resonance imaging (fMRI), Multi-class, Residual neural networks", "chunk": "Alzheimer's disease (AD) is an incurable neurodegenerative disorder accounting for 70%-80% dementia cases worldwide. Although, research on AD has increased in recent years, however, the complexity associated with brain structure and functions makes the early diagnosis of this disease a challenging task. Resting-state functional magnetic resonance imaging (rs-fMRI) is a neuroimaging technology that has been widely used to study the pathogenesis of neurodegenerative diseases. In literature, the computer-aided diagnosis of AD is limited to binary classification or diagnosis of AD and MCI stages. However, its applicability to diagnose multiple progressive stages of AD is relatively under-studied. This study explores the effectiveness of rs-fMRI for multi-class classification of AD and its associated stages including CN, SMC, EMCI, MCI, LMCI, and AD. A longitudinal cohort of resting-state fMRI of 138 subjects (25 CN, 25 SMC, 25 EMCI, 25 LMCI, 13 MCI, and 25 AD) from Alzheimer's Disease Neuroimaging Initiative (ADNI) is studied.", "source": "PubMed"}, {"chunk_id": "31853655_1", "pmid": "31853655", "title": "A Deep Learning Approach for Automated Diagnosis and Multi-Class Classification of Alzheimer's Disease Stages Using Resting-State fMRI and Residual Neural Networks.", "authors": "Ramzan F, Khan MUG, Rehmat A et al.", "year": "2019", "journal": "Journal of medical systems", "keywords": "Alzheimer\u2019s disease, Classification, Deep learning, Diagnosis, Functional magnetic resonance imaging (fMRI), Multi-class, Residual neural networks", "chunk": "A longitudinal cohort of resting-state fMRI of 138 subjects (25 CN, 25 SMC, 25 EMCI, 25 LMCI, 13 MCI, and 25 AD) from Alzheimer's Disease Neuroimaging Initiative (ADNI) is studied. To provide a better insight into deep learning approaches and their applications to AD classification, we investigate ResNet-18 architecture in detail. We consider the training of the network from scratch by using single-channel input as well as performed transfer learning with and without fine-tuning using an extended network architecture. We experimented with residual neural networks to perform AD classification task and compared it with former research in this domain. The performance of the models is evaluated using precision, recall, f1-measure, AUC and ROC curves. We found that our networks were able to significantly classify the subjects. We achieved improved results with our fine-tuned model for all the AD stages with an accuracy of 100%, 96.85%, 97.38%, 97.43%, 97.40% and 98.01%", "source": "PubMed"}, {"chunk_id": "31853655_2", "pmid": "31853655", "title": "A Deep Learning Approach for Automated Diagnosis and Multi-Class Classification of Alzheimer's Disease Stages Using Resting-State fMRI and Residual Neural Networks.", "authors": "Ramzan F, Khan MUG, Rehmat A et al.", "year": "2019", "journal": "Journal of medical systems", "keywords": "Alzheimer\u2019s disease, Classification, Deep learning, Diagnosis, Functional magnetic resonance imaging (fMRI), Multi-class, Residual neural networks", "chunk": "able to significantly classify the subjects. We achieved improved results with our fine-tuned model for all the AD stages with an accuracy of 100%, 96.85%, 97.38%, 97.43%, 97.40% and 98.01% for CN, SMC, EMCI, LMCI, MCI, and AD respectively. However, in terms of overall performance, we achieved state-of-the-art results with an average accuracy of 97.92% and 97.88% for off-the-shelf and fine-tuned models respectively. The Analysis of results indicate that classification and prediction of neurodegenerative brain disorders such as AD using functional magnetic resonance imaging and advanced deep learning methods is promising for clinical decision making and have the potential to assist in early diagnosis of AD and its associated stages.", "source": "PubMed"}, {"chunk_id": "39730532_0", "pmid": "39730532", "title": "A proficient approach for the classification of Alzheimer's disease using a hybridization of machine learning and deep learning.", "authors": "Raza HA, Ansari SU, Javed K et al.", "year": "2024", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Classification, Convolutional neural network, Hybrid features learning, Machine learning", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder. It causes progressive degeneration of the nervous system, affecting the cognitive ability of the human brain. Over the past two decades, neuroimaging data from Magnetic Resonance Imaging (MRI) scans has been increasingly used in the study of brain pathology related to the birth and growth of AD. Recent studies have employed machine learning to detect and classify AD. Deep learning models have also been increasingly utilized with varying degrees of success. This paper presents a novel hybrid approach for early detection and classification of AD using structural MRI (sMRI). The proposed model employs a unique combination of machine learning and deep learning approaches to optimize the precision and accuracy of the detection and classification of AD. The proposed approach surpassed multi-modal machine learning algorithms in accuracy, precision, and F-measure performance measures. Results confirm an outperformance compared to the state-of-the-art in AD versus CN", "source": "PubMed"}, {"chunk_id": "39730532_1", "pmid": "39730532", "title": "A proficient approach for the classification of Alzheimer's disease using a hybridization of machine learning and deep learning.", "authors": "Raza HA, Ansari SU, Javed K et al.", "year": "2024", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Classification, Convolutional neural network, Hybrid features learning, Machine learning", "chunk": "classification of AD. The proposed approach surpassed multi-modal machine learning algorithms in accuracy, precision, and F-measure performance measures. Results confirm an outperformance compared to the state-of-the-art in AD versus CN and sMCI versus pMCI paradigms. Within the CN versus AD paradigm, the designed model achieves 91.84% accuracy on test data.", "source": "PubMed"}, {"chunk_id": "39864561_0", "pmid": "39864561", "title": "APOE4, Alzheimer's and periodontal disease: A scoping review.", "authors": "Ar\u00e9valo-Caro C, Arce Retana M, Losada Amaya S et al.", "year": "2025", "journal": "Ageing research reviews", "keywords": "APOE4, Alzheimer disease, Apolipoprotein E, Periodontal disease", "chunk": "The \u03b54 allele of the apolipoprotein E gene (APOE4) is recognized as the primary genetic risk factor for Alzheimer's disease (AD) and has been associated with chronic inflammatory conditions, such as periodontal disease (PD). PD has been identified as having a potentiating effect that favors the development and progression of AD. This scoping review investigates the potential relationship between PD and AD through APOE4. The Joanna Briggs Institute methodology and PRISMA guidelines were followed. The search included articles published in PubMed and Embase, focusing on human studies, and excluding case series, in vitro studies, reviews, and animal studies. Among the studies that evaluated the relationship between PD, APOE4, and AD, a correlation was identified between the gingival index and cognitive impairment in APO\u03954 carriers. Additionally, higher levels of apolipoprotein E4 were found in the crevicular fluid of patients with both AD and PD, compared to individuals without AD. APOE4 may", "source": "PubMed"}, {"chunk_id": "39864561_1", "pmid": "39864561", "title": "APOE4, Alzheimer's and periodontal disease: A scoping review.", "authors": "Ar\u00e9valo-Caro C, Arce Retana M, Losada Amaya S et al.", "year": "2025", "journal": "Ageing research reviews", "keywords": "APOE4, Alzheimer disease, Apolipoprotein E, Periodontal disease", "chunk": "impairment in APO\u03954 carriers. Additionally, higher levels of apolipoprotein E4 were found in the crevicular fluid of patients with both AD and PD, compared to individuals without AD. APOE4 may link PD and AD through shared genetic variants, inflammatory pathways, and dyslipidemia, involving both peripheral and central pathways. More comprehensive studies are required to ascertain the relationship between PD, AD, and APOE4, and to determine whether these associations are causal or non-causal in nature.", "source": "PubMed"}, {"chunk_id": "36314203_0", "pmid": "36314203", "title": "Sex Modifies the Associations of APOE\u025b4 with Neuropsychiatric Symptom Burden in Both At-Risk and Clinical Cohorts of Alzheimer's Disease.", "authors": "Dissanayake AS, Tan YB, Bowie CR et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE4, Alzheimer\u2019s disease, Neuropsychiatric Inventory Questionnaire, behavioral and psychological symptoms of dementia, biomarkers, gender differences, major depressive disorder, mild cognitive impairment, neuropsychiatry, psychosis", "chunk": "Recent work suggests that APOE\u025b4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS). To examine the interaction of sex and APOE\u025b4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n = 252) and 2) patients with probable AD (n = 7,261). Regression models examined the interactive effects of sex and APOE\u025b4 on the number of NPS experienced and NPS Severity. APOE\u025b3/4 and APOE\u025b4/4 were pooled in the at-risk cohort due to the sample size. In the at-risk cohort, there was a significant sex*APOE\u025b4 interaction (p = 0.007) such that the association of APOE\u025b4 with NPS was greater in females than in males (incident rate ratio (IRR) = 2.0). APOE\u025b4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical", "source": "PubMed"}, {"chunk_id": "36314203_1", "pmid": "36314203", "title": "Sex Modifies the Associations of APOE\u025b4 with Neuropsychiatric Symptom Burden in Both At-Risk and Clinical Cohorts of Alzheimer's Disease.", "authors": "Dissanayake AS, Tan YB, Bowie CR et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE4, Alzheimer\u2019s disease, Neuropsychiatric Inventory Questionnaire, behavioral and psychological symptoms of dementia, biomarkers, gender differences, major depressive disorder, mild cognitive impairment, neuropsychiatry, psychosis", "chunk": "males (incident rate ratio (IRR) = 2.0). APOE\u025b4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical cohort, APOE\u025b4/4 females had significantly more NPS (IRR = 1.1, p = 0.001, mean = 3.1) and higher severity scores (b = 0.31, p = 0.015, mean = 3.7) than APOE\u025b3/3 females (meanNPS = 2.9, meanSeverity = 3.3). No association was found in males. Our study suggests that sex modifies the association of APOE\u025b4 on NPS burden. APOE\u025b4/4 females may be particularly susceptible to increased NPS burden among individuals with AD and among individuals at risk for AD. Further investigation into the mechanisms behind these associations are needed.", "source": "PubMed"}, {"chunk_id": "39835816_0", "pmid": "39835816", "title": "Multiple-Signal Amplification Strategy to Fabricate an Ultrasensitive Electrochemiluminescence Magnetic Immunosensor for Detecting Biomarkers of Alzheimer's Disease via Iridium-Based Self-Enhancing Nanoemitters.", "authors": "Dai C, Xu Y, Ke L et al.", "year": "2025", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease, ECL immunosensor, iridium(III) complex, self-enhanced, signal amplification", "chunk": "Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive decline, significantly impairing the daily life of elderly individuals. The low abundance of blood-based biomarkers in AD necessitates higher analytical technique requirements. Herein, one novel iridium-based ECL self-enhanced nanoemitter (TPrA@Ir-SiO<sub>2</sub>) was unprecedentedly reported, and it was further used to construct an ultrasensitive ECL magnetic immunosensor by a multiple-signal amplification strategy to unequally sensitively and accurately detect the AD blood-based biomarker (P-tau181) in this work. The initial signal amplification was accomplished via incorporating a new efficient iridium-based luminophore named Ir(mdq)<sub>2</sub>(acac) and a corresponding coreactant into silica nanoparticles to successfully obtain TPrA@Ir-SiO<sub>2</sub>. In addition, the specific and high-affinity interactions between streptavidin and biotin were subsequently employed to further facilitate signal amplification. Based on the advantages of the luminophore itself and the high-affinity interactions between biotin and streptavidin, the corresponding ECL immunosensor proposed in this work exhibited remarkable sensitivity, covering a wide", "source": "PubMed"}, {"chunk_id": "39835816_1", "pmid": "39835816", "title": "Multiple-Signal Amplification Strategy to Fabricate an Ultrasensitive Electrochemiluminescence Magnetic Immunosensor for Detecting Biomarkers of Alzheimer's Disease via Iridium-Based Self-Enhancing Nanoemitters.", "authors": "Dai C, Xu Y, Ke L et al.", "year": "2025", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease, ECL immunosensor, iridium(III) complex, self-enhanced, signal amplification", "chunk": "Based on the advantages of the luminophore itself and the high-affinity interactions between biotin and streptavidin, the corresponding ECL immunosensor proposed in this work exhibited remarkable sensitivity, covering a wide linear range from 0.1 pg/mL to 0.1 \u03bcg/mL, and achieved an ultralow limit of detection of 68.58 fg/mL (S/N = 3), and it also exhibited outstanding recovery (98-104%) and RSD (1.92-4.86%) in the detection of serum samples by the spiking method. These remarkable results undoubtedly demonstrate the potential of self-enhanced ECL nanoemitters combined with a synergistic signal amplification strategy bearing streptavidin-biotin in detecting AD blood-based biomarkers, providing accurate and reliable solutions for early diagnosis and monitoring of AD, which would open a new avenue to effectively reduce the burden on AD patients' families and society in the future.", "source": "PubMed"}, {"chunk_id": "39835816_2", "pmid": "39835816", "title": "Multiple-Signal Amplification Strategy to Fabricate an Ultrasensitive Electrochemiluminescence Magnetic Immunosensor for Detecting Biomarkers of Alzheimer's Disease via Iridium-Based Self-Enhancing Nanoemitters.", "authors": "Dai C, Xu Y, Ke L et al.", "year": "2025", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease, ECL immunosensor, iridium(III) complex, self-enhanced, signal amplification", "chunk": "AD patients' families and society in the future.", "source": "PubMed"}, {"chunk_id": "41399206_0", "pmid": "41399206", "title": "Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.", "authors": "Guo D, Cai M, Xian Y et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "neuroinflammation, neurological disorders, neuroprotection, therapeutic strategy, transient receptor potential ion channels", "chunk": "Transient receptor potential (TRP) ion channels, a ubiquitous family of nonselective cation channels, are extensively expressed across the nervous system, immune system, and peripheral tissues. These channels serve as critical sensors for detecting temperature, mechanical forces, and chemical stimuli, thereby regulating numerous physiological and pathological processes. Over the past decade, their pivotal role in neuroimmune crosstalk and inflammatory signaling has emerged as a key focus within neuroscience research. A comprehensive literature review was conducted in PubMed using key terms \"TRP channel,\" \"neuroinflammation,\" and each of the following neurological disorders: neuropathic pain, migraine, stroke, multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), epilepsy, and psychiatric disorders. This review synthesizes the current evidence to elucidate the dual-edged contributions of TRP channels as mediators of inflammation in neuropathic pain, migraine, stroke, MS, AD, PD, ASD, epilepsy, and psychiatric disorders. Furthermore, we also evaluate emerging therapeutic strategies targeting TRP", "source": "PubMed"}, {"chunk_id": "41399206_1", "pmid": "41399206", "title": "Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.", "authors": "Guo D, Cai M, Xian Y et al.", "year": "2025", "journal": "CNS neuroscience & therapeutics", "keywords": "neuroinflammation, neurological disorders, neuroprotection, therapeutic strategy, transient receptor potential ion channels", "chunk": "contributions of TRP channels as mediators of inflammation in neuropathic pain, migraine, stroke, MS, AD, PD, ASD, epilepsy, and psychiatric disorders. Furthermore, we also evaluate emerging therapeutic strategies targeting TRP channels, encompassing both nonpharmacological approaches and pharmacological interventions. By integrating mechanistic insights with translational perspectives, this review highlights TRP channels as promising targets for precision medicine and underscores their potential in the development of novel, mechanism-based therapies for complex neurological disorders, thereby advancing a new era of targeted neuroimmunomodulation.", "source": "PubMed"}, {"chunk_id": "41751215_0", "pmid": "41751215", "title": "Blood Pressure Variability (BPV) as a Novel Digital Biomarker of Multisystem Risk and Diagnostic Insight: Measurement, Mechanisms, and Emerging Artificial Intelligence Methods.", "authors": "Pugalenthi LS, Senapati SG, Gohri J et al.", "year": "2026", "journal": "Biomedicines", "keywords": "ambulatory blood pressure monitoring, autonomic dysfunction, vascular stiffness, visit-to-visit variability, wearable monitoring", "chunk": "Hypertension has been traditionally known to be highlighted by mean blood pressure; however, emerging evidence exhibits that blood pressure variability (BPV), including short-term, day-to-day, and visit-to-visit fluctuations can have an implication across multiple body systems. Elevated BPV reflects repetitive hemodynamic stress, affecting the physiologic hemostasis contributing to vascular injury and end organ damage. This narrative review is a compilation of recent evidence on the prognostic value of BPV, explained by pathophysiology, various devices with its measurement approaches, and, essentially, the clinical implication of BPV and the use of such devices utilizing artificial intelligence. A comprehensive literature search across PubMed, Cochrane Library, Scopus, and Web of Science were conducted, focusing on observational studies, cohorts, randomized trials, and meta-analyses. Higher BPV has been associated with an increased risk of cardiovascular mortality, stroke, coronary events, and heart failure, the progression of chronic kidney disease, cognitive decline, and preeclampsia, among other end organ damage,", "source": "PubMed"}, {"chunk_id": "41751215_1", "pmid": "41751215", "title": "Blood Pressure Variability (BPV) as a Novel Digital Biomarker of Multisystem Risk and Diagnostic Insight: Measurement, Mechanisms, and Emerging Artificial Intelligence Methods.", "authors": "Pugalenthi LS, Senapati SG, Gohri J et al.", "year": "2026", "journal": "Biomedicines", "keywords": "ambulatory blood pressure monitoring, autonomic dysfunction, vascular stiffness, visit-to-visit variability, wearable monitoring", "chunk": "been associated with an increased risk of cardiovascular mortality, stroke, coronary events, and heart failure, the progression of chronic kidney disease, cognitive decline, and preeclampsia, among other end organ damage, despite mean blood pressure. The various pathophysiologic mechanisms include autonomic dysregulation, arterial stiffness, endothelial dysfunction, circadian rhythm alteration, and systemic inflammation, which result in vascular remodeling and multisystem damage. Antihypertensive medications such as calcium channel blockers and renin-angiotensin-aldosterone system inhibitors seem to reduce BPV; randomized trials have not specifically investigated their BPV-reducing effects. The aim of this review is to highlight that BPV is a dynamic marker of multisystem risk, and question how various AI-based devices can aid continuous BPV monitoring and patient specific risk stratification.", "source": "PubMed"}, {"chunk_id": "40474028_0", "pmid": "40474028", "title": "Bioactive compound nanoparticles for Alzheimer's disease.", "authors": "Kshirsagar N, Patil A, Suryawanshi M", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer, Amyloid beta, Bioactive, Nanoparticles, Tau pathology", "chunk": "Alzheimer's disease is regarded as a type of dementia that has significantly affected a large population, thus posing a global health concern. The amyloid beta hypothesis and tau pathology define the disease pathology. The hallmarks of this disease are defined by the presence of neurofibrillary tangles and senile plaques, thus supporting the theories presented above. Oxidative stress and neuroinflammation can also serve as therapeutic targets for treatment. Current conventional treatments have focused on managing the symptoms rather than modifying the disease. One of the major challenges this delivery systems face is their inability to cross the blood-brain barrier; hence, the development of nanoparticle delivery systems incorporates the required active component and utilizes different mechanisms such as transcytosis, cell-mediated transport, or advanced techniques to surpass the blood-brain barrier. Bioactive components possess multiple advantages such as being anti-inflammatory and antioxidant in nature. They also target the main pathology involved in the aggregation", "source": "PubMed"}, {"chunk_id": "40474028_1", "pmid": "40474028", "title": "Bioactive compound nanoparticles for Alzheimer's disease.", "authors": "Kshirsagar N, Patil A, Suryawanshi M", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer, Amyloid beta, Bioactive, Nanoparticles, Tau pathology", "chunk": "advanced techniques to surpass the blood-brain barrier. Bioactive components possess multiple advantages such as being anti-inflammatory and antioxidant in nature. They also target the main pathology involved in the aggregation of amyloid fibres and hyperphosphorylation of tau proteins. Various bioactive nanoparticles have been demonstrated in disease models to operate on certain targets and facilitate blood-brain barrier crossing. The article also covers the salient features of some of the nanoparticle systems under investigation separating them based on the norms of those aimed at addressing various disease pathologies. Despite being able to address the main issues with traditional drug delivery, they nevertheless have some disadvantages, such as toxicity, bioavailability, and regulatory barriers. However, the prospects for bioactive nanoparticles appear bright.", "source": "PubMed"}, {"chunk_id": "41545748_0", "pmid": "41545748", "title": "CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.", "authors": "Wang L, Liu Y, Li F et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "Alzheimer's disease, CX3CL1, aging, amnestic mild cognitive impairment, cognitively normal, inflammatory chemokines, plasma", "chunk": "Alzheimer's disease (AD) is characterized by amyloid-beta plaques, tau tangles, and neuroinflammation. C-X3-C motif chemokine ligand 1 (CX3CL1, also known as fractalkine), a neuroimmune chemokine implicated in AD pathogenesis, shows inconsistent alterations in plasma/serum across studies. Specifically examining age-dependency and diagnostic utility, we investigated plasma CX3CL1 levels across the cognitive continuum (cognitively normal [CN], amnestic mild cognitive impairment [aMCI], AD) in a Chinese cohort. A total of 443 participants, including 130 patients with AD, 72 patients with aMCI, and 99 age-and sex-matched CN controls, as well as a cohort of 142 CN subjects of different ages, were enrolled from Chongqing General Hospital. Plasma CX3CL1 levels were determined using Enzyme-Linked Immunosorbent Assay (ELISA). Apolipoprotein E genotypes (APOE) were performed. The correlations between Plasma CX3CL1 levels and cognition test scores or age were analyzed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. Plasma CX3CL1 levels significantly", "source": "PubMed"}, {"chunk_id": "41545748_1", "pmid": "41545748", "title": "CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.", "authors": "Wang L, Liu Y, Li F et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "Alzheimer's disease, CX3CL1, aging, amnestic mild cognitive impairment, cognitively normal, inflammatory chemokines, plasma", "chunk": "between Plasma CX3CL1 levels and cognition test scores or age were analyzed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. Plasma CX3CL1 levels significantly increased with age in CN individuals. No significant sex difference was found. Plasma CX3CL1 levels did not differ significantly between APOE \u03b54 carriers and non-carriers. Stepwise elevation across continuum: CX3CL1 levels showed a significant stepwise increase: CN controls (1.73 \u00b1 0.51 ng/mL) < aMCI (2.40 \u00b1 1.06 ng/mL) < AD (4.15 \u00b1 1.24 ng/mL) (p < 0.001 between all groups). This pattern persisted in both male and female subgroups, between the AD group and the aMCI group, between the AD group and the CN control group (p < 0.001), between the aMCI group and the CN control group, and between the male and female subgroups (p < 0.05). CX3CL1 levels negatively correlated with Mini-Mental State Examination (MMSE) scores and positively", "source": "PubMed"}, {"chunk_id": "41545748_2", "pmid": "41545748", "title": "CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.", "authors": "Wang L, Liu Y, Li F et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "Alzheimer's disease, CX3CL1, aging, amnestic mild cognitive impairment, cognitively normal, inflammatory chemokines, plasma", "chunk": "the aMCI group and the CN control group, and between the male and female subgroups (p < 0.05). CX3CL1 levels negatively correlated with Mini-Mental State Examination (MMSE) scores and positively correlated with age. Plasma CX3CL1 levels exhibit a significant age-dependent increase in cognitively normal individuals, peak in midlife (40-49 years), and demonstrate a stepwise elevation across the AD continuum (CN \u2192 aMCI \u2192 AD). Strong inverse correlations with cognitive scores in disease groups and high diagnostic accuracy for AD, particularly against CN, support its role as a biomarker reflecting both physiological aging and AD-related pathological decline. Its regulation appears independent of APOE \u03b54 status. The midlife peak suggests potential relevance for preclinical processes, warranting further investigation of CX3CL1 as a biomarker and therapeutic target.", "source": "PubMed"}, {"chunk_id": "41545748_3", "pmid": "41545748", "title": "CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.", "authors": "Wang L, Liu Y, Li F et al.", "year": "2026", "journal": "Annals of clinical and translational neurology", "keywords": "Alzheimer's disease, CX3CL1, aging, amnestic mild cognitive impairment, cognitively normal, inflammatory chemokines, plasma", "chunk": "biomarker and therapeutic target.", "source": "PubMed"}, {"chunk_id": "41347197_0", "pmid": "41347197", "title": "Toward Personalized Medicine in Parkinson's Disease: A Scoping Review of Biomarkers, Genetics, and Treatment Stratification.", "authors": "Abola P, Jabishvili G", "year": "2025", "journal": "Journal of clinical practice and research", "keywords": "Biomarkers, Parkinson\u2019s disease, genetics, personalized medicine, stratification", "chunk": "Personalized medicine is transforming Parkinson's disease (PD) care by tailoring therapies to patients' genetic, biomarker, and clinical profiles. Given PD's heterogeneity, this strategy offers new possibilities for disease-modifying interventions beyond symptom management. A systematic search of PubMed and EBSCO MegaFILE was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Studies addressed genetic profiling, biomarker discovery, individualized therapeutic strategies, or experimental/computational models relevant to personalized PD care. Twenty studies were included. Major themes identified were the use of genetic markers such as <i>LRRK2</i> and <i>GBA</i> mutations for patient stratification; advances in alpha-synuclein and other biomarkers for early diagnosis, though standardization remains a barrier; the application of patient-derived induced pluripotent stem cell (iPSC) models and brain organoids to test genotype-specific therapies; and the integration of multi-omics and machine learning to refine disease subtyping and drug discovery. Challenges included limited access to genetic testing, a lack of", "source": "PubMed"}, {"chunk_id": "41347197_1", "pmid": "41347197", "title": "Toward Personalized Medicine in Parkinson's Disease: A Scoping Review of Biomarkers, Genetics, and Treatment Stratification.", "authors": "Abola P, Jabishvili G", "year": "2025", "journal": "Journal of clinical practice and research", "keywords": "Biomarkers, Parkinson\u2019s disease, genetics, personalized medicine, stratification", "chunk": "organoids to test genotype-specific therapies; and the integration of multi-omics and machine learning to refine disease subtyping and drug discovery. Challenges included limited access to genetic testing, a lack of validated biomarkers, and barriers to clinical translation. Personalized medicine in PD is progressing rapidly, but significant barriers remain before it can be fully integrated into routine care. Future priorities include validating biomarkers, expanding pharmacogenetic infrastructure, and translating biologically informed strategies into clinical practice.", "source": "PubMed"}, {"chunk_id": "34731771_0", "pmid": "34731771", "title": "Degenerative adversarial neuroimage nets for brain scan simulations: Application in ageing and dementia.", "authors": "Ravi D, Blumberg SB, Ingala S et al.", "year": "2022", "journal": "Medical image analysis", "keywords": "4D-DANI-Net, 4D-MRI, Adversarial training, Ageing, Brain, Dementia, Disease progression modelling, Generative models, Neuro-image, Neurodegeneration, Synthetic-images", "chunk": "Accurate and realistic simulation of high-dimensional medical images has become an important research area relevant to many AI-enabled healthcare applications. However, current state-of-the-art approaches lack the ability to produce satisfactory high-resolution and accurate subject-specific images. In this work, we present a deep learning framework, namely 4D-Degenerative Adversarial NeuroImage Net (4D-DANI-Net), to generate high-resolution, longitudinal MRI scans that mimic subject-specific neurodegeneration in ageing and dementia. 4D-DANI-Net is a modular framework based on adversarial training and a set of novel spatiotemporal, biologically-informed constraints. To ensure efficient training and overcome memory limitations affecting such high-dimensional problems, we rely on three key technological advances: i) a new 3D training consistency mechanism called Profile Weight Functions (PWFs), ii) a 3D super-resolution module and iii) a transfer learning strategy to fine-tune the system for a given individual. To evaluate our approach, we trained the framework on 9852 T1-weighted MRI scans from 876 participants in the Alzheimer's", "source": "PubMed"}, {"chunk_id": "34731771_1", "pmid": "34731771", "title": "Degenerative adversarial neuroimage nets for brain scan simulations: Application in ageing and dementia.", "authors": "Ravi D, Blumberg SB, Ingala S et al.", "year": "2022", "journal": "Medical image analysis", "keywords": "4D-DANI-Net, 4D-MRI, Adversarial training, Ageing, Brain, Dementia, Disease progression modelling, Generative models, Neuro-image, Neurodegeneration, Synthetic-images", "chunk": "transfer learning strategy to fine-tune the system for a given individual. To evaluate our approach, we trained the framework on 9852 T1-weighted MRI scans from 876 participants in the Alzheimer's Disease Neuroimaging Initiative dataset and held out a separate test set of 1283 MRI scans from 170 participants for quantitative and qualitative assessment of the personalised time series of synthetic images. We performed three evaluations: i) image quality assessment; ii) quantifying the accuracy of regional brain volumes over and above benchmark models; and iii) quantifying visual perception of the synthetic images by medical experts. Overall, both quantitative and qualitative results show that 4D-DANI-Net produces realistic, low-artefact, personalised time series of synthetic T1 MRI that outperforms benchmark models.", "source": "PubMed"}, {"chunk_id": "37357279_0", "pmid": "37357279", "title": "Adding the Topographical Information from Tau-PET to the A/T/(N) Framework: Steps Towards Staging AD in Vivo.", "authors": "Therriault J, Gauthier S, Rosa-Neto P", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Positron Emission Tomography, Tau, disease staging", "chunk": "Biomarkers have revolutionized the study and clinical diagnosis of Alzheimer's disease (AD). While amyloid-\u03b2 accumulation begins decades before the onset of clinical dementia in AD, tau pathology is more closely associated in both space and time to neurodegeneration and to clinical dysfunction. Correspondingly, tau-PET may prove useful in determining the severity of AD. Building on the biological research framework for AD, we review here methods and rationale to stage the severity of AD in vivo using the topographical distribution of tau-PET. We discuss how tau-PET can be used to detect early and subthreshold tau accumulation in medial temporal cortices prior to the onset of cognitive symptoms. Furthermore, tau-PET can be used to monitor the severity of AD as tau-PET spreads to association cortices and finally primary sensory cortices. We discuss the utility of tau-PET to monitor the progression of AD, the flexibility of potential approaches, and applications for clinical trials.", "source": "PubMed"}, {"chunk_id": "37357279_1", "pmid": "37357279", "title": "Adding the Topographical Information from Tau-PET to the A/T/(N) Framework: Steps Towards Staging AD in Vivo.", "authors": "Therriault J, Gauthier S, Rosa-Neto P", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Positron Emission Tomography, Tau, disease staging", "chunk": "to association cortices and finally primary sensory cortices. We discuss the utility of tau-PET to monitor the progression of AD, the flexibility of potential approaches, and applications for clinical trials. In this regard, topographical information from tau-PET is a useful addition to the A/T/(N) framework.", "source": "PubMed"}, {"chunk_id": "41174069_0", "pmid": "41174069", "title": "Elevated plasma GFAP levels in MCI link APOE \u03b54 allele with impaired gait speed.", "authors": "Sakurai R, Suzuki H, Fujiwara Y et al.", "year": "2025", "journal": "GeroScience", "keywords": "APOE \u03b54, AD pathology, GFAP, Slow gait", "chunk": "The presence of at least one copy of the apolipoprotein \u03b54 allele (APOE \u03b54) is a known predictor of gait impairment risk among older adults. However, the mechanisms by which APOE \u03b54 affects gait performance remain unclear. This cross-sectional study aimed to reveal underlying pathological mechanisms linking APOE \u03b54 carriage to slow gait. This secondary analysis used baseline assessments from the J-MINT multicenter intervention trial, focusing on older adults with mild cognitive impairment. Gait speed was measured at baseline, with slow gait (SG) defined as speeds one standard deviation below the age- and sex-specific mean. APOE phenotype and plasma biomarkers related to Alzheimer's disease (AD), including amyloid-\u03b2 composite biomarker, phosphorylated Tau 181, neurofilament light, and glial fibrillary acidic protein (GFAP), were also measured. The analysis included 236 non-APOE \u03b54 carriers and 84 carriers of at least one APOE \u03b54. APOE \u03b54 carriers exhibited significantly slower gait speed than non-carriers (1.20", "source": "PubMed"}, {"chunk_id": "41174069_1", "pmid": "41174069", "title": "Elevated plasma GFAP levels in MCI link APOE \u03b54 allele with impaired gait speed.", "authors": "Sakurai R, Suzuki H, Fujiwara Y et al.", "year": "2025", "journal": "GeroScience", "keywords": "APOE \u03b54, AD pathology, GFAP, Slow gait", "chunk": "were also measured. The analysis included 236 non-APOE \u03b54 carriers and 84 carriers of at least one APOE \u03b54. APOE \u03b54 carriers exhibited significantly slower gait speed than non-carriers (1.20 m/s [SD = 0.22] vs 1.26 m/s [SD = 0.23], p = 0.042). Significant interaction between APOE \u03b54 carriage and SG was observed only in plasma GFAP levels (F<sub>1, 312</sub> = 7.17, p = 0.008), indicating that individuals with APOE \u03b54 and SG had significantly higher plasma GFAP levels. Elevated plasma GFAP levels fully mediated the association between APOE \u03b54 carriage and gait speed (partially standardized indirect effect = -0.059: -0.12 to -0.013]). No other AD-related biomarkers mediated this association. Our results suggest that APOE \u03b54-related gait changes may reflect AD pathology, as indicated by elevated GFAP levels, and could potentially accelerate dementia symptoms.", "source": "PubMed"}, {"chunk_id": "41174069_2", "pmid": "41174069", "title": "Elevated plasma GFAP levels in MCI link APOE \u03b54 allele with impaired gait speed.", "authors": "Sakurai R, Suzuki H, Fujiwara Y et al.", "year": "2025", "journal": "GeroScience", "keywords": "APOE \u03b54, AD pathology, GFAP, Slow gait", "chunk": "AD pathology, as indicated by elevated GFAP levels, and could potentially accelerate dementia symptoms.", "source": "PubMed"}, {"chunk_id": "39177596_0", "pmid": "39177596", "title": "Long-Term Safety of Gantenerumab in Participants with Alzheimer's Disease: A Phase III, Double-Blind, and Open-Label Extension Study (Marguerite RoAD).", "authors": "Neve A, Das B, Wojtowicz J et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, clinical efficacy, clinical trial, gantenerumab, safety", "chunk": "Gantenerumab is an anti-amyloid-\u03b2 immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in Marguerite RoAD (MR; NCT02051608), a Phase III, double-blind (DB), placebo-controlled study in participants with mild Alzheimer's disease (AD) dementia. Following a preplanned futility analysis of the SCarlet RoAD study (NCT01224106), MR was converted into an open-label extension (OLE). The DB study aimed to assess the efficacy of gantenerumab compared with placebo from baseline to Week 104 in participants with mild AD dementia. Following conversion to an OLE, this objective became exploratory, as the OLE assessed the long-term safety and tolerability of SC gantenerumab at doses of up to 1,200 mg every 4 weeks (Q4W) in OLE participants. Eligible DB study participants were offered the opportunity to receive gantenerumab up-titrated to 1,200 mg Q4W. Safety and tolerability were assessed using magnetic resonance imaging (MRI),", "source": "PubMed"}, {"chunk_id": "39177596_1", "pmid": "39177596", "title": "Long-Term Safety of Gantenerumab in Participants with Alzheimer's Disease: A Phase III, Double-Blind, and Open-Label Extension Study (Marguerite RoAD).", "authors": "Neve A, Das B, Wojtowicz J et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, clinical efficacy, clinical trial, gantenerumab, safety", "chunk": "(Q4W) in OLE participants. Eligible DB study participants were offered the opportunity to receive gantenerumab up-titrated to 1,200 mg Q4W. Safety and tolerability were assessed using magnetic resonance imaging (MRI), physical and neurologic examinations, and adverse event monitoring. Overall, 225 participants were rolled over from the DB part of MR and received \u22651 gantenerumab dose in the OLE. The median treatment duration was 123 weeks. Fifty-nine (26.2%) and 41 (18.2%) participants had amyloid-related imaging abnormality (ARIA)-edema and ARIA-hemorrhage MRI findings, respectively. ARIA findings were manageable with MRI monitoring and dose intervention; most were asymptomatic. There were no unexpected safety findings. SC gantenerumab at doses of up to 1,200 mg Q4W were well tolerated in participants with mild AD dementia.", "source": "PubMed"}, {"chunk_id": "41503096_0", "pmid": "41503096", "title": "MethConvTransformer: A Deep Learning Framework for Cross-Tissue Alzheimer's Disease Detection.", "authors": "Qu G, Li G, Zhao Z", "year": "2026", "journal": "ArXiv", "keywords": "Alzheimer\u2019s disease (AD), DNA methylation, biomarkers, cross-tissue analysis, deep learning, explainable artificial intelligence (XAI), transformer models", "chunk": "Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline and widespread epigenetic dysregulation in the brain. DNA methylation, as a stable yet dynamic epigenetic modification, holds promise as a noninvasive biomarker for early AD detection. However, methylation signatures vary substantially across tissues and studies, limiting reproducibility and translational utility. To address these challenges, we develop MethConvTransformer, a transformer-based deep learning framework that integrates DNA methylation profiles from both brain and peripheral tissues to enable biomarker discovery. The model couples a CpG-wise linear projection with convolutional and self-attention layers to capture local and long-range dependencies among CpG sites, while incorporating subject-level covariates and tissue embeddings to disentangle shared and region-specific methylation effects. In experiments across six GEO datasets and an independent ADNI validation cohort, our model consistently outperforms conventional machine-learning baselines, achieving superior discrimination and generalization. Moreover, interpretability analyses using linear projection, SHAP, and Grad-CAM++ reveal biologically", "source": "PubMed"}, {"chunk_id": "41503096_1", "pmid": "41503096", "title": "MethConvTransformer: A Deep Learning Framework for Cross-Tissue Alzheimer's Disease Detection.", "authors": "Qu G, Li G, Zhao Z", "year": "2026", "journal": "ArXiv", "keywords": "Alzheimer\u2019s disease (AD), DNA methylation, biomarkers, cross-tissue analysis, deep learning, explainable artificial intelligence (XAI), transformer models", "chunk": "datasets and an independent ADNI validation cohort, our model consistently outperforms conventional machine-learning baselines, achieving superior discrimination and generalization. Moreover, interpretability analyses using linear projection, SHAP, and Grad-CAM++ reveal biologically meaningful methylation patterns aligned with AD-associated pathways, including immune receptor signaling, glycosylation, lipid metabolism, and endomembrane (ER/Golgi) organization. Together, these results indicate that MethConvTransformer delivers robust, cross-tissue epigenetic biomarkers for AD while providing multi-resolution interpretability, thereby advancing reproducible methylation-based diagnostics and offering testable hypotheses on disease mechanisms.", "source": "PubMed"}, {"chunk_id": "20025930_0", "pmid": "20025930", "title": "Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease.", "authors": "Hashimoto T, Ogino K, Shin RW et al.", "year": "2010", "journal": "Neuroscience letters", "keywords": "None", "chunk": "Amyloid precursor protein (APP) is strongly related to the onset of Alzheimer's disease. It possesses cleavage sites for beta- and gamma-secretases, and the resulting cleaved products (amyloid-beta peptides) are capable of causing neurotoxicity. Such cleavage is promoted by the Swedish and London mutations (APPSwe/Lon) inside the APP gene. Here, we characterized APPSL transgenic mice (APPSL-Tg) to determine the effects of this mutation. We observed that both the amount of insoluble amyloid-beta and the ratio of amyloid-beta 42/40 increased promptly in the brain during 6-16 months of age. Amyloid-beta plaques were observed in whole brain sections at 12 months. In contrast, the spatial memory assessed by the Morris water maze task was already impaired at 3 months, which suggested that the APPSL-Tg mice may represent an early-onset model of familial Alzheimer's disease. Furthermore, the levels of LAMP-1, a marker protein of lysosome, increased in the brain at 28 months. Such LAMP-1", "source": "PubMed"}, {"chunk_id": "20025930_1", "pmid": "20025930", "title": "Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease.", "authors": "Hashimoto T, Ogino K, Shin RW et al.", "year": "2010", "journal": "Neuroscience letters", "keywords": "None", "chunk": "APPSL-Tg mice may represent an early-onset model of familial Alzheimer's disease. Furthermore, the levels of LAMP-1, a marker protein of lysosome, increased in the brain at 28 months. Such LAMP-1 protein was detected around the amyloid-beta plaques at the hippocampal regions of the APPSL-Tg mice. Our results suggested that the increase in LAMP-1 was enhanced by the accumulation of amyloid-beta occurring during aging. Our findings coincided with the pathological hallmarks of Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "40951922_0", "pmid": "40951922", "title": "Emerging biomarkers of postoperative delirium at the intersection of neuroinflammation and neurodegeneration.", "authors": "Leng K, Maze M, Barreto Chang OL", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, GFAP, IL-6 (interleukin 6), neurofilament light (NfL), neuroinflammation, perioperative neurocognitive disorders (PND), postoperative delirium (POD), tau", "chunk": "Postoperative delirium (POD) is a common and severe neuropsychiatric complication affecting older adults after surgery. POD is characterized by fluctuating cognitive disturbances, impaired attention, and altered consciousness, resulting in increased morbidity and mortality, prolonged hospital stays, and higher healthcare costs. Systemic inflammation induced by surgical trauma is implicated in the pathophysiology of POD, although the subsequent mechanisms that produce blood-brain barrier (BBB) dysfunction, neuroinflammation, and interactions with underlying dementia neuropathology have not been resolved. Recent advances in biomarker research have shed light on predictive and diagnostic tools for POD. Biomarkers linked to dementia neuropathology (e.g., hyperphosphorylated tau, amyloid beta), neuronal injury (e.g., total tau, neurofilament light chain), glial activation (e.g., glial fibrillary acidic protein), and systemic inflammation (e.g., interleukin-6) have shown promise. The feasibility of measuring the above biomarkers in easy-to-obtain biofluids such as blood is enhanced by technologies like single-molecule array immunoassays, enabling sensitive detection of central nervous system", "source": "PubMed"}, {"chunk_id": "40951922_1", "pmid": "40951922", "title": "Emerging biomarkers of postoperative delirium at the intersection of neuroinflammation and neurodegeneration.", "authors": "Leng K, Maze M, Barreto Chang OL", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, GFAP, IL-6 (interleukin 6), neurofilament light (NfL), neuroinflammation, perioperative neurocognitive disorders (PND), postoperative delirium (POD), tau", "chunk": "shown promise. The feasibility of measuring the above biomarkers in easy-to-obtain biofluids such as blood is enhanced by technologies like single-molecule array immunoassays, enabling sensitive detection of central nervous system markers at femtomolar concentrations. Emerging evidence highlights associations between POD risk and these biomarkers, although findings often vary due to cohort heterogeneity and methodological differences. This review critically examines the existing literature on POD biomarkers, focusing on their relevance to dementia neuropathology, neuronal injury, neuroinflammation, and BBB integrity. While significant strides have been made, gaps in knowledge persist, emphasizing the need for larger, more standardized studies. Developing robust biomarkers could transform POD prediction, diagnosis, and management, ultimately improving outcomes for vulnerable surgical populations.", "source": "PubMed"}, {"chunk_id": "31614723_0", "pmid": "31614723", "title": "Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1.", "authors": "Bianchi M, D'Oria V, Braghini MR et al.", "year": "2019", "journal": "International journal of molecular sciences", "keywords": "2-deoxy-d-glucose, Alzheimer\u2019s disease, Pin1, brain glucotoxicity, brain insulin resistance, liraglutide, methylglyoxal, type 2 diabetes, type 3 diabetes", "chunk": "Post-translational modulation of peptidylprolyl isomerase Pin1 might link impaired glucose metabolism and neurodegeneration, being Pin1 effectors target for the glucagon-Like-Peptide1 analog liraglutide. We tested the hypotheses in Pin1 silenced cells (SH-SY5Y) treated with 2-deoxy-d-glucose (2DG) and methylglyoxal (MG), stressors causing altered glucose trafficking, glucotoxicity and protein glycation. Rescue by liraglutide was investigated. Pin1 silencing caused increased levels of reactive oxygen species, upregulated energy metabolism as suggested by raised levels of total ATP content and mRNA of SIRT1, PGC1\u03b1, NRF1; enhanced mitochondrial fission events as supported by raised protein expression of FIS1 and DRP1. 2DG and MG reduced significantly cell viability in all the cell lines. In Pin1 KD clones, 2DG exacerbated altered mitochondrial dynamics causing higher rate of fission events. Liraglutide influenced insulin signaling pathway (GSK3b/Akt); improved cell viability also in cells treated with 2DG; but it did not revert mitochondrial dysfunction in Pin1 KD model. In cells treated with", "source": "PubMed"}, {"chunk_id": "31614723_1", "pmid": "31614723", "title": "Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1.", "authors": "Bianchi M, D'Oria V, Braghini MR et al.", "year": "2019", "journal": "International journal of molecular sciences", "keywords": "2-deoxy-d-glucose, Alzheimer\u2019s disease, Pin1, brain glucotoxicity, brain insulin resistance, liraglutide, methylglyoxal, type 2 diabetes, type 3 diabetes", "chunk": "Liraglutide influenced insulin signaling pathway (GSK3b/Akt); improved cell viability also in cells treated with 2DG; but it did not revert mitochondrial dysfunction in Pin1 KD model. In cells treated with MG, liraglutide enhanced cell viability, reduced ROS levels and cell death (AnnexinV/PI); and trended to reduce anti-apoptotic signals (BAX, BCL2, CASP3). Pin1 silencing mimics neuronal metabolic impairment of patients with impaired glucose metabolism and neurodegeneration. Liraglutide rescues to some extent cellular dysfunctions induced by Pin1 silencing.", "source": "PubMed"}, {"chunk_id": "37589833_0", "pmid": "37589833", "title": "Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II.", "authors": "Scheinman SB, Tseng KY, Alford S et al.", "year": "2024", "journal": "Molecular neurobiology", "keywords": "APOE4, Angiotensin II, Hippocampus, Neuron activity", "chunk": "Progressive hippocampal degeneration is a key component of Alzheimer's disease (AD) progression. Therefore, identifying how hippocampal neuronal function is modulated early in AD is an important approach to eventually prevent degeneration. AD-risk factors and signaling molecules likely modulate neuronal function, including APOE genotype and angiotensin II. Compared to APOE3, APOE4 increases AD risk up to 12-fold, and high levels of angiotensin II are hypothesized to disrupt neuronal function in AD. However, the extent that APOE and angiotensin II modulates the hippocampal neuronal phenotype in AD-relevant models is unknown. To address this issue, we used electrophysiological techniques to assess the impact of APOE genotype and angiotensin II on basal synaptic transmission, presynaptic, and post-synaptic activity in mice that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce A\u03b2. We found that compared to E3FAD mice, E4FAD mice have lower synaptic activity, but higher levels of paired-pulse facilitation (PPF) and long-term potentiation", "source": "PubMed"}, {"chunk_id": "37589833_1", "pmid": "37589833", "title": "Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II.", "authors": "Scheinman SB, Tseng KY, Alford S et al.", "year": "2024", "journal": "Molecular neurobiology", "keywords": "APOE4, Angiotensin II, Hippocampus, Neuron activity", "chunk": "(E3FAD) or APOE4 (E4FAD) and overproduce A\u03b2. We found that compared to E3FAD mice, E4FAD mice have lower synaptic activity, but higher levels of paired-pulse facilitation (PPF) and long-term potentiation (LTP) in the Schaffer Collateral Commissural Pathway (SCCP) of the hippocampus. We also found that exogenous angiotensin II has a profound inhibitory effect on hippocampal LTP in both E3FAD and E4FAD mice. Collectively, our data suggests that APOE4 and A\u03b2 are associated with a hippocampal phenotype comprised of lower basal activity and higher responses to high-frequency stimulation, the latter of which is suppressed by angiotensin II. These novel data suggest a potential mechanistic link between hippocampal activity, APOE4 genotype, and angiotensin II in AD.", "source": "PubMed"}, {"chunk_id": "40842657_0", "pmid": "40842657", "title": "Probable lecanemab-associated pontine hemorrhage following cardiovascular intervention: Clinical implications for lecanemab use.", "authors": "Chen S, Sun Y, Yao L et al.", "year": "2025", "journal": "Journal of Alzheimer's disease reports", "keywords": "Alzheimer's disease, antithrombotic therapy, lecanemab, pontine hemorrhage", "chunk": "We report a 76-year-old patient with mild cognitive impairment and <i>APOE</i> \u03b53/\u03b53 genotype who developed a rare pontine hemorrhage following treatment with lecanemab, an anti-amyloid-\u03b2 monoclonal antibody for Alzheimer's disease. She was initially on clopidogrel and rivaroxaban; rivaroxaban was discontinued prior to lecanemab initiation. After two infusions, lecanemab was paused due to angina. She then underwent coronary stenting and was placed on dual antiplatelet therapy (aspirin and clopidogrel). Pontine hemorrhage occurred after twenty days. This case highlights heightened bleeding risk when lecanemab is combined with intensified antithrombotic therapy, even without <i>APOE</i> \u03b54 or significant cerebral small vessel disease load.", "source": "PubMed"}, {"chunk_id": "40388810_0", "pmid": "40388810", "title": "Charge Polarization-Enhanced Graphene Biosensors for the Attomole Detection of miRNA.", "authors": "Lou F, Guo B, Dai J et al.", "year": "2025", "journal": "ACS nano", "keywords": "Alzheimer, Debye screening, biosensors, charge polarization, graphene, miRNA", "chunk": "Due to graphene's structural and electrical properties, electrical biosensors made of this 2D material have drawn tremendous attention in the field of biosensing, enabling label-free, amplification-free, highly sensitive, and selective detection of diverse biological targets. However, the detection of biomolecules with minimal size and charge remains challenging due to the Debye electrostatic screening effect. This study introduces a surface chemistry treatment that employs fullerene derivatives to enhance charge transfer to the graphene biosensor interface, overcoming this limitation. Specifically, (1,2-methanofullerene C<sub>60</sub>)-61-carboxylic acid (MFCA) is used as a linker molecule, replacing the traditional 1-pyrenebutanoic acid succinimidyl ester (PBASE). This modification facilitates the movement of electrons from biomarkers, such as microRNA (miRNA), across the Debye screening layer through a charge attraction effect. This approach achieves a detection limit (LoD) as low as 1 aM for hsa-mir-125b miRNA, a critical biomarker for Alzheimer's disease, and this is an improvement of 2-3 orders of magnitude", "source": "PubMed"}, {"chunk_id": "40388810_1", "pmid": "40388810", "title": "Charge Polarization-Enhanced Graphene Biosensors for the Attomole Detection of miRNA.", "authors": "Lou F, Guo B, Dai J et al.", "year": "2025", "journal": "ACS nano", "keywords": "Alzheimer, Debye screening, biosensors, charge polarization, graphene, miRNA", "chunk": "approach achieves a detection limit (LoD) as low as 1 aM for hsa-mir-125b miRNA, a critical biomarker for Alzheimer's disease, and this is an improvement of 2-3 orders of magnitude over previous methods. The enhanced sensitivity is attributed to the efficient electron transfer from miRNA to the graphene surface, demonstrated by density functional theory (DFT) calculation and control experiment with the PBASE linker. Further, this method is also applied in the detection of another miR-34a with an ultralow LoD of 1 aM, showing its generalizability. This work enables the application of charge polarization-enhanced electrical biosensors in the early-stage diagnosis of various diseases with ultrahigh sensitivity.", "source": "PubMed"}, {"chunk_id": "37606391_0", "pmid": "37606391", "title": "Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report.", "authors": "Rossi S, Prodi E, Morese R et al.", "year": "2023", "journal": "Neurology international", "keywords": "Alzheimer\u2019s disease, FDG-PET, SARS-CoV-2, cognitive impairment, post-COVID-19", "chunk": "At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer's disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits.", "source": "PubMed"}, {"chunk_id": "41153236_0", "pmid": "41153236", "title": "Shifting Trends in Intensive Cardiovascular Care Unit Admission Patterns: Retrospective Insights and Prospective Implications.", "authors": "Loutati R, Taha L, Karmi M et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "admission trends, intensive cardiovascular care unit, one-year mortality", "chunk": "<b>Background</b>: Intensive Cardiovascular Care Units (ICCUs) are critical in managing high-acuity cardiovascular conditions, yet contemporary data on evolving admission patterns and their association with outcomes are limited. <b>Methods</b>: We conducted a retrospective cohort study of all patients admitted to a tertiary-care ICCU between July 2019 and December 2024. Patients were stratified by admission period: early (2019-2021) and late (2022-2024). Baseline characteristics, index diagnosis, interventions, complications, and mortality outcomes were compared. The primary endpoints were in-hospital and one-year mortality. <b>Results</b>: The study included 6266 patients (median age 69 years, 32% female). Of them, 3125 and 3141 patients were admitted in the early and late periods, respectively. Patients in the later period exhibited a higher burden of co-morbidities, including increased rates of atrial fibrillation, cognitive impairment, and dialysis (<i>p</i> < 0.05 for all). The pattern of index diagnoses shifted, showing an increase in heart failure (5.6% vs. 3.7%, <i>p</i> = 0.001) and", "source": "PubMed"}, {"chunk_id": "41153236_1", "pmid": "41153236", "title": "Shifting Trends in Intensive Cardiovascular Care Unit Admission Patterns: Retrospective Insights and Prospective Implications.", "authors": "Loutati R, Taha L, Karmi M et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "admission trends, intensive cardiovascular care unit, one-year mortality", "chunk": "atrial fibrillation, cognitive impairment, and dialysis (<i>p</i> < 0.05 for all). The pattern of index diagnoses shifted, showing an increase in heart failure (5.6% vs. 3.7%, <i>p</i> = 0.001) and malignant arrhythmia admissions (13.9% vs. 9.3%, <i>p</i> < 0.001), alongside a decline in cases of NSTEMI and pulmonary embolism. The use of urgent percutaneous coronary intervention, transcatheter valvular interventions, and microaxial pumps increased, whereas intra-aortic balloon pump usage declined. In-hospital mortality remained consistent between the periods at 2.7%. However, adjusted one-year mortality was significantly reduced in the later period (adjusted HR 0.84, 95% CI 0.71-0.98, <i>p</i> = 0.037). <b>Conclusions</b>: Over five years, ICCU admissions showed increasing complexity and evolving procedural trends. Despite higher acuity, adjusted one-year survival improved, highlighting care advances and the value of continuous data-driven ICCU optimization.", "source": "PubMed"}, {"chunk_id": "41153236_2", "pmid": "41153236", "title": "Shifting Trends in Intensive Cardiovascular Care Unit Admission Patterns: Retrospective Insights and Prospective Implications.", "authors": "Loutati R, Taha L, Karmi M et al.", "year": "2025", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "admission trends, intensive cardiovascular care unit, one-year mortality", "chunk": "advances and the value of continuous data-driven ICCU optimization.", "source": "PubMed"}, {"chunk_id": "32884267_0", "pmid": "32884267", "title": "Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer's Disease: A State-of-the-Art (2017-2020).", "authors": "Binda A, Murano C, Rivolta I", "year": "2020", "journal": "International journal of nanomedicine", "keywords": "Alzheimer\u2019s disease, green synthesis, intranasal route, nanomedicine, nanoparticles, nutraceutical, stem cells, therapy", "chunk": "The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies", "source": "PubMed"}, {"chunk_id": "32884267_1", "pmid": "32884267", "title": "Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer's Disease: A State-of-the-Art (2017-2020).", "authors": "Binda A, Murano C, Rivolta I", "year": "2020", "journal": "International journal of nanomedicine", "keywords": "Alzheimer\u2019s disease, green synthesis, intranasal route, nanomedicine, nanoparticles, nutraceutical, stem cells, therapy", "chunk": "performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.", "source": "PubMed"}, {"chunk_id": "30804341_0", "pmid": "30804341", "title": "Disturbed homocysteine metabolism is associated with cancer.", "authors": "Hasan T, Arora R, Bansal AK et al.", "year": "2019", "journal": "Experimental & molecular medicine", "keywords": "None", "chunk": "Hyperhomocysteinemia/Homocysteinuria is characterized by an increased level of toxic homocysteine in the plasma. The plasma concentration of homocysteine is 5-15 \u03bcmol/L in healthy individuals, while in hyperhomocysteinemic patients, it can be as high as 500 \u03bcmol/L. While increased homocysteine levels can cause symptoms such as osteoporosis and eye lens dislocation, high homocysteine levels are most closely associated with cardiovascular complications. Recent advances have shown that increased plasma Hcy is also a fundamental cause of neurodegenerative diseases (including Alzheimer's disease, Parkinson's disease, and dementia), diabetes, Down syndrome, and megaloblastic anemia, among others. In recent years, increased plasma homocysteine has also been shown to be closely related to cancer. In this review, we discuss the relation between elevated plasma Hcy levels and cancer, and we conclude that disturbed homocysteine metabolism is associated with cancer. Future clinical perspectives are also discussed.", "source": "PubMed"}, {"chunk_id": "30804341_1", "pmid": "30804341", "title": "Disturbed homocysteine metabolism is associated with cancer.", "authors": "Hasan T, Arora R, Bansal AK et al.", "year": "2019", "journal": "Experimental & molecular medicine", "keywords": "None", "chunk": "cancer, and we conclude that disturbed homocysteine metabolism is associated with cancer. Future clinical perspectives are also discussed.", "source": "PubMed"}, {"chunk_id": "36815663_0", "pmid": "36815663", "title": "Placental growth factor as a sensitive biomarker for vascular cognitive impairment.", "authors": "Hinman JD, Elahi F, Chong D et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "biomarker, diagnosis, placental growth factor, vascular cognitive impairment", "chunk": "High-performing biomarkers measuring the vascular contributions to cognitive impairment and dementia are lacking. Using a multi-site observational cohort study design, we examined the diagnostic accuracy of plasma placental growth factor (PlGF) within the MarkVCID Consortium (n = 335; CDR 0-1). Subjects underwent clinical evaluation, cognitive testing, MRI, and blood sampling as defined by Consortium protocols. In the prospective population of 335 subjects (72.2 \u00b1 7.8 years of age, 49.3% female), plasma PlGF (pg/mL) shows an ordinal odds ratio (OR) of 1.16 (1.07-1.25; P = .0003) for increasing Fazekas score and ordinal OR of 1.22 (1.14-1.32; P < .0001) for functional cognitive impairment measured by the Clinical Dementia Rating scale. We achieved the primary study outcome of a site-independent association of plasma PlGF (pg/mL) with white matter injury and cognitive impairment in two of three study cohorts. Secondary outcomes using the full MarkVCID cohort demonstrated that plasma PlGF can significantly discriminate", "source": "PubMed"}, {"chunk_id": "36815663_1", "pmid": "36815663", "title": "Placental growth factor as a sensitive biomarker for vascular cognitive impairment.", "authors": "Hinman JD, Elahi F, Chong D et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "biomarker, diagnosis, placental growth factor, vascular cognitive impairment", "chunk": "plasma PlGF (pg/mL) with white matter injury and cognitive impairment in two of three study cohorts. Secondary outcomes using the full MarkVCID cohort demonstrated that plasma PlGF can significantly discriminate individuals with Fazekas \u2265 2 and CDR = 0.5 (area under the curve [AUC] = 0.74) and CDR = 1 (AUC = 0.89) from individuals with CDR = 0. Plasma PlGF measured by standardized immunoassay functions as a stable, reliable, diagnostic biomarker for cognitive impairment associated with substantial white matter burden.", "source": "PubMed"}, {"chunk_id": "36202546_0", "pmid": "36202546", "title": "Measures of intracranial compartments in acute intracerebral haemorrhage: data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial (RIGHT-2).", "authors": "Krishnan K, Law ZK, Woodhouse LJ et al.", "year": "2023", "journal": "Stroke and vascular neurology", "keywords": "CT, Clinical Trial, Hemorrhage, Stroke", "chunk": "Intracerebral haemorrhage volume (ICHV) is prognostically important but does not account for intracranial volume (ICV) and cerebral parenchymal volume (CPV). We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes. We also assessed if cistern effacement, midline shift, old infarcts, leukoaraiosis and brain atrophy were associated with outcomes. Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were analysed. Measures included ICHV (using ABC/2) and ICV (XYZ/2) (by independent observers); ICHV, ICV and CPV (semiautomated segmentation, SAS); atrophy (intercaudate distance, ICD, Sylvian fissure ratio, SFR); midline shift; leukoaraiosis and cistern effacement (visual assessment). The effects of these measures on death at day 4 and poor functional outcome at day 90 (modified Rankin scale, mRS of >3) was assessed. ICV was significantly different between XYZ and SAS: mean (SD) of 1357 (219) vs", "source": "PubMed"}, {"chunk_id": "36202546_1", "pmid": "36202546", "title": "Measures of intracranial compartments in acute intracerebral haemorrhage: data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial (RIGHT-2).", "authors": "Krishnan K, Law ZK, Woodhouse LJ et al.", "year": "2023", "journal": "Stroke and vascular neurology", "keywords": "CT, Clinical Trial, Hemorrhage, Stroke", "chunk": "4 and poor functional outcome at day 90 (modified Rankin scale, mRS of >3) was assessed. ICV was significantly different between XYZ and SAS: mean (SD) of 1357 (219) vs 1420 (196), mean difference (MD) 62 mL (p<0.001). There was no significant difference in ICHV between ABC/2 and SAS. There was very good agreement for ICV measured by SAS, CPV, ICD, SFR, leukoaraiosis and cistern score (all interclass correlations, n=10: interobserver 0.72-0.99, intraobserver 0.73-1.00). ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90, death at day 4 and acute neurological deterioration (all p<0.05), similar to ICHV. Midline shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts, leukoaraiosis and brain atrophy were not. Intracranial compartment measures and visual estimates are reproducible. ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke. The presence of midline shift and cistern effacement", "source": "PubMed"}, {"chunk_id": "36202546_2", "pmid": "36202546", "title": "Measures of intracranial compartments in acute intracerebral haemorrhage: data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial (RIGHT-2).", "authors": "Krishnan K, Law ZK, Woodhouse LJ et al.", "year": "2023", "journal": "Stroke and vascular neurology", "keywords": "CT, Clinical Trial, Hemorrhage, Stroke", "chunk": "Intracranial compartment measures and visual estimates are reproducible. ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke. The presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.", "source": "PubMed"}, {"chunk_id": "31665653_0", "pmid": "31665653", "title": "Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol.", "authors": "Sugasini D, Yalagala PCR, Goggin A et al.", "year": "2019", "journal": "The Journal of nutritional biochemistry", "keywords": "BDNF, Blood brain barrier, Brain omega-3 fatty acids, Intestinal barrier, Neuroinflammatory diseases", "chunk": "Docosahexaenoic acid (DHA) is highly concentrated in the brain, and its deficiency is associated with several neurological disorders including Alzheimer's disease. However, the currently used supplements do not appreciably enrich brain DHA, although they enrich most other tissues. We tested the hypothesis that the ability of the dietary carrier to augment brain DHA depends upon the generation of DHA-lysophosphatidylcholine (LPC), the preferred carrier of DHA across the blood brain barrier. We compared the efficacy of DHA-triacylglycerol (TAG), di-DHA phosphatidylcholine (PC) and DHA-LPC to enrich brain DHA following their gavage to normal rats for 30 days, all at a dose of 10 mg DHA/day. The results show that DHA from TAG, which is released as free DHA or monoacylglycerol during digestion and is absorbed as TAG in chylomicrons, was incorporated preferentially into adipose tissue and heart but not into brain. In contrast, LPC-DHA increased brain DHA by up to 100% but", "source": "PubMed"}, {"chunk_id": "31665653_1", "pmid": "31665653", "title": "Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol.", "authors": "Sugasini D, Yalagala PCR, Goggin A et al.", "year": "2019", "journal": "The Journal of nutritional biochemistry", "keywords": "BDNF, Blood brain barrier, Brain omega-3 fatty acids, Intestinal barrier, Neuroinflammatory diseases", "chunk": "and is absorbed as TAG in chylomicrons, was incorporated preferentially into adipose tissue and heart but not into brain. In contrast, LPC-DHA increased brain DHA by up to 100% but had no effect on adipose tissue. Di-DHA PC, which generates both free DHA and LPC-DHA during the digestion, enriched DHA in brain, as well as in heart and liver. Brain-derived neurotrophic factor was increased by di-DHA PC and DHA-LPC, but not by TAG-DHA, showing that enrichment of brain DHA correlated with its functional effect. We conclude that dietary DHA from TAG or from natural PC (sn-2 position) is not suitable for brain enrichment, whereas DHA from LPC (at either sn-1 or sn-2 position) or from sn-1 position of PC efficiently enriches the brain and is functionally effective.", "source": "PubMed"}, {"chunk_id": "31665653_2", "pmid": "31665653", "title": "Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol.", "authors": "Sugasini D, Yalagala PCR, Goggin A et al.", "year": "2019", "journal": "The Journal of nutritional biochemistry", "keywords": "BDNF, Blood brain barrier, Brain omega-3 fatty acids, Intestinal barrier, Neuroinflammatory diseases", "chunk": "enriches the brain and is functionally effective.", "source": "PubMed"}, {"chunk_id": "41788046_0", "pmid": "41788046", "title": "Alzheimer's Biomarkers and Visuospatial Cognition in Parkinson's Disease: Modification by \u03b1-Synuclein and Mediation of Age Effects.", "authors": "Ledingham D, Sathyanarayana S, Stewart CB et al.", "year": "2026", "journal": "Movement disorders clinical practice", "keywords": "Alzheimer's disease, Parkinson's disease, biomarkers, pTau181/A\u03b242 ratio, seeding amplification assay (SAA), visuospatial cognition", "chunk": "Visuospatial deficits in Parkinson's disease (PD) often precede dementia and complicate daily functioning. Alzheimer's disease (AD) pathology and \u03b1-synuclein aggregation frequently co-occur in PD, but their combined impact on cognition is unclear. To examine whether AD biomarker burden relates to visuospatial performance in PD, whether this effect differs by \u03b1-synuclein status, and whether AD biomarkers mediate age-related decline. We analyzed 416 participants from the Parkinson's Progression Markers Initiative. AD biomarker burden was indexed by the cerebrospinal fluid pTau181/A\u03b242 ratio; \u03b1-synuclein aggregation was assessed using seed amplification assay. Models adjusted for age, sex, education, and motor severity. Sensitivity analyses included genetic stratification and subgroup exclusion. Higher AD biomarker burden was associated with poorer visuospatial performance and delayed recall. In participants with concurrent biomarker data (n = 246), AD burden interacted with \u03b1-synuclein status to predict worse visuospatial outcomes, with the greatest impairment observed in individual's positive for both biomarkers. Mediation analysis", "source": "PubMed"}, {"chunk_id": "41788046_1", "pmid": "41788046", "title": "Alzheimer's Biomarkers and Visuospatial Cognition in Parkinson's Disease: Modification by \u03b1-Synuclein and Mediation of Age Effects.", "authors": "Ledingham D, Sathyanarayana S, Stewart CB et al.", "year": "2026", "journal": "Movement disorders clinical practice", "keywords": "Alzheimer's disease, Parkinson's disease, biomarkers, pTau181/A\u03b242 ratio, seeding amplification assay (SAA), visuospatial cognition", "chunk": "concurrent biomarker data (n = 246), AD burden interacted with \u03b1-synuclein status to predict worse visuospatial outcomes, with the greatest impairment observed in individual's positive for both biomarkers. Mediation analysis indicated that AD biomarker burden accounts for approximately 10-14% of the age effect on visuospatial performance. AD and \u03b1-synuclein biomarkers show associations consistent with synergistic effects on visuospatial cognition in PD. These findings are exploratory and require replication in pre-specified independent cohorts. However, if validated, testing both biomarkers could help identify individuals at higher risk of early visuospatial decline and inform hypothesis-driven stratification in future clinical trials.", "source": "PubMed"}, {"chunk_id": "40390204_0", "pmid": "40390204", "title": "Relationships between neuropsychiatric symptoms, subtypes of astrocyte activities, and brain pathologies in Alzheimer's disease and Parkinson's disease.", "authors": "Li OY, Shin S, Zhou S et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Parkinson's disease, astrocyte, neuropsychiatric symptoms, tauopathy", "chunk": "Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative diseases (NDs). This study examined astrocytic contributions to neuropsychiatric symptoms (NPS), focusing on astrocytic protein activity and its relationship with NPS severity, accounting for clinical and pathological features of NDs. Cerebrospinal astrocytic proteins (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and aquaporin-4 [AQP4]) from Alzheimer's Disease Neuroimaging Initiative (ADNI) (AD) and Parkinson's Progression Markers Initiative (PPMI) (PD) were analyzed using K-means clustering. Six NPS domains, ND-specific pathologies (amyloid-beta/A\u03b2 for AD, alpha-synuclein/\u03b1Syn for PD), and nonspecific pathology (phosphorylated tau/ptau) were assessed. In both samples, three astrocytic clusters were identified, and the \"highYKL|lowOthers\" cluster (high YKL-40, low GFAP/AQP4) consistently showed lower ptau and NPS severity compared to the \"highAll\" cluster (high GFAP, YKL-40, AQP4). In PPMI, the \"highYKL|lowOthers\" cluster also attenuated the relationship between \u03b1Syn and NPS compared to the \"highAll\" cluster. Astrocytic activity relates to NPS, highlighting astrocytic proteins as", "source": "PubMed"}, {"chunk_id": "40390204_1", "pmid": "40390204", "title": "Relationships between neuropsychiatric symptoms, subtypes of astrocyte activities, and brain pathologies in Alzheimer's disease and Parkinson's disease.", "authors": "Li OY, Shin S, Zhou S et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Parkinson's disease, astrocyte, neuropsychiatric symptoms, tauopathy", "chunk": "GFAP, YKL-40, AQP4). In PPMI, the \"highYKL|lowOthers\" cluster also attenuated the relationship between \u03b1Syn and NPS compared to the \"highAll\" cluster. Astrocytic activity relates to NPS, highlighting astrocytic proteins as potential therapeutic targets for NPS in NDs. Astrocytic protein clusters were linked to NPS severity in AD and PD cohorts. The \"highYKL|lowOthers\" cluster showed lower ptau and NPS severity than \"allhigh\" cluster in AD and PD cohorts. Astrocytic proteins may serve as therapeutic targets for managing NPS in NDs.", "source": "PubMed"}, {"chunk_id": "40817783_0", "pmid": "40817783", "title": "Transferrin receptor-mediated transport at the blood-brain barrier is elevated during early development and maintained across aging and in an Alzheimer's mouse model.", "authors": "Torres VO, Pizzo ME, Chan D et al.", "year": "2026", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Alzheimer\u2019s disease, antibody transport vehicle, blood-brain barrier, healthy aging, transferrin receptor", "chunk": "Transferrin receptor (TfR)-targeting of biologics has emerged as a promising strategy to improve drug delivery across the blood-brain barrier (BBB). However, most preclinical studies evaluating TfR-enabled drugs have been conducted in young adult animals. It remains unclear whether age and aging-related diseases impact TfR protein levels and/or BBB transport capacity. Here, we utilized a previously described TfR-targeting antibody transport vehicle (ATV<sup>TfR</sup>) to investigate how healthy aging and disease progression in the 5xFAD mouse model of Alzheimer's disease (AD) impact TfR protein and TfR-mediated brain delivery. ATV<sup>TfR</sup> transport capacity remained stable across 3- to 24-month-old healthy mice and 5xFAD progression did not impair ATV<sup>TfR</sup> brain transport up to 10.5 months, despite significant amyloid burden. Interestingly, neonates exhibited significantly elevated levels of vascular TfR protein and ATV<sup>TfR</sup> brain exposure compared to adult mice. Furthermore, vascular TfR in AD patient brains was similar to age-matched controls, suggesting conserved TfR transport is also likely", "source": "PubMed"}, {"chunk_id": "40817783_1", "pmid": "40817783", "title": "Transferrin receptor-mediated transport at the blood-brain barrier is elevated during early development and maintained across aging and in an Alzheimer's mouse model.", "authors": "Torres VO, Pizzo ME, Chan D et al.", "year": "2026", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Alzheimer\u2019s disease, antibody transport vehicle, blood-brain barrier, healthy aging, transferrin receptor", "chunk": "vascular TfR protein and ATV<sup>TfR</sup> brain exposure compared to adult mice. Furthermore, vascular TfR in AD patient brains was similar to age-matched controls, suggesting conserved TfR transport is also likely in human AD. Overall, our data demonstrates broad functional utility for TfR-based brain delivery in both healthy aging and in an AD mouse model. Additionally, elevated TfR-mediated brain delivery during early mouse development highlights the potential of added efficacy in utilizing such platforms in disease treatment of infants and children.", "source": "PubMed"}, {"chunk_id": "41259269_0", "pmid": "41259269", "title": "Modeling the age-specific incidence of mild cognitive impairment incorporating the time-varying relationship of Alzheimer's disease biomarkers over 28 years.", "authors": "Wang K, Zhu Y, Albert M et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE genotype, Alzheimer's disease, entorhinal cortex volume, magnetic resonance imaging, mild cognitive impairment, phosphorylated tau, sex effect, total tau", "chunk": "BackgroundAs life expectancy increases, the prevalence of mild cognitive impairment (MCI) due to Alzheimer's disease is expected to rise. Biomarkers from cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI), combined with age-specific modeling, may enhance understanding of the timing and risk factors of MCI onset.ObjectiveTo estimate age-specific incidence rates of MCI onset and examine the impact of biomarkers and demographic factors on risk.MethodsWe analyzed data from 307 cognitively unimpaired BIOCARD participants with one or more CSF and MRI measurements. To account for competing risk of death, we applied age-specific cumulative incidence functions and cause-specific Cox proportional hazard models. Time-varying biomarker values were incorporated to assess their influence on MCI risk.ResultsThe cumulative incidence rate of MCI onset estimated in age brackets from 50 to 80 was 2.33% at age 55, 5.03% at age 60, 12.38% at age 65, 17.91% at age 70, 28.84% at age 75, and 46.91% at age 80.", "source": "PubMed"}, {"chunk_id": "41259269_1", "pmid": "41259269", "title": "Modeling the age-specific incidence of mild cognitive impairment incorporating the time-varying relationship of Alzheimer's disease biomarkers over 28 years.", "authors": "Wang K, Zhu Y, Albert M et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE genotype, Alzheimer's disease, entorhinal cortex volume, magnetic resonance imaging, mild cognitive impairment, phosphorylated tau, sex effect, total tau", "chunk": "from 50 to 80 was 2.33% at age 55, 5.03% at age 60, 12.38% at age 65, 17.91% at age 70, 28.84% at age 75, and 46.91% at age 80. <i>APOE4</i> carriers had a significantly increased risk before age 70 (HR = 9.55, p = 0.005). Female <i>APOE4</i> carriers showed a non-significant trend toward reduced risk compared to males (HR = 0.35, p = 0.127). Faster decline in entorhinal cortex volume (HR = 1.24, p = 0.028) and elevated p-tau<sub>181</sub> levels (HR = 1.51, p = 0.012) were both associated with increased MCI risk.ConclusionsThis study presents age-specific incidence rates of MCI and highlights the age-dependent influence of genetic and biomarker risk factors. Incorporating time-varying biomarkers provides valuable insights into dynamic risk prediction for MCI onset.", "source": "PubMed"}, {"chunk_id": "41259269_2", "pmid": "41259269", "title": "Modeling the age-specific incidence of mild cognitive impairment incorporating the time-varying relationship of Alzheimer's disease biomarkers over 28 years.", "authors": "Wang K, Zhu Y, Albert M et al.", "year": "2026", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE genotype, Alzheimer's disease, entorhinal cortex volume, magnetic resonance imaging, mild cognitive impairment, phosphorylated tau, sex effect, total tau", "chunk": "risk prediction for MCI onset.", "source": "PubMed"}, {"chunk_id": "40140189_0", "pmid": "40140189", "title": "Unveiling Gaps and Demographic Influences in Alzheimer's Therapy: A Data-Centric Study of FDA-Approved Late-Phase Clinical Trials.", "authors": "Kalokhe VM, Simran S, Ahmad A et al.", "year": "2025", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Alzheimer\u2019s disease, Clinical trials, Over-representation, Participation to prevalence ratio value, Phase 4, Under-representation", "chunk": "Alzheimer's disease is more prevalent in women than in men. In this study, the author examined the U.S. Food and Drug Administration (FDA) completed phase 4 clinical trials associated with Alzheimer's. The research aims to evaluate the women's participation-to-prevalence ratio (PPR) for Alzheimer's disease. Using the FDA's publicly available clinical trial database, 45 Phase 4 Alzheimer's trials from 2003 to 2019 were assessed. Further, the total PPR and yearly PPR value are calculated by dividing the percentage of women in clinical trials by the total percentage of women affected by Alzheimer's disease. The PPR value equal to 1 showcases the balanced participation of females in the Phase 4 clinical trial and the diseased affected population. Out of 45 trials, 41 were completed and four were terminated. The gender data was unavailable for three trials. In 38 clinical trials associated with Alzheimer's disease, 4502 participants were enrolled. Among 4502, 2604 (57.84%)", "source": "PubMed"}, {"chunk_id": "40140189_1", "pmid": "40140189", "title": "Unveiling Gaps and Demographic Influences in Alzheimer's Therapy: A Data-Centric Study of FDA-Approved Late-Phase Clinical Trials.", "authors": "Kalokhe VM, Simran S, Ahmad A et al.", "year": "2025", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Alzheimer\u2019s disease, Clinical trials, Over-representation, Participation to prevalence ratio value, Phase 4, Under-representation", "chunk": "were completed and four were terminated. The gender data was unavailable for three trials. In 38 clinical trials associated with Alzheimer's disease, 4502 participants were enrolled. Among 4502, 2604 (57.84%) were found to be female and 1898 (42.15%) were male. The PPR for women was 0.80, reflecting an adequate representation of women participants in late-phase clinical trials. The yearly PPR reduction has been seen in female participants. In the year-based PPR, the range was from 0.72-1.0. In the initial year, the range was 1, which was reduced to 0.72 in 2007. In total, 38 completed clinical trials, 18 trials used placebo treatment, and the gender ratio in placebo was adequate. More transparency is essential in gender concerning SAE in publicly available databases.", "source": "PubMed"}, {"chunk_id": "40140189_2", "pmid": "40140189", "title": "Unveiling Gaps and Demographic Influences in Alzheimer's Therapy: A Data-Centric Study of FDA-Approved Late-Phase Clinical Trials.", "authors": "Kalokhe VM, Simran S, Ahmad A et al.", "year": "2025", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Alzheimer\u2019s disease, Clinical trials, Over-representation, Participation to prevalence ratio value, Phase 4, Under-representation", "chunk": "available databases.", "source": "PubMed"}, {"chunk_id": "41073382_0", "pmid": "41073382", "title": "Magnitude and predictors of mild cognitive impairment among older populations in Africa: a systematic review and meta-analysis.", "authors": "Asnakew S, Nealon J, Semachew Kasa A et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "With an increasingly older population, age-related health issues such as mild cognitive impairment and dementia are serious public health concerns. Emerging data suggest that public health and preventative intervention strategies can modify early risk factors for the development of mild cognitive impairment and dementia. However, there is inadequate evidence of mild cognitive impairment in older populations in Africa. Therefore, this review aimed to provide pooled evidence of mild cognitive impairment among older populations and its predictors in Africa. All the available primary studies were searched through Google Scholar, HINARI, PubMed, Psych Info, CINAHL, Embase, Web of Science, and Cochrane Library databases. The quality of the included studies was critically appraised by the Joanna Briggs Institute (JBI) assessment tool adapted for observational studies. All the data were extracted on an Excel spreadsheet and exported to Stata version 17. During critical appraisal, disagreements between the two authors were resolved by the involvement", "source": "PubMed"}, {"chunk_id": "41073382_1", "pmid": "41073382", "title": "Magnitude and predictors of mild cognitive impairment among older populations in Africa: a systematic review and meta-analysis.", "authors": "Asnakew S, Nealon J, Semachew Kasa A et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "observational studies. All the data were extracted on an Excel spreadsheet and exported to Stata version 17. During critical appraisal, disagreements between the two authors were resolved by the involvement of a third author. Effect sizes were pooled using the random-effects model, and the presence of publication bias was detected from the asymmetry of the funnel plot and statistically significant Egger's test (p < 0.05). The pooled magnitude of mild cognitive impairment among older populations was 29.39% (95% CI:24.73, 34.04, I<sup>2</sup> = 98.05%, P = 0.00). Increased age 1.56 (95%CI:1.36, 1.79), being female 2.65 (95%CI:2.06, 3.400), participants who could not read and write 4.66 (95%CI:2.83, 7.67), have no spouse 4.27 (95%CI:1.06, 17.11), having hypertension 2.95 (95%CI:1.67, 5.20), severely dependent 7.66 (95%CI:3.74, 15.68), high level of alcohol intake 2.48 (95%CI:1.49, 4.09), having depression 3.17(95%CI:2.14, 4.68), low income 3.21 (95%CI:1.98, 5.19), poor social support 2.41 (95%CI:1.65, 3.51) and poor nutritional intake 2.77", "source": "PubMed"}, {"chunk_id": "41073382_2", "pmid": "41073382", "title": "Magnitude and predictors of mild cognitive impairment among older populations in Africa: a systematic review and meta-analysis.", "authors": "Asnakew S, Nealon J, Semachew Kasa A et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "(95%CI:3.74, 15.68), high level of alcohol intake 2.48 (95%CI:1.49, 4.09), having depression 3.17(95%CI:2.14, 4.68), low income 3.21 (95%CI:1.98, 5.19), poor social support 2.41 (95%CI:1.65, 3.51) and poor nutritional intake 2.77 (95%CI:1.83, 4.19) were significantly associated with mild cognitive impairment. The magnitude of mild cognitive impairment among Africa's older populations is significant. This suggests that cognitive disorders should be routinely screened among older people who visit healthcare facilities regarding physical health to enable early detection and treatment of reversible causes of neurocognitive impairment. Furthermore, identifying modifiable factors would inform evidence-based policies to reduce the health and societal burden of cognitive decline.", "source": "PubMed"}, {"chunk_id": "40805906_0", "pmid": "40805906", "title": "Healthcare Complexities in Neurodegenerative Proteinopathies: A Narrative Review.", "authors": "Fereshtehnejad SM, L\u00f6kk J", "year": "2025", "journal": "Healthcare (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, Lewy body disease, Parkinson\u2019s disease, complexity, frontotemporal dementia, healthcare, neurodegenerative diseases, pathogenesis", "chunk": "<b>Background/Objectives</b>: Neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB), are increasingly prevalent worldwide mainly due to population aging. These conditions are marked by complex etiologies, overlapping pathologies, and progressive clinical decline, with significant consequences for patients, caregivers, and healthcare systems. This review aims to synthesize evidence on the healthcare complexities of major neurodegenerative proteinopathies to highlight current knowledge gaps, and to inform future care models, policies, and research directions. <b>Methods</b>: We conducted a comprehensive literature search in PubMed/MEDLINE using combinations of MeSH terms and keywords related to neurodegenerative diseases, proteinopathies, diagnosis, sex, management, treatment, caregiver burden, and healthcare delivery. Studies were included if they addressed the clinical, pathophysiological, economic, or care-related complexities of aging-related neurodegenerative proteinopathies. <b>Results</b>: Key themes identified include the following: (1) multifactorial and unclear etiologies with frequent co-pathologies; (2) long prodromal phases with emerging biomarkers; (3) lack of effective", "source": "PubMed"}, {"chunk_id": "40805906_1", "pmid": "40805906", "title": "Healthcare Complexities in Neurodegenerative Proteinopathies: A Narrative Review.", "authors": "Fereshtehnejad SM, L\u00f6kk J", "year": "2025", "journal": "Healthcare (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, Lewy body disease, Parkinson\u2019s disease, complexity, frontotemporal dementia, healthcare, neurodegenerative diseases, pathogenesis", "chunk": "of aging-related neurodegenerative proteinopathies. <b>Results</b>: Key themes identified include the following: (1) multifactorial and unclear etiologies with frequent co-pathologies; (2) long prodromal phases with emerging biomarkers; (3) lack of effective disease-modifying therapies; (4) progressive nature requiring ongoing and individualized care; (5) high caregiver burden; (6) escalating healthcare and societal costs; and (7) the critical role of multidisciplinary and multi-domain care models involving specialists, primary care, and allied health professionals. <b>Conclusions</b>: The complexity and cost of neurodegenerative proteinopathies highlight the urgent need for prevention-focused strategies, innovative care models, early interventions, and integrated policies that support patients and caregivers. Prevention through the early identification of risk factors and prodromal signs is critical. Investing in research to develop effective disease-modifying therapies and improve early detection will be essential to reducing the long-term burden of these disorders.", "source": "PubMed"}, {"chunk_id": "40805906_2", "pmid": "40805906", "title": "Healthcare Complexities in Neurodegenerative Proteinopathies: A Narrative Review.", "authors": "Fereshtehnejad SM, L\u00f6kk J", "year": "2025", "journal": "Healthcare (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, Lewy body disease, Parkinson\u2019s disease, complexity, frontotemporal dementia, healthcare, neurodegenerative diseases, pathogenesis", "chunk": "early detection will be essential to reducing the long-term burden of these disorders.", "source": "PubMed"}, {"chunk_id": "37874106_0", "pmid": "37874106", "title": "Plasma Oligomer \u03b2-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition.", "authors": "Wang SM, Kang DW, Um YH et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Oligomerization, beta amyloid, blood-Based biomarker, preclinical Alzheimer\u2019s disease, white matter", "chunk": "Multimer detection system-oligomeric amyloid-\u03b2 (MDS-OA\u03b2) measure plasma OA\u03b2 level, which is associated with earlier Alzheimer's disease (AD) pathology. However, no study has investigated MDS-OA\u03b2 differences in cognitive normal older adults (CN) with or without cerebral A\u03b2 burden and its correlation with A\u03b2 deposition and white matter (WM) integrity. To investigate associations among cerebral A\u03b2 burden, MDS-OA\u03b2, and WM integrity in CN. This is a single center, cross-sectional study which used data from Catholic Aging Brain Imaging (CABI) database. CABI database contains brain scans of patients who visited the outpatient clinic at Catholic Brain Health Center, Yeouido St. Mary's Hospital, The Catholic University of Korea, between 2017 and 2022. A total 34 amyloid-PET negative CN and 23 amyloid-PET positive CN were included. Plasma A\u03b2 level using MDS-OA\u03b2, cerebral A\u03b2 deposition level using global standardized uptake value ratio (SUVR) values, WM integrity using fractional anisotropy (FA) and mean diffusivity (MD), and cortical", "source": "PubMed"}, {"chunk_id": "37874106_1", "pmid": "37874106", "title": "Plasma Oligomer \u03b2-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition.", "authors": "Wang SM, Kang DW, Um YH et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Oligomerization, beta amyloid, blood-Based biomarker, preclinical Alzheimer\u2019s disease, white matter", "chunk": "included. Plasma A\u03b2 level using MDS-OA\u03b2, cerebral A\u03b2 deposition level using global standardized uptake value ratio (SUVR) values, WM integrity using fractional anisotropy (FA) and mean diffusivity (MD), and cortical thickness from structural MRI were utilized. The amyloid-PET positive group showed higher MDS-OA\u03b2 level than the amyloid-PET negative group (0.997 \u00b1 0.19 vs. 0.79 \u00b1 0.28, P <0.005), but they did not differ in WM integrity or cortical thickness. The MDS-OA\u03b2 positive group showed higher global cerebral A\u03b2 deposition or mean global SUVR values (0.609 \u00b1 0.135 vs. 0.533 \u00b1 0.121 vs. P <0.05), lower regional FA of left forceps minor and the right superior longitudinal fasciculus (family-wise error rate, p <0.05), and lower cortical thickness of left fusiform (p <0.05, Monte Carlo simulation) than the MDS-OA\u03b2 negative group. MDS-OA\u03b2 was positively associated with global cerebral A\u03b2 deposition (r=0.278, P <0.05) and negatively associated (r = - 0.324, P <", "source": "PubMed"}, {"chunk_id": "37874106_2", "pmid": "37874106", "title": "Plasma Oligomer \u03b2-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition.", "authors": "Wang SM, Kang DW, Um YH et al.", "year": "2023", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Oligomerization, beta amyloid, blood-Based biomarker, preclinical Alzheimer\u2019s disease, white matter", "chunk": "<0.05, Monte Carlo simulation) than the MDS-OA\u03b2 negative group. MDS-OA\u03b2 was positively associated with global cerebral A\u03b2 deposition (r=0.278, P <0.05) and negatively associated (r = - 0.324, P < 0.05) with regional WM integrity. In this study, MDS-OA\u03b2 value demonstrated earlier and different AD pathology than cerebral A\u03b2 retention according to amyloid-PET. Longitudinal studies are needed to elucidate the causal relationships of plasma OA\u03b2 and cerebral A\u03b2 with WM integrity disturbance and cortical atrophy during the AD trajectory.", "source": "PubMed"}, {"chunk_id": "33344887_0", "pmid": "33344887", "title": "Dysregulation of Insulin-Linked Metabolic Pathways in Alzheimer's Disease: Co-Factor Role of Apolipoprotein E <i>\u025b</i>4.", "authors": "Robbins J, Busquets O, Tong M et al.", "year": "2020", "journal": "Journal of Alzheimer's disease reports", "keywords": "APOE, Alzheimer\u2019s disease, Braak stage, human brain, incretins, insulin resistance, leptin, multiplex ELISA, neurodegeneration, neuroinflammation", "chunk": "Brain insulin resistance and deficiency are well-recognized abnormalities in Alzheimer's disease (AD) and likely mediators of impaired energy metabolism. Since apolipoprotein E (<i>APOE</i>) is a major risk factor for late-onset AD, it was of interest to examine its potential contribution to altered insulin-linked signaling networks in the brain. The main goal was to evaluate the independent and interactive contributions of AD severity and <i>APOE</i> <i>\u025b</i>4 dose on brain expression of insulin-related polypeptides and inflammatory mediators of metabolic dysfunction. Postmortem fresh frozen frontal lobe tissue from banked cases with known <i>APOE</i> genotypes and different AD Braak stages were used to measure insulin network polypeptide immunoreactivity with a commercial multiplex enzyme-linked immunosorbent assay (ELISA). Significant AD Braak stage and <i>APOE</i> genotype-related abnormalities in insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucaton-like peptide-1 (GLP-1), leptin, ghrelin, glucagon, resistin, and plasminogen activator inhibitor-1 (PAI-1) were detected. The main factors inhibiting polypeptide expression and promoting neuro-inflammatory", "source": "PubMed"}, {"chunk_id": "33344887_1", "pmid": "33344887", "title": "Dysregulation of Insulin-Linked Metabolic Pathways in Alzheimer's Disease: Co-Factor Role of Apolipoprotein E <i>\u025b</i>4.", "authors": "Robbins J, Busquets O, Tong M et al.", "year": "2020", "journal": "Journal of Alzheimer's disease reports", "keywords": "APOE, Alzheimer\u2019s disease, Braak stage, human brain, incretins, insulin resistance, leptin, multiplex ELISA, neurodegeneration, neuroinflammation", "chunk": "in insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucaton-like peptide-1 (GLP-1), leptin, ghrelin, glucagon, resistin, and plasminogen activator inhibitor-1 (PAI-1) were detected. The main factors inhibiting polypeptide expression and promoting neuro-inflammatory responses included AD Braak stage and <i>APOE</i> <i>\u025b</i>4/<i>\u025b</i>4 rather than <i>\u025b</i>3/<i>\u025b</i>4. This study demonstrates an expanded role for impaired expression of insulin-related network polypeptides as well as neuroinflammatory mediators of brain insulin resistance in AD pathogenesis and progression. In addition, the findings show that <i>APOE</i> has independent and additive effects on these aberrations in brain polypeptide expression, but the impact is decidedly greater for <i>APOE</i> <i>\u025b</i>4/<i>\u025b</i>4 than <i>\u025b</i>3/<i>\u025b</i>4.", "source": "PubMed"}, {"chunk_id": "37075703_0", "pmid": "37075703", "title": "Meta-analysis of published cerebrospinal fluid proteomics data identifies and validates metabolic enzyme panel as Alzheimer's disease biomarkers.", "authors": "van Zalm PW, Ahmed S, Fatou B et al.", "year": "2023", "journal": "Cell reports. Medicine", "keywords": "ALDOA, LDHB, PKM, biomarkers, glycolysis, logistic regression, meta-analysis, metabolism", "chunk": "To develop therapies for Alzheimer's disease, we need accurate in vivo diagnostics. Multiple proteomic studies mapping biomarker candidates in cerebrospinal fluid (CSF) resulted in little overlap. To overcome this shortcoming, we apply the rarely used concept of proteomics meta-analysis to identify an effective biomarker panel. We combine ten independent datasets for biomarker identification: seven datasets from 150 patients/controls for discovery, one dataset with 20 patients/controls for down-selection, and two datasets with 494 patients/controls for validation. The discovery results in 21 biomarker candidates and down-selection in three, to be validated in the two additional large-scale proteomics datasets with 228 diseased and 266 control samples. This resulting 3-protein biomarker panel differentiates Alzheimer's disease (AD) from controls in the two validation cohorts with areas under the receiver operating characteristic curve (AUROCs) of 0.83 and 0.87, respectively. This study highlights the value of systematically re-analyzing previously published proteomics data and the need for more", "source": "PubMed"}, {"chunk_id": "37075703_1", "pmid": "37075703", "title": "Meta-analysis of published cerebrospinal fluid proteomics data identifies and validates metabolic enzyme panel as Alzheimer's disease biomarkers.", "authors": "van Zalm PW, Ahmed S, Fatou B et al.", "year": "2023", "journal": "Cell reports. Medicine", "keywords": "ALDOA, LDHB, PKM, biomarkers, glycolysis, logistic regression, meta-analysis, metabolism", "chunk": "areas under the receiver operating characteristic curve (AUROCs) of 0.83 and 0.87, respectively. This study highlights the value of systematically re-analyzing previously published proteomics data and the need for more stringent data deposition.", "source": "PubMed"}, {"chunk_id": "35118644_0", "pmid": "35118644", "title": "Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.", "authors": "Barbu M, J\u00f3nsson K, Zetterberg H et al.", "year": "2022", "journal": "Acta anaesthesiologica Scandinavica", "keywords": "None", "chunk": "Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery. Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood-brain barrier injury marker \u03b2-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients' age, operation time, and degree of hemolysis. No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145%", "source": "PubMed"}, {"chunk_id": "35118644_1", "pmid": "35118644", "title": "Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.", "authors": "Barbu M, J\u00f3nsson K, Zetterberg H et al.", "year": "2022", "journal": "Acta anaesthesiologica Scandinavica", "keywords": "None", "chunk": "significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145% (783%-2158%), GFAP +17% (-3%-43%), NSE +168% (106%-228%), while \u03b2-trace protein was reduced (-11% (-17-3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis. Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood-brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.", "source": "PubMed"}, {"chunk_id": "35118644_2", "pmid": "35118644", "title": "Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.", "authors": "Barbu M, J\u00f3nsson K, Zetterberg H et al.", "year": "2022", "journal": "Acta anaesthesiologica Scandinavica", "keywords": "None", "chunk": "postoperative cognitive function and clinical outcome.", "source": "PubMed"}, {"chunk_id": "34770565_0", "pmid": "34770565", "title": "Transfer Learning for Alzheimer's Disease through Neuroimaging Biomarkers: A Systematic Review.", "authors": "Agarwal D, Marques G, de la Torre-D\u00edez I et al.", "year": "2021", "journal": "Sensors (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, magnetic resonance imaging, neuroimaging biomarkers, positron emission tomography, transfer learning", "chunk": "Alzheimer's disease (AD) is a remarkable challenge for healthcare in the 21st century. Since 2017, deep learning models with transfer learning approaches have been gaining recognition in AD detection, and progression prediction by using neuroimaging biomarkers. This paper presents a systematic review of the current state of early AD detection by using deep learning models with transfer learning and neuroimaging biomarkers. Five databases were used and the results before screening report 215 studies published between 2010 and 2020. After screening, 13 studies met the inclusion criteria. We noted that the maximum accuracy achieved to date for AD classification is 98.20% by using the combination of 3D convolutional networks and local transfer learning, and that for the prognostic prediction of AD is 87.78% by using pre-trained 3D convolutional network-based architectures. The results show that transfer learning helps researchers in developing a more accurate system for the early diagnosis of AD. However,", "source": "PubMed"}, {"chunk_id": "34770565_1", "pmid": "34770565", "title": "Transfer Learning for Alzheimer's Disease through Neuroimaging Biomarkers: A Systematic Review.", "authors": "Agarwal D, Marques G, de la Torre-D\u00edez I et al.", "year": "2021", "journal": "Sensors (Basel, Switzerland)", "keywords": "Alzheimer\u2019s disease, magnetic resonance imaging, neuroimaging biomarkers, positron emission tomography, transfer learning", "chunk": "is 87.78% by using pre-trained 3D convolutional network-based architectures. The results show that transfer learning helps researchers in developing a more accurate system for the early diagnosis of AD. However, there is a need to consider some points in future research, such as improving the accuracy of the prognostic prediction of AD, exploring additional biomarkers such as tau-PET and amyloid-PET to understand highly discriminative feature representation to separate similar brain patterns, managing the size of the datasets due to the limited availability.", "source": "PubMed"}, {"chunk_id": "39639173_0", "pmid": "39639173", "title": "Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy.", "authors": "Labrador-Espinosa MA, Silva-Rodriguez J, Okkels N et al.", "year": "2025", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [<sup>18</sup>F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [<sup>18</sup>F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated", "source": "PubMed"}, {"chunk_id": "39639173_1", "pmid": "39639173", "title": "Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy.", "authors": "Labrador-Espinosa MA, Silva-Rodriguez J, Okkels N et al.", "year": "2025", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated proportion: 43%, p < 0.001). In combined models, posterior cBF atrophy explained more variance in cortical hypometabolism (R<sup>2</sup> = 0.26, p < 0.001) than local atrophy in the cortical areas themselves (R<sup>2</sup> = 0.16, p = 0.01). Topographic correspondence analysis with the [<sup>18</sup>F]FEOBV-PET pattern revealed that cortical areas showing most pronounced cBF-associated hypometabolism correspond to those showing most severe cholinergic denervation in PD (Spearman's \u03c1 = 0.57, p < 0.001). In conclusion, posterior cBF atrophy in PD is selectively associated with hypometabolism in denervated cortical target areas, which mediates the effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD.", "source": "PubMed"}, {"chunk_id": "39639173_2", "pmid": "39639173", "title": "Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy.", "authors": "Labrador-Espinosa MA, Silva-Rodriguez J, Okkels N et al.", "year": "2025", "journal": "Molecular psychiatry", "keywords": "None", "chunk": "effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD.", "source": "PubMed"}, {"chunk_id": "40236395_0", "pmid": "40236395", "title": "The expression of insulin signaling and N-methyl-D-aspartate receptor genes in areas of gray matter atrophy is associated with cognitive function in type 2 diabetes.", "authors": "Kesler SR, Cuevas H, Lewis KA et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "Type 2 diabetes (T2DM) is associated with brain abnormalities and cognitive dysfunction, including increased risk for Alzheimer's disease. However, the mechanisms of T2DM-related dementia remain poorly understood. We obtained retrospective data from the Mayo Clinic Study of Aging for 271 individuals with T2DM and 542 demographically matched non-diabetic controls (age 51-89, 62% male). We identified regions of significant gray matter atrophy in the T2DM group and then determined which genes were significantly expressed in these brain regions using imaging transcriptomics. We selected 15 candidate genes involved in insulin signaling, lipid metabolism, amyloid processing, N-methyl-D-aspartate-mediated neurotransmission, and calcium signaling. The T2DM group demonstrated significant gray matter atrophy in regions of the default mode, frontal-parietal, and sensorimotor networks (p < 0.05 cluster threshold corrected for false discovery rate, FDR). <i>IRS1, AKT1, PPARG, PRKAG2</i>, and <i>GRIN2B</i> genes were significantly expressed in these same regions (R<sup>2</sup> > 0.10, p < 0.03, FDR corrected). Bayesian", "source": "PubMed"}, {"chunk_id": "40236395_1", "pmid": "40236395", "title": "The expression of insulin signaling and N-methyl-D-aspartate receptor genes in areas of gray matter atrophy is associated with cognitive function in type 2 diabetes.", "authors": "Kesler SR, Cuevas H, Lewis KA et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "threshold corrected for false discovery rate, FDR). <i>IRS1, AKT1, PPARG, PRKAG2</i>, and <i>GRIN2B</i> genes were significantly expressed in these same regions (R<sup>2</sup> > 0.10, p < 0.03, FDR corrected). Bayesian network analysis indicated significant directional paths among all 5 genes as well as the Clinical Dementia Rating score. Directional paths among genes were significantly altered in the T2DM group (Structural Hamming Distance = 12, p = 0.004), with <i>PPARG</i> expression becoming more important in the context of T2DM-related pathophysiology. Alterations of brain transcriptome patterns occurred in the absence of significant cognitive deficit or amyloid accumulation, potentially representing an early biomarker of T2DM-related dementia.", "source": "PubMed"}, {"chunk_id": "29572601_0", "pmid": "29572601", "title": "Multi-Modality Cascaded Convolutional Neural Networks for Alzheimer's Disease Diagnosis.", "authors": "Liu M, Cheng D, Wang K et al.", "year": "2018", "journal": "Neuroinformatics", "keywords": "Alzheimer\u2019s disease diagnosis, Cascaded CNNs, Convolutional neural networks (CNNs), Image classification, Multi-modality brain images", "chunk": "Accurate and early diagnosis of Alzheimer's disease (AD) plays important role for patient care and development of future treatment. Structural and functional neuroimages, such as magnetic resonance images (MRI) and positron emission tomography (PET), are providing powerful imaging modalities to help understand the anatomical and functional neural changes related to AD. In recent years, machine learning methods have been widely studied on analysis of multi-modality neuroimages for quantitative evaluation and computer-aided-diagnosis (CAD) of AD. Most existing methods extract the hand-craft imaging features after image preprocessing such as registration and segmentation, and then train a classifier to distinguish AD subjects from other groups. This paper proposes to construct cascaded convolutional neural networks (CNNs) to learn the multi-level and multimodal features of MRI and PET brain images for AD classification. First, multiple deep 3D-CNNs are constructed on different local image patches to transform the local brain image into more compact high-level features.", "source": "PubMed"}, {"chunk_id": "29572601_1", "pmid": "29572601", "title": "Multi-Modality Cascaded Convolutional Neural Networks for Alzheimer's Disease Diagnosis.", "authors": "Liu M, Cheng D, Wang K et al.", "year": "2018", "journal": "Neuroinformatics", "keywords": "Alzheimer\u2019s disease diagnosis, Cascaded CNNs, Convolutional neural networks (CNNs), Image classification, Multi-modality brain images", "chunk": "MRI and PET brain images for AD classification. First, multiple deep 3D-CNNs are constructed on different local image patches to transform the local brain image into more compact high-level features. Then, an upper high-level 2D-CNN followed by softmax layer is cascaded to ensemble the high-level features learned from the multi-modality and generate the latent multimodal correlation features of the corresponding image patches for classification task. Finally, these learned features are combined by a fully connected layer followed by softmax layer for AD classification. The proposed method can automatically learn the generic multi-level and multimodal features from multiple imaging modalities for classification, which are robust to the scale and rotation variations to some extent. No image segmentation and rigid registration are required in pre-processing the brain images. Our method is evaluated on the baseline MRI and PET images of 397 subjects including 93 AD patients, 204 mild cognitive impairment (MCI, 76", "source": "PubMed"}, {"chunk_id": "29572601_2", "pmid": "29572601", "title": "Multi-Modality Cascaded Convolutional Neural Networks for Alzheimer's Disease Diagnosis.", "authors": "Liu M, Cheng D, Wang K et al.", "year": "2018", "journal": "Neuroinformatics", "keywords": "Alzheimer\u2019s disease diagnosis, Cascaded CNNs, Convolutional neural networks (CNNs), Image classification, Multi-modality brain images", "chunk": "required in pre-processing the brain images. Our method is evaluated on the baseline MRI and PET images of 397 subjects including 93 AD patients, 204 mild cognitive impairment (MCI, 76 pMCI +128 sMCI) and 100 normal controls (NC) from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results show that the proposed method achieves an accuracy of 93.26% for classification of AD vs. NC and 82.95% for classification pMCI vs. NC, demonstrating the promising classification performance.", "source": "PubMed"}, {"chunk_id": "41671614_0", "pmid": "41671614", "title": "Cobrotoxin mitigates neuroinflammation and cognitive impairment by suppressing CD8<sup>+</sup> T cell-microglia interactions in male 5\u00a0\u00d7\u00a0FAD mice.", "authors": "Li Z, Tan B, Dong K et al.", "year": "2026", "journal": "Biochemical pharmacology", "keywords": "Alzheimer\u2019sdisease, CD8(+) Tcells, Neuroinflammation, Synapticplasticity, cobrotoxin(CTX)", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline accompanied by chronic neuroinflammation. Emerging evidence implicates T-cell infiltration and microglial activation as key immune events that accelerate AD pathology, yet therapeutic approaches targeting this neuroimmune interface remain scarce. Cobrotoxin (CTX), a short-chain neurotoxin derived from Naja atra venom, exhibits potent anti-inflammatory and immunomodulatory properties and is clinically approved in China for the treatment of chronic pain syndromes. Here, we investigated whether CTX could alleviate neuroinflammation and cognitive deficits in 5 \u00d7 FAD mice, a transgenic model of AD. Intranasal CTX administration for nine weeks enhanced spatial learning and memory in the Morris water maze without altering amyloid-\u03b2 burden. Flow cytometry and immunofluorescence revealed that CTX markedly reduced brain-infiltrating CD8<sup>+</sup> T cells and downregulated chemokines implicated in T cell-microglia communication, including Cxcl9, Cxcl10, Cxcl16, and Ccl5. Consistent with this, CTX attenuated microglial activation and pro-inflammatory cytokine release while", "source": "PubMed"}, {"chunk_id": "41671614_1", "pmid": "41671614", "title": "Cobrotoxin mitigates neuroinflammation and cognitive impairment by suppressing CD8<sup>+</sup> T cell-microglia interactions in male 5\u00a0\u00d7\u00a0FAD mice.", "authors": "Li Z, Tan B, Dong K et al.", "year": "2026", "journal": "Biochemical pharmacology", "keywords": "Alzheimer\u2019sdisease, CD8(+) Tcells, Neuroinflammation, Synapticplasticity, cobrotoxin(CTX)", "chunk": "brain-infiltrating CD8<sup>+</sup> T cells and downregulated chemokines implicated in T cell-microglia communication, including Cxcl9, Cxcl10, Cxcl16, and Ccl5. Consistent with this, CTX attenuated microglial activation and pro-inflammatory cytokine release while preserving plaque-associated microglia (disease-associated microglia, DAM). Morphological and electrophysiological analyses demonstrated that CTX restored dendritic complexity, spine density, and hippocampal long-term potentiation (LTP), indicating improved synaptic integrity. Collectively, these findings identify CTX as a potent modulator of neuroimmune signaling that mitigates neuroinflammation and synaptic dysfunction in AD, suggesting its potential for repurposing as an immunomodulatory therapy for neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "34743360_0", "pmid": "34743360", "title": "Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study.", "authors": "Wilke C, Reich S, van Swieten JC et al.", "year": "2022", "journal": "Annals of neurology", "keywords": "None", "chunk": "Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both", "source": "PubMed"}, {"chunk_id": "34743360_1", "pmid": "34743360", "title": "Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study.", "authors": "Wilke C, Reich S, van Swieten JC et al.", "year": "2022", "journal": "Annals of neurology", "keywords": "None", "chunk": "years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD. ANN NEUROL 2022;91:33-47.", "source": "PubMed"}, {"chunk_id": "34743360_2", "pmid": "34743360", "title": "Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study.", "authors": "Wilke C, Reich S, van Swieten JC et al.", "year": "2022", "journal": "Annals of neurology", "keywords": "None", "chunk": "the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD. ANN NEUROL 2022;91:33-47.", "source": "PubMed"}, {"chunk_id": "41676923_0", "pmid": "41676923", "title": "Structural insights into SHIP2 reveal its membrane regulatory mechanisms.", "authors": "Gupta J, Le Coq J, Lietha D et al.", "year": "2026", "journal": "Protein science : a publication of the Protein Society", "keywords": "Alzheimer's disease, PI3K AKT pathway, PIP3, cancer signaling, cryoEM, insulin resistance, membrane regulation, neurodegeneration, phosphoinositide signaling, protein oligomerization, type 2 diabetes", "chunk": "Src homology 2 domain-containing inositol-5 phosphatase 2 (SHIP2) is a key player in regulating the signaling by phosphoinositides and is involved in the modulation of cellular functions such as proliferation, adhesion, migration, and survival. SHIP2 works by dephosphorylating PIP<sub>3</sub> to modulate the PI3K/AKT pathway, which plays a role in different standard and pathological conditions. SHIP2 appears to play a dual part in cancer, serving as a tumor suppressor in some instances and a tumor promoter in others. It is also involved in neurodegenerative diseases, including Alzheimer's disease. To understand the molecular mechanism of SHIP2, we solved its cryogenic electron microscopy (cryoEM) structure. Unexpectedly, the SHIP2 pleckstrin homology-related domain was found to associate with its C2 and phosphatase domains. This arrangement enables the catalytic domain to interact with the substrate, especially at higher concentrations of PIP<sub>3</sub> or PI(3,4)P<sub>2</sub>. Furthermore, SHIP2 forms oligomers on the membrane. Our findings suggest a mechanism by", "source": "PubMed"}, {"chunk_id": "41676923_1", "pmid": "41676923", "title": "Structural insights into SHIP2 reveal its membrane regulatory mechanisms.", "authors": "Gupta J, Le Coq J, Lietha D et al.", "year": "2026", "journal": "Protein science : a publication of the Protein Society", "keywords": "Alzheimer's disease, PI3K AKT pathway, PIP3, cancer signaling, cryoEM, insulin resistance, membrane regulation, neurodegeneration, phosphoinositide signaling, protein oligomerization, type 2 diabetes", "chunk": "enables the catalytic domain to interact with the substrate, especially at higher concentrations of PIP<sub>3</sub> or PI(3,4)P<sub>2</sub>. Furthermore, SHIP2 forms oligomers on the membrane. Our findings suggest a mechanism by which SHIP2 activity may be regulated through interactions with membrane lipids. This provides structural insights into how domain organization and membrane association regulate its function in various physiological contexts.", "source": "PubMed"}, {"chunk_id": "41844500_0", "pmid": "41844500", "title": "Differential patterns of central synucleinopathy and catecholaminergic abnormalities in Lewy body diseases and multiple system atrophy.", "authors": "Goldstein DS, Concha-Marambio L, Alam P et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "Biomarker, Cerebrospinal fluid, Lewy, Parkinson, Synuclein", "chunk": "Parkinson's disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) feature intracellular deposition of alpha-synuclein and catecholamine deficiency in the putamen or heart. This retrospective, cross-sectional, observational study assessed relationships of cerebrospinal fluid alpha-synuclein seed amplification assay (CSF SAA) data with catecholamine deficiency indicated by positron emission tomography (PET). In groups with PD, PAF, parkinsonian MSA (MSA-P), or cerebellar MSA (MSA-C) SAAs were conducted by Rocky Mountain Laboratories (RML) and Amprion, Inc. using different assay conditions. <sup>18</sup>F-DOPA PET examined putamen dopaminergic innervation, and <sup>18</sup>F-dopamine PET assessed cardiac noradrenergic innervation. CSF SAAs by both RML and Amprion separated PD or PAF from MSA. The Amprion assay detected type 1 seeding associated with Lewy body diseases (LBDs) in 22/24 (92%) PD patients and 15/16 (94%) PAF patients and type 2 seeding associated with MSA in 9/10 (90%) MSA-P and 3/4 (75%) MSA-C patients (p < 0.0001). All of 24 PD", "source": "PubMed"}, {"chunk_id": "41844500_1", "pmid": "41844500", "title": "Differential patterns of central synucleinopathy and catecholaminergic abnormalities in Lewy body diseases and multiple system atrophy.", "authors": "Goldstein DS, Concha-Marambio L, Alam P et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "Biomarker, Cerebrospinal fluid, Lewy, Parkinson, Synuclein", "chunk": "PD patients and 15/16 (94%) PAF patients and type 2 seeding associated with MSA in 9/10 (90%) MSA-P and 3/4 (75%) MSA-C patients (p < 0.0001). All of 24 PD and all of 9 MSA-P patients had low putamen/occipital cortex ratios of <sup>18</sup>F-DOPA-derived radioactivity, while 11/13 (85%) PAF patients and 4/4 (100%) MSA-C patients had normal ratios. Contingency analyses of CSF SAA and brain <sup>18</sup>F-DOPA PET efficiently separated the 4 groups (p < 0.0001). CSF SAAs and cardiac <sup>18</sup>F-dopamine PET distinguish LBDs from MSA but not PAF from PD or MSA-P from MSA-C. <sup>18</sup>F-DOPA PET separates PAF from PD and MSA-P from MSA-C. Combining biomarkers differentiates among these synucleinopathies.", "source": "PubMed"}, {"chunk_id": "41812815_0", "pmid": "41812815", "title": "Harmine and its derivatives: A promising multi-target therapeutic avenue for Alzheimer's disease.", "authors": "Shen X, Dong X, Nao J", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s disease, DYRK1A, Derivatives, Harmine, Multi-target therapeutics, Pharmacological effects", "chunk": "Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by \u03b2-amyloid (A\u03b2) deposition, tau hyperphosphorylation, neuroinflammation, and cholinergic dysfunction. Currently, no disease-modifying drugs are available, and existing symptomatic treatments offer limited efficacy while posing safety concerns, highlighting the urgent need for multi\u2011target therapeutic strategies. The natural \u03b2\u2011carboline alkaloid harmine has attracted considerable attention due to its favorable blood-brain barrier penetration and multi\u2011target profile. Accumulating preclinical evidence indicates that harmine can concurrently modulate several core pathological processes of AD. Mechanistically, it potently inhibits dual\u2011specificity tyrosine phosphorylation\u2011regulated kinase 1A (DYRK1A), thereby reducing tau hyperphosphorylation, suppressing aberrant amyloid precursor protein processing, and enhancing neprilysin\u2011mediated A\u03b2 clearance. Concurrently, harmine attenuates neuroinflammation via negative regulation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF\u2011\u03baB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, improves cholinergic neurotransmission through acetylcholinesterase inhibition, and alleviates glutamate excitotoxicity by upregulating astrocytic glutamate transporter 1/excitatory amino acid transporter", "source": "PubMed"}, {"chunk_id": "41812815_1", "pmid": "41812815", "title": "Harmine and its derivatives: A promising multi-target therapeutic avenue for Alzheimer's disease.", "authors": "Shen X, Dong X, Nao J", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s disease, DYRK1A, Derivatives, Harmine, Multi-target therapeutics, Pharmacological effects", "chunk": "and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, improves cholinergic neurotransmission through acetylcholinesterase inhibition, and alleviates glutamate excitotoxicity by upregulating astrocytic glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) expression. Structurally optimized harmine derivatives have demonstrated enhanced dual inhibitory activity and improved cognitive outcomes in preclinical models. Despite these promising findings, challenges such as pharmacokinetic limitations, insufficient target selectivity, and a lack of clinical data remain. In conclusion, the harmine scaffold represents a mechanistically grounded and promising direction for the development of multi\u2011target therapeutics for AD.", "source": "PubMed"}, {"chunk_id": "40863992_0", "pmid": "40863992", "title": "Correlation of Neurodegenerative Biomarkers and Functional Outcome in Patients with Relapsing-Remitting Multiple Sclerosis.", "authors": "Polunosika E, Feldmane M, Pastare D et al.", "year": "2025", "journal": "Neurology international", "keywords": "Brief Visuospatial Memory Test-Revised, Symbol Digit Modalities Test, biomarkers, disability, magnetic resonance imaging, neurodegeneration, neurofilament light chain, relapsing\u2013remitting multiple sclerosis", "chunk": "<b>Background and Objectives</b>: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. <b>Materials and Methods</b>: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing-remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). <b>Results</b>: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative", "source": "PubMed"}, {"chunk_id": "40863992_1", "pmid": "40863992", "title": "Correlation of Neurodegenerative Biomarkers and Functional Outcome in Patients with Relapsing-Remitting Multiple Sclerosis.", "authors": "Polunosika E, Feldmane M, Pastare D et al.", "year": "2025", "journal": "Neurology international", "keywords": "Brief Visuospatial Memory Test-Revised, Symbol Digit Modalities Test, biomarkers, disability, magnetic resonance imaging, neurodegeneration, neurofilament light chain, relapsing\u2013remitting multiple sclerosis", "chunk": "indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. <b>Conclusions</b>: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL.", "source": "PubMed"}, {"chunk_id": "40863992_2", "pmid": "40863992", "title": "Correlation of Neurodegenerative Biomarkers and Functional Outcome in Patients with Relapsing-Remitting Multiple Sclerosis.", "authors": "Polunosika E, Feldmane M, Pastare D et al.", "year": "2025", "journal": "Neurology international", "keywords": "Brief Visuospatial Memory Test-Revised, Symbol Digit Modalities Test, biomarkers, disability, magnetic resonance imaging, neurodegeneration, neurofilament light chain, relapsing\u2013remitting multiple sclerosis", "chunk": "cognitive function and disability in RRMS than plasma NfL.", "source": "PubMed"}, {"chunk_id": "26440450_0", "pmid": "26440450", "title": "Imaging \u03b2-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis.", "authors": "Heurling K, Leuzy A, Zimmer ER et al.", "year": "2016", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Mild cognitive impairment, Positron emission tomography, Vizamyl, [18F]Flutemetamol, \u03b2-amyloid", "chunk": "In Alzheimer's disease (AD), the deposition of \u03b2-amyloid (A\u03b2) is hypothesized to result in a series of secondary neurodegenerative processes, leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of the first A\u03b2-specific positron emission tomography (PET) ligand, (11)C-Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed that circumvent the limitations of [(11)C]PIB tied to its short half-life. To date, three such compounds have been approved for clinical use by the US and European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir; Amyvid\u2122), [(18)F]-BAY94-9172 ([(18)F]florbetaben; Neuraceq\u2122) and [(18)F]3'-F-PIB ([(18)F]flutemetamol; Vizamyl\u2122). The present review aims to summarize and discuss the currently available knowledge on [(18)F]flutemetamol PET. As the (18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the differentiation of AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its", "source": "PubMed"}, {"chunk_id": "26440450_1", "pmid": "26440450", "title": "Imaging \u03b2-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis.", "authors": "Heurling K, Leuzy A, Zimmer ER et al.", "year": "2016", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Mild cognitive impairment, Positron emission tomography, Vizamyl, [18F]Flutemetamol, \u03b2-amyloid", "chunk": "AD from related neurodegenerative disorders and may help with subject selection and measurement of target engagement in the context of clinical trials testing anti-amyloid therapeutics. We will also discuss its potential use in non-AD amyloidopathies.", "source": "PubMed"}, {"chunk_id": "41336391_0", "pmid": "41336391", "title": "Toward Inclusive Large-Scale Alzheimer's Disease Detection via Speech and Language Modeling.", "authors": "Favaro A, Novotny K, He Y et al.", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "Previous speech-based detection methods for Alzheimer's Disease and Related Dementias (ADRD) have been constrained by small sample sizes, reliance on single corpora, languages, tasks, and recording conditions, limiting their generalizability. Moreover, many studies have simplified cognitive decline progression through binary classification. To address these limitations, we developed a multimodal framework integrating language-agnostic, multilingual, and language-dependent models with demographic data to enhance adaptability across diverse cohorts. We applied this model to a three-class classification problem-cognitively normal controls (CNs), Mild Cognitive Impairment (MCI), and ADRD-using the PREPARE Challenge corpus, which includes 2058 speakers (1140 CNs, 268 MCI, and 650 ADRD). Our best-performing model achieved an F1 score of 0.71 and a log loss of 0.63 on the internal test set, with strong generalization to external test data. Bias mitigation strategies addressed demographic imbalances, including model fusion, data augmentation, and weighted cross-entropy loss. However, challenges remain for underrepresented subgroups. This study highlights the", "source": "PubMed"}, {"chunk_id": "41336391_1", "pmid": "41336391", "title": "Toward Inclusive Large-Scale Alzheimer's Disease Detection via Speech and Language Modeling.", "authors": "Favaro A, Novotny K, He Y et al.", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "generalization to external test data. Bias mitigation strategies addressed demographic imbalances, including model fusion, data augmentation, and weighted cross-entropy loss. However, challenges remain for underrepresented subgroups. This study highlights the importance of integrating generalizable and language-specific features for scalable, accurate ADRD detection. Future work will expand the dataset to include more languages, improve task diversity, and refine fusion strategies to enhance robustness and scalability in clinical settings.Clinical relevance-The proposed framework provides clinicians with a scalable, inclusive system for early ADRD detection, leveraging multilingual and language-agnostic models to support timely interventions and personalized care, even in resource-constrained or underserved settings.", "source": "PubMed"}, {"chunk_id": "40576521_0", "pmid": "40576521", "title": "Clinically Accurate Diagnosis of Alzheimer's Disease via Single-Molecule Bioelectronic Label-Free Profiling of Multiple Blood Extracellular Vesicle Biomarkers.", "authors": "Zheng J, Jiang X, Bai S et al.", "year": "2025", "journal": "Advanced materials (Deerfield Beach, Fla.)", "keywords": "alzheimer's disease, blood extracellular vesicles, label\u2010free bioelectronic platform, multiplexed diagnostic model, organic electrochemical transistor", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no cure, making early diagnosis critical for mitigating its impact. Blood extracellular vesicles (EVs) hold promises as biomarkers for AD diagnosis, but current detection technologies lack the sensitivity and multiplexing capabilities needed for efficient diagnosis. Here, a novel label-free bioelectronic platform is presented based on an organic electrochemical transistor (OECT) integrated with a microelectrode array (MEA) for ultrasensitive detection of AD biomarkers in blood EVs, including amyloid-\u03b2 (A\u03b2<sub>1-40</sub> and A\u03b2<sub>1-42</sub>), total tau (t-tau), and phosphorylated tau (p-tau<sup>181</sup>). This platform achieves a detection limit as low as the zeptomolar (zM) level, enabling the detection of single-molecule targets. It provides a comprehensive multiplexed diagnostic model capable of delivering results within 20 min. Notably, the systematic integration of multiple AD biomarkers in blood EVs is demonstrated to significantly enhance diagnostic accuracy. This study presents a novel EVs-based multiplexed diagnostic model for AD, correctly classifying", "source": "PubMed"}, {"chunk_id": "40576521_1", "pmid": "40576521", "title": "Clinically Accurate Diagnosis of Alzheimer's Disease via Single-Molecule Bioelectronic Label-Free Profiling of Multiple Blood Extracellular Vesicle Biomarkers.", "authors": "Zheng J, Jiang X, Bai S et al.", "year": "2025", "journal": "Advanced materials (Deerfield Beach, Fla.)", "keywords": "alzheimer's disease, blood extracellular vesicles, label\u2010free bioelectronic platform, multiplexed diagnostic model, organic electrochemical transistor", "chunk": "the systematic integration of multiple AD biomarkers in blood EVs is demonstrated to significantly enhance diagnostic accuracy. This study presents a novel EVs-based multiplexed diagnostic model for AD, correctly classifying all clinical samples (n = 40), far exceeding the accuracy of a single biomarker. With its high sensitivity and rapid turnaround, this platform enables reliable AD diagnosis and holds the potential for tracking disease progression, offering a transformative tool to combat the societal burden of AD.", "source": "PubMed"}, {"chunk_id": "40519128_0", "pmid": "40519128", "title": "A nomogram including serum iron metabolism-related indicator and cerebral microbleeds for predicting vascular cognitive impairment in patients.", "authors": "Sun R, Xie X, Meng Y et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cerebral microbleeds, cognitive impairment, ferritin, middle-aged and elderly people, predictive model", "chunk": "BackgroundDetection of serum iron metabolism and peripheral blood ferroptosis indicators may to some extent reflect pathological changes in central nervous system iron deposition such as Alzheimer's disease and vascular cognitive impairment (VCI).ObjectiveThe study sought to establish the first clinical prediction model related to the iron metabolism model, which helps in the early detection and prevention of VCI.MethodsThe study included 255 patients at Hebei Provincial People's Hospital from January 2023 to November 2024. They were divided into two groups based on VCI diagnostic criteria, with 144 cases in the VCI group and 111 cases in the control group. The nomogram of the VCI diagnostic prediction model was built using logistic regression. The accuracy and discriminative ability of the model were confirmed in three areas: differentiation, calibration, and clinical practicability.ResultsA logistic regression model identified four significant independent predictors of VCI: ferritin (odds ratio (OR) = 1.003, 95% CI: 1.001\u223c1.006), education (OR =", "source": "PubMed"}, {"chunk_id": "40519128_1", "pmid": "40519128", "title": "A nomogram including serum iron metabolism-related indicator and cerebral microbleeds for predicting vascular cognitive impairment in patients.", "authors": "Sun R, Xie X, Meng Y et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, cerebral microbleeds, cognitive impairment, ferritin, middle-aged and elderly people, predictive model", "chunk": "in three areas: differentiation, calibration, and clinical practicability.ResultsA logistic regression model identified four significant independent predictors of VCI: ferritin (odds ratio (OR) = 1.003, 95% CI: 1.001\u223c1.006), education (OR = 0.929, 95% CI: 0.871\u223c0.992), cerebral small vessel disease total load scores (OR = 1.319, 95% CI: 1.039\u223c1.673), and cerebral microbleeds (OR = 2.020, 95% CI: 1.092\u223c3.736) after adjustment for potential confounding factors (p < 0.05). The predictive nomogram has good discriminatory ability, calibration ability, and clinical applicability.ConclusionsSerum ferritin was a significant predictor of VCI in middle-aged elderly people. The predictive model developed for the risk of developing VCI has good clinical applicability, calibration, and discrimination for early VCI screening.", "source": "PubMed"}, {"chunk_id": "39406040_0", "pmid": "39406040", "title": "Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer's dementia.", "authors": "Pecher H, Storch M, Beyer F et al.", "year": "2024", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Hypothalamic atrophy, Mild cognitive impairment, Structural covariance networks, Volumetry", "chunk": "Alzheimer's disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet only few studies have investigated hypothalamic atrophy in AD and its early stages in particular. We applied semi-automated volumetry of the hypothalamus (HTH) in 3 T MRI in a sample N = 175 participants [age 74.9 \u00b1 7.22; gender 85 m/90f; cognitively normal controls (CN; N = 56); amnestic mild cognitive impairment (MCI; N = 78); AD (N = 41)] from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In addition, we used voxel-based morphometry (VBM), cortical thickness (CTH) analyses and source-based morphometry (SBM) derived networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, \u03b2-amyloid (AB) positivity and apolipoprotein E (APOE) \u03b54 status. Hypothalamic atrophy was", "source": "PubMed"}, {"chunk_id": "39406040_1", "pmid": "39406040", "title": "Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer's dementia.", "authors": "Pecher H, Storch M, Beyer F et al.", "year": "2024", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Hypothalamic atrophy, Mild cognitive impairment, Structural covariance networks, Volumetry", "chunk": "networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, \u03b2-amyloid (AB) positivity and apolipoprotein E (APOE) \u03b54 status. Hypothalamic atrophy was observed in both early and advanced disease stages (i.e. hypothalamic volume CN > MCI > AD). VBM, CTH analysis and SBM revealed positive associations between hypothalamic volume (HV) and AD-vulnerable regions, largely corresponding to the Papez circuit and brain regions implicated in autonomic regulation, however, group differences regarding HTH structural covariance were not observed. Similar observations were made in carriers and non-carriers of the \u03b54 allele, yet more pronounced in \u03b54 carriers. Although not reaching significance, comparisons of AB positive vs. negative subjects indicated stronger HTH atrophy in biomarker positive participants. HV was not associated with body mass index or longitudinal weight change. Our findings support early structural changes of the HTH in AD. HV covaries with regional volumes of", "source": "PubMed"}, {"chunk_id": "39406040_2", "pmid": "39406040", "title": "Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer's dementia.", "authors": "Pecher H, Storch M, Beyer F et al.", "year": "2024", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Hypothalamic atrophy, Mild cognitive impairment, Structural covariance networks, Volumetry", "chunk": "participants. HV was not associated with body mass index or longitudinal weight change. Our findings support early structural changes of the HTH in AD. HV covaries with regional volumes of AD-vulnerable regions. This could point to secondary atrophy of the HTH following atrophy of the hippocampus and other structures of the Papez circuit in AD.", "source": "PubMed"}, {"chunk_id": "41789119_0", "pmid": "41789119", "title": "Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial.", "authors": "H\u00f6glinger G, Vandenberghe W, Woitalla D et al.", "year": "2026", "journal": "BMJ neurology open", "keywords": "ALZHEIMER'S DISEASE, CLINICAL NEUROLOGY, RANDOMISED TRIALS, SUPRANUCLEAR PALSY", "chunk": "Preclinical evidence suggests targeting the mid-region of tau as a viable therapeutic strategy in diseases such as progressive supranuclear palsy (PSP): a rare, fatal, neurodegenerative tauopathy with no currently approved treatments. Bepranemab is a recombinant, humanised, full-length immunoglobulin G4 monoclonal antibody binding to a mid-region tau epitope. We assessed safety, tolerability and pharmacokinetics of bepranemab in participants with PSP. PSP003 (NCT04185415), a multicentre, double-blind, placebo-controlled, phase 1b study, recruited participants in hospital settings across 13 centres. Participants (aged \u226540 years) met Movement Disorder Society-PSP criteria for possible/probable PSP, could walk \u22655 steps with minimal/no assistance and were stable on treatment for \u22652 weeks prior to baseline. Participants were randomised 3:1 to receive intravenous bepranemab (90 mg/kg) or placebo every 4 weeks for 52 weeks. Primary endpoint: incidence of treatment-emergent adverse events (TEAEs) from baseline to last visit. Twenty-five participants were enrolled (male: 44%; bepranemab n=18, placebo n=7). Seventeen (94.4%) in", "source": "PubMed"}, {"chunk_id": "41789119_1", "pmid": "41789119", "title": "Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial.", "authors": "H\u00f6glinger G, Vandenberghe W, Woitalla D et al.", "year": "2026", "journal": "BMJ neurology open", "keywords": "ALZHEIMER'S DISEASE, CLINICAL NEUROLOGY, RANDOMISED TRIALS, SUPRANUCLEAR PALSY", "chunk": "weeks for 52 weeks. Primary endpoint: incidence of treatment-emergent adverse events (TEAEs) from baseline to last visit. Twenty-five participants were enrolled (male: 44%; bepranemab n=18, placebo n=7). Seventeen (94.4%) in the bepranemab group reported \u22651 TEAE (five participants; ten investigational medicinal product (IMP)-related TEAEs), versus placebo (n=7; 100%). In the bepranemab and placebo groups, respectively, three participants (16.7%) and one participant (14.3%) discontinued due to TEAEs. Incidence of IMP-related TEAEs and severe TEAEs was similar between groups; no deaths were reported. Reduction (80.41%) in mean free tau cerebrospinal fluid levels was observed in the bepranemab group. Multiple doses of bepranemab 90 mg/kg were well tolerated with an acceptable safety profile in participants with PSP. High target occupancy was observed.", "source": "PubMed"}, {"chunk_id": "38623902_0", "pmid": "38623902", "title": "[Not Available].", "authors": "Pasternak M, Mirza SS, Luciw N et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "arterial spin labeling, cerebral perfusion, frontotemporal dementia, presymptomatic biomarker", "chunk": "Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset. Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. Gray matter", "source": "PubMed"}, {"chunk_id": "38623902_1", "pmid": "38623902", "title": "[Not Available].", "authors": "Pasternak M, Mirza SS, Luciw N et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "arterial spin labeling, cerebral perfusion, frontotemporal dementia, presymptomatic biomarker", "chunk": "versus asymptomatic carriers past their expected age of disease onset. Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups . Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.", "source": "PubMed"}, {"chunk_id": "38917881_0", "pmid": "38917881", "title": "Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates.", "authors": "Hroudov\u00e1 J, Fi\u0161ar Z", "year": "2024", "journal": "Progress in neuro-psychopharmacology & biological psychiatry", "keywords": "Alzheimer's disease, Amyloid beta, Clinical trial, Drug development, Tau protein, disease-modifying drugs", "chunk": "The strategy for the development of new drugs for Alzheimer's disease (AD) recognizes that an effective therapy requires early therapeutic intervention and a multifactorial approach that considers the individual initiators of AD development. Current knowledge of AD includes the understanding of pathophysiology, risk factors, biomarkers, and the evolving patterns of biomarker abnormalities. This knowledge is essential in identifying potential molecular targets for new drug development. This review summarizes promising AD drug candidates, many of which are currently in phase 2 or 3 clinical trials. New agents are classified according to the Common Alzheimer's Disease Research Ontology (CADRO). The main targets of new drugs for AD are processes related to amyloid beta and tau neurotoxicity, neurotransmission, inflammation, metabolism and bioenergetics, synaptic plasticity, and oxidative stress. These interventions are aimed at preventing disease onset and slowing or eliminating disease progression. The efficacy of pharmacotherapy may be enhanced by combining these drugs with", "source": "PubMed"}, {"chunk_id": "38917881_1", "pmid": "38917881", "title": "Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates.", "authors": "Hroudov\u00e1 J, Fi\u0161ar Z", "year": "2024", "journal": "Progress in neuro-psychopharmacology & biological psychiatry", "keywords": "Alzheimer's disease, Amyloid beta, Clinical trial, Drug development, Tau protein, disease-modifying drugs", "chunk": "plasticity, and oxidative stress. These interventions are aimed at preventing disease onset and slowing or eliminating disease progression. The efficacy of pharmacotherapy may be enhanced by combining these drugs with other treatments, antioxidants, and dietary supplements. Ongoing research into AD pathophysiology, risk factors, biomarkers, and the dynamics of biomarker abnormalities may contribute to the understanding of AD and offer hope for effective therapeutic strategies in the near future.", "source": "PubMed"}, {"chunk_id": "33991694_0", "pmid": "33991694", "title": "Deep recurrent model for individualized prediction of Alzheimer's disease progression.", "authors": "Jung W, Jun E, Suk HI et al.", "year": "2021", "journal": "NeuroImage", "keywords": "Alzheimer\u2019s Disease, Cognitive tests, Conversion-Time Prediction, Deep Learning, Disease Progression Modeling, Longitudinal Data, Mild Cognitive Impairment, Missing Value Imputation, Recurrent Neural Networks", "chunk": "Alzheimer's disease (AD) is known as one of the major causes of dementia and is characterized by slow progression over several years, with no treatments or available medicines. In this regard, there have been efforts to identify the risk of developing AD in its earliest time. While many of the previous works considered cross-sectional analysis, more recent studies have focused on the diagnosis and prognosis of AD with longitudinal or time series data in a way of disease progression modeling. Under the same problem settings, in this work, we propose a novel computational framework that can predict the phenotypic measurements of MRI biomarkers and trajectories of clinical status along with cognitive scores at multiple future time points. However, in handling time series data, it generally faces many unexpected missing observations. In regard to such an unfavorable situation, we define a secondary problem of estimating those missing values and tackle it", "source": "PubMed"}, {"chunk_id": "33991694_1", "pmid": "33991694", "title": "Deep recurrent model for individualized prediction of Alzheimer's disease progression.", "authors": "Jung W, Jun E, Suk HI et al.", "year": "2021", "journal": "NeuroImage", "keywords": "Alzheimer\u2019s Disease, Cognitive tests, Conversion-Time Prediction, Deep Learning, Disease Progression Modeling, Longitudinal Data, Mild Cognitive Impairment, Missing Value Imputation, Recurrent Neural Networks", "chunk": "time series data, it generally faces many unexpected missing observations. In regard to such an unfavorable situation, we define a secondary problem of estimating those missing values and tackle it in a systematic way by taking account of temporal and multivariate relations inherent in time series data. Concretely, we propose a deep recurrent network that jointly tackles the four problems of (i) missing value imputation, (ii) phenotypic measurements forecasting, (iii) trajectory estimation of a cognitive score, and (iv) clinical status prediction of a subject based on his/her longitudinal imaging biomarkers. Notably, the learnable parameters of all the modules in our predictive models are trained in an end-to-end manner by taking the morphological features and cognitive scores as input, with our circumspectly defined loss function. In our experiments over The Alzheimers Disease Prediction Of Longitudinal Evolution (TADPOLE) challenge cohort, we measured performance for various metrics and compared our method to competing", "source": "PubMed"}, {"chunk_id": "33991694_2", "pmid": "33991694", "title": "Deep recurrent model for individualized prediction of Alzheimer's disease progression.", "authors": "Jung W, Jun E, Suk HI et al.", "year": "2021", "journal": "NeuroImage", "keywords": "Alzheimer\u2019s Disease, Cognitive tests, Conversion-Time Prediction, Deep Learning, Disease Progression Modeling, Longitudinal Data, Mild Cognitive Impairment, Missing Value Imputation, Recurrent Neural Networks", "chunk": "circumspectly defined loss function. In our experiments over The Alzheimers Disease Prediction Of Longitudinal Evolution (TADPOLE) challenge cohort, we measured performance for various metrics and compared our method to competing methods in the literature. Exhaustive analyses and ablation studies were also conducted to better confirm the effectiveness of our method.", "source": "PubMed"}, {"chunk_id": "41185962_0", "pmid": "41185962", "title": "The Roles of EDA2R in Ageing and Disease.", "authors": "Farrington G, Tonge L, Branagan T et al.", "year": "2025", "journal": "Aging cell", "keywords": "EDA2R, ageing, alopecia, inflammation, muscle wasting, therapeutic treatment", "chunk": "Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clock, are associated with a wide range of conditions, including cardiovascular diseases, dementia, Parkinson's disease, mood disorders, post-traumatic stress disorder, various cancers, osteoarthritis, digestive diseases, diabetes, obesity, chronic obstructive pulmonary disease, ear and eye diseases, renal impairment, systemic autoimmune diseases, anaemia, bacterial infections, myositis, frailty, accelerated biological ageing, shorter telomere length, decreased healthspan and longevity, higher all-cause mortality and overall poor health. Beyond serving as a biomarker,", "source": "PubMed"}, {"chunk_id": "41185962_1", "pmid": "41185962", "title": "The Roles of EDA2R in Ageing and Disease.", "authors": "Farrington G, Tonge L, Branagan T et al.", "year": "2025", "journal": "Aging cell", "keywords": "EDA2R, ageing, alopecia, inflammation, muscle wasting, therapeutic treatment", "chunk": "systemic autoimmune diseases, anaemia, bacterial infections, myositis, frailty, accelerated biological ageing, shorter telomere length, decreased healthspan and longevity, higher all-cause mortality and overall poor health. Beyond serving as a biomarker, EDA2R actively drives ageing, as its overexpression induces inflammation and tissue damage, whereas its inhibition mitigates these effects. Mechanistically, EDA2R activates non-canonical and canonical NF-\u03baB signalling, promoting pro-inflammatory and catabolic processes that accelerate ageing phenotypes. Genetic variants of EDA2R are linked to alopecia, facial ageing, lipid profiles and prostate cancer. This review explores the structure and function of the EDA2R gene and protein, its role in tissue-specific ageing, and its therapeutic potential for multiple diseases. Although specific EDA2R antagonists are not yet available, interventions like calorie restriction, physical activity and specific supplements show promise in lowering EDA2R levels.", "source": "PubMed"}, {"chunk_id": "41185962_2", "pmid": "41185962", "title": "The Roles of EDA2R in Ageing and Disease.", "authors": "Farrington G, Tonge L, Branagan T et al.", "year": "2025", "journal": "Aging cell", "keywords": "EDA2R, ageing, alopecia, inflammation, muscle wasting, therapeutic treatment", "chunk": "specific supplements show promise in lowering EDA2R levels.", "source": "PubMed"}, {"chunk_id": "41225647_0", "pmid": "41225647", "title": "Prognostic value of plasma biomarkers in early Alzheimer's disease: a longitudinal clinical and neuroimaging study.", "authors": "Clemmensen FK, Gramkow MH, Gonzalez-Ortiz F et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Blood biomarkers, Dementia, Disease progression, Memory clinic, Neurodegeneration, Prognosis, Variability", "chunk": "While blood biomarkers for AD have proven useful in identifying AD pathology from other neurodegenerative conditions, their prognostic value in real-world clinical settings, such as memory clinics, remains unexplored. We aimed to examine the prognostic value of AD plasma biomarkers and their short-term changes within 4 months, for predicting clinical and neuroradiological progression over two years. We performed a prospective observational longitudinal cohort study of patients with early stages of AD and followed them for up to 2 years. Plasma was analysed for neurofilament light (NfL), brain-derived tau (BD-tau), phosphorylated tau 217 (p-tau217), and glial fibrillary acidic protein (GFAP) on single molecule array. The outcomes were annual changes in clinical dementia rating scale, sum of boxes (CDR-SB) and changes in [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography ([<sup>18</sup>F]FDG-PET) and magnetic resonance imaging (MRI) brain scans. We performed linear regression models with baseline and short-term plasma biomarker changes as predictors, adjusted for age, sex,", "source": "PubMed"}, {"chunk_id": "41225647_1", "pmid": "41225647", "title": "Prognostic value of plasma biomarkers in early Alzheimer's disease: a longitudinal clinical and neuroimaging study.", "authors": "Clemmensen FK, Gramkow MH, Gonzalez-Ortiz F et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Blood biomarkers, Dementia, Disease progression, Memory clinic, Neurodegeneration, Prognosis, Variability", "chunk": "[<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography ([<sup>18</sup>F]FDG-PET) and magnetic resonance imaging (MRI) brain scans. We performed linear regression models with baseline and short-term plasma biomarker changes as predictors, adjusted for age, sex, and creatinine. In total, 94 patients with MCI or dementia due to AD had baseline and one-year follow-up, with 85 patients completing two-year follow-up. We found that baseline plasma NfL was significantly associated with an increase in CDR-SB at one- and two-year follow-up. Neither plasma BD-tau, p-tau217 or GFAP were associated with future clinical progression. Short-term changes of plasma NfL were associated with reduced glucose metabolism in the hippocampus and temporal cortex on [<sup>18</sup>F]FDG-PET. Short-term changes in plasma p-tau217 were significantly associated with reduced hippocampal glucose metabolism, and further, short-term changes in the p-tau217/BD-tau ratio were significantly associated with reduced metabolism in hippocampal and isthmus cingulate cortex on [<sup>18</sup>F]FDG-PET. We found no association between plasma biomarkers and MRI volumetric changes", "source": "PubMed"}, {"chunk_id": "41225647_2", "pmid": "41225647", "title": "Prognostic value of plasma biomarkers in early Alzheimer's disease: a longitudinal clinical and neuroimaging study.", "authors": "Clemmensen FK, Gramkow MH, Gonzalez-Ortiz F et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Blood biomarkers, Dementia, Disease progression, Memory clinic, Neurodegeneration, Prognosis, Variability", "chunk": "changes in the p-tau217/BD-tau ratio were significantly associated with reduced metabolism in hippocampal and isthmus cingulate cortex on [<sup>18</sup>F]FDG-PET. We found no association between plasma biomarkers and MRI volumetric changes after multiple testing correction. Our findings indicate that plasma NfL can serve as a predictor for subsequent clinical progression in early AD. Short-term changes in AD-related plasma biomarkers may reflect underlying disease processes, however, several limitations affect their interpretability. Therefore, short-term changes should be evaluated carefully and always in the context of baseline levels and clinical characteristics. Clinicaltrials.gov (NCT05175664), date of registration 2021\u201312-01. The online version contains supplementary material available at 10.1186/s13195-025-01892-7.", "source": "PubMed"}, {"chunk_id": "37461300_0", "pmid": "37461300", "title": "Truncated TDP-43 proteoforms diagnostic of frontotemporal dementia with TDP-43 pathology.", "authors": "Forgrave LM, Moon KM, Hamden JE et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "TDP-43, biomarkers, frontotemporal dementia, frontotemporal lobar degeneration, mass spectrometry, post-translational protein processing, proteoforms, proteomics", "chunk": "Biomarkers of TDP-43 pathology are needed to distinguish frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) from phenotypically related disorders. While normal physiological TDP-43 is not a promising biomarker, low-resolution techniques have suggested truncated forms of TDP-43 may be specific to TDP-43 pathology. To advance biomarker efforts for FTLD-TDP, we employed a high-resolution structural technique to characterize TDP-43 post-translational modifications in FTLD-TDP. High-resolution mass spectrometry was used to characterize TDP-43 proteoforms in brain tissue from FTLD-TDP, non-TDP-43 dementias and neuropathologically unaffected cases. Findings were then verified in a larger cohort of FTLD-TDP and non-TDP-43 dementias via targeted quantitative mass spectrometry. In the discovery phase, truncated TDP-43 identified FTLD-TDP with 85% sensitivity and 100% specificity. The verification phase revealed similar findings, with 83% sensitivity and 89% specificity. The concentration of truncated TDP-43 proteoforms-in particular, in vivo generated C-terminal fragments-have high diagnostic accuracy for FTLD-TDP. Discovery: Truncated TDP-43 differentiates FTLD-TDP from related dementias.", "source": "PubMed"}, {"chunk_id": "37461300_1", "pmid": "37461300", "title": "Truncated TDP-43 proteoforms diagnostic of frontotemporal dementia with TDP-43 pathology.", "authors": "Forgrave LM, Moon KM, Hamden JE et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "TDP-43, biomarkers, frontotemporal dementia, frontotemporal lobar degeneration, mass spectrometry, post-translational protein processing, proteoforms, proteomics", "chunk": "83% sensitivity and 89% specificity. The concentration of truncated TDP-43 proteoforms-in particular, in vivo generated C-terminal fragments-have high diagnostic accuracy for FTLD-TDP. Discovery: Truncated TDP-43 differentiates FTLD-TDP from related dementias. Verification: Truncated TDP-43 concentration has high accuracy for FTLD-TDP. TDP-43 proteoforms <28 kDa have highest discriminatory power for TDP-43 pathology.", "source": "PubMed"}, {"chunk_id": "41724104_0", "pmid": "41724104", "title": "The association between temporal-lobe tensor-based morphometry and plasma amyloid-\u03b2 in mild cognitive impairment.", "authors": "Nasiri H, Khosravi F, Ashrafi M et al.", "year": "2026", "journal": "Clinical neurology and neurosurgery", "keywords": "Alzheimer's Disease, Amyloid beta-Peptides, Apolipoproteins E, Biomarkers, Brain Atrophy, Longitudinal Studies, Magnetic Resonance Imaging, Mild Cognitive Impairment", "chunk": "Alzheimer's disease (AD) is characterized by amyloid-\u03b2 (A\u03b2) accumulation and brain atrophy; however, the assocation between plasma A\u03b2 biomarkers and regional neurodegeneration remains unclear. We investigated whether plasma A\u03b242, A\u03b240, and the A\u03b242/40 ratio are associated with temporal lobe atrophy measured using tensor-based morphometry (TBM) in cognitively healthy controls (HC) and participants with mild cognitive impairment (MCI). We analyzed longitudinal MRI and plasma biomarkers data from 29 participants from ADNI (HC = 14, MCI = 15) with imaging and blood samples available at baseline, 24 months, and 48 months. TBM Jacobian maps were summarized within temporal lobe regions of interest (ROIs). Associations between plasma A\u03b2 measures and TBM-derived atrophy were examined with linear mixed-effects models, adjusting for age, sex, and APOE \u03b54 status, with false-discovery-rate correction. Participants with MCI showed greater temporal lobe atrophy compared with HC people, with significantly lower TBM values at follow-up. Plasma A\u03b242, A\u03b240, and A\u03b242/40", "source": "PubMed"}, {"chunk_id": "41724104_1", "pmid": "41724104", "title": "The association between temporal-lobe tensor-based morphometry and plasma amyloid-\u03b2 in mild cognitive impairment.", "authors": "Nasiri H, Khosravi F, Ashrafi M et al.", "year": "2026", "journal": "Clinical neurology and neurosurgery", "keywords": "Alzheimer's Disease, Amyloid beta-Peptides, Apolipoproteins E, Biomarkers, Brain Atrophy, Longitudinal Studies, Magnetic Resonance Imaging, Mild Cognitive Impairment", "chunk": "APOE \u03b54 status, with false-discovery-rate correction. Participants with MCI showed greater temporal lobe atrophy compared with HC people, with significantly lower TBM values at follow-up. Plasma A\u03b242, A\u03b240, and A\u03b242/40 levels showed no consistent or robust differences between diagnostic groups. After covariate adjustment and FDR correction, no plasma A\u03b2-TBM associations were significant at baseline or 24 months. At 48 months, positive associations were identified between A\u03b242 and temporal lobe atrophy (measure 2) in HC participants (\u03b2 = 0.70, p = 0.046) and between A\u03b240 and measure 2 in participants with MCI (\u03b2 = 0.60, p = 0.036). In contrast, a negative association was observed between the A\u03b242/40 and temporal lobe atrophy (measure 2) in MCI group (\u03b2 = -0.53, p = 0.049). TBM captured greater temporal lobe atrophy in participants with MCI compared with HC. Plasma amyloids showed only limited and inconsistent associations with temporal lobe atrophy over time. These", "source": "PubMed"}, {"chunk_id": "41724104_2", "pmid": "41724104", "title": "The association between temporal-lobe tensor-based morphometry and plasma amyloid-\u03b2 in mild cognitive impairment.", "authors": "Nasiri H, Khosravi F, Ashrafi M et al.", "year": "2026", "journal": "Clinical neurology and neurosurgery", "keywords": "Alzheimer's Disease, Amyloid beta-Peptides, Apolipoproteins E, Biomarkers, Brain Atrophy, Longitudinal Studies, Magnetic Resonance Imaging, Mild Cognitive Impairment", "chunk": "= 0.049). TBM captured greater temporal lobe atrophy in participants with MCI compared with HC. Plasma amyloids showed only limited and inconsistent associations with temporal lobe atrophy over time. These findings suggest that plasma A\u03b2 measures alone may not reliably reflect longitudinal regional neurodegeneration in early AD.", "source": "PubMed"}, {"chunk_id": "41603883_0", "pmid": "41603883", "title": "Estimating the long-term health outcomes of treatment with lecanemab in early Alzheimer's disease: a modelling study.", "authors": "Burn O, Molloy K, Kanekiyo M et al.", "year": "2026", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, B41, P46, lecanemab, long-term outcomes, markov model, multistate survival analysis", "chunk": "To assess the long-term effects of lecanemab plus standard of care (SoC) compared with SoC alone in a cohort of patients with early Alzheimer's disease (AD; mild cognitive impairment [MCI] due to AD, or mild AD dementia) using different modeling approaches and data from Clarity AD (NCT0388745538). A Markov model was employed using health states based on disease severity, long-term institutionalization, and death, with disease severity defined using the Clinical Dementia Rating - Sum of Boxes (CDR-SB) classification for MCI due to AD, and Mild, Moderate, and Severe AD. State transitions during the first 18 months of treatment were estimated using either patient count data (Approach 1) or multistate survival analysis (Approach 2). Transition probabilities beyond 18 months for the lifetime of the cohort were informed by longitudinal natural history data for the SoC arm with a hazard ratio for time-to-worsening health state applied to estimate outcomes in the lecanemab", "source": "PubMed"}, {"chunk_id": "41603883_1", "pmid": "41603883", "title": "Estimating the long-term health outcomes of treatment with lecanemab in early Alzheimer's disease: a modelling study.", "authors": "Burn O, Molloy K, Kanekiyo M et al.", "year": "2026", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, B41, P46, lecanemab, long-term outcomes, markov model, multistate survival analysis", "chunk": "lifetime of the cohort were informed by longitudinal natural history data for the SoC arm with a hazard ratio for time-to-worsening health state applied to estimate outcomes in the lecanemab arm. Over a lifetime horizon, the model predicted a delayed time to Mild, Moderate, and Severe AD for patients treated with lecanemab compared to SoC by 1.31, 1.85, and 2.04 years, respectively when using Approach 1. Patients treated with lecanemab experienced a survival benefit of 1.36 years, comprised of an additional 1.85 years in early AD and 0.49 years less in moderate and severe AD, compared to patients treated with SoC alone. The model also predicted that compared to SoC, lecanemab increased the time in community care and reduced time spent in institutional care. Results were similar when using Approach 2. Long-term disease progression was informed by constant annual transition probabilities derived from the published literature. Patients treated with lecanemab", "source": "PubMed"}, {"chunk_id": "41603883_2", "pmid": "41603883", "title": "Estimating the long-term health outcomes of treatment with lecanemab in early Alzheimer's disease: a modelling study.", "authors": "Burn O, Molloy K, Kanekiyo M et al.", "year": "2026", "journal": "Journal of medical economics", "keywords": "Alzheimer\u2019s disease, B41, P46, lecanemab, long-term outcomes, markov model, multistate survival analysis", "chunk": "spent in institutional care. Results were similar when using Approach 2. Long-term disease progression was informed by constant annual transition probabilities derived from the published literature. Patients treated with lecanemab experience delayed progression to Moderate and Severe AD, resulting in additional life-years (LYs) and reduced time in institutional care.", "source": "PubMed"}, {"chunk_id": "41289288_0", "pmid": "41289288", "title": "Musical intervention to reduce stress during botulinum toxin injection for spasticity: Protocol for a randomized controlled trial (MUSIBOT).", "authors": "Angelvy P, Badin M, Pelletier-Visa M et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "Botulinum toxin injections are a common treatment for managing spasticity resulting from central nervous system damage, including stroke, multiple sclerosis, and traumatic brain injury. However, the injections are associated with perceived pain, and many patients experience significant anticipatory stress regarding future sessions. The intensity of this stress varies among individuals. Music therapy, particularly receptive musical interventions structured around a U-shaped sequence, promotes progressive relaxation through distinct musical phases. This method has demonstrated efficacy in reducing pain and anxiety across various clinical contexts, including chronic and acute pain, Alzheimer's disease, fibromyalgia, and neurologically mediated pain. Given the painful nature of botulinum toxin injections, this study proposes the use of receptive music therapy to improve patient tolerance of the procedure. We hypothesize that receptive musical intervention can reduce injection-induced stress in adults undergoing botulinum toxin treatment. To our knowledge, no studies have specifically investigated the effect of music therapy on stress related", "source": "PubMed"}, {"chunk_id": "41289288_1", "pmid": "41289288", "title": "Musical intervention to reduce stress during botulinum toxin injection for spasticity: Protocol for a randomized controlled trial (MUSIBOT).", "authors": "Angelvy P, Badin M, Pelletier-Visa M et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "that receptive musical intervention can reduce injection-induced stress in adults undergoing botulinum toxin treatment. To our knowledge, no studies have specifically investigated the effect of music therapy on stress related to botulinum toxin injections. We aim to conduct a prospective randomized (1:1) controlled trial to evaluate the impact of receptive music intervention on stress levels, measured via heart rate variability (HRV), during botulinum toxin injection sessions. The primary objective is to assess the effect of receptive musical intervention during botulinum toxin injections on injection-induced stress, measured by HRV. Secondary objectives include evaluating the intervention's effects on pain intensity and anxiety levels. Patient satisfaction following the music-assisted injection session will also be assessed. Additionally, the physician's evaluation of the procedure and the patient's perception of time during the session will be recorded. All participants will provide written informed consent prior to enrollment. The study has received approval from the relevant institutional", "source": "PubMed"}, {"chunk_id": "41289288_2", "pmid": "41289288", "title": "Musical intervention to reduce stress during botulinum toxin injection for spasticity: Protocol for a randomized controlled trial (MUSIBOT).", "authors": "Angelvy P, Badin M, Pelletier-Visa M et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "the patient's perception of time during the session will be recorded. All participants will provide written informed consent prior to enrollment. The study has received approval from the relevant institutional ethics committee (Comit\u00e9 de Protection des Personnes - ID: 25.00156.000468, Sud-M\u00e9diterran\u00e9e IV, approved on 3 April 2025). Findings will be disseminated through peer-reviewed publications and presentations at scientific conferences. ClinicalTrials.gov NCT06920524.", "source": "PubMed"}, {"chunk_id": "36028734_0", "pmid": "36028734", "title": "Naringenin Attenuates Cognitive Impairment in a Rat Model of Vascular Dementia by Inhibiting Hippocampal Oxidative Stress and Inflammatory Response and Promoting N-Methyl-D-Aspartate Receptor Signaling Pathway.", "authors": "Zhang J, Zhang Y, Liu Y et al.", "year": "2022", "journal": "Neurochemical research", "keywords": "Cognitive impairment, Inflammatory response, N-methyl-D-aspartate receptor signaling pathway, Naringenin, Oxidative stress, Vascular dementia", "chunk": "Vascular dementia (VaD) is the second most common form of dementia globally, yet there are no efficient treatments. Naringenin, a natural flavonoid, exerts antioxidative, anti-inflammatory, and neuroprotective properties; however, its potential effect on VaD remain unclear. Herein, the purpose of present study was to elucidate whether naringenin attenuates cognitive dysfunction in VaD via inhibiting hippocampal oxidative stress and inflammatory response, and promoting N-methyl-D-aspartate receptors (NMDARs) signaling pathway. A rat model of VaD was established by permanent bilateral common carotid artery occlusion [2-vessel occlusion (2VO)]. Behavioral performance analyses results revealed that administration of naringenin improves cognitive impairment in rats with VaD according to the new object recognition test and the Morris water maze test. In addition, naringenin attenuated hippocampal oxidative stress by reducing reactive oxygen species generation, decreasing malondialdehyde content and recombinant reactive oxygen species modulator 1 (Romo-1) expression, and increasing superoxide dismutase and glutathione peroxidase activities in the hippocampus of", "source": "PubMed"}, {"chunk_id": "36028734_1", "pmid": "36028734", "title": "Naringenin Attenuates Cognitive Impairment in a Rat Model of Vascular Dementia by Inhibiting Hippocampal Oxidative Stress and Inflammatory Response and Promoting N-Methyl-D-Aspartate Receptor Signaling Pathway.", "authors": "Zhang J, Zhang Y, Liu Y et al.", "year": "2022", "journal": "Neurochemical research", "keywords": "Cognitive impairment, Inflammatory response, N-methyl-D-aspartate receptor signaling pathway, Naringenin, Oxidative stress, Vascular dementia", "chunk": "by reducing reactive oxygen species generation, decreasing malondialdehyde content and recombinant reactive oxygen species modulator 1 (Romo-1) expression, and increasing superoxide dismutase and glutathione peroxidase activities in the hippocampus of VaD rats. Moreover, naringenin decreased the proinflammatory cytokines (IL-1\u03b2, IL-6, and TNF-\u03b1) levels and increased the anti-inflammatory cytokines (IL-10 and IL-4) levels in the hippocampus of 2VO surgery-treated rats, attenuating hippocampal inflammatory response during VaD. Furthermore, naringenin promoted synaptophysin (SYP), postsynaptic density protein 95 (PSD95), N-methyl-Daspartic acid receptor 1 (NR1) and N-methyl-D-aspartate receptor subunit 2B (NR2B) expressions levels in hippocampus of VaD rats. Collectively, these findings indicated that naringenin mitigates cognitive impairment in VaD rats partly via inhibiting hippocampal oxidative stress and inflammatory response and restoring NMDARs signaling pathway.", "source": "PubMed"}, {"chunk_id": "41507065_0", "pmid": "41507065", "title": "Effect of cognitive training on cortisol levels in patients with neurocognitive disorders.", "authors": "De Rui M, Salerno Trapella G, Ceolin C et al.", "year": "2026", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Alzheimer\u2019s disease, Cognitive stimulation, Mild cognitive impairment", "chunk": "Elevated cortisol levels are linked to a greater risk and faster progression of neurocognitive disorders (NCDs). While interventions such as exercise and mindfulness have shown benefits in reducing cortisol, the impact of cognitive training (CT) on cortisol regulation remains unexplored. This study investigated whether CT affects cortisol levels and secretion patterns in individuals with minor or major NCD and compared its effects with those of pharmacological treatment. Sixty-two older adults with NCD and 43 healthy controls were recruited from the University Hospital of Padua in Italy. Among patients with NCD, 34 underwent CT (CT-NCD group), and 28 received pharmacological treatment (PH-NCD group). Salivary cortisol was measured at six points during the day, at baseline, and at 3 months (T1) and 6 months (T2) post-intervention. Compared with pharmacological treatment (PH), CT showed a larger percentage decrease of daily cortisol exposure area under the curve (AUC) from baseline; however, the between-group difference", "source": "PubMed"}, {"chunk_id": "41507065_1", "pmid": "41507065", "title": "Effect of cognitive training on cortisol levels in patients with neurocognitive disorders.", "authors": "De Rui M, Salerno Trapella G, Ceolin C et al.", "year": "2026", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Alzheimer\u2019s disease, Cognitive stimulation, Mild cognitive impairment", "chunk": "6 months (T2) post-intervention. Compared with pharmacological treatment (PH), CT showed a larger percentage decrease of daily cortisol exposure area under the curve (AUC) from baseline; however, the between-group difference did not remain statistically significant after covariate adjustment, and the only robust time-point effect was in the afternoon (F(1,47)=5.13; p = .028). Morning values decreased within groups, but between-group differences in the CAR were not significant; at bedtime, CT showed only a trend towards lower cortisol than PH (p = .071). Median morning values changed from 7.75 to 6.20 in CT and from 5.80 to 5.15 in PH. Cognitive training may help lower cortisol levels and enhance cognitive function in NCD patients, suggesting its potential as a nonpharmacological tool to modulate hypothalamic-pituitary-adrenal axis activity. Larger randomized studies are needed to confirm and extend these findings.", "source": "PubMed"}, {"chunk_id": "41507065_2", "pmid": "41507065", "title": "Effect of cognitive training on cortisol levels in patients with neurocognitive disorders.", "authors": "De Rui M, Salerno Trapella G, Ceolin C et al.", "year": "2026", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Alzheimer\u2019s disease, Cognitive stimulation, Mild cognitive impairment", "chunk": "modulate hypothalamic-pituitary-adrenal axis activity. Larger randomized studies are needed to confirm and extend these findings.", "source": "PubMed"}, {"chunk_id": "33642368_0", "pmid": "33642368", "title": "Sleep disorders in Alzheimer's disease: the predictive roles and potential mechanisms.", "authors": "Kuang H, Zhu YG, Zhou ZF et al.", "year": "2021", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, GABAergic system, amyloid-\u03b2accumulation, circadian rhythm, glutamatergic system, non-rapid eye movement sleep, orexinergic system, sleep disorders, sleep fragmentation, sleep-disordered breathing", "chunk": "Sleep disorders are common in patients with Alzheimer's disease, and can even occur in patients with amnestic mild cognitive impairment, which appears before Alzheimer's disease. Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-\u03b2 and tau in patients with Alzheimer's disease. At present, sleep disorders are considered as a risk factor for, and may be a predictor of, Alzheimer's disease development. Given that sleep disorders are encountered in other types of dementia and psychiatric conditions, sleep-related biomarkers to predict Alzheimer's disease need to have high specificity and sensitivity. Here, we summarize the major Alzheimer's disease-specific sleep changes, including abnormal non-rapid eye movement sleep, sleep fragmentation, and sleep-disordered breathing, and describe their ability to predict the onset of Alzheimer's disease at its earliest stages. Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer's disease. This paper", "source": "PubMed"}, {"chunk_id": "33642368_1", "pmid": "33642368", "title": "Sleep disorders in Alzheimer's disease: the predictive roles and potential mechanisms.", "authors": "Kuang H, Zhu YG, Zhou ZF et al.", "year": "2021", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, GABAergic system, amyloid-\u03b2accumulation, circadian rhythm, glutamatergic system, non-rapid eye movement sleep, orexinergic system, sleep disorders, sleep fragmentation, sleep-disordered breathing", "chunk": "Alzheimer's disease at its earliest stages. Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer's disease. This paper therefore explores some potential mechanisms that may contribute to sleep disorders, including dysregulation of the orexinergic, glutamatergic, and \u03b3-aminobutyric acid systems and the circadian rhythm, together with amyloid-\u03b2 accumulation. This review could provide a theoretical basis for the development of drugs to treat Alzheimer's disease based on sleep disorders in future work.", "source": "PubMed"}, {"chunk_id": "27444168_0", "pmid": "27444168", "title": "Sweet old memories: a review of the experimental models of the association between diabetes, senility and dementia.", "authors": "Akinola OB", "year": "2016", "journal": "Metabolic brain disease", "keywords": "Aging, Dementia, Diabetes mellitus, Models", "chunk": "As the burden of Alzheimer's dementia rises, so does our understanding of the cellular and molecular basis of this neurodegenerative disease. Some of the recent advances in the aetiopathogenesis of neurodegeneration include the finding that insulin receptor signalling is key to neurogenesis and synaptogenesis in the brain, especially in areas related to memory formation and storage, including the hippocampus. This suggests an association between impaired insulin receptor signalling and neurodegenerative events. To decipher this association, several animal models are being employed. Such models include transgenic and non-transgenic animals that range from invertebrates (Drosophila melanogaster and Caenorhabditis elegans), to vertebrates (mouse, rats and primates). The current review is an account of such models and how they have contributed to our understanding of the relationship between type 2 diabetes mellitus, ageing and dementia.", "source": "PubMed"}, {"chunk_id": "27444168_1", "pmid": "27444168", "title": "Sweet old memories: a review of the experimental models of the association between diabetes, senility and dementia.", "authors": "Akinola OB", "year": "2016", "journal": "Metabolic brain disease", "keywords": "Aging, Dementia, Diabetes mellitus, Models", "chunk": "of the relationship between type 2 diabetes mellitus, ageing and dementia.", "source": "PubMed"}, {"chunk_id": "37986913_0", "pmid": "37986913", "title": "Boston criteria v2.0 for cerebral amyloid angiopathy without hemorrhage: An MRI-neuropathological validation study.", "authors": "Switzer A, Charidimou A, McCarter SJ et al.", "year": "2023", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without intracerebral hemorrhage (ICH) or transient focal neurological episodes (TFNE) is unknown. We assessed the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals presenting without symptomatic ICH. Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer's Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared to v1.5 using histopathologically verified CAA as the reference standard. Median age at MRI was 75 years (IQR 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95%CI: 13.2-48.7%) and 65.3% (95%CI: 44.3-82.8%) for probable", "source": "PubMed"}, {"chunk_id": "37986913_1", "pmid": "37986913", "title": "Boston criteria v2.0 for cerebral amyloid angiopathy without hemorrhage: An MRI-neuropathological validation study.", "authors": "Switzer A, Charidimou A, McCarter SJ et al.", "year": "2023", "journal": "medRxiv : the preprint server for health sciences", "keywords": "None", "chunk": "verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95%CI: 13.2-48.7%) and 65.3% (95%CI: 44.3-82.8%) for probable CAA diagnosis (AUC 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC: 0.57), respectively. The v2.0 Boston criteria was not superior in performance compared to the prior v1.5 criteria for either CAA diagnostic category. The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms.. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.", "source": "PubMed"}, {"chunk_id": "41338085_0", "pmid": "41338085", "title": "\"Objective sleep apnea severity, cognitive impairment and AD pathology: Insights from the ALBION cohort\".", "authors": "Foukarakis I, Androni X, Sampatakakis SN et al.", "year": "2026", "journal": "Sleep medicine", "keywords": "\u201cAHI\u201d, \u201cAlzheimer's disease\u201d, \u201cCSF pTau181/A\u03b242\u2033, \u201cMild cognitive impairment\u201d, \u201cOSA\u201d, \u201cWatchPAT\u201d", "chunk": "Obstructive sleep apnea (OSA) appears to be closely related to cognitive status. This study explored the association between the Apnea-Hypopnea Index (AHI), cognitive status, and cerebrospinal fluid (CSF) biomarker pTau181/A\u03b242 (AD pathology) in non-demented individuals. In this cross-sectional study, 115 non-demented participants from the ALBION cohort (mean age 64.4 \u00b1 8.9 years, 70 % female, median education 14 years, median BMI 25.7 kg/m<sup>2</sup>) underwent a one-night WatchPAT evaluation to determine AHI (blood oxygen desaturation \u22653 %). Participants were categorized based on both cognitive status (patients with Mild Cognitive Impairment (MCI)[n = 27] or cognitively normal individuals (CN) [n = 88]) and AD pathology (AD+ [n = 25] or AD- [n = 90]). Binary logistic regression analysis, adjusted for age, sex, years of education, and BMI was used to assess the association of cognitive status and AD pathology with AHI. Participants were further divided into low (<15/h) and high (\u226515/h) AHI", "source": "PubMed"}, {"chunk_id": "41338085_1", "pmid": "41338085", "title": "\"Objective sleep apnea severity, cognitive impairment and AD pathology: Insights from the ALBION cohort\".", "authors": "Foukarakis I, Androni X, Sampatakakis SN et al.", "year": "2026", "journal": "Sleep medicine", "keywords": "\u201cAHI\u201d, \u201cAlzheimer's disease\u201d, \u201cCSF pTau181/A\u03b242\u2033, \u201cMild cognitive impairment\u201d, \u201cOSA\u201d, \u201cWatchPAT\u201d", "chunk": "years of education, and BMI was used to assess the association of cognitive status and AD pathology with AHI. Participants were further divided into low (<15/h) and high (\u226515/h) AHI levels and a joint analysis with AD pathology was performed with cognitive status as the outcome. After adjusting for confounders, for each unit increase in AHI, the odds of being classified as MCI were 7 % higher (OR = 1.07, p = 0.003) and the odds of being classified as AD+ were 4 % higher (OR = 1.04, p = 0.043). Compared to the reference group [AD (-)/AHI(low)], the odds ratio of being classified as MCI was 4.48 (p = 0.022) in the AD (-)/AHI(high) and 15.30 (p = 0.0017) in the AD (+)/AHI(high) group. We find that higher AHI levels may contribute to cognitive impairment, either independently or alongside AD pathology. Further longitudinal studies are warranted to clarify causality", "source": "PubMed"}, {"chunk_id": "41338085_2", "pmid": "41338085", "title": "\"Objective sleep apnea severity, cognitive impairment and AD pathology: Insights from the ALBION cohort\".", "authors": "Foukarakis I, Androni X, Sampatakakis SN et al.", "year": "2026", "journal": "Sleep medicine", "keywords": "\u201cAHI\u201d, \u201cAlzheimer's disease\u201d, \u201cCSF pTau181/A\u03b242\u2033, \u201cMild cognitive impairment\u201d, \u201cOSA\u201d, \u201cWatchPAT\u201d", "chunk": "in the AD (+)/AHI(high) group. We find that higher AHI levels may contribute to cognitive impairment, either independently or alongside AD pathology. Further longitudinal studies are warranted to clarify causality and potential therapeutic benefits of OSA management on cognitive health.", "source": "PubMed"}, {"chunk_id": "37279069_0", "pmid": "37279069", "title": "APOE-\u03b54 synergizes with sleep disruption to accelerate A\u03b2 deposition and A\u03b2-associated tau seeding and spreading.", "authors": "Wang C, Nambiar A, Strickland MR et al.", "year": "2023", "journal": "The Journal of clinical investigation", "keywords": "Alzheimer disease, Lipoproteins, Neurodegeneration, Neuroscience", "chunk": "Alzheimer's disease (AD) is the most common cause of dementia. The APOE-\u03b54 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. The APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis, which is relatively unexplored. We hypothesized that apoE modifies A\u03b2 deposition and A\u03b2 plaque-associated tau seeding and spreading in the form of neuritic plaque-tau (NP-tau) pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-\u03b53 or -\u03b54 with or without AD-tau injection. We found that SD in APPPS1 mice significantly increased A\u03b2 deposition and peri-plaque NP-tau pathology in the presence of APOE4 but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence", "source": "PubMed"}, {"chunk_id": "37279069_1", "pmid": "37279069", "title": "APOE-\u03b54 synergizes with sleep disruption to accelerate A\u03b2 deposition and A\u03b2-associated tau seeding and spreading.", "authors": "Wang C, Nambiar A, Strickland MR et al.", "year": "2023", "journal": "The Journal of clinical investigation", "keywords": "Alzheimer disease, Lipoproteins, Neurodegeneration, Neuroscience", "chunk": "NP-tau pathology in the presence of APOE4 but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence of APOE4 but not APOE3. We also found that sleep-deprived APPPS1:E4 mice injected with AD-tau had significantly altered sleep behaviors compared with APPPS1:E3 mice. These findings suggest that the APOE-\u03b54 genotype is a critical modifier in the development of AD pathology in response to SD.", "source": "PubMed"}, {"chunk_id": "40545029_0", "pmid": "40545029", "title": "Advancements and challenges in using AI for biomarker detection in early Alzheimer's disease.", "authors": "Beheshti I, Albensi BC, Freitas A et al.", "year": "2025", "journal": "Drug discovery today", "keywords": "Alzheimer\u2019s disease, CSF, artificial intelligence, biomarkers, clinical implementation, machine learning, neuroimaging", "chunk": "The rapid growth in Alzheimer's disease (AD) research has led to an unprecedented accumulation of biomedical and clinical data, including longitudinal patient datasets and comprehensive observational cohort databases comprising clinical, biomedical, neuroimaging and lifestyle data. Expert use of machine learning algorithms is indispensable in order to realize the full potential of the data for diagnosis and drug target discovery. Here, we provide an overview of the biomedical and neuroimaging measures for AD diagnosis and staging. We then critically review the application of machine learning (classification) methods to AD data and provide insight for future improvements and research directions. Future research should aim to improve interpretability, accessibility and thorough validation of the models, enabling translation into clinical applications.", "source": "PubMed"}, {"chunk_id": "39490626_0", "pmid": "39490626", "title": "Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats.", "authors": "Li W, Li AA, Nie X et al.", "year": "2025", "journal": "Experimental neurology", "keywords": "Biomarker, Cognitive impairment, Diabetes, Diffusion MRI, VCID", "chunk": "Diabetes is a major risk factor for all types of dementia. The underlying reasons are not fully understood, and preventive therapeutic strategies are lacking. Previously we have shown that diabetic but not control rats developed a progressive cognitive decline in a microemboli (ME) model of vascular contributions to cognitive impairment & dementia (VCID). Given the cerebrovascular dysfunction is a mutual pathological change between diabetes and VCID, we hypothesized that the cognitive impairment in this ME model can be prevented by improving the endothelial function in diabetes. Our treatment paradigm was based on the LACI-2 Trial which assessed the efficacy of isosorbide mononitrate (ISMN) and cilostazol (Cil) treatments in small vessel disease progression. Control and diabetic rats were treated with ISMN/Cil or vehicle for 4 weeks, then injected with cholesterol crystal ME and the behavioral outcomes were monitored. Brain microstructure integrity was assessed by diffusion MRI. Plasma biomarkers were assessed using", "source": "PubMed"}, {"chunk_id": "39490626_1", "pmid": "39490626", "title": "Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats.", "authors": "Li W, Li AA, Nie X et al.", "year": "2025", "journal": "Experimental neurology", "keywords": "Biomarker, Cognitive impairment, Diabetes, Diffusion MRI, VCID", "chunk": "or vehicle for 4 weeks, then injected with cholesterol crystal ME and the behavioral outcomes were monitored. Brain microstructure integrity was assessed by diffusion MRI. Plasma biomarkers were assessed using angiogenesis, neurology and amyloid \u03b2 42/40 panels recommended by the MarkVCID consortium. Behavioral deficits and the loss of tissue integrity previously observed in untreated diabetic rats were not noted in the treated animals in this study. Treatment improved tissue perfusion but there were no differences in plasma biomarkers. These results suggest that restoration of endothelial function with ISMN/Cil before ME injection prevented the possible deleterious effects of ME in diabetic rats by improving the endothelial integrity and it is a practical preventive and therapeutic strategy for VCID.", "source": "PubMed"}, {"chunk_id": "41439666_0", "pmid": "41439666", "title": "Detecting Mild Cognitive Impairment Using Follow-Up Call Speech and Electronic Health Record Data in Home Health Care Settings.", "authors": "Zolnoori M, Zolnour A, Rashidi S et al.", "year": "2026", "journal": "Journal of gerontological nursing", "keywords": "None", "chunk": "Alzheimer's disease and related dementias often remain undiagnosed in home health care, where early symptoms are rarely documented in electronic health records (EHRs). The current study aimed to develop and evaluate a speech-based screening algorithm for detecting mild cognitive impairment (MCI) using routine follow-up calls. Speech data were collected from brief, semi-structured follow-up calls between nurse assistants and patients, Clinical Dementia Rating (CDR) interviews, and structured EHR data (Outcome and Assessment Information Set [OASIS]). Machine learning models were trained on these modalities individually and in combination. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic and secondary metrics. Among 114 participants, the multimodal model combining follow-up call speech and OASIS variables achieved the best performance (AUC = 91.03), outperforming models based on CDR interviews (AUC = 80.67), follow-up calls alone (AUC = 81.09), and OASIS alone (AUC = 78.53). Patients with MCI showed", "source": "PubMed"}, {"chunk_id": "41439666_1", "pmid": "41439666", "title": "Detecting Mild Cognitive Impairment Using Follow-Up Call Speech and Electronic Health Record Data in Home Health Care Settings.", "authors": "Zolnoori M, Zolnour A, Rashidi S et al.", "year": "2026", "journal": "Journal of gerontological nursing", "keywords": "None", "chunk": "best performance (AUC = 91.03), outperforming models based on CDR interviews (AUC = 80.67), follow-up calls alone (AUC = 81.09), and OASIS alone (AUC = 78.53). Patients with MCI showed greater comorbidity burden, higher rates of dual eligibility, and lower health literacy compared with cognitively healthy participants. Speech collected from routine follow-up calls, when combined with structured clinical data, can enhance early detection of MCI in home health care. This multimodal, low-burden approach leverages existing care coordination workflows and holds promise for scalable cognitive screening in diverse, aging populations.", "source": "PubMed"}, {"chunk_id": "41612173_0", "pmid": "41612173", "title": "Precise A\u03b2 clearance and antioxidant therapy in Alzheimer's disease via photoacoustic imaging-guided palladium hydride nanosheet-mediated photothermal treatment.", "authors": "Yu L, Zhao M, Zhang W et al.", "year": "2026", "journal": "BMC neuroscience", "keywords": "Alzheimer\u2019s disease, Palladium hydride nanosheets, Photothermal treatment, Synergistic treatment strategy", "chunk": "Inflammation and oxidative stress are critical pathological hallmarks of Alzheimer\u2019s disease (AD). Hydrogen therapy shows promise due to its selective hydroxyl radical (\u2219OH) scavenging capacity, yet conventional hydrogen delivery fails to effectively accumulate in the brain due to low solubility and rapid diffusion. Here, we report ultra-small palladium hydride (PdH) nanosheets as a dual-functional nanomedicine for AD treatment. The PdH nanosheets exhibit high hydrogen-releasing efficiency via autocatalysis, enabling in situ \u2219OH scavenging in the brain. Concurrently, their near-infrared (NIR) photothermal effect, degrading amyloid-\u03b2 (A\u03b2) aggregates and transiently enhancing blood-brain barrier (BBB) permeability for improved drug delivery. In AD mice, intravenous PdH treatment combined with NIR irradiation significantly reduced escape latency in the Morris water maze, paralleling reductions in brain A\u03b2 plaques and ROS levels. This study establishes a synergistic strategy of nanoscale hydrogen delivery and photothermal therapy, addressing the dual challenges of BBB penetration and multi-pathology intervention in AD.", "source": "PubMed"}, {"chunk_id": "41612173_1", "pmid": "41612173", "title": "Precise A\u03b2 clearance and antioxidant therapy in Alzheimer's disease via photoacoustic imaging-guided palladium hydride nanosheet-mediated photothermal treatment.", "authors": "Yu L, Zhao M, Zhang W et al.", "year": "2026", "journal": "BMC neuroscience", "keywords": "Alzheimer\u2019s disease, Palladium hydride nanosheets, Photothermal treatment, Synergistic treatment strategy", "chunk": "plaques and ROS levels. This study establishes a synergistic strategy of nanoscale hydrogen delivery and photothermal therapy, addressing the dual challenges of BBB penetration and multi-pathology intervention in AD.", "source": "PubMed"}, {"chunk_id": "40842786_0", "pmid": "40842786", "title": "Cognitive Decline in Chronic Inflammatory Conditions: Exploring Links Between Systemic Inflammation and Neurodegeneration.", "authors": "Jaramillo Ramos JJ, Galindo Pupo NM, Mena D et al.", "year": "2025", "journal": "Cureus", "keywords": "autoimmune diseases, chronic inflammation, cognitive decline, neurodegeneration, systemic inflammatory markers", "chunk": "Chronic inflammatory diseases (CIDs), such as rheumatoid arthritis (RA), obesity, type 2 diabetes mellitus (T2DM), systemic lupus erythematosus (SLE), fibromyalgia (FM), and chronic infection, are risk factors for neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review synthesizes evidence from longitudinal cohort studies and clinical trials, highlighting the contrasting evidence to explain the complex association between systemic inflammation and neurodegeneration. These important mechanisms are disruption of the blood-brain barrier, microglial activation, cytokine-related neurotoxicity (e.g., IL-6, TNF-alpha), lysosomal maladaptation, and metabolic imbalance (e.g., insulin resistance, hyperglycemia). Disease-specific correlations present study outcomes that are paradoxical, including that RA has genetic protection against PD but an increased risk of AD, whereas obesity and T2D associations are the same across studies, persistent associations of these terms with worsened cognitive decline. The risk of dementia is worsened by autoimmune diseases, such as SLE and FM, involving neuroinflammation caused by autoantibodies and", "source": "PubMed"}, {"chunk_id": "40842786_1", "pmid": "40842786", "title": "Cognitive Decline in Chronic Inflammatory Conditions: Exploring Links Between Systemic Inflammation and Neurodegeneration.", "authors": "Jaramillo Ramos JJ, Galindo Pupo NM, Mena D et al.", "year": "2025", "journal": "Cureus", "keywords": "autoimmune diseases, chronic inflammation, cognitive decline, neurodegeneration, systemic inflammatory markers", "chunk": "studies, persistent associations of these terms with worsened cognitive decline. The risk of dementia is worsened by autoimmune diseases, such as SLE and FM, involving neuroinflammation caused by autoantibodies and central sensitization in the latter, respectively. The new markers, such as glial fibrillary acidic protein (GFAP) (neuroinflammation) and neurofilament light (NfL) (axonal injury), have prospects in early detection, but there is a need for validation in future studies. Therapeutic approaches emphasize the need for immunomodulation (e.g., disease-modifying antirheumatic drugs {DMARDs} in RA), glycemic control in T2DM, and lifestyle interventions, with a lack of targeting the non-amyloid pathways. New studies should emphasize longitudinal studies, multiome-based methods, and clinical trials in an attempt to create precision treatment. Considering the inflammatory risk stratification in the prevention of neurodegeneration, this review sheds light on the possibility of early preventative action that may offset the progressive cognitive decline in especially vulnerable groups.", "source": "PubMed"}, {"chunk_id": "40842786_2", "pmid": "40842786", "title": "Cognitive Decline in Chronic Inflammatory Conditions: Exploring Links Between Systemic Inflammation and Neurodegeneration.", "authors": "Jaramillo Ramos JJ, Galindo Pupo NM, Mena D et al.", "year": "2025", "journal": "Cureus", "keywords": "autoimmune diseases, chronic inflammation, cognitive decline, neurodegeneration, systemic inflammatory markers", "chunk": "in the prevention of neurodegeneration, this review sheds light on the possibility of early preventative action that may offset the progressive cognitive decline in especially vulnerable groups.", "source": "PubMed"}, {"chunk_id": "26064835_0", "pmid": "26064835", "title": "New Prophylactic and Therapeutic Strategies for Spinal Cord Injury.", "authors": "Park S, Park K, Lee Y et al.", "year": "2013", "journal": "Journal of lifestyle medicine", "keywords": "Exercise therapy, Melatonin, Neuroprotectant, Secondary damage, Spinal cord injury", "chunk": "Melatonin production by the pineal gland in the vertebrate brain has attracted much scientific attention. Pineal melatonin is regulated by photoperiodicity, whereas circadian secretion of melatonin produced in the gastrointestinal tract is regulated by food intake. Thus, the circadian rhythm of pineal melatonin depends upon whether a species is diurnal or nocturnal. Spinal cord injury (SCI) involves damage to the spinal cord caused by trauma or disease that results in compromise or loss of body function. Melatonin is the most efficient and commonly used pharmacological antioxidant treatment for SCI. Melatonin is an indolamine secreted by the pineal gland during the dark phase of the circadian cycle. Neurorehabilitation is a complex medical process that focuses on improving function and repairing damaged connections in the brain and nervous system following injury. Physical activity associated with an active lifestyle reduces the risk of obesity, cardiovascular disease, type 2 diabetes, osteoporosis, and depression and", "source": "PubMed"}, {"chunk_id": "26064835_1", "pmid": "26064835", "title": "New Prophylactic and Therapeutic Strategies for Spinal Cord Injury.", "authors": "Park S, Park K, Lee Y et al.", "year": "2013", "journal": "Journal of lifestyle medicine", "keywords": "Exercise therapy, Melatonin, Neuroprotectant, Secondary damage, Spinal cord injury", "chunk": "connections in the brain and nervous system following injury. Physical activity associated with an active lifestyle reduces the risk of obesity, cardiovascular disease, type 2 diabetes, osteoporosis, and depression and protects against neurological conditions, including Parkinson's disease, Alzheimer's disease, and ischemic stroke. Physical activity has been shown to increase the gene expression of several brain neurotrophins (brain-derived neurotrophic factor [BDNF], nerve growth factor, and galanin) and the production of mitochondrial uncoupling protein 2, which promotes neuronal survival, differentiation, and growth. In summary, melatonin is a neural protectant, and when combined with therapeutic exercise, the hormone prevents the progression of secondary neuronal degeneration in SCI. The present review briefly describes the pathophysiological mechanisms underlying SCI, focusing on therapeutic targets and combined melatonin and exercise therapy, which can attenuate secondary injury mechanisms with minimal side effects.", "source": "PubMed"}, {"chunk_id": "26064835_2", "pmid": "26064835", "title": "New Prophylactic and Therapeutic Strategies for Spinal Cord Injury.", "authors": "Park S, Park K, Lee Y et al.", "year": "2013", "journal": "Journal of lifestyle medicine", "keywords": "Exercise therapy, Melatonin, Neuroprotectant, Secondary damage, Spinal cord injury", "chunk": "melatonin and exercise therapy, which can attenuate secondary injury mechanisms with minimal side effects.", "source": "PubMed"}, {"chunk_id": "38427191_0", "pmid": "38427191", "title": "Diffusion Tensor Imaging in Alzheimer's Studies.", "authors": "Ruiz-Rizzo AL, Finke K, Archila-Mel\u00e9ndez ME", "year": "2024", "journal": "Methods in molecular biology (Clifton, N.J.)", "keywords": "Alzheimer\u2019s disease, DTI, Diffusion metrics, Diffusion-weighted imaging, Major tracts, Structural connectivity, White matterWhite matter", "chunk": "In this chapter, we describe the use of quantitative metrics of white matter obtained from the diffusion tensor model based on diffusion-weighted imaging in Alzheimer's disease (AD). Our description synthesizes insights not only from patient populations with AD dementia but also from participants at risk for AD dementia (e.g., amnestic mild cognitive impairment, subjective cognitive decline, or familial AD mutation carriers). A reference to studies examining correlations with behavioral variables is also included. Our main message is to caution against the overinterpretation of diffusion metrics and to favor analyses that focus on regions of interest or major white matter tracts for biomarker studies in AD.", "source": "PubMed"}, {"chunk_id": "41349546_0", "pmid": "41349546", "title": "A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis.", "authors": "Lorenz SM, Wahida A, Bostock MJ et al.", "year": "2026", "journal": "Cell", "keywords": "Alzheimer\u2019s disease, GPX4, SSMD, Sedaghatian type, cell death, ferroptosis, neurodegeneration, neuroinflammation, spondylometaphyseal dysplasia", "chunk": "Ferroptosis, driven by uncontrolled peroxidation of membrane phospholipids, is distinct from other cell death modalities because it lacks an initiating signal and is surveilled by endogenous antioxidant defenses. Glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, although its membrane-protective function remains poorly understood. Here, structural and functional analyses of a missense mutation in GPX4 (p.R152H), which causes early-onset neurodegeneration, revealed that this variant disrupts membrane anchoring without considerably impairing its catalytic activity. Spatiotemporal Gpx4 deletion or neuron-specific GPX4<sup>R152H</sup> expression in mice induced degeneration of cortical and cerebellar neurons, accompanied by progressive neuroinflammation. Patient induced pluripotent stem cell (iPSC)-derived cortical neurons and forebrain organoids displayed increased ferroptotic vulnerability, mirroring key pathological features, and were sensitive to ferroptosis inhibition. Neuroproteomics revealed Alzheimer's-like signatures in affected brains. These findings highlight the necessity of proper GPX4 membrane anchoring, establish ferroptosis as a key driver of neurodegeneration, and provide the rationale for targeting ferroptosis", "source": "PubMed"}, {"chunk_id": "41349546_1", "pmid": "41349546", "title": "A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis.", "authors": "Lorenz SM, Wahida A, Bostock MJ et al.", "year": "2026", "journal": "Cell", "keywords": "Alzheimer\u2019s disease, GPX4, SSMD, Sedaghatian type, cell death, ferroptosis, neurodegeneration, neuroinflammation, spondylometaphyseal dysplasia", "chunk": "Alzheimer's-like signatures in affected brains. These findings highlight the necessity of proper GPX4 membrane anchoring, establish ferroptosis as a key driver of neurodegeneration, and provide the rationale for targeting ferroptosis as a therapeutic strategy in neurodegenerative disease.", "source": "PubMed"}, {"chunk_id": "41317599_0", "pmid": "41317599", "title": "Retinal structural changes in Parkinson's disease: differences in pRNFL thickness between GBA1-associated and idiopathic cases.", "authors": "Portaro G, Giacomelli M, Grisanti S et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "GBA, Genetic PD, OCT, PD, Parkinson disease, Retina, pRNFL", "chunk": "In recent years, retinal structural changes have attracted considerable attention as a potential biomarker of neurodegeneration in Parkinson's disease (PD). Several studies have reported a reduced Retinal Nerve Fiber Layer (pRNFL) thickness in patients with PD compared with age-matched controls. However, potential retinal differences between \"idiopathic\" PD and GBA1-associated PD (GBA-PD) remain largely unexplored. In this single-center observational study, we enrolled 59 PD patients: 32 GBA-PD and 27 non-mutated (NM-PD). A comprehensive clinical assessment included MoCA, MDS-UPDRS and Hoehn-Yahr. Spectral-domain OCT measured pRNFL thickness at 3.5, 4.1 and 4.7 mm diameters across six sectors. Statistical analysis assessed intergroup differences and associations with clinical variables. NM-PD exhibited significantly thinner temporal sectors compared to GBA-PD (p < .05, Mann-Whitney U test). In NM-PD, positive correlations emerged between temporal-superior pRNFL and MoCA scores, in line with previous studies, and, more surprisingly, between nasal-inferior sector and MDS-UPDRS part-IV. No robust associations with clinical variables", "source": "PubMed"}, {"chunk_id": "41317599_1", "pmid": "41317599", "title": "Retinal structural changes in Parkinson's disease: differences in pRNFL thickness between GBA1-associated and idiopathic cases.", "authors": "Portaro G, Giacomelli M, Grisanti S et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "GBA, Genetic PD, OCT, PD, Parkinson disease, Retina, pRNFL", "chunk": "NM-PD, positive correlations emerged between temporal-superior pRNFL and MoCA scores, in line with previous studies, and, more surprisingly, between nasal-inferior sector and MDS-UPDRS part-IV. No robust associations with clinical variables were found in GBA-PD. This study demonstrates differences in retinal thickness between GBA-PD and NM-PD. In particular, a lower pRNFL in NM-PD may be the product of a different pathophysiological mechanism. Moreover, sector-specific retinal thickness showed correlations to cognitive impairment and motor complications in NM-PD. These observations provide novel insights into genotype-specific mechanisms of neurodegeneration in PD and suggest that retinal imaging may offer a window into both cognitive and motor complications. Further longitudinal studies, including healthy controls and expanded retinal layer analyses, are needed to confirm and expand these findings.", "source": "PubMed"}, {"chunk_id": "41317599_2", "pmid": "41317599", "title": "Retinal structural changes in Parkinson's disease: differences in pRNFL thickness between GBA1-associated and idiopathic cases.", "authors": "Portaro G, Giacomelli M, Grisanti S et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "GBA, Genetic PD, OCT, PD, Parkinson disease, Retina, pRNFL", "chunk": "findings.", "source": "PubMed"}, {"chunk_id": "28482635_0", "pmid": "28482635", "title": "The Anti-Amyloid-\u03b2 and Neuroprotective Properties of a Novel Tricyclic Pyrone Molecule.", "authors": "Maezawa I, Zou B, Di Lucente J et al.", "year": "2017", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, NMDA, amyloid, hippocampus, neuroprotection, neurotoxicity", "chunk": "There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-\u03b2 (A\u03b2) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-A\u03b2 and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models. Here we report the selection and initial characterization of a new lead TP70, which exhibited an anti-A\u03b2 therapeutic index even higher than CP2. Moreover, TP70 was able to reduce oxidative stress, inhibit acyl-coenzyme A:cholesterol acyltransferase (ACAT), and upregulate the expression of ATP-binding cassette subfamily A, member 1 (ABCA1), actions considered neuroprotective in AD. TP70 further showed excellent pharmacokinetic properties, including brain penetration and oral availability. When administered to", "source": "PubMed"}, {"chunk_id": "28482635_1", "pmid": "28482635", "title": "The Anti-Amyloid-\u03b2 and Neuroprotective Properties of a Novel Tricyclic Pyrone Molecule.", "authors": "Maezawa I, Zou B, Di Lucente J et al.", "year": "2017", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, NMDA, amyloid, hippocampus, neuroprotection, neurotoxicity", "chunk": "the expression of ATP-binding cassette subfamily A, member 1 (ABCA1), actions considered neuroprotective in AD. TP70 further showed excellent pharmacokinetic properties, including brain penetration and oral availability. When administered to 5xFAD mice via intraperitoneal or oral route, TP70 enhanced the overall solubility and decreased the level of cerebral A\u03b2, including both fibrillary and soluble A\u03b2 species. Interestingly, TP70 enhanced N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic potential (EPSP) in the hippocampal CA1 area, increased the magnitude of NMDA-dependent hippocampal long-term potentiation (LTP), a cellular model of learning and memory, and prevented the A\u03b2 oligomer-impaired LTP. Significantly, a single dose of TP70 administered to aged 5xFAD mice was effective in mitigating the impaired LTP induction, recorded at 24 h after administration. Our results support a potential of TP70 in clinical development for AD in view of its synergistic neuroprotective actions, ability to positively modulate NMDA receptor-mediated hippocampal plasticity, and favorable pharmacokinetic properties in", "source": "PubMed"}, {"chunk_id": "28482635_2", "pmid": "28482635", "title": "The Anti-Amyloid-\u03b2 and Neuroprotective Properties of a Novel Tricyclic Pyrone Molecule.", "authors": "Maezawa I, Zou B, Di Lucente J et al.", "year": "2017", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, NMDA, amyloid, hippocampus, neuroprotection, neurotoxicity", "chunk": "support a potential of TP70 in clinical development for AD in view of its synergistic neuroprotective actions, ability to positively modulate NMDA receptor-mediated hippocampal plasticity, and favorable pharmacokinetic properties in rodents.", "source": "PubMed"}, {"chunk_id": "41401892_0", "pmid": "41401892", "title": "Neuroanatomical-based machine learning prediction of Alzheimer's Disease across sex and age.", "authors": "Jogeshwar BK, Lu S, Nephew BC", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s Disease, Anatomical MRI, Feature Importance, Machine Learning, Neuroimaging, Random Forest, Sex and Age Differences", "chunk": "Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. In 2024 it affected approximately 1 in 9 people aged 65 and older in the U.S., 6.9 million individuals. Early detection and accurate AD diagnosis are crucial for improving patient outcomes. Magnetic resonance imaging (MRI) has emerged as a valuable tool for examining brain structure and identifying potential AD biomarkers. This study performs predictive analyses by employing machine learning techniques to identify key brain regions associated with AD using numerical data derived from anatomical MRI scans, going beyond standard statistical methods. Using the Random Forest Algorithm, we achieved 92.87 % accuracy in detecting AD from Mild Cognitive Impairment and Cognitive Normals. Subgroup analyses across nine sex- and age-based cohorts (69-76 years, 77-84 years, and unified 69-84 years) revealed the hippocampus, amygdala, and entorhinal cortex as con- sistent top-rank predictors. These regions showed distinct volume reductions", "source": "PubMed"}, {"chunk_id": "41401892_1", "pmid": "41401892", "title": "Neuroanatomical-based machine learning prediction of Alzheimer's Disease across sex and age.", "authors": "Jogeshwar BK, Lu S, Nephew BC", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s Disease, Anatomical MRI, Feature Importance, Machine Learning, Neuroimaging, Random Forest, Sex and Age Differences", "chunk": "sex- and age-based cohorts (69-76 years, 77-84 years, and unified 69-84 years) revealed the hippocampus, amygdala, and entorhinal cortex as con- sistent top-rank predictors. These regions showed distinct volume reductions across age and sex groups, reflecting distinct age- and sex-related neuroanatomical patterns. Younger males and females (aged 69-76) exhibited volume decreases in the right hippocampus, suggesting its importance in the early stages of AD. Older males (77-84) showed substantial volume decreases in the left inferior temporal cortex. The left middle temporal cortex showed decreased volume in females, suggesting a potential female-specific influence, while the right entorhinal cortex may have a male-specific impact. These age-specific sex differences could inform clinical research and treatment strategies, aiding in identifying neuroanatomical markers and therapeutic targets for future clinical interventions.", "source": "PubMed"}, {"chunk_id": "41401892_2", "pmid": "41401892", "title": "Neuroanatomical-based machine learning prediction of Alzheimer's Disease across sex and age.", "authors": "Jogeshwar BK, Lu S, Nephew BC", "year": "2026", "journal": "Neuroscience", "keywords": "Alzheimer\u2019s Disease, Anatomical MRI, Feature Importance, Machine Learning, Neuroimaging, Random Forest, Sex and Age Differences", "chunk": "targets for future clinical interventions.", "source": "PubMed"}, {"chunk_id": "41271114_0", "pmid": "41271114", "title": "Decoding blood-brain barrier dysfunction in Alzheimer's Disease: Innovations and challenges in multimodal MRI and PET imaging biomarkers.", "authors": "Yin H, Lu Z, Deng Y et al.", "year": "2026", "journal": "Ageing research reviews", "keywords": "Alzheimer's disease, Biomarkers, Blood-brain barrier, Magnetic resonance imaging, Positron emission tomography, Psychoradiology", "chunk": "Alzheimer's disease (AD), a leading neurodegenerative disorder, involves blood-brain barrier (BBB) dysfunction as a critical contributor to its pathogenesis. This review synthesizes current advancements in in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques for imaging BBB breakdown in AD. The BBB, a dynamic neurovascular interface, regulates amyloid-beta (A\u03b2) and tau clearance through specialized transporters and cellular interactions. BBB dysfunction, driven by tight junction disruption, transporter deficits, and pericyte degeneration, exacerbates A\u03b2accumulation and neuroinflammation. Dynamic contrast-enhanced MRI quantifies subtle leakage via gadolinium kinetics, while water-exchange MRI probes trans-BBB water dynamics without contrast agents. Dynamic glucose-enhanced MRI maps glucose transport anomalies linked to glucose transporter- 1 dysfunction. PET imaging with tracers like [<sup>18</sup>F]-fluorodeoxyglucose and [<sup>11</sup>C]-verapamil evaluates glucose metabolism and efflux transporter activity, revealing early metabolic deficits and impaired A\u03b2 clearance. Challenges include low sensitivity for subtle leakage, model-dependent quantification, and spatial-temporal resolution trade-offs. Emerging strategies emphasize multimodal integration,", "source": "PubMed"}, {"chunk_id": "41271114_1", "pmid": "41271114", "title": "Decoding blood-brain barrier dysfunction in Alzheimer's Disease: Innovations and challenges in multimodal MRI and PET imaging biomarkers.", "authors": "Yin H, Lu Z, Deng Y et al.", "year": "2026", "journal": "Ageing research reviews", "keywords": "Alzheimer's disease, Biomarkers, Blood-brain barrier, Magnetic resonance imaging, Positron emission tomography, Psychoradiology", "chunk": "and efflux transporter activity, revealing early metabolic deficits and impaired A\u03b2 clearance. Challenges include low sensitivity for subtle leakage, model-dependent quantification, and spatial-temporal resolution trade-offs. Emerging strategies emphasize multimodal integration, ultrahigh-field systems, and artificial intelligence-driven analytics to decode region-specific BBB pathology. Longitudinal studies correlating imaging biomarkers with clinical progression and novel PET tracer development are pivotal for early diagnosis and personalized therapies. These innovations promise to elucidate BBB's role and promote a paradigm shift in diagnostic and therapeutic strategies from solely targeting amyloid proteins to multi-target interventions in AD.", "source": "PubMed"}, {"chunk_id": "40618273_0", "pmid": "40618273", "title": "MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.", "authors": "Huang Y, Chen Y, He Z et al.", "year": "2025", "journal": "Neural regeneration research", "keywords": "Alzheimer's disease, amyloid-\u03b2, diagnostic biomarker, glial cells, microRNA, neuroinflammatory, neuronal death, synapses, tau protein, therapeutic targets", "chunk": "MicroRNAs (miRNAs), small non-coding RNAs ranging from 19 to 25 nucleotides in length, are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs. Recent studies have suggested that miRNAs play important roles in regulating key aspects in the pathology of Alzheimer's disease, including the modulation and accumulation of amyloid-beta and tau proteins. Moreover, miRNAs have been implicated in the regulation of neuroinflammation through various inflammatory pathways, notably the nuclear factor kappa B signaling cascade. Additional emerging evidence has shown that miRNAs regulate synaptic growth and maturation, and they perform promising roles in regulating neuronal death and development. miRNAs also offer a novel avenue for direct reprogramming of neurons, representing a promising strategy for Alzheimer's disease treatment. The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology, influencing miRNA activity and disease progression. In this review, we", "source": "PubMed"}, {"chunk_id": "40618273_1", "pmid": "40618273", "title": "MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.", "authors": "Huang Y, Chen Y, He Z et al.", "year": "2025", "journal": "Neural regeneration research", "keywords": "Alzheimer's disease, amyloid-\u03b2, diagnostic biomarker, glial cells, microRNA, neuroinflammatory, neuronal death, synapses, tau protein, therapeutic targets", "chunk": "disease treatment. The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology, influencing miRNA activity and disease progression. In this review, we comprehensively explore the role of different miRNAs in regulating various pathological processes associated with Alzheimer's disease, focusing primarily on four representative miRNAs: miR-9, miR-29, miR-126, and miR-146a for further exploration. We also discuss the influence of miRNA biogenesis on Alzheimer's disease, emphasizing how dysregulation of miRNA processing may contribute to the disease. Additionally, we highlight the potential of miRNAs as both diagnostic biomarkers and therapeutic targets in Alzheimer's disease, along with promising vector delivery strategies aimed at improving clinical outcomes. Finally, we discuss the challenges and limitations associated with the use of miRNAs in the diagnosis and treatment of Alzheimer's disease. By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents, we aim to provide insights that", "source": "PubMed"}, {"chunk_id": "40618273_2", "pmid": "40618273", "title": "MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.", "authors": "Huang Y, Chen Y, He Z et al.", "year": "2025", "journal": "Neural regeneration research", "keywords": "Alzheimer's disease, amyloid-\u03b2, diagnostic biomarker, glial cells, microRNA, neuroinflammatory, neuronal death, synapses, tau protein, therapeutic targets", "chunk": "use of miRNAs in the diagnosis and treatment of Alzheimer's disease. By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents, we aim to provide insights that will inform future research and development in this promising field.", "source": "PubMed"}, {"chunk_id": "41256716_0", "pmid": "41256716", "title": "APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance.", "authors": "Palmer JA, Billinger SA", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "Emerging research indicates cognitive dual-tasking is an early marker for cognitive impairment, with particular implications for <i>Apolipoprotein E4 (APOE4)</i> carriers who are at higher genetic risk for Alzheimer's disease. While <i>APOE4</i> carriers typically show accelerated cognitive decline and impaired cerebrovascular function with aging, exceptions to this norm exist and may provide insights into resilience mechanisms. The relationship between cerebrovascular response and cognitive-motor dual-task performance in cognitively-normal <i>APOE4</i> carriers who maintain preserved function remains unclear. Thirty cognitively-normal older adults (76\u00b14 years, 8 <i>APOE4</i> carriers, 22 noncarriers) completed clinical balance and cognitive testing under single-task and dual-task conditions. Balance performance was assessed as distance traversed during challenging beam walking. Cognitive performance was assessed as response time during an auditory Stroop test. Transcranial Doppler ultrasound measured cerebrovascular response to moderate-intensity aerobic exercise. We tested group differences in cognitive-balance dual task performance and relationships between cerebrovascular response and dual-task interference (DTI) in balance and", "source": "PubMed"}, {"chunk_id": "41256716_1", "pmid": "41256716", "title": "APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance.", "authors": "Palmer JA, Billinger SA", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "Doppler ultrasound measured cerebrovascular response to moderate-intensity aerobic exercise. We tested group differences in cognitive-balance dual task performance and relationships between cerebrovascular response and dual-task interference (DTI) in balance and cognitive domains, and effects of APOE4 genotype on these relationships. No differences in cerebrovascular response or dual-task performance were observed between <i>APOE4</i> carriers and noncarriers. However, <i>APOE4</i> carriers displayed unique cerebrovascular-behavioral relationships. In <i>APOE4</i> carriers, higher cerebrovascular response to exercise was associated with less balance DTI (r=0.839, p=0.009) and less cognitive DTI (r=0.832, p=0.020), while no relationships were observed in noncarriers (p>0.187). Cognitively-normal <i>APOE4</i> carriers with preserved cognitive-balance dual-task function represent exceptions that may model aging resilience mechanisms. The unique cerebrovascular-behavioral relationships suggest that maintaining cerebrovascular function provides preliminary support for neuromotor and neurocognitive resilience to dual-task challenges in genetically vulnerable populations.", "source": "PubMed"}, {"chunk_id": "41256716_2", "pmid": "41256716", "title": "APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance.", "authors": "Palmer JA, Billinger SA", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "None", "chunk": "for neuromotor and neurocognitive resilience to dual-task challenges in genetically vulnerable populations.", "source": "PubMed"}, {"chunk_id": "37609510_0", "pmid": "37609510", "title": "Family History of Alzheimer's Disease Increases the Risk of COVID-19 Positivity: A SUMS Employees Cohort-based Study.", "authors": "Masoumi SJ, Haghani M, Mokkaram P et al.", "year": "2023", "journal": "Journal of biomedical physics & engineering", "keywords": "APOe4 Gene, Alzheimer\u2019s Disease, COVID-19, SARS-CoV-2", "chunk": "Substantial data indicate that genetic and environmental factors play a key role in determining the risk of Alzheimer's disease (AD). Moreover, it is known that having relatives with AD increases the risk of developing this disease. This study is aimed at investigating whether having a family history of AD, may increase the risk of COVID-19 in a cohort-based study. Participants of this retrospective cohort study were previously enrolled in the SUMS Employees Cohort (SUMSEC). All participants including those whose SARS-CoV-2 infection was confirmed by positive PCR test and chest CT scan were requested to respond to interviewer-administered questionnaires. Moreover, AD was diagnosed via memory and thinking impairment, concentration problems, confusion with location, and problems in finishing daily tasks. The total numbers of female and male participants with a family history of AD were 463 and 222 individuals, respectively. When all types of family history of AD were considered, a 51.3%", "source": "PubMed"}, {"chunk_id": "37609510_1", "pmid": "37609510", "title": "Family History of Alzheimer's Disease Increases the Risk of COVID-19 Positivity: A SUMS Employees Cohort-based Study.", "authors": "Masoumi SJ, Haghani M, Mokkaram P et al.", "year": "2023", "journal": "Journal of biomedical physics & engineering", "keywords": "APOe4 Gene, Alzheimer\u2019s Disease, COVID-19, SARS-CoV-2", "chunk": "numbers of female and male participants with a family history of AD were 463 and 222 individuals, respectively. When all types of family history of AD were considered, a 51.3% increase was found in the relative frequency of the participants with both family history of AD and confirmed COVID-19 compared with those only with a family history of AD. Despite the limitations of our study, and from a broader perspective, our findings can further support the concept that AD risk haplotypes including APOE are linked to the same morbidities from cardiovascular disease and obesity that increase vulnerability to COVID-19. Given this consideration, millions of APOE \u03b54 carriers around the globe should be advised to take additional precautions to prevent life-threatening diseases such as COVID-19.", "source": "PubMed"}, {"chunk_id": "37609510_2", "pmid": "37609510", "title": "Family History of Alzheimer's Disease Increases the Risk of COVID-19 Positivity: A SUMS Employees Cohort-based Study.", "authors": "Masoumi SJ, Haghani M, Mokkaram P et al.", "year": "2023", "journal": "Journal of biomedical physics & engineering", "keywords": "APOe4 Gene, Alzheimer\u2019s Disease, COVID-19, SARS-CoV-2", "chunk": "diseases such as COVID-19.", "source": "PubMed"}, {"chunk_id": "36787293_0", "pmid": "36787293", "title": "Effects of sex and APOE \u03b54 genotype on brain mitochondrial high-energy phosphates in midlife individuals at risk for Alzheimer's disease: A 31Phosphorus MR spectroscopy study.", "authors": "Jett S, Dyke JP, Boneu Yepez C et al.", "year": "2023", "journal": "PloS one", "keywords": "None", "chunk": "Age, female sex, and APOE epsilon 4 (APOE4) genotype are the three greatest risk factors for late-onset Alzheimer's disease (AD). The convergence of these risks creates a hypometabolic AD-risk profile unique to women, which may help explain their higher lifetime risk of AD. Less is known about APOE4 effects in men, although APOE4 positive men also experience an increased AD risk. This study uses 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) to examine effects of sex and APOE4 status on brain high-energy phosphates [adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi)] and membrane phospholipids [phosphomonoesters (PME), phosphodiesters (PDE)] in 209 cognitively normal individuals at risk for AD, ages 40-65, 80% female, 46% APOE4 carriers (APOE4+). Women exhibited lower PCr/ATP and PCr/Pi levels than men in AD-vulnerable regions, including frontal, posterior cingulate, lateral and medial temporal cortex (multi-variable adjusted p\u22640.037). The APOE4+ group exhibited lower PCr/ATP and PCr/Pi in frontal regions as compared", "source": "PubMed"}, {"chunk_id": "36787293_1", "pmid": "36787293", "title": "Effects of sex and APOE \u03b54 genotype on brain mitochondrial high-energy phosphates in midlife individuals at risk for Alzheimer's disease: A 31Phosphorus MR spectroscopy study.", "authors": "Jett S, Dyke JP, Boneu Yepez C et al.", "year": "2023", "journal": "PloS one", "keywords": "None", "chunk": "than men in AD-vulnerable regions, including frontal, posterior cingulate, lateral and medial temporal cortex (multi-variable adjusted p\u22640.037). The APOE4+ group exhibited lower PCr/ATP and PCr/Pi in frontal regions as compared to non-carriers (APOE4-) (multi-variable adjusted p\u22640.005). Sex by APOE4 status interactions were observed in frontal regions (multi-variable adjusted p\u22640.046), where both female groups and APOE4+ men exhibited lower PCr/ATP and PCr/Pi than APOE4- men. Among men, APOE4 homozygotes exhibited lower frontal PCr/ATP than heterozygotes and non-carriers. There were no significant effects of sex or APOE4 status on Pi/ATP and PME/PDE measures. Among midlife individuals at risk for AD, women exhibit lower PCr/ATP (e.g. higher ATP utilization) and lower PCr/Pi (e.g. higher energy demand) than age-controlled men, independent of APOE4 status. However, a double dose of APOE4 allele shifted men's brains to a similar metabolic range as women's brains. Examination of brain metabolic heterogeneity can support identification of AD-specific pathways within", "source": "PubMed"}, {"chunk_id": "36787293_2", "pmid": "36787293", "title": "Effects of sex and APOE \u03b54 genotype on brain mitochondrial high-energy phosphates in midlife individuals at risk for Alzheimer's disease: A 31Phosphorus MR spectroscopy study.", "authors": "Jett S, Dyke JP, Boneu Yepez C et al.", "year": "2023", "journal": "PloS one", "keywords": "None", "chunk": "However, a double dose of APOE4 allele shifted men's brains to a similar metabolic range as women's brains. Examination of brain metabolic heterogeneity can support identification of AD-specific pathways within at-risk subgroups, further advancing both preventive and precision medicine for AD.", "source": "PubMed"}, {"chunk_id": "38111597_0", "pmid": "38111597", "title": "Exploratory correlation of the human structural connectome with non-MRI variables in Alzheimer's disease.", "authors": "Aganj I, Mora J, Frau-Pascual A et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, aging, dementia, diffusion MRI, human connectome, multi\u2010synaptic neural pathways, structural brain connectivity", "chunk": "Discovery of the associations between brain structural connectivity and clinical and demographic variables can help to better understand the vulnerability and resilience of the brain architecture to neurodegenerative diseases and to discover biomarkers. We used four diffusion-MRI databases, three related to Alzheimer's disease (AD), to exploratorily correlate structural connections between 85 brain regions with non-MRI variables, while stringently correcting the significance values for multiple testing and ruling out spurious correlations via careful visual inspection. We repeated the analysis with brain connectivity augmented with multi-synaptic neural pathways. We found 85 and 101 significant relationships with direct and augmented connectivity, respectively, which were generally stronger for the latter. Age was consistently linked to decreased connectivity, and healthier clinical scores were generally linked to increased connectivity. Our findings help to elucidate which structural brain networks are affected in AD and aging and highlight the importance of including indirect connections.", "source": "PubMed"}, {"chunk_id": "38111597_1", "pmid": "38111597", "title": "Exploratory correlation of the human structural connectome with non-MRI variables in Alzheimer's disease.", "authors": "Aganj I, Mora J, Frau-Pascual A et al.", "year": "2023", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease, aging, dementia, diffusion MRI, human connectome, multi\u2010synaptic neural pathways, structural brain connectivity", "chunk": "to increased connectivity. Our findings help to elucidate which structural brain networks are affected in AD and aging and highlight the importance of including indirect connections.", "source": "PubMed"}, {"chunk_id": "40961173_0", "pmid": "40961173", "title": "Comparison of diagnostic accuracy of Alzheimer's disease cerebrospinal fluid core biomarkers using INNOTEST, Lumipulse G, and Elecsys assays: Insights from the PUMCH dementia cohort study.", "authors": "Mao C, Zou Y, Wang T et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, accuracy, assays, biomarker, cerebrospinal fluid, cutoff", "chunk": "BackgroundCerebrospinal fluid (CSF) core biomarkers play a pivotal role in the biological diagnosis of Alzheimer's disease (AD). While various commercial assays and kits are available for quantifying these biomarkers, their performance across diverse clinical settings remains insufficiently evaluated.ObjectiveThis study aimed to compare the diagnostic accuracy of AD core biomarkers using four measurement methods in a Chinese population and to establish method-specific cutoff values tailored to different clinical scenarios.MethodsA total of 309 participants were enrolled from the PUMCH dementia cohort, comprising 176 AD, 114 non-AD dementia cases, and 19 cognitively normal controls (CN). For biomarker quantification, we employed one manual immunoassay (INNOTEST, conducted in two independent laboratories) and two fully automated immunoassay platforms (Lumipulse G and Roche Elecsys). These methods were used to measure CSF A\u03b2<sub>1-40</sub>, A\u03b2<sub>1-42</sub>, t-tau, and p-tau<sub>181</sub>, and to calculate three biomarker ratios (A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub>, t-tau/A\u03b2<sub>1-42</sub>, and p-tau<sub>181</sub>/A\u03b2<sub>1-42</sub>).ResultsOur findings provide method-specific and clinical context-optimized cutoff values for each application", "source": "PubMed"}, {"chunk_id": "40961173_1", "pmid": "40961173", "title": "Comparison of diagnostic accuracy of Alzheimer's disease cerebrospinal fluid core biomarkers using INNOTEST, Lumipulse G, and Elecsys assays: Insights from the PUMCH dementia cohort study.", "authors": "Mao C, Zou Y, Wang T et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, accuracy, assays, biomarker, cerebrospinal fluid, cutoff", "chunk": "used to measure CSF A\u03b2<sub>1-40</sub>, A\u03b2<sub>1-42</sub>, t-tau, and p-tau<sub>181</sub>, and to calculate three biomarker ratios (A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub>, t-tau/A\u03b2<sub>1-42</sub>, and p-tau<sub>181</sub>/A\u03b2<sub>1-42</sub>).ResultsOur findings provide method-specific and clinical context-optimized cutoff values for each application scenario including clinically diagnosed AD versus non-AD dementia, amyloid PET-positive versus PET-negative dementia, and AD versus CN. The accuracy of differential diagnosis was higher using biomarker ratios (A\u03b2<sub>1-42</sub>/A\u03b2<sub>1-40</sub>, t-tau/A\u03b2<sub>1-42</sub>, p-tau<sub>181</sub>/A\u03b2<sub>1-42</sub>) than absolute values. Most of the high accuracy was achieved using automated assays especially Lumipulse G rather than manual assays.ConclusionsIn this first comparative study of three immunoassays in a Chinese cohort, automated assays demonstrated superior performance compared to manual assays. We established assay-specific cutoff values tailored to different clinical contexts in a Chinese population.", "source": "PubMed"}, {"chunk_id": "41373649_0", "pmid": "41373649", "title": "Multimodal Biomarker Characterization of the ALS/FTD Spectrum: A Real-World Clinical Dataset Analysis.", "authors": "Mukhija S, Hering L, Schreiner SJ et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, amyotrophic lateral sclerosis, cerebrospinal fluid, diagnostic biomarkers, frontotemporal dementia, pTau:tTau ratio", "chunk": "Diagnosis and prognosis of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) spectrum remain largely dependent on clinical assessments due to a lack of established fluid biomarkers. While neurofilaments and the cerebrospinal fluid (CSF) phosphorylated-tau/total-tau ratio (pTau:tTau) have been studied, their limitations, including their lack of clinical implementation and low specificity, necessitate multimodal approaches. This study aimed to characterize the biological features of the ALS/FTD spectrum through integration of clinically available parameters. We conducted a retrospective, single-center, cross-sectional study analyzing routinely collected clinical, neuroimaging, CSF, and serum data from 229 samples, including 45 from patients with ALS, 26 from patients with FTD, 158 from patients with other neurodegenerative diseases, and 29 from cognitively healthy controls. We implemented propensity score-weighted comparisons, an F1 score-based optimal cut-point determination for the pTau:tTau ratio, and a regularized XGBoost-based multimodal feature modeling approach. The biomarker and model performance was evaluated by the area under the", "source": "PubMed"}, {"chunk_id": "41373649_1", "pmid": "41373649", "title": "Multimodal Biomarker Characterization of the ALS/FTD Spectrum: A Real-World Clinical Dataset Analysis.", "authors": "Mukhija S, Hering L, Schreiner SJ et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, amyotrophic lateral sclerosis, cerebrospinal fluid, diagnostic biomarkers, frontotemporal dementia, pTau:tTau ratio", "chunk": "an F1 score-based optimal cut-point determination for the pTau:tTau ratio, and a regularized XGBoost-based multimodal feature modeling approach. The biomarker and model performance was evaluated by the area under the precision-recall curve (AUC-PR). Feature importance analysis identified characteristic indicators of the ALS/FTD spectrum. Consistent with the prior literature, the pTau:tTau ratio was significantly reduced in ALS/FTD, but the classification performance was modest (AUC-PR 0.32). A multimodal model integrating clinical, biofluid, and neuroimaging features achieved a notably better performance (AUC-PR 0.75). Feature importance analysis revealed an ALS/FTD signature beyond the pTau:tTau ratio characterized by higher global cognition, younger age, an altered A\u03b242/pTau ratio, and immunoglobulin changes (CSF IgG:IgA, serum IgG). Integration of clinical routine data centered on tau, amyloid, and immunological pathophysiology as well as temporal disease dynamics provide a contextualized biological characterization of the ALS/FTD spectrum. This approach offers a foundation for hypothesis generation regarding ALS/FTD pathophysiology and biomarker-supported diagnosis.", "source": "PubMed"}, {"chunk_id": "41373649_2", "pmid": "41373649", "title": "Multimodal Biomarker Characterization of the ALS/FTD Spectrum: A Real-World Clinical Dataset Analysis.", "authors": "Mukhija S, Hering L, Schreiner SJ et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, amyotrophic lateral sclerosis, cerebrospinal fluid, diagnostic biomarkers, frontotemporal dementia, pTau:tTau ratio", "chunk": "pathophysiology as well as temporal disease dynamics provide a contextualized biological characterization of the ALS/FTD spectrum. This approach offers a foundation for hypothesis generation regarding ALS/FTD pathophysiology and biomarker-supported diagnosis.", "source": "PubMed"}, {"chunk_id": "36940322_0", "pmid": "36940322", "title": "Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.", "authors": "Kaplan H, Hooper PL, Gatz M et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "Tsimane, brain volume, evolutionary medicine, mismatch", "chunk": "Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized", "source": "PubMed"}, {"chunk_id": "36940322_1", "pmid": "36940322", "title": "Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.", "authors": "Kaplan H, Hooper PL, Gatz M et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "Tsimane, brain volume, evolutionary medicine, mismatch", "chunk": "that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.", "source": "PubMed"}, {"chunk_id": "36940322_2", "pmid": "36940322", "title": "Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.", "authors": "Kaplan H, Hooper PL, Gatz M et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "Tsimane, brain volume, evolutionary medicine, mismatch", "chunk": "EOR model, with implications for interventions to improve brain health.", "source": "PubMed"}, {"chunk_id": "41654970_0", "pmid": "41654970", "title": "CI-994 is a dual modulator of class I HDACs and Wnt/\u03b2-catenin signaling for the treatment of Alzheimer's disease.", "authors": "Lu W, Kawatani K, Ren Y et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "CI-994, Drug repurposing, Histone deacetylases, Wnt/\u03b2-catenin signaling, iPSC-derived cerebral organoids, iPSC-derived neurons", "chunk": "Growing evidence supports that epigenetic dysregulation through histone deacetylases (HDACs) plays a critical role in synaptic dysfunction and memory loss in Alzheimer\u2019s disease (AD), and that HDACs have been highlighted as an attractive class of targets for AD therapy. Moreover, restoring Wnt/\u03b2-catenin signaling, which is greatly suppressed in AD brains, is a promising therapeutic strategy. CI-994 is an orally active class I HDAC inhibitor that has undergone several phase II/III clinical trials on cancer treatment. Importantly, CI-994 can cross the blood\u2013brain barrier and is a cognitive enhancer. Wnt activity was initially examined by Wnt reporter activity assay in Wnt3A-expression HEK293 cells, and profiling HDAC inhibition was performed against 10 individual HDACs. Activities of CI-994 on class I HDACs and Wnt/\u03b2-catenin signaling were further tested in HEK293 cells, LRP6-expressing HT1080 cells and neuronal SH-SY5Y cells. The therapeutic effects of CI-994 were examined in patient-specific iPSC-derived neurons and cerebral organoids carrying <i>APOE</i>", "source": "PubMed"}, {"chunk_id": "41654970_1", "pmid": "41654970", "title": "CI-994 is a dual modulator of class I HDACs and Wnt/\u03b2-catenin signaling for the treatment of Alzheimer's disease.", "authors": "Lu W, Kawatani K, Ren Y et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "CI-994, Drug repurposing, Histone deacetylases, Wnt/\u03b2-catenin signaling, iPSC-derived cerebral organoids, iPSC-derived neurons", "chunk": "signaling were further tested in HEK293 cells, LRP6-expressing HT1080 cells and neuronal SH-SY5Y cells. The therapeutic effects of CI-994 were examined in patient-specific iPSC-derived neurons and cerebral organoids carrying <i>APOE</i> \u03b54/\u03b54 genotype or <i>MAPT</i> p.P301L mutation. We herein report that CI-994 is not only a potent class I HDAC inhibitor but also an activator of Wnt/\u03b2-catenin signaling. Mechanistically, activation of Wnt/\u03b2-catenin signaling by CI-994 is associated with stabilizing Wnt co-receptor LRP6 protein and modulating HDAC activity. Importantly, CI-994 significantly increases histone acetylation, activates Wnt/\u03b2-catenin signaling, and decreases tau phosphorylation in patient-specific iPSC-derived cerebral organoids carrying <i>APOE</i> \u03b54/\u03b54 genotype or <i>MAPT</i> p.P301L mutation. Moreover, studies with the specific Wnt inhibitor LGK974 demonstrate that activation of Wnt/\u03b2-catenin signaling contributes to CI-994-induced the inhibition of tau phosphorylation in the iPSC-derived cerebral organoids. Additionally, CI-994 increases synaptic protein levels, enhances spontaneous synaptic firing and network formation and decreases tau phosphorylation in iPSC-derived neurons. Finally,", "source": "PubMed"}, {"chunk_id": "41654970_2", "pmid": "41654970", "title": "CI-994 is a dual modulator of class I HDACs and Wnt/\u03b2-catenin signaling for the treatment of Alzheimer's disease.", "authors": "Lu W, Kawatani K, Ren Y et al.", "year": "2026", "journal": "Alzheimer's research & therapy", "keywords": "CI-994, Drug repurposing, Histone deacetylases, Wnt/\u03b2-catenin signaling, iPSC-derived cerebral organoids, iPSC-derived neurons", "chunk": "inhibition of tau phosphorylation in the iPSC-derived cerebral organoids. Additionally, CI-994 increases synaptic protein levels, enhances spontaneous synaptic firing and network formation and decreases tau phosphorylation in iPSC-derived neurons. Finally, RNA sequencing, combined with RT-qPCR validation, of the iPSC-derived cerebral organoids reveals that CI-994 significantly regulates genes associated with synapse plasticity and cognitive function including <i>NEUROD1</i>, <i>CACNA1G</i>, <i>NRGN, NRTN, SLC7A10 and OMG</i>. Our findings suggest that CI-994 can be repurposed as a novel therapeutic agent for AD therapy. The online version contains supplementary material available at 10.1186/s13195-026-01982-0.", "source": "PubMed"}, {"chunk_id": "37956285_0", "pmid": "37956285", "title": "In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.", "authors": "Bodily TA, Ramanathan A, Wei S et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "Alzheimer\u2019s disease, aptamer, biosensor, dementia, graphene", "chunk": "Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (A\u03b2), Tau (\u03c4), and \u03b1-Synuclein (\u03b1S) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for A\u03b2, \u03c4, and \u03b1S, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds,", "source": "PubMed"}, {"chunk_id": "37956285_1", "pmid": "37956285", "title": "In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.", "authors": "Bodily TA, Ramanathan A, Wei S et al.", "year": "2023", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "keywords": "Alzheimer\u2019s disease, aptamer, biosensor, dementia, graphene", "chunk": "10 fM, 1-10 pM, 10-100 fM for A\u03b2, \u03c4, and \u03b1S, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; A\u03b2, \u03c4, and \u03b1S peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.", "source": "PubMed"}, {"chunk_id": "41332870_0", "pmid": "41332870", "title": "The spectrum of Alzheimer's disease.", "authors": "Novotny JS, \u010carn\u00e1 M, Lyburn I et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, cerebrospinal fluid Ab, choroid plexus, cognitive scores, dementia, diagnostics, hippocampus, inferior parietal lobule, mild cognitive impairment, tau and phospho-tau", "chunk": "While hippocampal (H) and inferior parietal lobule (IPL) atrophy are used routinely in Alzheimer's disease (AD) diagnostics, the role of enlarged choroid plexus (ChP) remains unclear. We here examined the AD Neuroimaging Initiative (ADNI) cohort (N=872) to investigate the contribution of enlarged ChP in predicting AD using MRI volumetry. Analyses revealed that no individual volumetric brain changes, nor their combination, can predict AD. Among AD patients, only ~ 19%, 12% and 5% exhibited changes in H, ChP or IPL volumes, while 45% showed no volumetric brain changes at all, not even longitudinally. Amyloid-b peptides, therefore, contribute to brain atrophy and neuronal loss at best only in a subset of amyloid PET-CT positive AD patients. These findings suggest that despite shared amyloidopathy, the observed brain volumetric phenotypes, together with their corresponding cognitive and CSF biomarker profiles, represent unique entities within the AD spectrum much like the synucleinopathies, tauopathies and TDP43-proteinopathies.", "source": "PubMed"}, {"chunk_id": "41332870_1", "pmid": "41332870", "title": "The spectrum of Alzheimer's disease.", "authors": "Novotny JS, \u010carn\u00e1 M, Lyburn I et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, cerebrospinal fluid Ab, choroid plexus, cognitive scores, dementia, diagnostics, hippocampus, inferior parietal lobule, mild cognitive impairment, tau and phospho-tau", "chunk": "amyloidopathy, the observed brain volumetric phenotypes, together with their corresponding cognitive and CSF biomarker profiles, represent unique entities within the AD spectrum much like the synucleinopathies, tauopathies and TDP43-proteinopathies.", "source": "PubMed"}, {"chunk_id": "22561330_0", "pmid": "22561330", "title": "Current epidemiological approaches to the metabolic-cognitive syndrome.", "authors": "Panza F, Solfrizzi V, Logroscino G et al.", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "In the last decade, cumulative epidemiological evidence suggested that vascular- and metabolic-based risk factors may be important in the development of mild cognitive impairment and dementia. Epidemiological and basic research have also proposed a model of cognitive impairment linked to metabolic syndrome (MetS) and metabolic disorders, suggesting for research purposes a \"metabolic-cognitive syndrome\" (MCS) in patients with MetS plus cognitive impairment of degenerative or vascular origin. In particular, MetS has been associated with the risk of age-related cognitive decline and vascular dementia, but contrasting findings also existed on the possible role of MetS in overall dementia and Alzheimer's disease. Among metabolic determinants of cognitive impairment, a better approach to the understanding of mechanisms could be to hypothesize a continuum leading to various degrees of late-life cognitive disorders in older subjects with metabolic-based risk factors. The MCS model could help us to explain the complex relationship between metabolic disorders and cognitive", "source": "PubMed"}, {"chunk_id": "22561330_1", "pmid": "22561330", "title": "Current epidemiological approaches to the metabolic-cognitive syndrome.", "authors": "Panza F, Solfrizzi V, Logroscino G et al.", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "to various degrees of late-life cognitive disorders in older subjects with metabolic-based risk factors. The MCS model could help us to explain the complex relationship between metabolic disorders and cognitive disturbances and the boundaries between normal and pathological conditions, with a better understanding of clinical and neuropathological features of these metabolic-based cognitive disorders. Strategies toward early and effective risk factor management could be of value in reducing the risk of MCS, so delaying the onset or preventing the progression of predementia syndromes. In the near future, clinical trials could be undertaken to determine if addressing MetS and metabolic-based risk factors, including inflammation, through lifestyle modification holds out the possibility of slowing down or ameliorating the cognitive aging process itself.", "source": "PubMed"}, {"chunk_id": "40453977_0", "pmid": "40453977", "title": "Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.", "authors": "Nakashima S, Sato K, Niimi Y et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "ADNI, Alzheimer's disease, NACC, disease\u2010modifying therapy, therapeutic window", "chunk": "Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited \"therapeutic time window,\" after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities. We analyzed longitudinal data from two observational cohorts, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). At each visit, individuals were deemed eligible if they were amyloid-positive and had a Mini-Mental State Examination (MMSE) score of 22-30 (lecanemab) or 20-30 (donanemab), plus a Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1. We then applied survival analyses and Cox proportional hazards models to estimate time-to-ineligibility based on baseline cognitive status. Across both datasets, higher baseline CDR-GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard", "source": "PubMed"}, {"chunk_id": "40453977_1", "pmid": "40453977", "title": "Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.", "authors": "Nakashima S, Sato K, Niimi Y et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "ADNI, Alzheimer's disease, NACC, disease\u2010modifying therapy, therapeutic window", "chunk": "proportional hazards models to estimate time-to-ineligibility based on baseline cognitive status. Across both datasets, higher baseline CDR-GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard ratio of 1.601 for CDR-GS of 1 vs. 0.5, and pooled hazard ratio of 0.660 per 1-point increase in MMSE score above the lower limit of eligibility). The estimated 75% survival time for patients with baseline CDR-GS 0.5 was over 12 months, suggesting only 25% would become ineligible within 12 months. For those with CDR-GS 1, the estimated 50% survival time was approximately 12 months, depending on the data, indicating that half might become ineligible within 1 year. We quantitatively outlined the duration of the therapeutic time window for early AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR-GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and", "source": "PubMed"}, {"chunk_id": "40453977_2", "pmid": "40453977", "title": "Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.", "authors": "Nakashima S, Sato K, Niimi Y et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "ADNI, Alzheimer's disease, NACC, disease\u2010modifying therapy, therapeutic window", "chunk": "AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR-GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited. We examined the \"therapeutic time window\" eligibility for disease-modifying therapy.Longitudinal data from National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to quantify eligibility duration.Higher Clinical Dementia Rating-Global Score (CDR-GS) or lower Mini-Mental State Examination (MMSE) at baseline were associated with shorter window length.Our results will help optimize the management of the wait time for disease-modifying therapies (DMT) treatment.", "source": "PubMed"}, {"chunk_id": "35489824_0", "pmid": "35489824", "title": "Therapeutic news in Alzheimer's disease: Soon a disease-modifying therapy?", "authors": "Villain N", "year": "2022", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Amyloid beta-peptides, Drug therapy, Passive Immunization", "chunk": "Research on disease-modifying treatments for Alzheimer's disease has resulted in a series of failures over the past 20 years. However, in the last three years, four molecules have shown significant effects on clinical endpoints in phase II or III clinical trials (i.e., slowing of cognitive decline). Among these four molecules, three are anti-amyloid immunotherapies: aducanumab, donanemab, and lecanemab, responsible for a significant clearance of cerebral beta-amyloid deposits. These provisional data are still awaiting confirmation to put an end to the controversy surrounding the 2021 Food and Drug Administration's decision to give conditional approval to aducanumab, which is considered premature by many specialists. Confirmation is also necessary to assess the benefit (magnitude of the slowing of cognitive decline) and risk (edema and cerebral hemorrhage induced by these treatments) balance of these molecules. Masitinib, a treatment whose probable mechanism of action is neuroinflammation, has also shown positive effects that need to be", "source": "PubMed"}, {"chunk_id": "35489824_1", "pmid": "35489824", "title": "Therapeutic news in Alzheimer's disease: Soon a disease-modifying therapy?", "authors": "Villain N", "year": "2022", "journal": "Revue neurologique", "keywords": "Alzheimer's disease, Amyloid beta-peptides, Drug therapy, Passive Immunization", "chunk": "and cerebral hemorrhage induced by these treatments) balance of these molecules. Masitinib, a treatment whose probable mechanism of action is neuroinflammation, has also shown positive effects that need to be confirmed. Therapies targeting the tau protein are less advanced and have yet to be proven. Patients have renewed hope since it may not be unreasonable that these disease-modifying therapies will be part of the French therapeutic arsenal within the next five years.", "source": "PubMed"}, {"chunk_id": "38452244_0", "pmid": "38452244", "title": "Integrative Multimodal Metabolomics to Early Predict Cognitive Decline Among Amyloid Positive Community-Dwelling Older Adults.", "authors": "Tremblay-Franco M, Canlet C, Carriere A et al.", "year": "2024", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "Alzheimer\u2019s disease, Bimodal metabolomics, Cognitive decline, Early prediction, Metabolite signature, Multiomics integrative method", "chunk": "Alzheimer's disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals who progressed to cognitive decline from those who remained cognitively intact. A plasma-derived metabolite signature was developed from Supercritical Fluid chromatography coupled with high-resolution mass spectrometry (SFC-HRMS) and nuclear magnetic resonance (NMR) metabolomics. The 2 metabolomics data sets were analyzed by Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO), to identify a minimum set of metabolites that could describe cognitive decline status. NMR or SFC-HRMS data alone cannot predict cognitive decline. However, among the 320 metabolites identified, a statistical method that integrated the 2 data sets enabled the identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine,", "source": "PubMed"}, {"chunk_id": "38452244_1", "pmid": "38452244", "title": "Integrative Multimodal Metabolomics to Early Predict Cognitive Decline Among Amyloid Positive Community-Dwelling Older Adults.", "authors": "Tremblay-Franco M, Canlet C, Carriere A et al.", "year": "2024", "journal": "The journals of gerontology. Series A, Biological sciences and medical sciences", "keywords": "Alzheimer\u2019s disease, Bimodal metabolomics, Cognitive decline, Early prediction, Metabolite signature, Multiomics integrative method", "chunk": "However, among the 320 metabolites identified, a statistical method that integrated the 2 data sets enabled the identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine, glucose, serine, sphingomyelin d18:1/C26:0 and triglyceride C48:3) with a statistically significant ability to predict cognitive decline more than 3 years before decline. This metabolic fingerprint obtained during this exploratory study may help to predict amyloid-positive individuals who will develop cognitive decline. Due to the high prevalence of brain amyloid-positivity in older adults, identifying adults who will have cognitive decline will enable the development of personalized and early interventions.", "source": "PubMed"}, {"chunk_id": "41411602_0", "pmid": "41411602", "title": "Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age.", "authors": "Bos L, Wink AM, Cole JH et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "The brain-predicted age difference (brain-PAD) is a novel marker of neurodegeneration in multiple sclerosis (MS). Brain-PAD has been associated with clinical disability in heterogeneous MS patient cohorts of varying ages and disease durations. In this study, we investigate the relation between clinical disability and brain-PAD in a unique birth-year cohort of people with MS (pwMS) and healthy controls (HCs) of the same age all born in 1966, eliminating age as a confounding factor. This was a cross-sectional cohort study conducted in the Netherlands. Disability was quantified using the expanded disability status scale (EDSS), 9-hole peg test (9HPT), and the timed 25-foot walk test (T25FWT). Cognition was assessed using the Minimal Assessment of Cognitive Function in MS battery. The brain-PAD was calculated by subtracting the person's chronological age from the predicted brain age derived from 3-dimensional T1-weighted brain MRI scans using machine learning (brainageR software). Brain-PAD for HCs and MS subtypes", "source": "PubMed"}, {"chunk_id": "41411602_1", "pmid": "41411602", "title": "Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age.", "authors": "Bos L, Wink AM, Cole JH et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "calculated by subtracting the person's chronological age from the predicted brain age derived from 3-dimensional T1-weighted brain MRI scans using machine learning (brainageR software). Brain-PAD for HCs and MS subtypes (relapsing remitting, secondary progressive, and primary progressive) were compared using a generalized linear model. The relation between brain-PAD and disease duration and disability and cognitive measures were tested using univariate linear regression. In addition, the clinical explanatory value added by brain-PAD to those of brain parenchymal fraction (BPF) and T2 lesion volume was investigated. The study included 116 HC (mean age 52.9 \u00b1 1.1 years, 61% female) and 237 pwMS (mean age 52.9 \u00b1 0.9 years, median disease duration 16.3 years [interquartile range 8.2-24.4] and a median EDSS of 3.5 [interquartile range 2.5-4.0]). Brain-PAD was higher in pwMS compared with HC by 9.7 years (SE = 0.82, <i>p</i> < 0.0001). Longer disease duration was associated with a higher brain-PAD (\u03b2", "source": "PubMed"}, {"chunk_id": "41411602_2", "pmid": "41411602", "title": "Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age.", "authors": "Bos L, Wink AM, Cole JH et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "[interquartile range 2.5-4.0]). Brain-PAD was higher in pwMS compared with HC by 9.7 years (SE = 0.82, <i>p</i> < 0.0001). Longer disease duration was associated with a higher brain-PAD (\u03b2 = 0.21, <i>p</i> < 0.001). A higher brain-PAD was associated with worse performance on the T25FWT (\u03b2 = 0.0063, <i>p</i> < 0.05), 9HPT (\u03b2 = 0.0074, <i>p</i> < 0.001), and EDSS (\u03b2 = 0.028, <i>p</i> < 0.05). Brain-PAD was higher for cognitively impaired people with MS, compared with cognitively preserved pwMS and HC (<i>p</i> < 0.0001). Brain-PAD had added explanatory value over BPF in clinical outcome measures. In a cohort unbiased by age differences, greater brain ageing was associated with worse performance on disability and cognitive tests, underscoring the potential of brain-PAD as a marker for neurodegeneration and disease severity in MS.", "source": "PubMed"}, {"chunk_id": "41411602_3", "pmid": "41411602", "title": "Association of Brain Age With Physical Disability and Cognitive Impairment in People With Multiple Sclerosis of the Same Age.", "authors": "Bos L, Wink AM, Cole JH et al.", "year": "2026", "journal": "Neurology", "keywords": "None", "chunk": "of brain-PAD as a marker for neurodegeneration and disease severity in MS.", "source": "PubMed"}, {"chunk_id": "35449033_0", "pmid": "35449033", "title": "The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals.", "authors": "L\u00f3pez-de-Eguileta A, L\u00f3pez-Garc\u00eda S, Lage C et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Amyloid, Ganglion cell layer, Hippocampal volume, Neurodegeneration, Optical coherence tomography, Retinal nerve fiber layer, Tau", "chunk": "To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer's disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI). We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (A\u03b2 1-42), and beta-amyloid 1-40 (A\u03b2 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch's membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student's t-test.", "source": "PubMed"}, {"chunk_id": "35449033_1", "pmid": "35449033", "title": "The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals.", "authors": "L\u00f3pez-de-Eguileta A, L\u00f3pez-Garc\u00eda S, Lage C et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Amyloid, Ganglion cell layer, Hippocampal volume, Neurodegeneration, Optical coherence tomography, Retinal nerve fiber layer, Tau", "chunk": "(GCL), the retinal nerve fiber layer (RFNL), the Bruch's membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student's t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1. We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The A\u03b2 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between", "source": "PubMed"}, {"chunk_id": "35449033_2", "pmid": "35449033", "title": "The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals.", "authors": "L\u00f3pez-de-Eguileta A, L\u00f3pez-Garc\u00eda S, Lage C et al.", "year": "2022", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Amyloid, Ganglion cell layer, Hippocampal volume, Neurodegeneration, Optical coherence tomography, Retinal nerve fiber layer, Tau", "chunk": "measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant. We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.", "source": "PubMed"}, {"chunk_id": "31353917_0", "pmid": "31353917", "title": "Association Between Individual Components of Metabolic Syndrome and Cognitive Function in Northeast Rural China.", "authors": "Wang X, Luan D, Xin S et al.", "year": "2019", "journal": "American journal of Alzheimer's disease and other dementias", "keywords": "MMSE, abdominal obesity, cognitive function, elderly, \u00b7metabolic syndrome", "chunk": "The aim of this article was to examine associations between metabolic syndrome and its individual components with cognitive function among rural elderly population in northeast China. Our study included 1047 residents aged older than 60 years in a northeast rural area. All were interviewed and data were obtained including sociodemographic and medical histories. Cognitive function was assessed by Mini-Mental State Examination. Metabolic syndrome was defined by NCEP-ATP III. After adjusted for confounding factors, metabolic syndrome was inversely associated with cognitive function (odds ratio [OR] = 1.79; 95% confidence interval [CI]: 1.06-3.01) especially in participants aged less than 70 years old (OR = 2.60; 95% CI: 1.27-5.26). In addition, participants with metabolic syndrome had worse language function, which is a part of cognitive function (OR = 2.64; 95% CI: 1.39-5.00). Individual metabolic syndrome components, especially abdominal obesity and hyperglycemia, had significant association with cognitive function (OR = 0.72, 95% CI: 0.56-0.92", "source": "PubMed"}, {"chunk_id": "31353917_1", "pmid": "31353917", "title": "Association Between Individual Components of Metabolic Syndrome and Cognitive Function in Northeast Rural China.", "authors": "Wang X, Luan D, Xin S et al.", "year": "2019", "journal": "American journal of Alzheimer's disease and other dementias", "keywords": "MMSE, abdominal obesity, cognitive function, elderly, \u00b7metabolic syndrome", "chunk": "of cognitive function (OR = 2.64; 95% CI: 1.39-5.00). Individual metabolic syndrome components, especially abdominal obesity and hyperglycemia, had significant association with cognitive function (OR = 0.72, 95% CI: 0.56-0.92 and OR = 1.41; 95% CI: 1.12-1.78, respectively). Abdominal obesity might be a protective factor for cognitive function. However, hyperglycemia might be a risk factor.", "source": "PubMed"}, {"chunk_id": "20600609_0", "pmid": "20600609", "title": "Phospholipids and a phospholipid-rich diet alter the in vitro amyloid-beta peptide levels and amyloid-beta 42/40 ratios.", "authors": "Amtul Z, Uhrig M, Supino R et al.", "year": "2010", "journal": "Neuroscience letters", "keywords": "None", "chunk": "Amyloid-beta peptides (Abeta) generated by proteolysis of the beta-amyloid precursor protein (APP) by beta- and gamma-secretases play an important role in the pathogenesis of Alzheimer's disease (AD). There is mounting evidence that the lipid matrix of neuronal cell membranes plays an important role in the accumulation of Abeta peptides into senile plaques, one of the hallmarks of AD. With the aim to clarify the molecular basis of the interaction between Abeta and cellular membranes, we investigated the effects of various phospholipids (PLs) and a PL-rich diet on Abeta production. Here we show that modulation of Abeta production and Abeta42:40 ratio is not limited to individual fatty acids, rather it is the composition of the PLs of the membrane bilayer, that influences the specificity and level of the regulated intramembranous proteolysis of APP by the gamma-secretase complex. We show that Abeta levels in the conditioned media, in response to some of", "source": "PubMed"}, {"chunk_id": "20600609_1", "pmid": "20600609", "title": "Phospholipids and a phospholipid-rich diet alter the in vitro amyloid-beta peptide levels and amyloid-beta 42/40 ratios.", "authors": "Amtul Z, Uhrig M, Supino R et al.", "year": "2010", "journal": "Neuroscience letters", "keywords": "None", "chunk": "influences the specificity and level of the regulated intramembranous proteolysis of APP by the gamma-secretase complex. We show that Abeta levels in the conditioned media, in response to some of the PL supplements, is increased in the center and decreased on either side of a graph that resembles bell-shaped distribution. This means that the PLs have less of a tendency to produce unusually extreme effects on Abeta production in SP-C99 transfected Cos-7 cultured cells. We proposed a mechanism-based hypothesis to rationalize PLs' effects on Abeta production.", "source": "PubMed"}, {"chunk_id": "38836991_0", "pmid": "38836991", "title": "A Framework for the Administration of Anti-amyloid Monoclonal Antibody Treatments in Early-Stage Alzheimer's Disease.", "authors": "Rosenbloom MH, O'Donohue T, Zhou-Clark D et al.", "year": "2024", "journal": "CNS drugs", "keywords": "None", "chunk": "The US Food and Drug Administration (FDA) approval of lecanemab for early-stage Alzheimer's disease (AD) represents an exciting new chapter in the management of neurodegenerative disease, but likewise presents numerous clinical, technical, and financial logistical challenges for both academic and non-academic medical institutions hoping to administer this drug. Minimal resources exist that provide guidance for establishing and maintaining a lecanemab treatment program at the institutional level. The current report aims to provide healthcare institutions a framework for the planning, onboarding, and longitudinal treatment of AD with anti-amyloid monoclonal antibody treatments. We present an implementation study involving three stages: (1) feasibility assessment, (2) operations and going live, and (3) monitoring assessment. We found that implementation of lecanemab in clinical practice was feasible due to the assignment of an enterprise-wide project manager to facilitate the planning phase, a cost analysis showing that lecanemab was financially sustainable, and the development of electronic medical", "source": "PubMed"}, {"chunk_id": "38836991_1", "pmid": "38836991", "title": "A Framework for the Administration of Anti-amyloid Monoclonal Antibody Treatments in Early-Stage Alzheimer's Disease.", "authors": "Rosenbloom MH, O'Donohue T, Zhou-Clark D et al.", "year": "2024", "journal": "CNS drugs", "keywords": "None", "chunk": "feasible due to the assignment of an enterprise-wide project manager to facilitate the planning phase, a cost analysis showing that lecanemab was financially sustainable, and the development of electronic medical record tools to support operational efficiency.", "source": "PubMed"}, {"chunk_id": "40667684_0", "pmid": "40667684", "title": "Donanemab exposure-response in early symptomatic Alzheimer's disease.", "authors": "Gueorguieva I, Chow K, Chua L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, CDR\u2010SB, amyloid plaque, cognitive/functional endpoint, disease progression, donanemab, exposure, iADRS, nonlinear mixed effects modeling", "chunk": "These analyses aimed to identify factors impacting donanemab exposure, amyloid plaque, and clinical efficacy in early symptomatic Alzheimer's disease using a population pharmacokinetic/pharmacodynamic (PK/PD) approach. Analyses included donanemab trial participants (NCT02624778; NCT03367403; NCT04640077; NCT04437511). Dose- and exposure-response relationships were characterized relative to amyloid plaque lowering using indirect response PK/PD and disease progression models. Donanemab population PK was described by a biphasic distribution with an estimated terminal elimination half-life of approximately 12.1 days for a typical participant (72 kg body weight, 1:2560 maximum antidrug antibody [ADA] titer). Amyloid reduction was associated with maintaining median serum donanemab concentrations over 15 \u00b5g/mL (95% confidence interval: 8.54, 18.0). After completing active treatment, simulations showed an estimated plaque reaccumulation rate (median, 95% confidence interval) of 2.8 (2.16, 3.11) Centiloids/year. The donanemab disease progression model showed a clear treatment effect. These donanemab models can inform dosing strategies in future clinical trials. Weight-based and flat dosing had", "source": "PubMed"}, {"chunk_id": "40667684_1", "pmid": "40667684", "title": "Donanemab exposure-response in early symptomatic Alzheimer's disease.", "authors": "Gueorguieva I, Chow K, Chua L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, CDR\u2010SB, amyloid plaque, cognitive/functional endpoint, disease progression, donanemab, exposure, iADRS, nonlinear mixed effects modeling", "chunk": "2.8 (2.16, 3.11) Centiloids/year. The donanemab disease progression model showed a clear treatment effect. These donanemab models can inform dosing strategies in future clinical trials. Weight-based and flat dosing had similar exposure metrics; flat dosing was adopted. Donanemab exposure was influenced by weight and titer (not clinically relevant). 2.8 Centiloids/year amyloid reaccumulation rate observed upon donanemab treatment completion. Around 30% reduction in disease progression rate on treatment for integrated Alzheimer's Disease Rating Scale (iADRS) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).", "source": "PubMed"}, {"chunk_id": "37651273_0", "pmid": "37651273", "title": "Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-\u03b2 Therapy.", "authors": "Agarwal A, Gupta V, Brahmbhatt P et al.", "year": "2023", "journal": "Radiographics : a review publication of the Radiological Society of North America, Inc", "keywords": "None", "chunk": "Alzheimer disease (AD) is the most common form of dementia worldwide. Treatment of AD has mainly been focused on symptomatic treatment until recently with the advent and approval of monoclonal antibody (MAB) immunotherapy. U.S. Food and Drug Administration-approved drugs such as aducanumab, as well as upcoming newer-generation drugs, have provided an exciting new therapy focused on reducing the amyloid plaque burden in AD. Although this new frontier has shown benefits for patients, it is not without complications, which are mainly neurologic. Increased use of MABs led to the discovery of amyloid-related imaging abnormalities (ARIA). ARIA has been further classified into two categories, ARIA-E and ARIA-H, representing edema and/or effusion and hemorrhage, respectively. ARIA is thought to be caused by increased vascular permeability following an inflammatory response, leading to the extravasation of blood products and proteinaceous fluid. Patients with ARIA may present with headaches, but they are usually asymptomatic and ARIA", "source": "PubMed"}, {"chunk_id": "37651273_1", "pmid": "37651273", "title": "Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-\u03b2 Therapy.", "authors": "Agarwal A, Gupta V, Brahmbhatt P et al.", "year": "2023", "journal": "Radiographics : a review publication of the Radiological Society of North America, Inc", "keywords": "None", "chunk": "vascular permeability following an inflammatory response, leading to the extravasation of blood products and proteinaceous fluid. Patients with ARIA may present with headaches, but they are usually asymptomatic and ARIA is only diagnosable at MRI; it is essential for the radiologist to recognize and monitor ARIA. Increased incidence and investigation into this concern have led to the creation of grading scales and monitoring guidelines to diagnose and guide treatment using MABs. Cerebral amyloid angiopathy has an identical pathogenesis to that of ARIA and is its closest differential diagnosis, with imaging findings being the same for both entities and only a history of MAB administration allowing differentiation. The authors discuss the use of MABs for treating AD, expand on ARIA and its consequences, and describe how to identify and grade ARIA to guide treatment properly. <sup>\u00a9</sup>RSNA, 2023 Quiz questions for this article are available through the Online Learning Center See the", "source": "PubMed"}, {"chunk_id": "37651273_2", "pmid": "37651273", "title": "Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-\u03b2 Therapy.", "authors": "Agarwal A, Gupta V, Brahmbhatt P et al.", "year": "2023", "journal": "Radiographics : a review publication of the Radiological Society of North America, Inc", "keywords": "None", "chunk": "its consequences, and describe how to identify and grade ARIA to guide treatment properly. <sup>\u00a9</sup>RSNA, 2023 Quiz questions for this article are available through the Online Learning Center See the invited commentary by Yu in this issue.", "source": "PubMed"}, {"chunk_id": "37957261_0", "pmid": "37957261", "title": "Molecular biomarkers for vascular cognitive impairment and dementia.", "authors": "Hosoki S, Hansra GK, Jayasena T et al.", "year": "2023", "journal": "Nature reviews. Neurology", "keywords": "None", "chunk": "As disease-specific interventions for dementia are being developed, the ability to identify the underlying pathology and dementia subtypes is increasingly important. Vascular cognitive impairment and dementia (VCID) is the second most common cause of dementia after Alzheimer disease, but progress in identifying molecular biomarkers for accurate diagnosis of VCID has been relatively limited. In this Review, we examine the roles of large and small vessel disease in VCID, considering the underlying pathophysiological processes that lead to vascular brain injury, including atherosclerosis, arteriolosclerosis, ischaemic injury, haemorrhage, hypoperfusion, endothelial dysfunction, blood-brain barrier breakdown, inflammation, oxidative stress, hypoxia, and neuronal and glial degeneration. We consider the key molecules in these processes, including proteins and peptides, metabolites, lipids and circulating RNA, and consider their potential as molecular biomarkers alone and in combination. We also discuss the challenges in translating the promise of these biomarkers into clinical application.", "source": "PubMed"}, {"chunk_id": "37957261_1", "pmid": "37957261", "title": "Molecular biomarkers for vascular cognitive impairment and dementia.", "authors": "Hosoki S, Hansra GK, Jayasena T et al.", "year": "2023", "journal": "Nature reviews. Neurology", "keywords": "None", "chunk": "potential as molecular biomarkers alone and in combination. We also discuss the challenges in translating the promise of these biomarkers into clinical application.", "source": "PubMed"}, {"chunk_id": "40906458_0", "pmid": "40906458", "title": "APOE4 Exacerbates Alzheimer-Like Pathologies and Cognitive Deficits Induced by Blood-Derived A\u03b2 in a Mouse Model.", "authors": "Yu ZY, Liu XY, Li QY et al.", "year": "2025", "journal": "Aging cell", "keywords": "APOE4, Alzheimer's disease, A\u03b2, bone marrow transplantation, cognitive deficits", "chunk": "Apolipoprotein E4 (APOE4) is a significant risk for both familial Alzheimer's disease (AD) and sporadic AD with elusive mechanisms. Previous studies mainly focused on the role of APOE4 in familial AD, with less attention to sporadic AD. Our previous study demonstrated that blood cell-derived amyloid-\u03b2 (A\u03b2) can enter the brain and induce AD-like pathologies, providing a novel animal model to study sporadic AD to a certain extent. The impacts of APOE4 on Alzheimer-like pathologies and cognitive deficits induced by blood-derived A\u03b2 remain unknown. In the present study, we found that APOE4 prompted the entry of blood A\u03b2 into the brain. APOE4 recipient mice showed impaired integrity of the blood-brain barrier and higher A\u03b2 levels in the brain after transplantation of bone marrow cells from APP/PS1\u2022APOE4 mice. In addition, we observed that the APOE4 recipient mice displayed aggravated tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits at the age of 12", "source": "PubMed"}, {"chunk_id": "40906458_1", "pmid": "40906458", "title": "APOE4 Exacerbates Alzheimer-Like Pathologies and Cognitive Deficits Induced by Blood-Derived A\u03b2 in a Mouse Model.", "authors": "Yu ZY, Liu XY, Li QY et al.", "year": "2025", "journal": "Aging cell", "keywords": "APOE4, Alzheimer's disease, A\u03b2, bone marrow transplantation, cognitive deficits", "chunk": "bone marrow cells from APP/PS1\u2022APOE4 mice. In addition, we observed that the APOE4 recipient mice displayed aggravated tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits at the age of 12 months. Our study demonstrates that APOE4 is capable of facilitating the entry of blood-derived A\u03b2 into the brain and enhancing the AD-like pathologies triggered by blood-derived A\u03b2. Our findings provide a possible way by which APOE4 elevates the risk of sporadic AD.", "source": "PubMed"}, {"chunk_id": "40972225_0", "pmid": "40972225", "title": "Plasma neurology-related proteins associated with cognition are modulated by lifestyle in adults.", "authors": "Margara-Escudero HJ, Paz-Graniel I, Garc\u00eda-Gavil\u00e1n JF et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Cognitive decline, Cognitive performance, Inflammation, Lifestyle intervention, Plasma, Proteomics", "chunk": "Cognitive decline (CD) is an age-related process exacerbated by metabolic syndrome (MetS), which may be mitigated by lifestyle interventions. Plasma biomarkers hold promise for early CD detection, but prospective evidence is limited. Therefore, we aimed to prospectively determine associations between peripheral neurology-related proteins and CD, and to assess whether the lifestyle intervention of the PREDIMED-Plus trial could modify these associations. A 6-year observational study including 314 PREDIMED-Plus participants with overweight/obesity and MetS (mean age: 65 years, 44% women) were randomised to an intensive weight-loss intervention or a control group. At baseline and 3-year follow-up, plasma neurological and inflammatory proteins were quantified using proximity extension assay (OLINK neurology panel, n = 92), ELISA (C-reactive protein, amyloid-beta 40, phosphorylated tau 231 and adiponectin, n = 4) and Luminex (interleukin-6, n = 1). Cognitive performance was assessed at baseline, 2, 4, and 6 years. Elastic net regression identified proteins predictive of four cognitive", "source": "PubMed"}, {"chunk_id": "40972225_1", "pmid": "40972225", "title": "Plasma neurology-related proteins associated with cognition are modulated by lifestyle in adults.", "authors": "Margara-Escudero HJ, Paz-Graniel I, Garc\u00eda-Gavil\u00e1n JF et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Cognitive decline, Cognitive performance, Inflammation, Lifestyle intervention, Plasma, Proteomics", "chunk": "adiponectin, n = 4) and Luminex (interleukin-6, n = 1). Cognitive performance was assessed at baseline, 2, 4, and 6 years. Elastic net regression identified proteins predictive of four cognitive domains, and protein composite scores of cognitive function were generated. Linear-mixed models assessed their associations with 6-year CD and tested for interactions with intervention. Distinct baseline protein composite scores, including 18, 18, 16, and 17 proteins, were identified for global cognitive function (GCF), attention, executive function, and general cognitive function (GenCF), respectively. Of these, seven proteins (RSPO1, CD200, EDA2R, VWC2, GDNF, CD38, and ADAM23) were consistently associated across all cognitive domains. Protein composite scores of GCF and GenCF were significantly associated with 6-year CD, with PREDIMED-Plus interventions modulating these associations only for changes in GCF (P = 0\u00b701). This study identified protein signatures that are associated with CD and observed that a weight loss, energy-reduced Mediterranean diet, and physical activity", "source": "PubMed"}, {"chunk_id": "40972225_2", "pmid": "40972225", "title": "Plasma neurology-related proteins associated with cognition are modulated by lifestyle in adults.", "authors": "Margara-Escudero HJ, Paz-Graniel I, Garc\u00eda-Gavil\u00e1n JF et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Cognitive decline, Cognitive performance, Inflammation, Lifestyle intervention, Plasma, Proteomics", "chunk": "only for changes in GCF (P = 0\u00b701). This study identified protein signatures that are associated with CD and observed that a weight loss, energy-reduced Mediterranean diet, and physical activity may influence the relationship between these protein signatures and cognitive outcomes in older adults with MetS. However, further research is needed to confirm these findings and clarify causal relationships. Instituto de Salud Carlos III (ISCIII) co-funded by the European Union, CIBER de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), European Union's Horizon 2020 research and innovation programme, UCD Ad Astra Programme, ICREA Academia program, Sociedad Espa\u00f1ola de Endocrinolog\u00eda y Nutrici\u00f3n (SEEN), Ag\u00e8ncia Catalana de Recerca i Universitats (AGAUR).", "source": "PubMed"}, {"chunk_id": "34542571_0", "pmid": "34542571", "title": "Head-to-Head Comparison of 8 Plasma Amyloid-\u03b2 42/40 Assays in Alzheimer Disease.", "authors": "Janelidze S, Teunissen CE, Zetterberg H et al.", "year": "2021", "journal": "JAMA neurology", "keywords": "None", "chunk": "Blood-based tests for brain amyloid-\u03b2 (A\u03b2) pathology are needed for widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening and monitoring of treatment responses in clinical trials. To compare the performance of plasma A\u03b242/40 measured using 8 different A\u03b2 assays when detecting abnormal brain A\u03b2 status in patients with early AD. This study included 182 cognitively unimpaired participants and 104 patients with mild cognitive impairment from the BioFINDER cohort who were enrolled at 3 different hospitals in Sweden and underwent A\u03b2 positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) and plasma collection from 2010 to 2014. Plasma A\u03b242/40 was measured using an immunoprecipitation-coupled mass spectrometry developed at Washington University (IP-MS-WashU), antibody-free liquid chromatography MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma A\u03b242/40 was also measured using an", "source": "PubMed"}, {"chunk_id": "34542571_1", "pmid": "34542571", "title": "Head-to-Head Comparison of 8 Plasma Amyloid-\u03b2 42/40 Assays in Alzheimer Disease.", "authors": "Janelidze S, Teunissen CE, Zetterberg H et al.", "year": "2021", "journal": "JAMA neurology", "keywords": "None", "chunk": "MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma A\u03b242/40 was also measured using an IP-MS-based method from Shimadzu in 200 participants (IP-MS-Shim) and an IP-MS-based method from the University of Gothenburg (IP-MS-UGOT) and another immunoassay from Quanterix (IA-Quan) among 227 participants. For validation, 122 participants (51 cognitively normal, 51 with mild cognitive impairment, and 20 with AD dementia) were included from the Alzheimer Disease Neuroimaging Initiative who underwent A\u03b2-PET and plasma A\u03b2 assessments using IP-MS-WashU, IP-MS-Shim, IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays. Discriminative accuracy of plasma A\u03b242/40 quantified using 8 different assays for abnormal CSF A\u03b242/40 and A\u03b2-PET status. A total of 408 participants were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF", "source": "PubMed"}, {"chunk_id": "34542571_2", "pmid": "34542571", "title": "Head-to-Head Comparison of 8 Plasma Amyloid-\u03b2 42/40 Assays in Alzheimer Disease.", "authors": "Janelidze S, Teunissen CE, Zetterberg H et al.", "year": "2021", "journal": "JAMA neurology", "keywords": "None", "chunk": "were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF A\u03b242/40 in the whole cohort, plasma IP-MS-WashU A\u03b242/40 showed significantly higher accuracy (area under the receiver operating characteristic curve [AUC], 0.86; 95% CI, 0.81-0.90) than LC-MS-Arc A\u03b242/40, IA-Elc A\u03b242/40, IA-EI A\u03b242/40, and IA-N4PE A\u03b242/40 (AUC range, 0.69-0.78; P < .05). Plasma IP-MS-WashU A\u03b242/40 performed significantly better than IP-MS-UGOT A\u03b242/40 and IA-Quan A\u03b242/40 (AUC, 0.84 vs 0.68 and 0.64, respectively; P < .001), while there was no difference in the AUCs between IP-MS-WashU A\u03b242/40 and IP-MS-Shim A\u03b242/40 (0.87 vs 0.83; P = .16) in the 2 subcohorts where these biomarkers were available. The results were similar when using A\u03b2-PET as outcome. Plasma IPMS-WashU A\u03b242/40 and IPMS-Shim A\u03b242/40 showed highest coefficients for correlations with CSF A\u03b242/40 (r range, 0.56-0.65). The BioFINDER results", "source": "PubMed"}, {"chunk_id": "34542571_3", "pmid": "34542571", "title": "Head-to-Head Comparison of 8 Plasma Amyloid-\u03b2 42/40 Assays in Alzheimer Disease.", "authors": "Janelidze S, Teunissen CE, Zetterberg H et al.", "year": "2021", "journal": "JAMA neurology", "keywords": "None", "chunk": "available. The results were similar when using A\u03b2-PET as outcome. Plasma IPMS-WashU A\u03b242/40 and IPMS-Shim A\u03b242/40 showed highest coefficients for correlations with CSF A\u03b242/40 (r range, 0.56-0.65). The BioFINDER results were replicated in the Alzheimer Disease Neuroimaging Initiative cohort (mean [SD] age, 72.4 [5.4] years; 43.4% women), where the IP-MS-WashU assay performed significantly better than the IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays but not the IP-MS-Shim assay. The results from 2 independent cohorts indicate that certain MS-based methods performed better than most of the immunoassays for plasma A\u03b242/40 when detecting brain A\u03b2 pathology.", "source": "PubMed"}, {"chunk_id": "37182874_0", "pmid": "37182874", "title": "Meta-Analysis of Variations in Association between APOE \u025b4 and Alzheimer's Disease and Related Dementias Across Hispanic Regions of Origin.", "authors": "Huggins LKL, Min SH, Kaplan S et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer disease, Hispanic or Latino, apolipoprotein E4, dementia", "chunk": "Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein \u025b4 (APOE \u025b4) allele and the risk of developing Alzheimer's disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results. To examine the association between the APOE \u025b4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin. PubMed, Embase, Scopus, and PsycInfo were searched for studies relating to Hispanic/Latin American origin, APOE \u025b4, and ADRD. Odds ratios (OR) of ADRD risk for individuals with APOE \u025b4 versus those without APOE \u025b4 were extracted and calculated using random effects analysis. 20 eligible studies represented Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE \u025b4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38-6.07). The association was", "source": "PubMed"}, {"chunk_id": "37182874_1", "pmid": "37182874", "title": "Meta-Analysis of Variations in Association between APOE \u025b4 and Alzheimer's Disease and Related Dementias Across Hispanic Regions of Origin.", "authors": "Huggins LKL, Min SH, Kaplan S et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer disease, Hispanic or Latino, apolipoprotein E4, dementia", "chunk": "Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE \u025b4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38-6.07). The association was only significant in the South American (OR: 4.61, 95% CI: 2.74-7.75) subgroup. There was an association between APOE \u025b4 and increased ADRD risk for the South American subgroup. The strength of this association varied across Hispanic subgroups. Data is limited with more studies especially needed for adjusted analysis on Spanish, Central American, Cuban Hispanic, and Caribbean Hispanic groups. Results suggest additional environmental or genetic risk factors are associated with ethnic variations.", "source": "PubMed"}, {"chunk_id": "40000032_0", "pmid": "40000032", "title": "Updates on vascular dementia.", "authors": "Ng S, Hornblass A, Habibi P et al.", "year": "2025", "journal": "Stroke and vascular neurology", "keywords": "Cerebrovascular Disorders, Cognitive Dysfunction, Neurodegenerative Diseases, Systematic Review", "chunk": "Vascular dementia (VaD) is the second leading cause of dementia after Alzheimer's disease (AD). In comparison to AD, there is a decline in the incidence of VaD due to recent improvements in cardiovascular risk factors. Brain hypoperfusion and hypoxia due to vascular pathologies have been postulated as the primary disease mechanism of VaD. However, other factors such as neuroinflammation may also contribute to the development of VaD. Non-modifiable and modifiable risk factors have been attributed to VaD. The clinical features overlapping between AD and VaD create significant challenges for physicians. Newly developed biomarkers may potentially help differentiate VaD from other forms of dementia. Unlike AD, there is no Food and Drug Administration-approved drug or device for treating VaD. Current treatment options mainly target symptoms rather than slowing the development or progression of VaD. There are ongoing research studies testing the efficacy of various therapeutic strategies for VaD. In this narrative", "source": "PubMed"}, {"chunk_id": "40000032_1", "pmid": "40000032", "title": "Updates on vascular dementia.", "authors": "Ng S, Hornblass A, Habibi P et al.", "year": "2025", "journal": "Stroke and vascular neurology", "keywords": "Cerebrovascular Disorders, Cognitive Dysfunction, Neurodegenerative Diseases, Systematic Review", "chunk": "options mainly target symptoms rather than slowing the development or progression of VaD. There are ongoing research studies testing the efficacy of various therapeutic strategies for VaD. In this narrative review, we will summarise current findings on epidemiology, attributed risk factors and disease mechanisms, as well as emphasise the importance of optimising lifestyle modifications and comorbid condition management in preventing or slowing down the development of VaD. Finally, current therapies and ongoing research studies of novel therapeutic interventions such as stem-cell therapy and neuromodulation are highlighted.", "source": "PubMed"}, {"chunk_id": "41751212_0", "pmid": "41751212", "title": "Mitochondria-Associated MicroRNAs: Emerging Roles in the Pathogenesis of Parkinson's Disease.", "authors": "Catanesi M, Di Leandro L, Colasante M et al.", "year": "2026", "journal": "Biomedicines", "keywords": "MiRNAs, Mito-MiRNA, Parkinson\u2019s disease, agomir, antagomir, mitochondrial dysfunction", "chunk": "Neurodegenerative diseases (NDs) are the most prevalent age-associated disorders, characterized by progressive neuronal loss and cognitive decline. Mitochondrial dysfunction is strictly associated with NDs and represent one of the hallmarks of these disorders, with neurological syndromes frequently representing the primary clinical manifestations of mitochondrial abnormalities. As central regulators of cellular bioenergetics, mitochondria play a pivotal role in both the physiological maintenance and pathogenesis of disease by different regulatory approaches. One of these, microRNAs (miRNAs), a class of small non-coding RNAs, are well-established regulators of gene expression across different biological pathways. These miRNAs were usually investigated within the cytoplasmic context, but recent discoveries have revealed the presence of these miRNAs in different parts of mitochondria, where they contribute to the regulation of gene expression and metabolic activity. These mitochondrial-localized miRNAs, termed mito-MiRNA, may originate from either nuclear or mitochondrial genomes and have been shown to modulate the translational machinery of the", "source": "PubMed"}, {"chunk_id": "41751212_1", "pmid": "41751212", "title": "Mitochondria-Associated MicroRNAs: Emerging Roles in the Pathogenesis of Parkinson's Disease.", "authors": "Catanesi M, Di Leandro L, Colasante M et al.", "year": "2026", "journal": "Biomedicines", "keywords": "MiRNAs, Mito-MiRNA, Parkinson\u2019s disease, agomir, antagomir, mitochondrial dysfunction", "chunk": "of gene expression and metabolic activity. These mitochondrial-localized miRNAs, termed mito-MiRNA, may originate from either nuclear or mitochondrial genomes and have been shown to modulate the translational machinery of the cells. Despite extensive research on cytoplasmic miRNAs, the functional roles of mito-MiRNA remain poorly understood, particularly in the context of neurodegenerative disorders. Based on these findings, this review aims to synthesize emerging evidence on the involvement of mito-MiRNA in in one of most prevalent neurodegenerative diseases-Parkinson's disease (PD).", "source": "PubMed"}, {"chunk_id": "40958766_0", "pmid": "40958766", "title": "MRI Epicenters Differentiate Spatiotemporal Patterns of Neurodegeneration in Parkinson's Disease.", "authors": "Duanmu X, Zhu Z, Wen J et al.", "year": "2025", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "keywords": "connectivity\u2010based epicenter model, deformation\u2010based morphometry, diffusion tensor imaging, quantitative susceptibility imaging", "chunk": "Parkinson's disease (PD) exhibits clinical and neuropathological heterogeneity, potentially driven by distinct spatiotemporal neurodegenerative patterns. This study utilizes a connectivity-based MRI epicenter model combined with unsupervised clustering to identify unique degenerative epicenters in PD. Analyzing cross-sectional multi-modal MRI data from 278 PD patients and 177 healthy controls, this work identifies two distinct neurodegenerative epicenter patterns. Subtype 1 exhibits epicenters predominantly in cerebellar and midbrain regions associated with severe motor symptoms and rapid progression. Subtype 2 shows epicenters primarily in cortical and striatal regions with milder progression. These patterns are validated in an independent cohort of 66 PD patients and shows consistency in longitudinal follow-up. Additionally, a predictive model incorporating epicenter traits and structural connectivity properties is developed, accurately forecasting individualized neurodegenerative progression. Spatial correlation analyses further reveal overlapping epicenter distributions between PD subtype 1 and other movement disorders, including essential tremor and multiple system atrophy, suggesting potential shared pathological mechanisms.", "source": "PubMed"}, {"chunk_id": "40958766_1", "pmid": "40958766", "title": "MRI Epicenters Differentiate Spatiotemporal Patterns of Neurodegeneration in Parkinson's Disease.", "authors": "Duanmu X, Zhu Z, Wen J et al.", "year": "2025", "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)", "keywords": "connectivity\u2010based epicenter model, deformation\u2010based morphometry, diffusion tensor imaging, quantitative susceptibility imaging", "chunk": "neurodegenerative progression. Spatial correlation analyses further reveal overlapping epicenter distributions between PD subtype 1 and other movement disorders, including essential tremor and multiple system atrophy, suggesting potential shared pathological mechanisms. These results delineate PD heterogeneity through distinct epicenter-driven neurodegenerative trajectories, bridging the gap between neuroanatomical spread patterns and clinical variability. This novel framework not only enhances the understanding of PD's neuropathological complexity but also advances personalized prognosis and highlights connectivity-based epicenters as promising biomarkers for PD subtyping and therapeutic targeting.", "source": "PubMed"}, {"chunk_id": "36155505_0", "pmid": "36155505", "title": "Sex Differences in Resilience and Resistance to Brain Pathology and Dysfunction Moderated by Cerebrovascular Response to Exercise and Genetic Risk for Alzheimer's Disease.", "authors": "Palmer JA, Kaufman CS, Vidoni ED et al.", "year": "2022", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Aging, Apolipoproteins E, amyloid, cardiovascular system, cerebrovascular circulation, cognition, female, hemodynamics, ultrasound", "chunk": "Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer's disease. We tested sex-based interactions between cerebrovascular function and APOE4 genotype on resistance and resilience to brain pathology and cognitive executive dysfunction in cognitively-normal older adults. Female APOE4 carriers had higher amyloid-\u03b2 deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-\u03b2. These results suggest a unique cognitive resilience and identify cerebrovascular function as a key mechanism for resistance to age-related brain pathology in females with high genetic vulnerability to Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "38252443_0", "pmid": "38252443", "title": "Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.", "authors": "Ashton NJ, Brum WS, Di Molfetta G et al.", "year": "2024", "journal": "JAMA neurology", "keywords": "None", "chunk": "Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. To determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid \u03b2 (A\u03b2) and longitudinal change across 3 selected cohorts. This cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without", "source": "PubMed"}, {"chunk_id": "38252443_1", "pmid": "38252443", "title": "Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.", "authors": "Ashton NJ, Brum WS, Di Molfetta G et al.", "year": "2024", "journal": "JAMA neurology", "keywords": "None", "chunk": "Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. Magnetic resonance imaging, A\u03b2 positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (A\u03b242/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Accuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated A\u03b2 (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining", "source": "PubMed"}, {"chunk_id": "38252443_2", "pmid": "38252443", "title": "Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.", "authors": "Ashton NJ, Brum WS, Di Molfetta G et al.", "year": "2024", "journal": "JAMA neurology", "keywords": "None", "chunk": "A\u03b2 (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal A\u03b2 pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in A\u03b2-positive individuals, with the highest increase observed in those with tau positivity. This study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.", "source": "PubMed"}, {"chunk_id": "37189726_0", "pmid": "37189726", "title": "Do Epilepsy Patients with Cognitive Impairment Have Alzheimer's Disease-like Brain Metabolism?", "authors": "He M, Kolesar TA, Goertzen AL et al.", "year": "2023", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s disease, FDG-PET, biomarker, epilepsy, machine learning, metabolic classification, neurodegenerative disease, support vector machine", "chunk": "Although not classically considered together, there is emerging evidence that Alzheimer's disease (AD) and epilepsy share a number of features and that each disease predisposes patients to developing the other. Using machine learning, we have previously developed an automated fluorodeoxyglucose positron emission tomography (FDG-PET) reading program (i.e., MAD), and demonstrated good sensitivity (84%) and specificity (95%) for differentiating AD patients versus healthy controls. In this retrospective chart review study, we investigated if epilepsy patients with/without mild cognitive symptoms also show AD-like metabolic patterns determined by the MAD algorithm. Scans from a total of 20 patients with epilepsy were included in this study. Because AD diagnoses are made late in life, only patients aged \u226540 years were considered. For the cognitively impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was", "source": "PubMed"}, {"chunk_id": "37189726_1", "pmid": "37189726", "title": "Do Epilepsy Patients with Cognitive Impairment Have Alzheimer's Disease-like Brain Metabolism?", "authors": "He M, Kolesar TA, Goertzen AL et al.", "year": "2023", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s disease, FDG-PET, biomarker, epilepsy, machine learning, metabolic classification, neurodegenerative disease, support vector machine", "chunk": "impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was identified as MAD+ (\u03c7<sup>2</sup> = 8.148, <i>p</i> = 0.017). These results potentially suggest the usability of FDG-PET in prognosticating later dementia development in non-demented epilepsy patients, especially when combined with machine learning algorithms. A longitudinal follow-up study is warranted to assess the effectiveness of this approach.", "source": "PubMed"}, {"chunk_id": "38513154_0", "pmid": "38513154", "title": "BV2 Membrane-Coated PEGylated-Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy.", "authors": "Wang HC, Yang W, Xu L et al.", "year": "2024", "journal": "Advanced healthcare materials", "keywords": "alzheimer's disease (AD), brain delivery, cerebral lymphatic vasculature, hFGF21, membrane\u2010coated pegylated liposomes", "chunk": "Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets A\u03b2<sub>1-42</sub>-induced BV2 cells, with uptake hindered by anti-VCAM-1 antibody, indicating the importance of VCAM-1 and integrin \u03b14/\u03b21 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM-LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (A\u03b2<sub>1-42</sub>)-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by A\u03b2<sub>1-42</sub> and", "source": "PubMed"}, {"chunk_id": "38513154_1", "pmid": "38513154", "title": "BV2 Membrane-Coated PEGylated-Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy.", "authors": "Wang HC, Yang W, Xu L et al.", "year": "2024", "journal": "Advanced healthcare materials", "keywords": "alzheimer's disease (AD), brain delivery, cerebral lymphatic vasculature, hFGF21, membrane\u2010coated pegylated liposomes", "chunk": "nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (A\u03b2<sub>1-42</sub>)-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by A\u03b2<sub>1-42</sub> and reduces levels of tau, p-Tau, and BACE1. It also decreases interleukin-6 (IL-6) and tumor necrosis factor-\u03b1 (TNF-\u03b1) release while increasing interleukin-10 (IL-10) release both in vivo and in vitro. These results indicate that hFGF21@BCM-LIP can be a promising treatment for AD, by effectively crossing the blood-brain barrier and targeting delivery to brain microglia via the neck-meningeal lymphatic vasculature-brain parenchyma pathways.", "source": "PubMed"}, {"chunk_id": "39468808_0", "pmid": "39468808", "title": "[Resistance exercise regulates hippocampal microglia polarization through TREM2/NF-\u03baB/STAT3 signal pathway to improve cognitive dysfunction in T2DM mice].", "authors": "Zhang BW, Li Y, Kou XJ", "year": "2024", "journal": "Sheng li xue bao : [Acta physiologica Sinica]", "keywords": "None", "chunk": "The study aimed to explore the effect and mechanism of resistance exercise (RE) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) mice. Six 8-week-old male m/m mice were used as control (Con) group, and db/db mice of the matched age were randomly divided into model control (db/db) group and db+RE group, with 6 mice in each group. The db+RE group was given 8 weeks of resistance climbing ladder exercise intervention. The fasting blood glucose and body weight of the mice were measured weekly. After the intervention, the spatial learning and memory of the mice were detected by Morris water maze, and the neuronal damage in the hippocampus of the mice was detected by Nissl staining. The protein expression levels of PSD93, PSD95, BDNF, CREB, p-CREB, IL-6, IL-1\u03b2, TNF-\u03b1, Iba-1, iNOS, CD206, Arg1, triggering receptor expressed on myeloid cells 2 (TREM2), NF-\u03baB, p-STAT3, and STAT3 were detected by Western blot.", "source": "PubMed"}, {"chunk_id": "39468808_1", "pmid": "39468808", "title": "[Resistance exercise regulates hippocampal microglia polarization through TREM2/NF-\u03baB/STAT3 signal pathway to improve cognitive dysfunction in T2DM mice].", "authors": "Zhang BW, Li Y, Kou XJ", "year": "2024", "journal": "Sheng li xue bao : [Acta physiologica Sinica]", "keywords": "None", "chunk": "of PSD93, PSD95, BDNF, CREB, p-CREB, IL-6, IL-1\u03b2, TNF-\u03b1, Iba-1, iNOS, CD206, Arg1, triggering receptor expressed on myeloid cells 2 (TREM2), NF-\u03baB, p-STAT3, and STAT3 were detected by Western blot. The mRNA expression levels of inflammatory factors and TREM2 in hippocampus were evaluated by qRT-PCR, and the expression and localization of Iba-1, CD206, CD86, and TREM2 were determined by immunofluorescence staining. The results showed that the spatial learning and memory of the db/db group were significantly declined, the neurons in the hippocampus were damaged, the protein levels of PSD93, PSD95, BDNF, CD206, Arg1, TREM2 and the ratio of p-CREB/CREB were significantly down-regulated, the mRNA and protein expression levels of IL-6, IL-1\u03b2 and TNF-\u03b1 were significantly up-regulated, and the protein levels of iNOS, Iba-1, NF-\u03baB and the ratio of p-STAT3/STAT3 were significantly increased compared with the Con group. However, the 8-week RE improved the spatial learning and memory of db/db mice,", "source": "PubMed"}, {"chunk_id": "39468808_2", "pmid": "39468808", "title": "[Resistance exercise regulates hippocampal microglia polarization through TREM2/NF-\u03baB/STAT3 signal pathway to improve cognitive dysfunction in T2DM mice].", "authors": "Zhang BW, Li Y, Kou XJ", "year": "2024", "journal": "Sheng li xue bao : [Acta physiologica Sinica]", "keywords": "None", "chunk": "of iNOS, Iba-1, NF-\u03baB and the ratio of p-STAT3/STAT3 were significantly increased compared with the Con group. However, the 8-week RE improved the spatial learning and memory of db/db mice, alleviated the damage of hippocampal neurons, promoted the polarization of M2 microglia, and inhibited the neuroinflammation. The above results suggest that RE can improve cognitive dysfunction in T2DM mice, and its mechanism may be related to regulating microglia polarization via TREM2/NF-\u03baB/STAT3 signaling pathway.", "source": "PubMed"}, {"chunk_id": "40646873_0", "pmid": "40646873", "title": "Evaluation of Blood-Based Diagnostic Biomarkers for Canine Cognitive Dysfunction Syndrome.", "authors": "Yoon JW, Nam CS, Lee KS et al.", "year": "2025", "journal": "Animals : an open access journal from MDPI", "keywords": "amyloid-beta, behavioral questionnaire, canine cognitive dysfunction syndrome, glial fibrillary acidic chain, neurodegeneration, neurofilament light chain", "chunk": "Canine cognitive dysfunction syndrome (CDS) is a progressive neurodegenerative disorder in aging dogs and serves as a natural model for Alzheimer's disease in humans. This study evaluated blood biomarkers-amyloid-beta (A\u03b240, A\u03b242), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-for diagnosing and staging CDS and assessed whether combining biomarkers with behavioral questionnaires improves diagnostic reliability. Seventy-seven dogs, including healthy controls and CDS cases, were assessed using the Canine Cognitive Dysfunction Rating Scale (CCDR), Canine Dementia Scale (CADES), and Canine Cognitive Assessment Scale (CCAS). Plasma A\u03b240, A\u03b242, GFAP, and serum NfL levels were measured via ELISA. While A\u03b240, A\u03b242, and GFAP were not significantly associated with CDS stage, serum NfL levels were elevated (<i>p</i> < 0.05) across all questionnaires. Receiver operating characteristic (ROC) analyses showed areas under the curve (AUCs) of 0.763 (CCDR), 0.722 (CADES), and 0.777 (CCAS), with cut-off values around 18.28-43.13 pg/mL. NfL shows promise as a blood", "source": "PubMed"}, {"chunk_id": "40646873_1", "pmid": "40646873", "title": "Evaluation of Blood-Based Diagnostic Biomarkers for Canine Cognitive Dysfunction Syndrome.", "authors": "Yoon JW, Nam CS, Lee KS et al.", "year": "2025", "journal": "Animals : an open access journal from MDPI", "keywords": "amyloid-beta, behavioral questionnaire, canine cognitive dysfunction syndrome, glial fibrillary acidic chain, neurodegeneration, neurofilament light chain", "chunk": "operating characteristic (ROC) analyses showed areas under the curve (AUCs) of 0.763 (CCDR), 0.722 (CADES), and 0.777 (CCAS), with cut-off values around 18.28-43.13 pg/mL. NfL shows promise as a blood biomarker correlated with CDS severity. Combining serum NfL measurements with questionnaire assessments may enhance diagnostic accuracy for CDS in veterinary practice.", "source": "PubMed"}, {"chunk_id": "41486750_0", "pmid": "41486750", "title": "The Enteric Nervous System as a Mediator of Microbiota-Gut-Brain Interactions in Parkinson's Disease.", "authors": "Valdetaro L, Ricciardi MC, Almeida PP et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "Parkinson's disease, enteric nervous system, gut microbiota, neuroinflammation, short\u2010chain fatty acids", "chunk": "Parkinson's disease (PD) is a multifactorial neurodegenerative disorder in which gastrointestinal dysfunction is highly prevalent and often precedes motor symptoms. Although research on gut microbiota alterations in PD has expanded rapidly, inconsistent findings and the absence of a reproducible microbial signature reveal the limitations of a microbiota-centered view. The enteric nervous system (ENS), the intrinsic neural network of the gut, has been comparatively overlooked and remains underexplored, yet mounting evidence indicates that it undergoes profound alterations in PD. Pathological changes in enteric neurons and glial cells, including \u03b1-synuclein accumulation, disrupted neurotransmission, impaired epithelial barrier regulation, and neuroinflammation, not only contribute to gastrointestinal dysfunction but may also drive disease propagation along the gut-brain axis. In parallel, PD-related dysbiosis alters microbial metabolites and immune signaling, disrupting ENS physiology. This review reframes PD gut pathology by emphasizing the ENS as a central mediator of microbiota-brain communication. We highlight potential key pathways underlying this", "source": "PubMed"}, {"chunk_id": "41486750_1", "pmid": "41486750", "title": "The Enteric Nervous System as a Mediator of Microbiota-Gut-Brain Interactions in Parkinson's Disease.", "authors": "Valdetaro L, Ricciardi MC, Almeida PP et al.", "year": "2026", "journal": "Journal of neurochemistry", "keywords": "Parkinson's disease, enteric nervous system, gut microbiota, neuroinflammation, short\u2010chain fatty acids", "chunk": "and immune signaling, disrupting ENS physiology. This review reframes PD gut pathology by emphasizing the ENS as a central mediator of microbiota-brain communication. We highlight potential key pathways underlying this crosstalk, including short-chain fatty acids (SCFAs), Toll-like receptor (TLR) signaling, and serotonergic circuits, which normally sustain ENS function but, in the context of PD, contribute to barrier impairment, neuroinflammation, and neuronal alterations. By integrating evidence from human studies and experimental models, we argue that investigating ENS-microbiota interactions provides a more comprehensive perspective on PD pathophysiology and may guide the identification of novel biomarkers and therapeutic approaches capable of addressing both gastrointestinal and neurological manifestations of the disease.", "source": "PubMed"}, {"chunk_id": "41387292_0", "pmid": "41387292", "title": "Modulation of cerebral blood flow and cognition by hyperthermia and hypoxia: An electroencephalographic event-related potentials perspective.", "authors": "Nakata H, Ogoh S, Shibasaki M", "year": "2025", "journal": "Experimental physiology", "keywords": "P300, event\u2010related potential, heat stress, hypoxia", "chunk": "Cerebral blood flow (CBF) is essential for sustaining neuronal metabolism and cognitive performance; however, the precise relationship between perfusion and cognition remains unclear. Although ageing and disease are associated with progressive declines in CBF and cognitive impairment, the acute effects of altered CBF under environmental stressors have not been elucidated fully. The influence of environmental stress on cognitive function is likely to depend on the degree of stress (e.g., its intensity and duration). Therefore, it is necessary to carry out a systematic review of a large number of studies, and objective evidence is required to build a comprehensive dataset. This review summarizes research examining the effects of mild to moderate passive heat stress (an increase in core temperature of \u223c1.0\u00b0C-1.5\u00b0C) and acute hypoxia on cognitive processing, as evaluated using electroencephalographic event-related potentials (EEG-ERPs), with the aim of facilitating future cross-experimental comparisons. During mild or greater hyperthermia, CBF decreases owing to", "source": "PubMed"}, {"chunk_id": "41387292_1", "pmid": "41387292", "title": "Modulation of cerebral blood flow and cognition by hyperthermia and hypoxia: An electroencephalographic event-related potentials perspective.", "authors": "Nakata H, Ogoh S, Shibasaki M", "year": "2025", "journal": "Experimental physiology", "keywords": "P300, event\u2010related potential, heat stress, hypoxia", "chunk": "and acute hypoxia on cognitive processing, as evaluated using electroencephalographic event-related potentials (EEG-ERPs), with the aim of facilitating future cross-experimental comparisons. During mild or greater hyperthermia, CBF decreases owing to blood flow redistribution and hypocapnia-induced by hyperventilation, whereas during hypoxia, CBF can either increase or decrease depending on the conditions (e.g., exposure time or intensity). To standardize comparisons, this review focuses on acute hypoxic exposures, during which CBF tends to decrease. Although it is undeniable that the content summarized here might be somewhat selective, it is hoped that this foundation will contribute to the future development of constructive and objective evaluations. Current evidence indicates that acute fluctuations in CBF are unlikely to predict cognitive outcomes. Rather, both heat and hypoxic stress appear to impair neural activity through mechanisms beyond perfusion alone.", "source": "PubMed"}, {"chunk_id": "41387292_2", "pmid": "41387292", "title": "Modulation of cerebral blood flow and cognition by hyperthermia and hypoxia: An electroencephalographic event-related potentials perspective.", "authors": "Nakata H, Ogoh S, Shibasaki M", "year": "2025", "journal": "Experimental physiology", "keywords": "P300, event\u2010related potential, heat stress, hypoxia", "chunk": "stress appear to impair neural activity through mechanisms beyond perfusion alone.", "source": "PubMed"}, {"chunk_id": "41177743_0", "pmid": "41177743", "title": "Efficacy and Safety of Lithium for Behavioral and Cognitive Symptoms in Alzheimer's Disease Dementia: A Systematic Review With Frequentist and Bayesian Meta-Analysis.", "authors": "Pereira da Silva AM, de Deus O, Ribeiro FV et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, Bayesian analysis, cognitive outcomes, dementia, functional outcomes, lithium, meta-analysis, neuropsychiatric symptoms", "chunk": "Alzheimer's disease (AD) dementia is the leading cause of cognitive decline in late life, yet treatment options remain limited. Lithium, widely used in bipolar disorder, has been suggested to exert neuroprotective effects through inhibition of GSK-3\u03b2 and modulation of amyloid and tau pathology. We aimed to evaluate the efficacy and safety of lithium in AD dementia. This systematic review and meta-analysis was prospectively registered in PROSPERO and conducted following PRISMA guidelines. We searched PubMed, Embase, and Cochrane Library through April 2025 for randomized controlled trials (RCTs) comparing lithium with placebo or standard therapy in patients with AD dementia or amnestic mild cognitive impairment. Outcomes included cognition (MMSE, ADAS-Cog, memory tasks), function (CDR-SB, conversion to AD), neuropsychiatric symptoms (NPI), CSF biomarkers, and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses. Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion", "source": "PubMed"}, {"chunk_id": "41177743_1", "pmid": "41177743", "title": "Efficacy and Safety of Lithium for Behavioral and Cognitive Symptoms in Alzheimer's Disease Dementia: A Systematic Review With Frequentist and Bayesian Meta-Analysis.", "authors": "Pereira da Silva AM, de Deus O, Ribeiro FV et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, Bayesian analysis, cognitive outcomes, dementia, functional outcomes, lithium, meta-analysis, neuropsychiatric symptoms", "chunk": "and safety (adverse events [AEs], serious AEs [SAEs]). Random-effects meta-analyses were complemented by Bayesian methods and trial sequential analyses. Six RCTs involving 394 participants (196 lithium, 198 placebo) met inclusion criteria. Lithium did not significantly improve global cognition (MMSE: MD -1.61, 95% CI -4.11 to 0.88; ADAS-Cog: MD -1.82, -3.05 to -0.60; both with high heterogeneity). Memory outcomes were mixed, with possible benefit for figure recall but not delayed verbal recall. No consistent benefits were observed for episodic memory, functional outcomes (CDR-SB), neuropsychiatric symptoms, or CSF biomarkers. Safety analyses showed no increased risk of SAEs; drug-related AEs were more frequent but heterogeneous across trials. Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.", "source": "PubMed"}, {"chunk_id": "41177743_2", "pmid": "41177743", "title": "Efficacy and Safety of Lithium for Behavioral and Cognitive Symptoms in Alzheimer's Disease Dementia: A Systematic Review With Frequentist and Bayesian Meta-Analysis.", "authors": "Pereira da Silva AM, de Deus O, Ribeiro FV et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, Bayesian analysis, cognitive outcomes, dementia, functional outcomes, lithium, meta-analysis, neuropsychiatric symptoms", "chunk": "support consistent cognitive or functional benefits in AD dementia. Larger, well-designed RCTs are warranted to clarify its potential therapeutic role.", "source": "PubMed"}, {"chunk_id": "30072890_0", "pmid": "30072890", "title": "Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer's Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study.", "authors": "Shigemoto Y, Sone D, Imabayashi E et al.", "year": "2018", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain atrophy, magnetic resonance imaging, partial volume correction, positron emission tomography, tau", "chunk": "The recent advent of tau-specific positron emission tomography (PET) has enabled <i>in vivo</i> assessment of tau pathology in Alzheimer's disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using <sup>18</sup>F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate", "source": "PubMed"}, {"chunk_id": "30072890_1", "pmid": "30072890", "title": "Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer's Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study.", "authors": "Shigemoto Y, Sone D, Imabayashi E et al.", "year": "2018", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain atrophy, magnetic resonance imaging, partial volume correction, positron emission tomography, tau", "chunk": "and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect <sup>18</sup>F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.", "source": "PubMed"}, {"chunk_id": "30072890_2", "pmid": "30072890", "title": "Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer's Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study.", "authors": "Shigemoto Y, Sone D, Imabayashi E et al.", "year": "2018", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, brain atrophy, magnetic resonance imaging, partial volume correction, positron emission tomography, tau", "chunk": "affect <sup>18</sup>F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy.", "source": "PubMed"}, {"chunk_id": "41428114_0", "pmid": "41428114", "title": "Genetic Evidence Linking Lactylation-Related Gene Expression To Dementia Risk.", "authors": "Zhang H, Li C, Song Y et al.", "year": "2025", "journal": "Neuromolecular medicine", "keywords": "Alzheimer\u2019s disease, Dementia subtypes, Epigenetic regulation, Gene expression, Lactylation, Mendelian randomization", "chunk": "Lactylation has been identified as a novel epigenetic modification involved in neuroinflammation, mitochondrial dysfunction, and tau pathology. Although its relevance has been suggested in Alzheimer's disease (AD), its causal contribution to distinct dementia subtypes remains unclear. We conducted a two-sample Mendelian randomization (MR) study to investigate whether the genetically predicted expression of 15 lactylation-related genes is causally associated with the risk of five dementia subtypes: Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and vascular dementia (VaD). Gene expression instruments were selected from whole-blood eQTL data (n = 31,684), and outcome data were derived from large-scale GWASs. The inverse-variance weighted (IVW) method served as the primary analytical approach, with Bonferroni correction (\u03b1 = 0.05/15) applied for multiple testing. After correction, six gene-dementia associations remained statistically significant. Increased expression of EP300 and PFKP was associated with higher AD risk, while SIRT1 and LDHC", "source": "PubMed"}, {"chunk_id": "41428114_1", "pmid": "41428114", "title": "Genetic Evidence Linking Lactylation-Related Gene Expression To Dementia Risk.", "authors": "Zhang H, Li C, Song Y et al.", "year": "2025", "journal": "Neuromolecular medicine", "keywords": "Alzheimer\u2019s disease, Dementia subtypes, Epigenetic regulation, Gene expression, Lactylation, Mendelian randomization", "chunk": "= 0.05/15) applied for multiple testing. After correction, six gene-dementia associations remained statistically significant. Increased expression of EP300 and PFKP was associated with higher AD risk, while SIRT1 and LDHC showed protective effects against PDD. NUP50 was associated with increased FTD risk, and STMN1 with reduced risk of DLB. No significant associations were detected for VaD. All findings were robust in sensitivity analyses and supported by brain expression evidence from GTEx. Genetic evidence was provided for a causal relationship between lactylation-related gene expression and dementia subtype risk, offering potential mechanistic insights and therapeutic targets.", "source": "PubMed"}, {"chunk_id": "37904560_0", "pmid": "37904560", "title": "Dendrimers: Patents for Alzheimer's Disease.", "authors": "Maheshwari S, Singh A", "year": "2025", "journal": "Recent patents on nanotechnology", "keywords": "Alzheimer's disease, Dendrimers, blood-brain barrier, central nervous system disorders., clinical trials, neurofibrillary tangles", "chunk": "Cells and nervous system connections that are crucial for movement, coordination, strength, sensation, and thought are gradually damaged in neurodegenerative illnesses. Amyloid beta (A\u03b2)- accumulating macromolecules in the brain are the primary cause of the disease's chronic symptoms, according to analysis carried out during the last 20 years. Plaques and clumps of amyloid- build up in the brain, obstructing neuronal signals and destroying neural connections. Tau, a protein that results in the formation of \"neurofibrillary tangles\" in the brain, another hallmark of neuronal death, has been the focus of a lot of research. Dendrimers Delivery (DDs) is one of the most promising advancements in nanotechnology for biomedical applications, particularly drug delivery. Some of the main categories of dendrimers employed in the successful management of neurodegenerative illnesses are polyamidoamine dendrimers (PAMAM) dendrimers, polypropylenimine dendrimers (PPI), Poly-l-lysine dendrimers (PLL), and carbosilane dendrimers. The tight blood-brain barrier (BBB), which limits the entry of", "source": "PubMed"}, {"chunk_id": "37904560_1", "pmid": "37904560", "title": "Dendrimers: Patents for Alzheimer's Disease.", "authors": "Maheshwari S, Singh A", "year": "2025", "journal": "Recent patents on nanotechnology", "keywords": "Alzheimer's disease, Dendrimers, blood-brain barrier, central nervous system disorders., clinical trials, neurofibrillary tangles", "chunk": "the successful management of neurodegenerative illnesses are polyamidoamine dendrimers (PAMAM) dendrimers, polypropylenimine dendrimers (PPI), Poly-l-lysine dendrimers (PLL), and carbosilane dendrimers. The tight blood-brain barrier (BBB), which limits the entry of medications or therapeutic agents, makes it difficult to treat central nervous system disorders. Dendrimers have attracted the attention of scientists more than other non-invasive methods of drug delivery across the BBB and improve the uptake of medicines in the brain's target tissues. The major benefits of dendrimers include their adaptability, biocompatibility, ability to load pharmaceuticals into the core and surface, and nanosize. The patents provide \"composition of matter\" protection for Starpharma's dendrimer technologies for drug delivery out to 2029 in the United States, which is the world's largest pharmaceutical market for several important drug classes. This review has updated the status of the patent and clinical trials literature pertaining to dendrimer use in AD.", "source": "PubMed"}, {"chunk_id": "37904560_2", "pmid": "37904560", "title": "Dendrimers: Patents for Alzheimer's Disease.", "authors": "Maheshwari S, Singh A", "year": "2025", "journal": "Recent patents on nanotechnology", "keywords": "Alzheimer's disease, Dendrimers, blood-brain barrier, central nervous system disorders., clinical trials, neurofibrillary tangles", "chunk": "for several important drug classes. This review has updated the status of the patent and clinical trials literature pertaining to dendrimer use in AD.", "source": "PubMed"}, {"chunk_id": "38644660_0", "pmid": "38644660", "title": "Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.", "authors": "Aranha MR, Montal V, van den Brink H et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, cerebral amyloid angiopathy, cerebral microbleeds, cortical microinfarcts, magnetic resonance imaging, neuroimaging, small vessel diseases", "chunk": "Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype.", "source": "PubMed"}, {"chunk_id": "38644660_1", "pmid": "38644660", "title": "Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.", "authors": "Aranha MR, Montal V, van den Brink H et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, cerebral amyloid angiopathy, cerebral microbleeds, cortical microinfarcts, magnetic resonance imaging, neuroimaging, small vessel diseases", "chunk": "infarcts, but not hemorrhagic lesions. In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.", "source": "PubMed"}, {"chunk_id": "38644660_2", "pmid": "38644660", "title": "Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.", "authors": "Aranha MR, Montal V, van den Brink H et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, Down syndrome, cerebral amyloid angiopathy, cerebral microbleeds, cortical microinfarcts, magnetic resonance imaging, neuroimaging, small vessel diseases", "chunk": "In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.", "source": "PubMed"}, {"chunk_id": "37843871_0", "pmid": "37843871", "title": "A New Framework for Dementia Nomenclature.", "authors": "Petersen RC, Weintraub S, Sabbagh M et al.", "year": "2023", "journal": "JAMA neurology", "keywords": "None", "chunk": "Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language. The result is a lack of clarity that produces confusion with patients and the general public and presents communication challenges among researchers. Therefore, the Advisory Council on Research, Care, and Services of the National Plan to Address Alzheimer's Disease authorized a committee to make recommendations for improvement. To establish a systematic neurodegenerative disease framework for information collection and communication to standardize language usage for research, clinical, and public health purposes. The Dementia Nomenclature Initiative organized into 3 major stakeholder working groups: clinicians, researchers, and the public (including individuals living with dementia and family caregivers). To inform the work, the initiative completed a narrative literature review of dementia nomenclature evolution", "source": "PubMed"}, {"chunk_id": "37843871_1", "pmid": "37843871", "title": "A New Framework for Dementia Nomenclature.", "authors": "Petersen RC, Weintraub S, Sabbagh M et al.", "year": "2023", "journal": "JAMA neurology", "keywords": "None", "chunk": "working groups: clinicians, researchers, and the public (including individuals living with dementia and family caregivers). To inform the work, the initiative completed a narrative literature review of dementia nomenclature evolution over the last century across the PubMed, CINAHL, PsycInfo, and Scopus databases (January 1, 2000, through July 31, 2020). Initiative working groups used the results as a foundation for understanding current challenges with dementia nomenclature and implications for research, clinical practice, and public understanding. The initiative obtained additional input via focus groups with individuals living with dementia and caregivers, with separate groups for race and ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic or Latino, and White) as an initial assessment of the meaning of dementia-related terms to these groups. From working group deliberations, the literature review, and focus group input, the initiative developed a framework clearly separating the clinical syndromic presentation experienced", "source": "PubMed"}, {"chunk_id": "37843871_2", "pmid": "37843871", "title": "A New Framework for Dementia Nomenclature.", "authors": "Petersen RC, Weintraub S, Sabbagh M et al.", "year": "2023", "journal": "JAMA neurology", "keywords": "None", "chunk": "meaning of dementia-related terms to these groups. From working group deliberations, the literature review, and focus group input, the initiative developed a framework clearly separating the clinical syndromic presentation experienced by affected individuals from possible underlying pathophysiologies. In the framework, domains of clinical impairment, such as cognitive, behavioral, motor, and other neurologic features, are graded by level of impairment between none and severe. Next, biomarker information describes underlying disease processes, explains the syndrome, and identifies possible disease labels: Alzheimer disease, frontotemporal degeneration, dementia with Lewy bodies, or vascular cognitive impairment dementia. The Dementia Nomenclature Initiative established a framework to guide communication about cognitive impairment among older adults. Wider testing and refinement of the framework will subsequently improve the information used in communicating about cognitive impairment and the way in which the information is used in clinical, research, and public settings.", "source": "PubMed"}, {"chunk_id": "37843871_3", "pmid": "37843871", "title": "A New Framework for Dementia Nomenclature.", "authors": "Petersen RC, Weintraub S, Sabbagh M et al.", "year": "2023", "journal": "JAMA neurology", "keywords": "None", "chunk": "in communicating about cognitive impairment and the way in which the information is used in clinical, research, and public settings.", "source": "PubMed"}, {"chunk_id": "40113193_0", "pmid": "40113193", "title": "Altered cerebellar activity and cognitive deficits in Type 2 diabetes: Insights from resting-state fMRI.", "authors": "He S, Lu JJ, Wu JJ et al.", "year": "2025", "journal": "Brain research", "keywords": "Cognitive impairment, Functional magnetic resonance imaging, Posterior circulation, Spontaneous brain activity, Type 2 diabetes", "chunk": "To investigate alterations in brain activity in patients with Type 2 Diabetes and explore the relationship between altered regions and neuropsychological performances. A total of 36 patients with Type 2 Diabetes and 40 age- and education-matched healthy controls were recruited for this case-control study. All participants underwent resting-state functional magnetic resonance imaging (Resting-state fMRI) and neuropsychological tests. The neuropsychological scales included the Auditory Verbal Learning Test (AVLT), Shape Trajectory Test B (STT-B), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Boston Naming Test (BNT), Symbol Digit Modality Test (SDMT), Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuations (ALFF) were used to assess differences in spontaneous regional brain activity. For functional connectivity (FC) analyses, the differences identified among the groups were selected as seed regions. Then, the correlations between neuropsychological scale scores (AVLT, HAMA, HAMD, STT-B, BNT, and SDMT) and ALFF/ReHo values were specifically analyzed in the focal regions", "source": "PubMed"}, {"chunk_id": "40113193_1", "pmid": "40113193", "title": "Altered cerebellar activity and cognitive deficits in Type 2 diabetes: Insights from resting-state fMRI.", "authors": "He S, Lu JJ, Wu JJ et al.", "year": "2025", "journal": "Brain research", "keywords": "Cognitive impairment, Functional magnetic resonance imaging, Posterior circulation, Spontaneous brain activity, Type 2 diabetes", "chunk": "groups were selected as seed regions. Then, the correlations between neuropsychological scale scores (AVLT, HAMA, HAMD, STT-B, BNT, and SDMT) and ALFF/ReHo values were specifically analyzed in the focal regions that exhibited significant alterations between the T2DM and control groups, as detailed in Tables 2 and 3. Patients with Type 2 Diabetes exhibited significantly higher ALFF values in the superior lobe of the cerebellum, specifically in the left cerebellar crus I (Cerebellum_Crus I_L), left cerebellar lobule VI (Cerebellum_6_L), and left cerebellar lobule IV-V (Cerebellum_4_5_L). Additionally, they exhibited elevated ReHo values in the Cerebellum_Crus I_L and Cerebellum_6_L. The findings were statistically significant with a family-wise error-corrected, cluster-level p-value of less than 0.05. However, the FC analysis was not significant. AVLT scores were significantly lower in the diabetes group. The correlation analysis demonstrated a negative association between ALFF values of the Cerebellum_6_L and AVLT scores (R<sup>2</sup> = 0.1375, P < 0.001). The", "source": "PubMed"}, {"chunk_id": "40113193_2", "pmid": "40113193", "title": "Altered cerebellar activity and cognitive deficits in Type 2 diabetes: Insights from resting-state fMRI.", "authors": "He S, Lu JJ, Wu JJ et al.", "year": "2025", "journal": "Brain research", "keywords": "Cognitive impairment, Functional magnetic resonance imaging, Posterior circulation, Spontaneous brain activity, Type 2 diabetes", "chunk": "were significantly lower in the diabetes group. The correlation analysis demonstrated a negative association between ALFF values of the Cerebellum_6_L and AVLT scores (R<sup>2</sup> = 0.1375, P < 0.001). The ReHo values within the Cerebellum_6_L also exhibited a negative association with AVLT scores (R<sup>2</sup> = 0.0937, P = 0.007). Patients with Type 2 Diabetes showed abnormal neural activities in diverse cerebellar regions mainly related to cognitive functions. This provides supplementary information to deepen our insight into the neural mechanisms by which Type 2 Diabetes affects the functional activity of the brain's posterior circulation, as well as the potential association of these changes with cognitive impairment.", "source": "PubMed"}, {"chunk_id": "40684250_0", "pmid": "40684250", "title": "Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial.", "authors": "Kacerova T, Yates AG, Dai J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "B vitamins, cognitive impairment, homocysteine, mass spectrometry, nuclear magnetic resonance, untargeted metabolomics", "chunk": "Elevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo-controlled study in mild cognitive impairment (MCI), previously showed that B vitamin supplementation lowered tHcy, slowing brain atrophy and cognitive decline; however, the underlying mechanisms remained unclear. We used untargeted, multi-platform metabolomics, with nuclear magnetic resonance and liquid chromatography-mass spectrometry to analyze serum samples from 89 B vitamin-treated and 84 placebo-treated MCI participants over a 2 year follow-up period. Multivariate modeling distinguished treated from placebo groups with 91.2 \u00b1 1.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, \u03b1-ketoglutarate, \u03b1-ketobutyrate, glucose, and glutamate. These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine-glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression.", "source": "PubMed"}, {"chunk_id": "40684250_1", "pmid": "40684250", "title": "Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial.", "authors": "Kacerova T, Yates AG, Dai J et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "B vitamins, cognitive impairment, homocysteine, mass spectrometry, nuclear magnetic resonance, untargeted metabolomics", "chunk": "reduction, particularly the tricarboxylic acid cycle and glutamine-glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression. Nuclear magnetic resonance and multi-platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin-treated and 84 placebo participants in the VITACOG trial. Multi-platform metabolomics revealed B vitamin-driven metabolic reprogramming, achieving 91% classification accuracy. B vitamin supplementation modulates key neuroprotective metabolic pathways. Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals. B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "35231697_0", "pmid": "35231697", "title": "\"Aducanumab\" making a comeback in Alzheimer's disease: An old wine in a new bottle.", "authors": "Behl T, Kaur I, Sehgal A et al.", "year": "2022", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Aducanumab, Alzheimer\u2019s Disease, Amyloid, Antibody, Controversy", "chunk": "Despite presence of substantial evidence suggesting the pivotal role of amyloid (A\u03b2) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace A\u03b2 clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases A\u03b2 concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being \"risen from the grave\", accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in", "source": "PubMed"}, {"chunk_id": "35231697_1", "pmid": "35231697", "title": "\"Aducanumab\" making a comeback in Alzheimer's disease: An old wine in a new bottle.", "authors": "Behl T, Kaur I, Sehgal A et al.", "year": "2022", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Aducanumab, Alzheimer\u2019s Disease, Amyloid, Antibody, Controversy", "chunk": "a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.", "source": "PubMed"}, {"chunk_id": "35231697_2", "pmid": "35231697", "title": "\"Aducanumab\" making a comeback in Alzheimer's disease: An old wine in a new bottle.", "authors": "Behl T, Kaur I, Sehgal A et al.", "year": "2022", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Aducanumab, Alzheimer\u2019s Disease, Amyloid, Antibody, Controversy", "chunk": "acceptance of the drug, and the treatment of the disease.", "source": "PubMed"}, {"chunk_id": "38591838_0", "pmid": "38591838", "title": "Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.", "authors": "Linz D, Andrade JG, Arbelo E et al.", "year": "2024", "journal": "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology", "keywords": "AFNET, Anticoagulation, Artificial intelligence, Atrial cardiomyopathy, Atrial fibrillation, Biomarkers, Bleeding, Catheter ablation, Cognitive function, Consensus statement, Cost, Dementia, EHRA, Guidelines, Heart failure, Integrated care, Outcomes, Quality of care, Research, Research priorities, Rhythm management, Screening, Stroke, Technology", "chunk": "Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in M\u00fcnster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules,", "source": "PubMed"}, {"chunk_id": "38591838_1", "pmid": "38591838", "title": "Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.", "authors": "Linz D, Andrade JG, Arbelo E et al.", "year": "2024", "journal": "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology", "keywords": "AFNET, Anticoagulation, Artificial intelligence, Atrial cardiomyopathy, Atrial fibrillation, Biomarkers, Bleeding, Catheter ablation, Cognitive function, Consensus statement, Cost, Dementia, EHRA, Guidelines, Heart failure, Integrated care, Outcomes, Quality of care, Research, Research priorities, Rhythm management, Screening, Stroke, Technology", "chunk": "and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.", "source": "PubMed"}, {"chunk_id": "38591838_2", "pmid": "38591838", "title": "Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.", "authors": "Linz D, Andrade JG, Arbelo E et al.", "year": "2024", "journal": "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology", "keywords": "AFNET, Anticoagulation, Artificial intelligence, Atrial cardiomyopathy, Atrial fibrillation, Biomarkers, Bleeding, Catheter ablation, Cognitive function, Consensus statement, Cost, Dementia, EHRA, Guidelines, Heart failure, Integrated care, Outcomes, Quality of care, Research, Research priorities, Rhythm management, Screening, Stroke, Technology", "chunk": "therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.", "source": "PubMed"}, {"chunk_id": "36067099_0", "pmid": "36067099", "title": "EEG-Based Graph Neural Network Classification of Alzheimer's Disease: An Empirical Evaluation of Functional Connectivity Methods.", "authors": "Klepl D, He F, Wu M et al.", "year": "2022", "journal": "IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society", "keywords": "None", "chunk": "Alzheimer's disease (AD) is the leading form of dementia worldwide. AD disrupts neuronal pathways and thus is commonly viewed as a network disorder. Many studies demonstrate the power of functional connectivity (FC) graph-based biomarkers for automated diagnosis of AD using electroencephalography (EEG). However, various FC measures are commonly utilised, as each aims to quantify a unique aspect of brain coupling. Graph neural networks (GNN) provide a powerful framework for learning on graphs. While a growing number of studies use GNN to classify EEG brain graphs, it is unclear which method should be utilised to estimate the brain graph. We use eight FC measures to estimate FC brain graphs from sensor-level EEG signals. GNN models are trained in order to compare the performance of the selected FC measures. Additionally, three baseline models based on literature are trained for comparison. We show that GNN models perform significantly better than the other baseline", "source": "PubMed"}, {"chunk_id": "36067099_1", "pmid": "36067099", "title": "EEG-Based Graph Neural Network Classification of Alzheimer's Disease: An Empirical Evaluation of Functional Connectivity Methods.", "authors": "Klepl D, He F, Wu M et al.", "year": "2022", "journal": "IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society", "keywords": "None", "chunk": "the performance of the selected FC measures. Additionally, three baseline models based on literature are trained for comparison. We show that GNN models perform significantly better than the other baseline models. Moreover, using FC measures to estimate brain graphs improves the performance of GNN compared to models trained using a fixed graph based on the spatial distance between the EEG sensors. However, no FC measure performs consistently better than the other measures. The best GNN reaches 0.984 area under sensitivity-specificity curve (AUC) and 92% accuracy, whereas the best baseline model, a convolutional neural network, has 0.924 AUC and 84.7% accuracy.", "source": "PubMed"}, {"chunk_id": "38668787_0", "pmid": "38668787", "title": "Behavioral and Metabolic Effects of ABCG4 KO in the APP<sup>swe,Ind</sup> (J9) Mouse Model of Alzheimer's Disease.", "authors": "Fong V, Kanuri B, Traubert O et al.", "year": "2024", "journal": "Journal of molecular neuroscience : MN", "keywords": "ABCG4, Alzheimer\u2019s disease, Behavior, Cholesterol metabolism, Glucose metabolism", "chunk": "The pathogenesis of Alzheimer's disease (AD) is complex and involves an imbalance between production and clearance of amyloid-\u00df peptides (A\u00df), resulting in accumulation of A\u00df in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of A\u00df. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS and has been suggested to play a role in cholesterol and A\u00df efflux from the brain. In this study, we bred Abcg4 knockout (KO) with the APP<sup>Swe,Ind</sup> (J9) mouse model of AD to test the hypothesis that loss of Abcg4 would exacerbate the AD phenotype. Unexpectedly, no differences were observed in novel object recognition (NOR) and novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled A\u00df from the brains did not differ between Abcg4", "source": "PubMed"}, {"chunk_id": "38668787_1", "pmid": "38668787", "title": "Behavioral and Metabolic Effects of ABCG4 KO in the APP<sup>swe,Ind</sup> (J9) Mouse Model of Alzheimer's Disease.", "authors": "Fong V, Kanuri B, Traubert O et al.", "year": "2024", "journal": "Journal of molecular neuroscience : MN", "keywords": "ABCG4, Alzheimer\u2019s disease, Behavior, Cholesterol metabolism, Glucose metabolism", "chunk": "novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled A\u00df from the brains did not differ between Abcg4 KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT), and insulin tolerance test (ITT) were also mostly similar between groups with only a few mild metabolic differences noted. Overall, these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype.", "source": "PubMed"}, {"chunk_id": "41401902_0", "pmid": "41401902", "title": "Cftr nominates a novel therapeutic target for Alzheimer's disease: Evidence from integrative omics and in vitro validation.", "authors": "Li HR, Shi JZ, Zhang MJ et al.", "year": "2026", "journal": "Neuropharmacology", "keywords": "Alzheimer's disease, Cftr, Metabolomics, NLRP3 inflammasome, Neuroinflammation, Transcriptomics", "chunk": "Alzheimer's disease (AD), among the most prevalent neurodegenerative disorders, poses substantial challenges for therapeutic development due to its complex pathophysiology, necessitating novel treatment strategies. This study applied an integrated transcriptomics and untargeted metabolomics approach to hippocampal tissues from wild-type and 3 \u00d7 Tg-AD mice to identify AD-associated molecular alterations and key pathways. KEGG pathway enrichment analysis of significantly differentially expressed genes and metabolites identified several core candidate genes, including C5ar1, Gabrg1, Ptger1, Tac1, Lpar2, Pnp2, Cftr, and Sstr3. PCR-based validation in both in vivo and in vitro models confirmed Cftr as the most promising candidate for further investigation. In A\u03b2<sub>25</sub>-<sub>35</sub>-induced cellular AD models, Cftr knockdown or pharmacological inhibition activated the NLRP3 inflammasome pathway, exacerbating neuroinflammation and oxidative stress, whereas enhancing Cftr activity attenuated these pathological processes. These results establish Cftr as a potential therapeutic target for AD and reveal that its modulation of NLRP3 inflammasome signaling represents a strategic avenue", "source": "PubMed"}, {"chunk_id": "41401902_1", "pmid": "41401902", "title": "Cftr nominates a novel therapeutic target for Alzheimer's disease: Evidence from integrative omics and in vitro validation.", "authors": "Li HR, Shi JZ, Zhang MJ et al.", "year": "2026", "journal": "Neuropharmacology", "keywords": "Alzheimer's disease, Cftr, Metabolomics, NLRP3 inflammasome, Neuroinflammation, Transcriptomics", "chunk": "Cftr activity attenuated these pathological processes. These results establish Cftr as a potential therapeutic target for AD and reveal that its modulation of NLRP3 inflammasome signaling represents a strategic avenue for mitigating neuroinflammation and oxidative stress, suggesting a promising direction for intervening in AD progression.", "source": "PubMed"}, {"chunk_id": "41463035_0", "pmid": "41463035", "title": "Pharmacological Interventions in Autism Spectrum Disorder: A Comprehensive Review of Mechanisms and Efficacy.", "authors": "Sclabassi E, Peret S, Qian C et al.", "year": "2025", "journal": "Biomedicines", "keywords": "antipsychotics, autism spectrum disorder, glutamatergic agents, neuroinflammation, oxidative stress, personalized medicine, pharmacology, selective serotonin reuptake inhibitors", "chunk": "<b>Background and Objectives:</b> Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficits, restricted interests, and repetitive behaviors. At present, there is no pharmacological intervention that reliably targets the core symptoms of ASD; instead, medications are primarily used to manage associated or concurrent symptoms such as irritability, aggression, anxiety, attention difficulties, and sleep disturbances. This review summarizes the current evidence for pharmacological treatments in ASD, emphasizing how these interventions are used in a symptom-focused, adjunctive manner, and highlighting efficacy, mechanisms, limitations, and emerging therapeutic targets. <b>Methods:</b> A comprehensive literature review was conducted across PubMed, Cochrane Library, and Embase to identify clinical trials, systematic reviews, meta-analyses, and preclinical studies on pharmacological interventions for ASD. Seventy-seven references were integrated to reflect the current state of evidence. <b>Results:</b> Established pharmacological strategies include atypical antipsychotics for severe irritability and aggression, as well as antidepressants, stimulants and non-stimulant agents, mood stabilizers,", "source": "PubMed"}, {"chunk_id": "41463035_1", "pmid": "41463035", "title": "Pharmacological Interventions in Autism Spectrum Disorder: A Comprehensive Review of Mechanisms and Efficacy.", "authors": "Sclabassi E, Peret S, Qian C et al.", "year": "2025", "journal": "Biomedicines", "keywords": "antipsychotics, autism spectrum disorder, glutamatergic agents, neuroinflammation, oxidative stress, personalized medicine, pharmacology, selective serotonin reuptake inhibitors", "chunk": "integrated to reflect the current state of evidence. <b>Results:</b> Established pharmacological strategies include atypical antipsychotics for severe irritability and aggression, as well as antidepressants, stimulants and non-stimulant agents, mood stabilizers, and anxiolytics for selected comorbid symptoms, although efficacy is often modest and variable, and side effects can be significant. Adjunctive and investigational approaches targeting glutamatergic and GABAergic neurotransmission, monoaminergic systems, and neuroinflammatory and oxidative stress pathways show preliminary promise but remain experimental. Across all categories, pharmacological treatments are most effective when embedded in individualized, multimodal care plans that integrate behavioral, rehabilitative, and psychological interventions. <b>Conclusions:</b> This review maps pharmacologic strategies in ASD onto their underlying neurobiological mechanisms and clarifies how evidence strength differs across drug classes and symptom domains. Ongoing advances in genetics, synaptic and circuit-level neuroscience, and neuroimmune signaling are expected to yield more specific, mechanism-based pharmacological approaches for autistic behaviors, with the potential to improve long-term functioning and", "source": "PubMed"}, {"chunk_id": "41463035_2", "pmid": "41463035", "title": "Pharmacological Interventions in Autism Spectrum Disorder: A Comprehensive Review of Mechanisms and Efficacy.", "authors": "Sclabassi E, Peret S, Qian C et al.", "year": "2025", "journal": "Biomedicines", "keywords": "antipsychotics, autism spectrum disorder, glutamatergic agents, neuroinflammation, oxidative stress, personalized medicine, pharmacology, selective serotonin reuptake inhibitors", "chunk": "advances in genetics, synaptic and circuit-level neuroscience, and neuroimmune signaling are expected to yield more specific, mechanism-based pharmacological approaches for autistic behaviors, with the potential to improve long-term functioning and quality of life when combined with comprehensive psychosocial care.", "source": "PubMed"}, {"chunk_id": "37149995_0", "pmid": "37149995", "title": "ROS-responsive nanomodulators downregulate IFITM3 expression and eliminate ROS for Alzheimer's disease combination treatment.", "authors": "Xu H, Liu Y", "year": "2023", "journal": "Journal of colloid and interface science", "keywords": "Alzheimer\u2019s disease, Blood\u2013brain barrier, Combination treatment, Nanomodulator, ROS-responsive", "chunk": "Neuronal damage caused by \u03b2-amyloid (A\u03b2) aggregates and excess reactive oxygen species (ROS) is a crucial pathogenic event in Alzheimer's disease (AD). However, current A\u03b2-targeting RNA interference (RNAi) treatments have shown limited therapeutic efficacy due to ineffective intracerebral siRNA delivery and overlooked crosstalk between excess ROS and A\u03b2 aggregates in the brain. Herein, a ROS-responsive nanomodulator (NM/CM) was developed for the combinational treatment of RNAi and ROS elimination for AD. NM/CM was coated with 4T1 cell membranes, which endowed NM/CM with the capability to cross blood-brain barrier (BBB). After being internalized by neural cells, NM/CM releases curcumin (Cur) and siIFITM3 spontaneously into the cytoplasm. The released Cur can eliminate ROS, protecting neurons from oxidative damage and reducing the production of A\u03b2 induced by ROS-related neuroinflammation. The released siIFITM3 can downregulate the expression of interferon-induced transmembrane protein 3 (IFITM3), thereby reducing the abnormal A\u03b2 production mediated by IFITM3. As a result,", "source": "PubMed"}, {"chunk_id": "37149995_1", "pmid": "37149995", "title": "ROS-responsive nanomodulators downregulate IFITM3 expression and eliminate ROS for Alzheimer's disease combination treatment.", "authors": "Xu H, Liu Y", "year": "2023", "journal": "Journal of colloid and interface science", "keywords": "Alzheimer\u2019s disease, Blood\u2013brain barrier, Combination treatment, Nanomodulator, ROS-responsive", "chunk": "A\u03b2 induced by ROS-related neuroinflammation. The released siIFITM3 can downregulate the expression of interferon-induced transmembrane protein 3 (IFITM3), thereby reducing the abnormal A\u03b2 production mediated by IFITM3. As a result, NM/CM remarkably alleviated ROS- and A\u03b2 aggregate-induced neurotoxicity in vitro, showing significant neuroprotective effects. This work demonstrates the potential of NM/CM in the development of novel and effective AD combination therapies.", "source": "PubMed"}, {"chunk_id": "40326513_0", "pmid": "40326513", "title": "Development of Simple Risk Scores for Prediction of Brain \u03b2-Amyloid and Tau Status in Older Adults With Mild Cognitive Impairment: A Machine Learning Approach.", "authors": "Petersen KK, Nallapu BT, Lipton RB et al.", "year": "2025", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Alzheimer\u2019s disease, Diagnosis, Risk score", "chunk": "The aim of this work is to use a machine learning framework to develop simple risk scores for predicting \u03b2-amyloid (A\u03b2) and tau positivity among individuals with mild cognitive impairment (MCI). Data for 657 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set were used. A modified version of AutoScore, a machine learning-based software tool, was used to develop risk scores based on hierarchical combinations of predictor categories, including demographics, neuropsychological assessments, APOE4 status, and imaging biomarkers. The highest area under the receiver operating characteristic curve (AUC) for predicting A\u03b2 positivity was 0.79, which was achieved by 2 separate models with predictors of age, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), APOE4 status, and either Trail Making Test Part B (TMT-B) or white matter hyperintensity. The best-performing model for tau positivity had an AUC of 0.91 using age, ADAS-13, and TMT-B scores, APOE4 information, abnormal hippocampal volume, and", "source": "PubMed"}, {"chunk_id": "40326513_1", "pmid": "40326513", "title": "Development of Simple Risk Scores for Prediction of Brain \u03b2-Amyloid and Tau Status in Older Adults With Mild Cognitive Impairment: A Machine Learning Approach.", "authors": "Petersen KK, Nallapu BT, Lipton RB et al.", "year": "2025", "journal": "The journals of gerontology. Series B, Psychological sciences and social sciences", "keywords": "Alzheimer\u2019s disease, Diagnosis, Risk score", "chunk": "Part B (TMT-B) or white matter hyperintensity. The best-performing model for tau positivity had an AUC of 0.91 using age, ADAS-13, and TMT-B scores, APOE4 information, abnormal hippocampal volume, and amyloid status as predictors. Simple integer-based risk scores using available data could be used for predicting A\u03b2 and tau positivity in individuals with MCI. Models have the potential to improve clinical trials through improved screening of individuals.", "source": "PubMed"}, {"chunk_id": "41582303_0", "pmid": "41582303", "title": "Evaluation of ASC as a therapeutic target for Alzheimer's disease.", "authors": "Clayton WB, Kulas JA, Liu J et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "ASC, Alzheimer's disease, PYCARD, cell assays, drug discovery", "chunk": "Neuroinflammation is increasingly recognized as a central contributor to the pathogenesis and progression of Alzheimer's disease (AD). The apoptosis-associated speck-like protein containing a CARD (ASC), encoded by the PYCARD gene, plays a critical role in the formation of multiple inflammasomes, including NLRP3, a key mediator of inflammation signaling. Beyond its role in inflammasome formation, extracellular ASC specks have been shown to promote amyloid-\u03b2 aggregation, showing a potential link between inflammation and plaque formation. In this review, we examine the role of ASC in AD pathology and highlight emerging tools to study ASC biology and strategies for ASC targeted drug discovery.", "source": "PubMed"}, {"chunk_id": "36793541_0", "pmid": "36793541", "title": "Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.", "authors": "Hu R, Gao B, Tian S et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "brain iron deposition, deep gray nuclei, heterogeneity, magnetic sensitivity value, quantitative susceptibility mapping, type 2 diabetes mellitus, volume", "chunk": "To quantitatively evaluate the iron deposition and volume changes in deep gray nuclei according to threshold-method of quantitative susceptibility mapping (QSM) acquired by strategically acquired gradient echo (STAGE) sequence, and to analyze the correlation between the magnetic susceptibility values (MSV) and cognitive scores in type 2 diabetes mellitus (T2DM) patients. Twenty-nine patients with T2DM and 24 healthy controls (HC) matched by age and gender were recruited in this prospective study. QSM images were used to evaluate whole-structural volumes (V<sub>wh</sub>), regional magnetic susceptibility values (MSV<sub>RII</sub>), and volumes (V<sub>RII</sub>) in high-iron regions in nine gray nuclei. All QSM data were compared between groups. Receiver operating characteristic (ROC) analysis was used to assess the discriminating ability between groups. The predictive model from single and combined QSM parameters was also established using logistic regression analysis. The correlation between MSV<sub>RII</sub> and cognitive scores was further analyzed. Multiple comparisons of all statistical values were corrected by", "source": "PubMed"}, {"chunk_id": "36793541_1", "pmid": "36793541", "title": "Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.", "authors": "Hu R, Gao B, Tian S et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "brain iron deposition, deep gray nuclei, heterogeneity, magnetic sensitivity value, quantitative susceptibility mapping, type 2 diabetes mellitus, volume", "chunk": "and combined QSM parameters was also established using logistic regression analysis. The correlation between MSV<sub>RII</sub> and cognitive scores was further analyzed. Multiple comparisons of all statistical values were corrected by false discovery rate (FDR). A statistically significant <i>P</i>-value was set at 0.05. Compared with HC group, the MSV<sub>RII</sub> of all gray matter nuclei in T2DM were increased by 5.1-14.8%, with significant differences found in bilateral head of caudate nucleus (HCN), right putamen (PUT), right globus pallidus (GP), and left dentate nucleus (DN) (<i>P</i> < 0.05). The V<sub>wh</sub> of most gray nucleus in T2DM group were decreased by 1.5-16.9% except bilateral subthalamic nucleus (STN). Significant differences were found in bilateral HCN, bilateral red nucleus (RN), and bilateral substantia nigra (SN) (<i>P</i> < 0.05). V<sub>RII</sub> was increased in bilateral GP, bilateral PUT (<i>P</i> < 0.05). V<sub>RII</sub>/V<sub>wh</sub> was also increased in bilateral GP, bilateral PUT, bilateral SN, left HCN and right STN (<i>P</i>", "source": "PubMed"}, {"chunk_id": "36793541_2", "pmid": "36793541", "title": "Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.", "authors": "Hu R, Gao B, Tian S et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "brain iron deposition, deep gray nuclei, heterogeneity, magnetic sensitivity value, quantitative susceptibility mapping, type 2 diabetes mellitus, volume", "chunk": "< 0.05). V<sub>RII</sub> was increased in bilateral GP, bilateral PUT (<i>P</i> < 0.05). V<sub>RII</sub>/V<sub>wh</sub> was also increased in bilateral GP, bilateral PUT, bilateral SN, left HCN and right STN (<i>P</i> < 0.05). Compared with the single QSM parameter, the combined parameter showed the largest area under curve (AUC) of 0.86, with a sensitivity of 87.5% and specificity of 75.9%. The MSV<sub>RII</sub> in the right GP was strongly associated with List A Long-delay free recall (List A LDFR) scores (<i>r</i> = -0.590, <i>P</i> = 0.009). In T2DM patients, excessive and heterogeneous iron deposition as well as volume loss occurs in deep gray nuclei. The MSV in high iron regions can better evaluate the distribution of iron, which is related to the decline of cognitive function.", "source": "PubMed"}, {"chunk_id": "36793541_3", "pmid": "36793541", "title": "Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.", "authors": "Hu R, Gao B, Tian S et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "brain iron deposition, deep gray nuclei, heterogeneity, magnetic sensitivity value, quantitative susceptibility mapping, type 2 diabetes mellitus, volume", "chunk": "decline of cognitive function.", "source": "PubMed"}, {"chunk_id": "41416535_0", "pmid": "41416535", "title": "The role of bilingualism on functional decline and neurodegeneration in distinct ADRD clinical syndromes.", "authors": "Tablante J, Casaletto K, VandeVrede L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "ADRD biomarkers, Alzheimer's disease, bilingualism, brain resilience, clinical dementia rating scale, cognitive resilience, frontotemporal dementia, neurofilament light chain", "chunk": "We evaluated a large cohort (N = 408) of monolingual and bilingual speakers with Alzheimer's disease and related dementias (ADRD) syndromes and longitudinal markers of functional decline and neurodegeneration to determine whether bilingual speakers show more cognitive resilience to neurodegenerative processes. Participants (338 monolingual, 70 bilingual) were diagnosed based on established criteria and then categorized into five clinical groups (healthy controls and memory, language, behavioral, motor-predominant syndromes from participants living with ADRD). Linear mixed-effects models estimated longitudinal functional decline (Clinical Dementia Rating) and fluid ADRD biomarker trajectories (plasma neurofilament light chain (NfL) and plasma phosphorylated tau-217 (p-tau217). Bilingual speakers showed slower progression of functional impairment and lower baseline NfL and p-tau217, but not slower biomarker trajectories, compared to monolingual speakers. We found a protective effect of bilingualism on baseline levels of neuropathology and neurodegeneration and longitudinal functional decline, supporting a role of bilingualism in cognitive resilience across ADRDs. Explored longitudinal", "source": "PubMed"}, {"chunk_id": "41416535_1", "pmid": "41416535", "title": "The role of bilingualism on functional decline and neurodegeneration in distinct ADRD clinical syndromes.", "authors": "Tablante J, Casaletto K, VandeVrede L et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "ADRD biomarkers, Alzheimer's disease, bilingualism, brain resilience, clinical dementia rating scale, cognitive resilience, frontotemporal dementia, neurofilament light chain", "chunk": "We found a protective effect of bilingualism on baseline levels of neuropathology and neurodegeneration and longitudinal functional decline, supporting a role of bilingualism in cognitive resilience across ADRDs. Explored longitudinal effects of bilingualism on functional decline, neurofilament light chain (NfL), andphosphorylated tau-217 (p-tau217). Used syndrome-defined cohorts of monolingual and bilingual speakers. First study using NfL and p-tau217 to study bilingualism's effects in cognitive resilience. Bilinguals showed slower progression of functional impairment. Bilinguals had lower baseline NfL and p-tau217 but longitudinal trajectories did not differ.", "source": "PubMed"}, {"chunk_id": "25035815_0", "pmid": "25035815", "title": "CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer's Disease.", "authors": "Lee S, Tong M, Hang S et al.", "year": "2013", "journal": "Journal of Alzheimer's disease & Parkinsonism", "keywords": "Amyloid, Biomarkers, Cerebrospinal fluid, Glucose metabolism, Insulin resistance, Luminex, Neurodegeneration, Neurotrophins, Tau", "chunk": "Alzheimer's disease (AD) is characterized by progressive impairments in cognitive and behavioral functions with deficits in learning, memory and executive reasoning. Growing evidence points toward brain insulin and insulin-like growth factor (IGF) resistance-mediated metabolic derangements as critical etiologic factors in AD. This suggests that indices of insulin/IGF resistance and their consequences, i.e. oxidative stress, neuro-inflammation, and reduced neuronal plasticity, should be included in biomarker panels for AD. Herein, we examine a range of metabolic, inflammatory, stress, and neuronal plasticity related proteins in early AD, late AD, and aged control postmortem brain, postmortem ventricular fluid (VF), and clinical cerebrospinal fluid (CSF) samples. In AD brain, VF, and CSF samples the trends with respect to alterations in metabolic, neurotrophin, and stress indices were similar, but for pro-inflammatory cytokines, the patterns were discordant. With the greater severities of dementia and neurodegeneration, the differences from control were more pronounced for late AD (VF and", "source": "PubMed"}, {"chunk_id": "25035815_1", "pmid": "25035815", "title": "CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer's Disease.", "authors": "Lee S, Tong M, Hang S et al.", "year": "2013", "journal": "Journal of Alzheimer's disease & Parkinsonism", "keywords": "Amyloid, Biomarkers, Cerebrospinal fluid, Glucose metabolism, Insulin resistance, Luminex, Neurodegeneration, Neurotrophins, Tau", "chunk": "were similar, but for pro-inflammatory cytokines, the patterns were discordant. With the greater severities of dementia and neurodegeneration, the differences from control were more pronounced for late AD (VF and brain) than early or moderate AD (brain, VF and CSF). The findings suggest that the inclusion of metabolic, neurotrophin, stress biomarkers in A\u03b2PP-A\u03b2+pTau CSF-based panels could provide more information about the status and progression of neurodegeneration, as well as aid in predicting progression from early- to late-stage AD. Furthermore, standardized multi-targeted molecular assays of neurodegeneration could help streamline postmortem diagnoses, including assessments of AD severity and pathology.", "source": "PubMed"}, {"chunk_id": "41830121_0", "pmid": "41830121", "title": "Advancing Smell Disorder Diagnostics: A Comparative Review of Portable Test Kits and Self-Reported Tools.", "authors": "Ramesh J, Kanakaraj L, Duza MB", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Olfactory dysfunction, neurodegenerative disease screening, portable smell test kits, self-administered olfactory testing., self-mini olfactory questionnaire (Self-MOQ), sensory diagnostics", "chunk": "<p> Olfactory Dysfunction (OD) is a prevalent yet underdiagnosed sensory disorder with profound implications for quality of life and for the early detection of neurodegenerative diseases such as Parkinson's and Alzheimer's. Beyond its sensory role, OD has emerged as an early, noninvasive biomarker of neurodegenerative pathology, often preceding measurable cognitive decline in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Quantitative smell loss correlates with pathological changes in the olfactory bulb and entorhinal cortex, highlighting its diagnostic potential for early screening and longitudinal monitoring. </p><p> Traditional diagnostic tools, though validated, often require specialized personnel, laboratory infrastructure, and extended testing time, limiting accessibility. This review critically examines recent innovations in the detection of olfactory dysfunction, focusing on portable, user-friendly smell test kits and their comparative performance with self-reported tools such as the Mini Olfactory Questionnaire (Self-MOQ) and 4-CAST. We synthesize evidence on diagnostic reliability, usability, and cultural adaptability, evaluating how these", "source": "PubMed"}, {"chunk_id": "41830121_1", "pmid": "41830121", "title": "Advancing Smell Disorder Diagnostics: A Comparative Review of Portable Test Kits and Self-Reported Tools.", "authors": "Ramesh J, Kanakaraj L, Duza MB", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Olfactory dysfunction, neurodegenerative disease screening, portable smell test kits, self-administered olfactory testing., self-mini olfactory questionnaire (Self-MOQ), sensory diagnostics", "chunk": "kits and their comparative performance with self-reported tools such as the Mini Olfactory Questionnaire (Self-MOQ) and 4-CAST. We synthesize evidence on diagnostic reliability, usability, and cultural adaptability, evaluating how these methods align with emerging needs in Alzheimer's and dementia research. </p><p> Portable kits such as PT-Smell and SSomix demonstrate high diagnostic precision and cultural adaptability, while self-administered and self-report tools enable scalable deployment in memory clinics and community screening programs. Within Alzheimer's research, these approaches present practical solutions for early identification of sensory biomarkers linked to cognitive decline. </p><p> To optimize diagnostic integration, a two-step framework is proposed: first-line screening with self-administered tools such as Self-MOQ or 4-CAST, followed by confirmatory psychophysical testing with portable kits such as PT-Smell or SSomix. This tiered model supports early AD and MCI detection, enhances accessibility, and promotes digital health integration for widespread olfactory monitoring. </p>.", "source": "PubMed"}, {"chunk_id": "41830121_2", "pmid": "41830121", "title": "Advancing Smell Disorder Diagnostics: A Comparative Review of Portable Test Kits and Self-Reported Tools.", "authors": "Ramesh J, Kanakaraj L, Duza MB", "year": "2026", "journal": "Current Alzheimer research", "keywords": "Olfactory dysfunction, neurodegenerative disease screening, portable smell test kits, self-administered olfactory testing., self-mini olfactory questionnaire (Self-MOQ), sensory diagnostics", "chunk": "SSomix. This tiered model supports early AD and MCI detection, enhances accessibility, and promotes digital health integration for widespread olfactory monitoring. </p>.", "source": "PubMed"}, {"chunk_id": "40675947_0", "pmid": "40675947", "title": "Complement C1q is associated with neuroinflammation and mediates the association between amyloid-\u03b2 and tau pathology in Alzheimer's disease.", "authors": "Guo F, Sheng ZH, Fu Y et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "Complement C1q initiates the classical complement pathway and becomes activated in Alzheimer's disease (AD), contributing to the association between amyloid-\u03b2 (A\u03b2) and tau pathologies. However, whether C1q influences AD pathology by modulating glial cell communication is unclear. We included 217 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to explore the associations of cerebrospinal fluid (CSF) C1q with soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP) and AD biomarkers. Additionally, we incorporated data from 535 participants in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study to explore associations. We employed 10,000 bootstrapped iterations of causal mediation analysis to examine the possible mediating role of sTREM2 or GFAP in the relationship between CSF C1q and AD pathology. We found that CSF rather than serum C1q were positively associated with CSF sTREM2, GFAP, A\u03b2<sub>42</sub>, phosphorylated-tau (P-tau) and total tau (T-tau) at baseline. CSF C1q was", "source": "PubMed"}, {"chunk_id": "40675947_1", "pmid": "40675947", "title": "Complement C1q is associated with neuroinflammation and mediates the association between amyloid-\u03b2 and tau pathology in Alzheimer's disease.", "authors": "Guo F, Sheng ZH, Fu Y et al.", "year": "2025", "journal": "Translational psychiatry", "keywords": "None", "chunk": "and AD pathology. We found that CSF rather than serum C1q were positively associated with CSF sTREM2, GFAP, A\u03b2<sub>42</sub>, phosphorylated-tau (P-tau) and total tau (T-tau) at baseline. CSF C1q was only longitudinally associated with CSF T-tau levels and AD assessment scale-cognitive subscale 13 (ADAS-Cog 13) scores. Mediation analysis demonstrated that A\u03b2 pathology partly mediated the association between CSF C1q and sTREM2 levels, which in turn impacted tau pathology progression. Serum C1q showed a significant association with CSF sTREM2 at baseline as well. CONCLUSIONS: C1q is associated with CSF sTREM2 and mediates the relationship between A\u03b2 and tau pathologies. This suggests that C1q may play a crucial role in the progression from A\u03b2 pathology to tau pathology.", "source": "PubMed"}, {"chunk_id": "41844810_0", "pmid": "41844810", "title": "Explainable artificial intelligence for early Alzheimer's diagnosis using enhanced grey relational features and multimodal data.", "authors": "Ullah W, Dai Q, Zulqarnain RM et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Deep neural network, Grey relational grade, Machine learning, Stacking ensemble", "chunk": "Alzheimer's disease, a progressive neurodegenerative disorder, presents a growing global health challenge due to its increasing prevalence and lack of accessible early diagnostic methods. Even though it has enhanced the diagnostic accuracy of machine learning, there is a major concern about striking a balance between predictive performance and interpretability. The proposed study presents an interpretable and sustainable machine learning architecture for early diagnosis of Alzheimer's disease based on multimodal, structured clinical and behavioral data, including demographics, vascular risk factors, lifestyle, and cognitive data. We perform extensive feature engineering to derive composite features, including blood pressure ratio, MMSE age ratio, cholesterol ratio, and cognitive decline score. The class imbalance is addressed using the Synthetic Minority Oversampling Technique. We also introduce a new strengthened Grey Relational Grade index based on the theory of grey system and the policy of sigmoid normalization. This greatly enhances the feature-diagnosis correlation (0.725 to 0.891), representing complicated", "source": "PubMed"}, {"chunk_id": "41844810_1", "pmid": "41844810", "title": "Explainable artificial intelligence for early Alzheimer's diagnosis using enhanced grey relational features and multimodal data.", "authors": "Ullah W, Dai Q, Zulqarnain RM et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Deep neural network, Grey relational grade, Machine learning, Stacking ensemble", "chunk": "new strengthened Grey Relational Grade index based on the theory of grey system and the policy of sigmoid normalization. This greatly enhances the feature-diagnosis correlation (0.725 to 0.891), representing complicated nonlinear associations. This paper compared seven mainstream classifiers, such as Logistic Regression, Random Forest, Extreme Gradient Boosting, Light Gradient Boosting Machine, CatBoost, Stacking Ensembles, and Deep Neural Networks, in the context of model comparison. Among them, Deep Neural Networks achieve the best performance (accuracy: 98.01%, AUC: 99.43%), followed by a CatBoost-based Stacking Ensemble (Accuracy: 97.91%, AUC: 98.10%). Shapley Additive Explanations make models easier to understand by showing important modifiable predictors like family history, smoking, and early cognitive symptoms. This study presents that combining enhanced Grey Relational Grade metrics with robust machine learning and deep learning models produces an accurate, interpretable, and potentially effective framework for early AD risk assessment, which can be used to implement effective, behavior-centric prevention strategies in", "source": "PubMed"}, {"chunk_id": "41844810_2", "pmid": "41844810", "title": "Explainable artificial intelligence for early Alzheimer's diagnosis using enhanced grey relational features and multimodal data.", "authors": "Ullah W, Dai Q, Zulqarnain RM et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s disease, Deep neural network, Grey relational grade, Machine learning, Stacking ensemble", "chunk": "machine learning and deep learning models produces an accurate, interpretable, and potentially effective framework for early AD risk assessment, which can be used to implement effective, behavior-centric prevention strategies in ageing demographics.", "source": "PubMed"}, {"chunk_id": "40093221_0", "pmid": "40093221", "title": "Characterizing multivariate regional hubs for schizophrenia classification, sex differences, and brain age estimation using explainable AI.", "authors": "Nie Y, Murad T, Miao HY et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Brain age prediction, Deep learning, Machine learning, Schizophrenia classification, Sex difference, Shapley additive explanations", "chunk": "To investigate multivariate regional patterns for schizophrenia (SZ) classification, sex differences, and brain age by utilizing structural MRI, demographics, and explainable artificial intelligence (AI). Various AI models were employed, and the outperforming model was identified for SZ classification, sex differences, and brain age predictions. For the SZ and sex classification tasks, support vector classifier (SVC), k-nearest neighbor (KNN), and deep learning neural network (DL) models were compared. In the case of regression-based brain age prediction, Lasso regression (LR), Ridge regression (RR), support vector regression (SVR), and DL models were compared. For each regression or classification task, the optimal model was further integrated with the Shapley additive explanations (SHAP) and the significant multivariate brain regional patterns were identified. Our results demonstrated that the DL model outperformed other models in SZ classification, sex differences, and brain age predictions. We then integrated outperforming DL model with SHAP, and this integrated DL-SHAP was used", "source": "PubMed"}, {"chunk_id": "40093221_1", "pmid": "40093221", "title": "Characterizing multivariate regional hubs for schizophrenia classification, sex differences, and brain age estimation using explainable AI.", "authors": "Nie Y, Murad T, Miao HY et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Brain age prediction, Deep learning, Machine learning, Schizophrenia classification, Sex difference, Shapley additive explanations", "chunk": "that the DL model outperformed other models in SZ classification, sex differences, and brain age predictions. We then integrated outperforming DL model with SHAP, and this integrated DL-SHAP was used to identify the individualized multivariate regional patterns associated with each prediction. Using DL-SHAP approach, we found that individuals with SZ had anatomical changes particularly in left pallidum, left posterior insula, left hippocampus, and left putamen regions, and such changes associated with SZ were different between female and male patients. Finally, we further applied DL-SHAP method to brain age prediction and suggested important brain regions related to aging in health controls (HC) and SZ processes. This study systematically utilized predictive modeling and novel explainable AI approaches and identified the complex multivariate brain regions involved with SZ classification, sex differences, and brain aging and built a deeper understanding of neurobiological mechanisms involved in the disease, offering new insights to future SZ diagnosis", "source": "PubMed"}, {"chunk_id": "40093221_2", "pmid": "40093221", "title": "Characterizing multivariate regional hubs for schizophrenia classification, sex differences, and brain age estimation using explainable AI.", "authors": "Nie Y, Murad T, Miao HY et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Brain age prediction, Deep learning, Machine learning, Schizophrenia classification, Sex difference, Shapley additive explanations", "chunk": "brain regions involved with SZ classification, sex differences, and brain aging and built a deeper understanding of neurobiological mechanisms involved in the disease, offering new insights to future SZ diagnosis and treatments and laying the foundation of the development of precision medicine.", "source": "PubMed"}, {"chunk_id": "30995986_0", "pmid": "30995986", "title": "Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis.", "authors": "Kivim\u00e4ki M, Singh-Manoux A, Pentti J et al.", "year": "2019", "journal": "BMJ (Clinical research ed.)", "keywords": "None", "chunk": "To examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia. Meta-analysis of 19 prospective observational cohort studies. The Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies. The search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer's disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis. Study population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical", "source": "PubMed"}, {"chunk_id": "30995986_1", "pmid": "30995986", "title": "Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis.", "authors": "Kivim\u00e4ki M, Singh-Manoux A, Pentti J et al.", "year": "2019", "journal": "BMJ (Clinical research ed.)", "keywords": "None", "chunk": "estimates were obtained using random effects meta-analysis. Study population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer's disease was 1602 in 5.2 million person-years. When measured <10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer's disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity \u226510 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and", "source": "PubMed"}, {"chunk_id": "30995986_2", "pmid": "30995986", "title": "Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis.", "authors": "Kivim\u00e4ki M, Singh-Manoux A, Pentti J et al.", "year": "2019", "journal": "BMJ (Clinical research ed.)", "keywords": "None", "chunk": "minimised by assessing physical activity \u226510 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed >10 before dementia onset 1.30, 0.79 to 2.14). In analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer's disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.", "source": "PubMed"}, {"chunk_id": "30995986_3", "pmid": "30995986", "title": "Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis.", "authors": "Kivim\u00e4ki M, Singh-Manoux A, Pentti J et al.", "year": "2019", "journal": "BMJ (Clinical research ed.)", "keywords": "None", "chunk": "of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.", "source": "PubMed"}, {"chunk_id": "35763451_0", "pmid": "35763451", "title": "AXS-05: an investigational treatment for Alzheimer's disease-associated agitation.", "authors": "Ward K, Citrome L", "year": "2022", "journal": "Expert opinion on investigational drugs", "keywords": "Agitation, Alzheimer\u2019s disease, aggression, bupropion, dextromethorphan, pharmacodynamics, pharmacokinetics", "chunk": "Agitation is common in patients with Alzheimer's disease (AD). Although nonpharmacologic de-escalation strategies are recommended as first-line treatment, medication is often needed to treat agitation. Currently, there are no FDA-approved medications for this indication. Psychotropics used to treat agitation include antipsychotics, which are notable for their efficacy but also their potential to cause serious side effects. AXS-05, a combination of dextromethorphan and bupropion, is currently being investigated for this indication. This review will discuss the pharmacology of AXS-05 and available clinical trial results from completed Phase I and Phase II/III studies assessing the potential for this compound to treat agitation in patients with AD. Ongoing research investigating AXS-05 for this indication will also be highlighted. Resources used for this review include PubMed, Embase, clinicaltrials.gov, and literature available on the manufacturer's website. Early released clinical trial data indicate that AXS-05 may be a useful option to treat agitation in patients with", "source": "PubMed"}, {"chunk_id": "35763451_1", "pmid": "35763451", "title": "AXS-05: an investigational treatment for Alzheimer's disease-associated agitation.", "authors": "Ward K, Citrome L", "year": "2022", "journal": "Expert opinion on investigational drugs", "keywords": "Agitation, Alzheimer\u2019s disease, aggression, bupropion, dextromethorphan, pharmacodynamics, pharmacokinetics", "chunk": "include PubMed, Embase, clinicaltrials.gov, and literature available on the manufacturer's website. Early released clinical trial data indicate that AXS-05 may be a useful option to treat agitation in patients with AD and that it appears to be generally well tolerated. AXS-05 may be especially helpful for patients with comorbid depression, when considering available data from separate phase III studies assessing the efficacy and safety of this compound in the treatment of depression.", "source": "PubMed"}, {"chunk_id": "40935239_0", "pmid": "40935239", "title": "Endocrine circuitry in autism spectrum disorders: A systematic review of mechanistic insights and clinical implications.", "authors": "Angelopoulou M, Siaperas P, Livadas S et al.", "year": "2025", "journal": "Neuroscience", "keywords": "Adrenal gland, Autism, Endocrine disruptors, Endocrine system, Hormones, Pituitary gland", "chunk": "The increasing global prevalence of Autism Spectrum Disorder (ASD) diagnoses-largely driven by heightened awareness, evolving diagnostic criteria, and improved detection-has intensified efforts to elucidate its complex neurobiological underpinnings, although the true change in occurrence remains uncertain. While much attention has been paid to genetic and neurodevelopmental factors, emerging evidence highlights the crucial role of the endocrine system in modulating social, cognitive, and behavioral outcomes associated with ASD. To systematically review the existing literature on endocrine dysfunction and hormonal signaling pathways implicated in ASD, with the aim of identifying common mechanistic links and evaluating their clinical relevance.A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar for studies published between 1980 and 2024. The review included 183 human studies evaluating associations between ASD and hormonal alterations, encompassing thyroid function, HPA axis dysregulation, growth hormone signaling, sex hormones, obesity, melatonin, oxytocin, vitamin D status, and exposure to endocrine-disrupting chemicals. Alterations", "source": "PubMed"}, {"chunk_id": "40935239_1", "pmid": "40935239", "title": "Endocrine circuitry in autism spectrum disorders: A systematic review of mechanistic insights and clinical implications.", "authors": "Angelopoulou M, Siaperas P, Livadas S et al.", "year": "2025", "journal": "Neuroscience", "keywords": "Adrenal gland, Autism, Endocrine disruptors, Endocrine system, Hormones, Pituitary gland", "chunk": "evaluating associations between ASD and hormonal alterations, encompassing thyroid function, HPA axis dysregulation, growth hormone signaling, sex hormones, obesity, melatonin, oxytocin, vitamin D status, and exposure to endocrine-disrupting chemicals. Alterations in multiple endocrine axes were consistently associated with ASD, including prenatal thyroid imbalances, cortisol rhythm dysregulation, aberrant IGF-1 levels, elevated fetal steroidogenic activity, and impaired oxytocin signaling. Endocrine disruptors such as phthalates and pesticides were also linked to increased ASD risk in susceptible populations. Endocrine dysfunctions are frequently associated with ASD, with multiple hormonal axes potentially influencing its pathophysiology, although causality remains unconfirmed. Understanding hormonal influences across developmental stages could inform early detection strategies and novel therapeutic approaches.", "source": "PubMed"}, {"chunk_id": "41223766_0", "pmid": "41223766", "title": "Exploring the impact of metformin on the central nervous system and neurotransmission: A systematic review.", "authors": "Maciejczyk A, Blecharz-Klin K", "year": "2025", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Central nervous system, Glucose metabolism, Metformin, Neuroprotection, Neurotransmission", "chunk": "Metformin, a well-established antidiabetic agent, has emerging neuroactive properties extending beyond glycemic control. Evidence suggests effects on neurotransmission, neuroprotection, and neuroinflammatory pathways, offering potential in neurodegenerative disorders. Following PRISMA 2020 guidelines and PROSPERO registration (CRD420251105355), we systematically searched PubMed, Scopus, Web of Science, and Google Scholar (November 2024-July 2025) for in vivo and clinical studies in humans or animals reporting CNS-related outcomes. Two reviewers independently screened and extracted data; risk of bias was assessed with validated tools appropriate to study design. A total of 166 studies met inclusion criteria, including animal models, mechanistic experiments, and clinical observations. Metformin crosses the blood-brain barrier and modulates CNS pathways through anti-inflammatory and mitochondrial-supportive actions. Crucially, it regulates major neurotransmitter systems - serotonin, dopamine, glutamate, GABA, acetylcholine, and norepinephrine - restoring excitatory/inhibitory balance and enhancing synaptic plasticity. Most of the current evidence arises from preclinical studies, which consistently demonstrate neuroprotective and neuromodulatory effects of", "source": "PubMed"}, {"chunk_id": "41223766_1", "pmid": "41223766", "title": "Exploring the impact of metformin on the central nervous system and neurotransmission: A systematic review.", "authors": "Maciejczyk A, Blecharz-Klin K", "year": "2025", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Central nervous system, Glucose metabolism, Metformin, Neuroprotection, Neurotransmission", "chunk": "glutamate, GABA, acetylcholine, and norepinephrine - restoring excitatory/inhibitory balance and enhancing synaptic plasticity. Most of the current evidence arises from preclinical studies, which consistently demonstrate neuroprotective and neuromodulatory effects of metformin in models of Alzheimer's disease, Parkinson's disease, stroke, and fragile X syndrome. Clinical data, while promising, remain limited and heterogeneous, mainly suggesting potential cognitive benefits. Metformin shows promise for repurposing in CNS disorders via direct neurotransmitter regulation alongside mitochondrial and anti-inflammatory effects. Given that the majority of available data are preclinical, translational studies and well-designed clinical trials are essential to establish efficacy, dosing, and target populations. These findings underscore the metabolic-neurological interface and suggest a shift from viewing metformin solely as a metabolic therapy to recognizing its neurotherapeutic potential. Long-term use warrants vitamin B12 monitoring.", "source": "PubMed"}, {"chunk_id": "41223766_2", "pmid": "41223766", "title": "Exploring the impact of metformin on the central nervous system and neurotransmission: A systematic review.", "authors": "Maciejczyk A, Blecharz-Klin K", "year": "2025", "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "keywords": "Central nervous system, Glucose metabolism, Metformin, Neuroprotection, Neurotransmission", "chunk": "Long-term use warrants vitamin B12 monitoring.", "source": "PubMed"}, {"chunk_id": "41550298_0", "pmid": "41550298", "title": "Unmasking early microglial remodeling in an Alzheimer's disease mouse model.", "authors": "Saminathan P, McArdle S, Corey M et al.", "year": "2025", "journal": "Frontiers in cellular neuroscience", "keywords": "Alzheimer\u2019s disease, Iba1 and CD68 quantification, QuPath, hippocampus, image segmentation, microglia morphometry, morphological remodeling, neuroinflammation", "chunk": "Early neuroimmune remodeling is a critical yet understudied component of Alzheimer's disease (AD) pathogenesis. To investigate microglial contributions to AD development prior to overt plaque deposition, we developed an open-source morphometric pipeline to systematically quantify hippocampal microglial structure and activation states in pre-plaque 5xFAD mice. Across \u223c11,000 cells, we extracted multidimensional parameters including area, circularity, convex hull, branch points, nearest-neighbor distance, and nuclear features, alongside Iba1 and CD68 intensity measurements. While no significant overt gliosis was observed at this early stage, microglia from 5xFAD mice exhibited subtle trends toward increased structural complexity compared to wild-type controls. Importantly, significant sex-specific differences were detected within the CA1 subregion: male 5xFAD microglia displayed hyper-ramified morphologies consistent with enhanced surveillance states, whereas female microglia demonstrated greater density and a more reactive phenotype. Correlation analyses revealed a conserved association between microglial complexity and Iba1/CD68 expression, independent of sex or genotype, underscoring a fundamental link between", "source": "PubMed"}, {"chunk_id": "41550298_1", "pmid": "41550298", "title": "Unmasking early microglial remodeling in an Alzheimer's disease mouse model.", "authors": "Saminathan P, McArdle S, Corey M et al.", "year": "2025", "journal": "Frontiers in cellular neuroscience", "keywords": "Alzheimer\u2019s disease, Iba1 and CD68 quantification, QuPath, hippocampus, image segmentation, microglia morphometry, morphological remodeling, neuroinflammation", "chunk": "demonstrated greater density and a more reactive phenotype. Correlation analyses revealed a conserved association between microglial complexity and Iba1/CD68 expression, independent of sex or genotype, underscoring a fundamental link between cytoskeletal remodeling and phagolysosomal activity. These findings highlight the capacity of morphometric profiling to sensitively detect early, region-specific, and sex-dependent shifts in microglial phenotype before amyloid deposition. By integrating quantitative morphology with canonical molecular markers, this framework provides a robust and unbiased approach for characterizing microglial activation trajectories. Such early readouts may inform biomarker discovery and therapeutic strategies aimed at modulating microglial responses to delay or prevent AD progression.", "source": "PubMed"}, {"chunk_id": "41588241_0", "pmid": "41588241", "title": "Exploratory RNA Sequencing Reveals Systemic Metabolic Dysregulation in Alzheimer's Disease: Insights from a Diverse Latin American Cohort.", "authors": "Villegas-Trujillo LM, Parra B, L\u00f3pez-\u00c1lvarez D et al.", "year": "2026", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Cognitive dysfunction, Gene expression profiling, RNA-Seq", "chunk": "Alzheimer's disease (AD) is characterized by an insidious onset and complex pathophysiology, necessitating the development of effective strategies for early detection and intervention. This exploratory study aimed to identify differentially expressed genes (DEGs) and disrupted molecular pathways in AD by analyzing blood samples from participants recruited in Valle del Cauca, Colombia, a region with high genetic admixture and persistent underrepresentation in genomic research. A total of 41 individuals (AD, n = 14; cognitively healthy controls (CHC), n = 27) were included. Groups did not differ significantly in age, education, sex distribution, or vascular comorbidities. Peripheral blood RNA was sequenced using 150-bp paired-end reads, and transcriptomic profiling revealed 399 DEGs, with 378 upregulated and 21 downregulated in the AD group. Key genes such as APOE, MMP2, PPARG, and TUBB3 were enriched in the Metabolism of Proteins pathway. At the same time, TUBB3, CACNA2D1, and GABBR2 were implicated in transmission across chemical", "source": "PubMed"}, {"chunk_id": "41588241_1", "pmid": "41588241", "title": "Exploratory RNA Sequencing Reveals Systemic Metabolic Dysregulation in Alzheimer's Disease: Insights from a Diverse Latin American Cohort.", "authors": "Villegas-Trujillo LM, Parra B, L\u00f3pez-\u00c1lvarez D et al.", "year": "2026", "journal": "Molecular neurobiology", "keywords": "Alzheimer\u2019s disease, Cognitive dysfunction, Gene expression profiling, RNA-Seq", "chunk": "genes such as APOE, MMP2, PPARG, and TUBB3 were enriched in the Metabolism of Proteins pathway. At the same time, TUBB3, CACNA2D1, and GABBR2 were implicated in transmission across chemical synapses, suggesting synaptic signaling and protein metabolism dysregulation. Multiple factor analysis (MFA), integrating gene expression with neurocognitive and functional outcomes, revealed distinct molecular signatures associated with cognitive decline and functional impairment. These findings highlight the role of systemic metabolic dysfunction and synaptic dysregulation in AD pathogenesis. By focusing on an ancestrally diverse cohort, this study underscores the critical need to expand the molecular characterization of AD beyond European-ancestry populations, informing the development of inclusive biomarkers and precision strategies for early diagnosis and intervention.", "source": "PubMed"}, {"chunk_id": "40605084_0", "pmid": "40605084", "title": "Tau seeding activity in the cerebrospinal fluid of Alzheimer disease patients predicts short-term cognitive decline.", "authors": "Houz\u00e9 L, Dhenain M, Lam S et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer, Biomarker, Biosensors, CSF, Cognitive decline, Seeding, Spread, Tauopathy", "chunk": "Alzheimer disease (AD) clinical progression is highly heterogeneous, making its prediction essential for the development of effective therapies. The advancement of cognitive decline in AD is tightly linked to the spread of pathological tau protein aggregates in the brain, through tau seeding properties. We developed a cellular biosensor to measure tau seeding activity from cerebrospinal fluid (CSF) and human brain lysates. Longitudinal analysis of cognitive function was correlated with biosensor response. Individuals with CSF exhibiting high or intermediate seeding activity experienced more rapid cognitive decline compared to those with low seeding. High tau seeding was associated with total and phosphorylated tau biomarkers in AD. The biosensor also predicts the potential of human AD brain lysates to induce tau aggregation upon experimental transmission in animal models. These results suggest that seeding activity might be a relevant biomarker to forecast AD pathogenicity and clinical progression.", "source": "PubMed"}, {"chunk_id": "40605084_1", "pmid": "40605084", "title": "Tau seeding activity in the cerebrospinal fluid of Alzheimer disease patients predicts short-term cognitive decline.", "authors": "Houz\u00e9 L, Dhenain M, Lam S et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer, Biomarker, Biosensors, CSF, Cognitive decline, Seeding, Spread, Tauopathy", "chunk": "experimental transmission in animal models. These results suggest that seeding activity might be a relevant biomarker to forecast AD pathogenicity and clinical progression.", "source": "PubMed"}, {"chunk_id": "40730571_0", "pmid": "40730571", "title": "A novel deep learning-based brain age prediction framework for routine clinical MRI scans.", "authors": "Kim H, Park S, Seo SW et al.", "year": "2025", "journal": "npj aging", "keywords": "None", "chunk": "Physiological brain aging is associated with cognitive impairment and neuroanatomical changes. Brain age prediction of routine clinical 2D brain MRI scans were understudied and often unsuccessful. We developed a novel brain age prediction framework for clinical 2D T1-weighted MRI scans using a deep learning-based model trained with research grade 3D MRI scans mostly from publicly available datasets (N = 8681; age = 51.76 \u00b1 21.74). Our model showed accurate and fast brain age prediction on clinical 2D MRI scans from cognitively unimpaired (CU) subjects (N = 175) with MAE of 2.73 years after age bias correction (Pearson's r = 0.918). Brain age gap of Alzheimer's disease (AD) subjects was significantly greater than CU subjects (p < 0.001) and increase in brain age gap was associated with disease progression in both AD (p < 0.05) and Parkinson's disease (p < 0.01). Our framework can be extended to other MRI modalities and", "source": "PubMed"}, {"chunk_id": "40730571_1", "pmid": "40730571", "title": "A novel deep learning-based brain age prediction framework for routine clinical MRI scans.", "authors": "Kim H, Park S, Seo SW et al.", "year": "2025", "journal": "npj aging", "keywords": "None", "chunk": "brain age gap was associated with disease progression in both AD (p < 0.05) and Parkinson's disease (p < 0.01). Our framework can be extended to other MRI modalities and potentially applied to routine clinical examinations, enabling early detection of structural anomalies and improve patient outcome.", "source": "PubMed"}, {"chunk_id": "41039123_0", "pmid": "41039123", "title": "Brain age as an accurate biomarker of preclinical cognitive decline: evidence from a 12-year longitudinal study.", "authors": "Elkana O, Beheshti I,  ", "year": "2025", "journal": "Journal of neurology", "keywords": "Aging, Alzheimer\u2019s disease, Brain-age prediction, Cognitive decline, Cortical thickness, Hippocampal volume, Longitudinal analysis, Machine learning, T1-weighted MRI", "chunk": "Cognitive decline in older adults, particularly during the preclinical stages of Alzheimer's disease (AD), presents a critical opportunity for early detection and intervention. While T1-weighted MRI is widely used in AD research, its capacity to identify early vulnerability and monitor longitudinal progression remains incompletely characterized. We analyzed longitudinal T1-weighted MRI data from 224 cognitively unimpaired older adults followed for up to 12 years. Participants were stratified by clinical outcome into converters to mild cognitive impairment (HC-converters, n = 112) and stable controls (HC-stable, n = 112). Groups were matched at baseline for age (mean ~ 74-75 years), education (~ 16.4 years), and cognitive scores (MMSE \u2248 29; CDR-SB \u2248 0.04). Four MRI-derived biomarkers were examined: brain-predicted age difference (brain-PAD), mean cortical thickness, AD-cortical signature, and hippocampal volume. Brain-PAD showed the strongest baseline association with future conversion (\u03b2 = 1.25, t = 3.52, p = 0.0009) and highest classification accuracy (AUC", "source": "PubMed"}, {"chunk_id": "41039123_1", "pmid": "41039123", "title": "Brain age as an accurate biomarker of preclinical cognitive decline: evidence from a 12-year longitudinal study.", "authors": "Elkana O, Beheshti I,  ", "year": "2025", "journal": "Journal of neurology", "keywords": "Aging, Alzheimer\u2019s disease, Brain-age prediction, Cognitive decline, Cortical thickness, Hippocampal volume, Longitudinal analysis, Machine learning, T1-weighted MRI", "chunk": "cortical thickness, AD-cortical signature, and hippocampal volume. Brain-PAD showed the strongest baseline association with future conversion (\u03b2 = 1.25, t = 3.52, p = 0.0009) and highest classification accuracy (AUC = 0.66; sensitivity = 62%, and specificity = 67%). Longitudinal mixed-effects models focusing on the group \u00d7 time interaction revealed a significant positive slope in brain-PAD for converters (\u03b2 = 0.0079, p = 0.003) and a non-significant trend in stable controls (\u03b2 = 0.0047, p = 0.075), indicating incipient divergence in brain aging trajectories during the preclinical window. Hippocampal volume and AD-cortical signature declined similarly in both groups. The mean cortical thickness had limited discriminative or dynamic utility. These findings support brain-PAD, derived from routine T1-weighted MRI using machine learning, as a sensitive, performance-independent biomarker for early risk stratification and monitoring of cognitive aging trajectories.", "source": "PubMed"}, {"chunk_id": "41039123_2", "pmid": "41039123", "title": "Brain age as an accurate biomarker of preclinical cognitive decline: evidence from a 12-year longitudinal study.", "authors": "Elkana O, Beheshti I,  ", "year": "2025", "journal": "Journal of neurology", "keywords": "Aging, Alzheimer\u2019s disease, Brain-age prediction, Cognitive decline, Cortical thickness, Hippocampal volume, Longitudinal analysis, Machine learning, T1-weighted MRI", "chunk": "as a sensitive, performance-independent biomarker for early risk stratification and monitoring of cognitive aging trajectories.", "source": "PubMed"}, {"chunk_id": "38675490_0", "pmid": "38675490", "title": "Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer's Disease Treatment.", "authors": "Stanciu GD, Ababei DC, Solcan C et al.", "year": "2024", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "APP/PS1 transgenic mice, Alzheimer\u2019s disease, cannabinoid receptor ligands, chronic intermittent therapy, expanded endocannabinoid system, therapeutic tools", "chunk": "Despite decades of rigorous research and numerous clinical trials, Alzheimer's disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive. Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing. Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified <i>Cannabis sativa</i> L. (Cannabixir<sup>\u00ae</sup> Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed", "source": "PubMed"}, {"chunk_id": "38675490_1", "pmid": "38675490", "title": "Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer's Disease Treatment.", "authors": "Stanciu GD, Ababei DC, Solcan C et al.", "year": "2024", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "APP/PS1 transgenic mice, Alzheimer\u2019s disease, cannabinoid receptor ligands, chronic intermittent therapy, expanded endocannabinoid system, therapeutic tools", "chunk": "as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of A\u03b2 plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment. Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment.", "source": "PubMed"}, {"chunk_id": "38675490_2", "pmid": "38675490", "title": "Exploring Cannabinoids with Enhanced Binding Affinity for Targeting the Expanded Endocannabinoid System: A Promising Therapeutic Strategy for Alzheimer's Disease Treatment.", "authors": "Stanciu GD, Ababei DC, Solcan C et al.", "year": "2024", "journal": "Pharmaceuticals (Basel, Switzerland)", "keywords": "APP/PS1 transgenic mice, Alzheimer\u2019s disease, cannabinoid receptor ligands, chronic intermittent therapy, expanded endocannabinoid system, therapeutic tools", "chunk": "for AD treatment.", "source": "PubMed"}, {"chunk_id": "41090759_0", "pmid": "41090759", "title": "Multi-Fused S,N-Heterocyclic Compounds for Targeting \u03b1-Synuclein Aggregates.", "authors": "Zheng C, Stehouwer JS, Ummenthala GR et al.", "year": "2025", "journal": "Cells", "keywords": "PET, Parkinson\u2019s disease, structure-activity relationships, \u03b1-Synuclein", "chunk": "The development of positron emission tomography (PET) tracers targeting \u03b1-synuclein (\u03b1-syn) aggregates is critical for the early diagnosis, differential classification, and therapeutic monitoring of synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Despite recent advances, challenges including the low abundance of \u03b1-syn aggregates (10-50\u00d7 lower than amyloid-beta (A\u03b2) or Tau), structural heterogeneity (e.g., flat fibrils in PD vs. cylindrical forms in DLB), co-pathology with A\u03b2/Tau, and poor metabolic stability have hindered PET tracer development for this target. To optimize our previously reported pyridothiophene-based radiotracer, [<sup>18</sup>F]asyn-44, we present the synthesis and evaluation of novel S,N-heterocyclic scaffold derivatives for \u03b1-syn. A library of 49 compounds was synthesized, with 8 potent derivatives (LMD-<b>006</b>, LMD-<b>022</b>, LMD-<b>029</b>, LMD-<b>044</b>, LMD-<b>045</b>, LMD-<b>046</b>, LMD-<b>051</b>, and LMD-<b>052</b>) demonstrating equilibrium inhibition constants (<i>K</i><sub>i</sub>) of 6-16 nM in PD brain homogenates, all of which are amenable for radiolabeling with fluorine-18. This work advances the", "source": "PubMed"}, {"chunk_id": "41090759_1", "pmid": "41090759", "title": "Multi-Fused S,N-Heterocyclic Compounds for Targeting \u03b1-Synuclein Aggregates.", "authors": "Zheng C, Stehouwer JS, Ummenthala GR et al.", "year": "2025", "journal": "Cells", "keywords": "PET, Parkinson\u2019s disease, structure-activity relationships, \u03b1-Synuclein", "chunk": "LMD-<b>045</b>, LMD-<b>046</b>, LMD-<b>051</b>, and LMD-<b>052</b>) demonstrating equilibrium inhibition constants (<i>K</i><sub>i</sub>) of 6-16 nM in PD brain homogenates, all of which are amenable for radiolabeling with fluorine-18. This work advances the molecular toolkit for synucleinopathies and provides a roadmap for overcoming barriers in PET tracer development, with lead compounds that can be considered for biomarker-guided clinical trials and targeted therapies.", "source": "PubMed"}, {"chunk_id": "33498908_0", "pmid": "33498908", "title": "Brain Asymmetry Detection and Machine Learning Classification for Diagnosis of Early Dementia.", "authors": "Herzog NJ, Magoulas GD", "year": "2021", "journal": "Sensors (Basel, Switzerland)", "keywords": "SVM, asymmetry detection, brain MRI, brain asymmetry, deep learning, dementia, machine learning methods", "chunk": "Early identification of degenerative processes in the human brain is considered essential for providing proper care and treatment. This may involve detecting structural and functional cerebral changes such as changes in the degree of asymmetry between the left and right hemispheres. Changes can be detected by computational algorithms and used for the early diagnosis of dementia and its stages (amnestic early mild cognitive impairment (EMCI), Alzheimer's Disease (AD)), and can help to monitor the progress of the disease. In this vein, the paper proposes a data processing pipeline that can be implemented on commodity hardware. It uses features of brain asymmetries, extracted from MRI of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, for the analysis of structural changes, and machine learning classification of the pathology. The experiments provide promising results, distinguishing between subjects with normal cognition (NC) and patients with early or progressive dementia. Supervised machine learning algorithms and convolutional", "source": "PubMed"}, {"chunk_id": "33498908_1", "pmid": "33498908", "title": "Brain Asymmetry Detection and Machine Learning Classification for Diagnosis of Early Dementia.", "authors": "Herzog NJ, Magoulas GD", "year": "2021", "journal": "Sensors (Basel, Switzerland)", "keywords": "SVM, asymmetry detection, brain MRI, brain asymmetry, deep learning, dementia, machine learning methods", "chunk": "learning classification of the pathology. The experiments provide promising results, distinguishing between subjects with normal cognition (NC) and patients with early or progressive dementia. Supervised machine learning algorithms and convolutional neural networks tested are reaching an accuracy of 92.5% and 75.0% for NC vs. EMCI, and 93.0% and 90.5% for NC vs. AD, respectively. The proposed pipeline offers a promising low-cost alternative for the classification of dementia and can be potentially useful to other brain degenerative disorders that are accompanied by changes in the brain asymmetries.", "source": "PubMed"}, {"chunk_id": "28116234_0", "pmid": "28116234", "title": "Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.", "authors": "Moradi E, Hallikainen I, H\u00e4nninen T et al.", "year": "2017", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer's disease, Elastic net, Magnetic resonance imaging, Penalized regression, Rey's Auditory Verbal Learning Test", "chunk": "Rey's Auditory Verbal Learning Test (RAVLT) is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD), thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting) and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI) data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed", "source": "PubMed"}, {"chunk_id": "28116234_1", "pmid": "28116234", "title": "Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.", "authors": "Moradi E, Hallikainen I, H\u00e4nninen T et al.", "year": "2017", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer's disease, Elastic net, Magnetic resonance imaging, Penalized regression, Rey's Auditory Verbal Learning Test", "chunk": "for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50) and RAVLT Percent Forgetting (R = 0.43) in a dataset consisting of 806 AD, mild cognitive impairment (MCI) or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy", "source": "PubMed"}, {"chunk_id": "28116234_2", "pmid": "28116234", "title": "Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.", "authors": "Moradi E, Hallikainen I, H\u00e4nninen T et al.", "year": "2017", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer's disease, Elastic net, Magnetic resonance imaging, Penalized regression, Rey's Auditory Verbal Learning Test", "chunk": "the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.", "source": "PubMed"}, {"chunk_id": "32530970_0", "pmid": "32530970", "title": "Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.", "authors": "Liu HC, Lin WC, Chiu MJ et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The preclinical properties, such as the standard curve, limit of detection (LoD), and dynamic range, were characterized. Thirty-one normal controls (NC), fifty-two patients with Parkinson's disease (PD) or PD dementia (PDD) and thirty-one patients with Alzheimer's disease (AD) were enrolled in the study evaluating the plasma NFL assay using an IMR kit. T-tests and receiver operating characteristic (ROC) curve analysis were performed to investigate the capability for discrimination among the clinical groups according to plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The", "source": "PubMed"}, {"chunk_id": "32530970_1", "pmid": "32530970", "title": "Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.", "authors": "Liu HC, Lin WC, Chiu MJ et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The NC group showed a plasma NFL level of 7.70 \u00b1 4.00 pg/ml, which is significantly lower than that of the PD/PDD (15.85 \u00b1 7.82 pg/ml, p < 0.001) and AD (19.24 \u00b1 8.99 pg/ml, p < 0.001) groups. A significant difference in plasma NFL levels was determined between the PD and AD groups (p < 0.01). Through ROC curve analysis, the cut-off value of the plasma NFL concentration for differentiating NCs from dementia patients (AD and PD/PDD) was found to be 12.71 pg/ml, with a clinical sensitivity and specificity of 73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cut-off value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a", "source": "PubMed"}, {"chunk_id": "32530970_2", "pmid": "32530970", "title": "Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.", "authors": "Liu HC, Lin WC, Chiu MJ et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cut-off value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a clinical sensitivity and specificity of 61.3% and 65.4%, respectively. The AUC was 0.630. An ultrasensitive assay for measuring plasma NFL utilizing IMR technology was developed. Clear differences in plasma NFL concentrations were observed among NCs and PD and AD patients. These results imply that the determination of plasma NFL is promising not only for screening dementia but also for differential diagnosis.", "source": "PubMed"}, {"chunk_id": "38154140_0", "pmid": "38154140", "title": "CRISPR-Powered Aptasensor for Diagnostics of Alzheimer's Disease.", "authors": "Jia Z, Maghaydah Y, Zdanys K et al.", "year": "2024", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease diagnosis, CRISPR-Cas12a detection, amyloid beta biomarker quantification, aptasensor, fluorescence detection", "chunk": "Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia, characterized by the accumulation of amyloid beta (A\u03b2) peptides in the brain. Here, we present a simple, rapid, and affordable CRISPR-powered aptasensor for the quantitative detection of A\u03b240 and A\u03b242 biomarkers in cerebrospinal fluid (CSF) samples, enabling early and accurate diagnostics of AD patients. The aptasensor couples the high specificity of aptamers for A\u03b2 biomarkers with CRISPR-Cas12a-based fluorescence detection. The CRISPR-powered aptasensor enables us to detect A\u03b240 and A\u03b242 in CSF samples within 60 min, achieving a detection sensitivity of 1 pg/mL and 0.1 pg/mL, respectively. To validate its clinical utility, we quantitatively detected A\u03b240 and A\u03b242 biomarkers in clinical CSF samples. Furthermore, by combining CSF A\u03b242 levels with the c(A\u03b242)/c(A\u03b240) ratio, we achieved an accurate diagnostic classification of AD patients and healthy individuals, showing superior performance over the conventional ELISA method. We believe that our", "source": "PubMed"}, {"chunk_id": "38154140_1", "pmid": "38154140", "title": "CRISPR-Powered Aptasensor for Diagnostics of Alzheimer's Disease.", "authors": "Jia Z, Maghaydah Y, Zdanys K et al.", "year": "2024", "journal": "ACS sensors", "keywords": "Alzheimer\u2019s disease diagnosis, CRISPR-Cas12a detection, amyloid beta biomarker quantification, aptasensor, fluorescence detection", "chunk": "A\u03b242 levels with the c(A\u03b242)/c(A\u03b240) ratio, we achieved an accurate diagnostic classification of AD patients and healthy individuals, showing superior performance over the conventional ELISA method. We believe that our innovative aptasensor approach holds promise for the early diagnostic classification of AD patients.", "source": "PubMed"}, {"chunk_id": "41425321_0", "pmid": "41425321", "title": "Single-Oligomer Characterization of Tau Phosphorylation and Mechanical State.", "authors": "Pillai VVS, Smeding T, Meng JX et al.", "year": "2025", "journal": "ACS measurement science au", "keywords": "atomic force microscopy, hyperphosphorylation, infrared nanospectroscopy, post-translational modifications, protein self-assembly, single-oligomer analysis, tau protein", "chunk": "Post-translational modifications have emerged as a key biomolecular process in the onset of neurodegenerative disorders, such as the hyperphosphorylation of tau protein in Alzheimer's disease (AD). High levels of phosphorylation are related to tau malfunction, self-assembly into amyloids forming neurofibrillary tangles in the brain, and cellular toxicity. These molecular processes are also reflected in human biofluids, allowing us to use tau phosphorylation as a biomarker of the disease onset and progression. However, it is not yet clear what structural changes the tau protein undergoes upon phosphorylation and what the early self-assembly steps are that lead to the formation of the final amyloid species. This knowledge gap is related in large part to the experimental challenge in achieving a multiparametric physical-chemical characterization of nanoscale size and heterogeneous amyloid at the single-molecule level. Here, we employ high-resolution and advanced atomic force microscopy methods to study the effect of phosphorylation on the tau", "source": "PubMed"}, {"chunk_id": "41425321_1", "pmid": "41425321", "title": "Single-Oligomer Characterization of Tau Phosphorylation and Mechanical State.", "authors": "Pillai VVS, Smeding T, Meng JX et al.", "year": "2025", "journal": "ACS measurement science au", "keywords": "atomic force microscopy, hyperphosphorylation, infrared nanospectroscopy, post-translational modifications, protein self-assembly, single-oligomer analysis, tau protein", "chunk": "characterization of nanoscale size and heterogeneous amyloid at the single-molecule level. Here, we employ high-resolution and advanced atomic force microscopy methods to study the effect of phosphorylation on the tau pathway of self-assembly and on the physical-chemical properties of the heterogeneous amyloid species formed, down to the single-oligomer level. We report the correlative analysis of single-oligomer structural and chemical properties and achieve, for the first time, the quantitative determination of their phosphorylation state. Our findings reveal that hyperphosphorylation results in the formation of smaller, stiffer, and more adhesive oligomers, which might be critical for their pathological role in AD. This nanoresolved information might be, in turn, useful to understand the early molecular mechanisms of disease, as well as to improve the detection of pathological tau species in biofluids as diagnostic biomarkers.", "source": "PubMed"}, {"chunk_id": "41425321_2", "pmid": "41425321", "title": "Single-Oligomer Characterization of Tau Phosphorylation and Mechanical State.", "authors": "Pillai VVS, Smeding T, Meng JX et al.", "year": "2025", "journal": "ACS measurement science au", "keywords": "atomic force microscopy, hyperphosphorylation, infrared nanospectroscopy, post-translational modifications, protein self-assembly, single-oligomer analysis, tau protein", "chunk": "the detection of pathological tau species in biofluids as diagnostic biomarkers.", "source": "PubMed"}, {"chunk_id": "38347458_0", "pmid": "38347458", "title": "In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol.", "authors": "Vanderlinden G, Carron C, Vandenberghe R et al.", "year": "2024", "journal": "BMC medical imaging", "keywords": "18F-FDG, 18F-SynVesT-1, Cognitive impairment, Dementia, Diagnosis, Glucose metabolism, PET-MR, Synaptic density", "chunk": "<sup>18</sup>F-FDG brain PET is clinically used for differential diagnosis in cognitive dysfunction of unclear etiology and for exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. <sup>18</sup>F-FDG PET measures regional glucose metabolism, which represents a combination of neuronal/synaptic activity but also astrocytic activity and neuroinflammation. Recently, imaging of synaptic vesicle protein 2 A (SV2A) has become available and was shown to be a proxy of synaptic density. This prospective study will investigate the use of <sup>18</sup>F-SynVesT-1 for imaging SV2A and its discriminative power for differential diagnosis in cognitive disorders in a head-to-head comparison to <sup>18</sup>F-FDG PET. In addition, simultaneous PET/MR allows an evaluation of contributing factors and the additional value of advanced MRI imaging to FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted. In this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment", "source": "PubMed"}, {"chunk_id": "38347458_1", "pmid": "38347458", "title": "In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol.", "authors": "Vanderlinden G, Carron C, Vandenberghe R et al.", "year": "2024", "journal": "BMC medical imaging", "keywords": "18F-FDG, 18F-SynVesT-1, Cognitive impairment, Dementia, Diagnosis, Glucose metabolism, PET-MR, Synaptic density", "chunk": "FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted. In this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment who are referred for <sup>18</sup>F-FDG PET brain imaging in their diagnostic work-up in a tertiary memory clinic will be recruited. In addition, 40 healthy volunteers (HV) between 18 and 85 years (M/F) will be included. All study participants will undergo simultaneous <sup>18</sup>F-SynVesT-1 PET/MR and an extensive neuropsychological evaluation. Amyloid status will be measured by PET using <sup>18</sup>FNAV4694, in HV above 50 years of age. Structural T1-weighted and T2-weighted fluid-attenuated inversion recovery MR images, triple-tagging arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) will be obtained. The study has been registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee. The main endpoint of the study will be the comparison of the diagnostic accuracy between <sup>18</sup>F-SynVesT-1 and", "source": "PubMed"}, {"chunk_id": "38347458_2", "pmid": "38347458", "title": "In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol.", "authors": "Vanderlinden G, Carron C, Vandenberghe R et al.", "year": "2024", "journal": "BMC medical imaging", "keywords": "18F-FDG, 18F-SynVesT-1, Cognitive impairment, Dementia, Diagnosis, Glucose metabolism, PET-MR, Synaptic density", "chunk": "registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee. The main endpoint of the study will be the comparison of the diagnostic accuracy between <sup>18</sup>F-SynVesT-1 and <sup>18</sup>F-FDG PET in cognitive disorders with uncertain etiology and in exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. The strength of the relationship between cognition and imaging data will be assessed, as well as the potential incremental diagnostic value of including MR volumetry, ASL perfusion and rs-fMRI.", "source": "PubMed"}, {"chunk_id": "33108404_0", "pmid": "33108404", "title": "Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia.", "authors": "Spotorno N, Lindberg O, Nilsson C et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma", "source": "PubMed"}, {"chunk_id": "33108404_1", "pmid": "33108404", "title": "Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia.", "authors": "Spotorno N, Lindberg O, Nilsson C et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.", "source": "PubMed"}, {"chunk_id": "33108404_2", "pmid": "33108404", "title": "Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia.", "authors": "Spotorno N, Lindberg O, Nilsson C et al.", "year": "2020", "journal": "PloS one", "keywords": "None", "chunk": "for FTD and the disease process.", "source": "PubMed"}, {"chunk_id": "41222140_0", "pmid": "41222140", "title": "Spatial Dissociation of Atrophy and Hypophysiology in Alzheimer's Disease: Implications for Biomarkers.", "authors": "Dang A, Wang D, Towne JM et al.", "year": "2025", "journal": "Human brain mapping", "keywords": "None", "chunk": "The Amyloid/Tau/Neurodegeneration (A/T/N) biomarker framework is used for in vivo pathological profiling of Alzheimer's disease. A binary (+/-) label is assigned for each pathology (A, T, N) based on its presence or absence as determined by imaging or fluid biomarkers. Using imaging, neurodegeneration is confirmed by either structural MRI (indicating atrophy) or 18F-FDG PET (indicating hypometabolism), implicitly assuming that both modalities identify equivalent pathology. Preliminary evidence suggests that atrophy and hypometabolism do not spatially co-localize and are likely caused by distinct underlying pathologies. Further, while MRI is widely available, many sites lack access to PET. Recent evidence indicates that hemodynamic indices, identified via functional MRI or SPECT, may be spatially concordant with hypometabolism identified by 18F-FDG-PET and able to serve as reliable proxies. Coordinate-based meta-analyses of voxel-based morphometry and voxel-based physiology reports in Alzheimer's disease, collectively analyzing 139 articles (4218 individuals) were performed to test the following hypotheses: (1) that", "source": "PubMed"}, {"chunk_id": "41222140_1", "pmid": "41222140", "title": "Spatial Dissociation of Atrophy and Hypophysiology in Alzheimer's Disease: Implications for Biomarkers.", "authors": "Dang A, Wang D, Towne JM et al.", "year": "2025", "journal": "Human brain mapping", "keywords": "None", "chunk": "as reliable proxies. Coordinate-based meta-analyses of voxel-based morphometry and voxel-based physiology reports in Alzheimer's disease, collectively analyzing 139 articles (4218 individuals) were performed to test the following hypotheses: (1) that atrophy and hypometabolism in AD are spatially dissociated; (2) that hemodynamic indices exhibit the same spatial distributions as hypometabolism identified by PET; (3) that regions of atrophy and hypometabolism involve different functional systems and cognitive operations. Results confirmed all three hypotheses. Separation of atrophy and hypometabolism into two distinct subcategories of neurodegeneration as well as the development of regionally specific biomarkers for each are in order.", "source": "PubMed"}, {"chunk_id": "41846157_0", "pmid": "41846157", "title": "Genetic and Hormonal Contributions to Psychosis Symptoms in Alzheimer's Disease: A Sex-Stratified Analysis.", "authors": "Rajkumar G, Uthayakumar H, Khoury MA et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, apoe4, biomarkers, delusions, estrogen, hallucinations", "chunk": "Psychosis in Alzheimer's disease (AD), including hallucinations and delusions, affects up to 50% of patients and is linked to faster cognitive decline. Delusions can occur across AD, with persecutory delusions early and misidentification delusions late, while hallucinations emerge in advanced stages and predict greater cognitive and functional decline. The APOE4 allele is the strongest genetic risk factor for late-onset AD, although its influence on neuropsychiatric symptoms, including psychosis, remains unclear. This study examined the interaction between APOE4 status, sex, EHT use, and psychosis symptoms in AD using data from participants in the National Alzheimer's Coordinating Center Uniform Data Set. Generalized Additive Models assessed nonlinear associations between predictors and psychosis outcomes, including the presence of delusions, hallucinations, and their visual and auditory subtypes. Analyses were stratified by sex (males: n = 13,841, females: n = 15,354). Predictor variables included APOE4 status, current use of estrogen hormone therapy (EHT) in females. Due", "source": "PubMed"}, {"chunk_id": "41846157_1", "pmid": "41846157", "title": "Genetic and Hormonal Contributions to Psychosis Symptoms in Alzheimer's Disease: A Sex-Stratified Analysis.", "authors": "Rajkumar G, Uthayakumar H, Khoury MA et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, apoe4, biomarkers, delusions, estrogen, hallucinations", "chunk": "auditory subtypes. Analyses were stratified by sex (males: n = 13,841, females: n = 15,354). Predictor variables included APOE4 status, current use of estrogen hormone therapy (EHT) in females. Due to limited data availability, CSF biomarkers (A\u03b21-42, p-tau181, t-tau) could not be included in the main models and were instead examined in a secondary sub analysis. APOE4 homozygosity was associated with significantly greater odds of delusions in the past month in both males and females, with a stronger effect in females (p<0.05). In females only, APOE4 homozygosity was significantly associated with hallucinations, with no effect in males (p<0.05). EHT was associated with lower risk of hallucinations in females (p<0.05). These findings underscore sex-specific genetic and biological contributors to psychosis in AD and support sex-stratified approaches to understanding and addressing psychosis symptoms in clinical settings.", "source": "PubMed"}, {"chunk_id": "41846157_2", "pmid": "41846157", "title": "Genetic and Hormonal Contributions to Psychosis Symptoms in Alzheimer's Disease: A Sex-Stratified Analysis.", "authors": "Rajkumar G, Uthayakumar H, Khoury MA et al.", "year": "2026", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Alzheimer\u2019s disease, apoe4, biomarkers, delusions, estrogen, hallucinations", "chunk": "AD and support sex-stratified approaches to understanding and addressing psychosis symptoms in clinical settings.", "source": "PubMed"}, {"chunk_id": "40220824_0", "pmid": "40220824", "title": "A multiscale model to explain the spatiotemporal progression of amyloid beta and tau pathology in Alzheimer's disease.", "authors": "Xu C, Xu E, Xiao Y et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Amyloid beta, Biomarker, Differential equation, Neurodegeneration, Neuroimaging, Tau", "chunk": "Amyloid-beta (A\u03b2) and tubulin-associated unit (tau) proteins are key biomarkers of Alzheimer's disease (AD), detectable by Positron Emission Tomography (PET) imaging and Cerebrospinal Fluid (CSF) assays. They reflect insoluble fibrils in the brain and soluble monomers in the cerebrospinal fluid, respectively. PET and CSF biomarkers have been utilized in diagnosing AD; however, their incomplete agreement significantly confounds the early detection. Additionally, the molecular mechanisms underlying the dynamics of AD biomarkers remain elusive and are yet to be quantitatively revealed. To answer these questions, we develop a multiscale mathematical model that characterizes various forms of AD biomarkers, including soluble molecules in cerebrospinal fluid, diffusive biomarkers across brain regions, and insoluble fibrils in the brain. Mathematical modeling of soluble and insoluble molecules enables the explanation of the asynchronous trajectory of AD biomarkers. Our model captures the spatiotemporal dynamics of A\u03b2 and tau with neurodegeneration in AD. Simulation results demonstrate that the PET-CSF", "source": "PubMed"}, {"chunk_id": "40220824_1", "pmid": "40220824", "title": "A multiscale model to explain the spatiotemporal progression of amyloid beta and tau pathology in Alzheimer's disease.", "authors": "Xu C, Xu E, Xiao Y et al.", "year": "2025", "journal": "International journal of biological macromolecules", "keywords": "Amyloid beta, Biomarker, Differential equation, Neurodegeneration, Neuroimaging, Tau", "chunk": "enables the explanation of the asynchronous trajectory of AD biomarkers. Our model captures the spatiotemporal dynamics of A\u03b2 and tau with neurodegeneration in AD. Simulation results demonstrate that the PET-CSF discordance is a typical stage in the natural history of protein aggregation, with CSF becoming abnormal before the onset of PET abnormality. Furthermore, correlation analysis reveals that neurodegeneration is more strongly associated with tau-PET than A\u03b2-PET. These findings suggest CSF A\u03b2 is recognized as a biomarker at the early stage of AD, while tau-PET is more suitable for neurodegeneration assessment. The proposed multiscale model explains the underlying neurobiological factors contributing to neurodegeneration and offers a valuable tool for improving early detection and treatment strategies in clinical trials.", "source": "PubMed"}, {"chunk_id": "41057861_0", "pmid": "41057861", "title": "Evidence for reduced choroid plexus volume in the aged brain.", "authors": "Youh R, Perera C, Katsiva C et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "None", "chunk": "The choroid plexus plays an important role in brain homeostasis, including the active secretion of cerebrospinal fluid. Its function and structure have been reported to be affected by normal ageing. However, existing measures of choroid plexus volume may be complicated by partial volume (in vivo MRI) and tissue fixation artefacts (histology). In this study, we investigate possible changes in choroid plexus volume within the lateral ventricles of aged mice utilising two structural MRI protocols explicitly designed for time-efficient, high-resolution in vivo imaging of the choroid plexus. Two MRI sequences were utilised to examine in vivo choroid plexus volume in the lateral ventricles of young (\u223c 6 months) and aged (\u223c 24 months) mouse brains: (1) an ultra-long echo-time T2 weighted fast-spin-echo and (2) a multi-TE T2* mapping protocol. A test-retest study was performed on a subset of the data to examine the reproducibility of choroid plexus volume estimation based on", "source": "PubMed"}, {"chunk_id": "41057861_1", "pmid": "41057861", "title": "Evidence for reduced choroid plexus volume in the aged brain.", "authors": "Youh R, Perera C, Katsiva C et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "None", "chunk": "fast-spin-echo and (2) a multi-TE T2* mapping protocol. A test-retest study was performed on a subset of the data to examine the reproducibility of choroid plexus volume estimation based on manual segmentation. A two-way ANOVA test was performed to determine possible differences in choroid plexus volume in young and aged mouse groups across the two distinct MRI protocols. Reproducibility tests showed a low test-retest variability of the manual segmentation pipeline for both MRI protocols. A statistically significant reduction of in vivo choroid plexus volume was found in the aged mouse brain. This finding is concordant with previous histological observations of a reduction in epithelial cell height with ageing across a wide range of species. We present an in vivo investigation of changes to lateral ventricle choroid plexus volume in the mouse brain utilising a manual segmentation approach based on two bespoke MRI protocols designed for time-efficient high resolution imaging of", "source": "PubMed"}, {"chunk_id": "41057861_2", "pmid": "41057861", "title": "Evidence for reduced choroid plexus volume in the aged brain.", "authors": "Youh R, Perera C, Katsiva C et al.", "year": "2025", "journal": "Fluids and barriers of the CNS", "keywords": "None", "chunk": "of changes to lateral ventricle choroid plexus volume in the mouse brain utilising a manual segmentation approach based on two bespoke MRI protocols designed for time-efficient high resolution imaging of the choroid plexus. Based on these protocols, we provide evidence for a reduction in choroid plexus volume in the aged brain. This research provides insight for studies utilising MRI measurements of choroid plexus volume as a biomarker of age-related neurologic conditions as it indicates that the ageing process itself does not result in hypertrophy of the choroid plexus, but a decrease in tissue volume. The online version contains supplementary material available at 10.1186/s12987-025-00716-y.", "source": "PubMed"}, {"chunk_id": "40710317_0", "pmid": "40710317", "title": "Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.", "authors": "Reed S, Taka E, Darling-Reed S et al.", "year": "2025", "journal": "Cells", "keywords": "metformin, neurodegeneration, neuroinflammation, oxidative stress, type 2 diabetes", "chunk": "Epidemiological studies have shown that individuals with type 2 diabetes have an increased risk of developing neurodegenerative diseases. These diseases and type 2 diabetes share several risk factors. Meanwhile, the antidiabetic drug metformin offers promising neuroprotective effects by reducing oxidative stress and neuroinflammation, two significant factors in neurodegenerative diseases. This review examines the mechanisms by which metformin mitigates neuronal damage. Metformin reduces neuroinflammation by inhibiting microglial activation and suppressing proinflammatory cytokines. It also triggers the nuclear factor erythroid-2-related factor-2 (Nrf2) pathway to combat oxidative stress, an essential regulator of antioxidant defenses. These outcomes support the possible neuroprotective roles of metformin in type 2 diabetes-related cognitive decline and conditions like Alzheimer's disease. Metformin's therapeutic potential is further supported by its capacity to strengthen the blood-brain barrier's (BBB's) integrity and increase autophagic flux. Metformin also offers several neuroprotective effects by targeting multiple pathological pathways. Moreover, metformin is being studied for its potential", "source": "PubMed"}, {"chunk_id": "40710317_1", "pmid": "40710317", "title": "Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.", "authors": "Reed S, Taka E, Darling-Reed S et al.", "year": "2025", "journal": "Cells", "keywords": "metformin, neurodegeneration, neuroinflammation, oxidative stress, type 2 diabetes", "chunk": "to strengthen the blood-brain barrier's (BBB's) integrity and increase autophagic flux. Metformin also offers several neuroprotective effects by targeting multiple pathological pathways. Moreover, metformin is being studied for its potential benefits beyond glycemic control, particularly in the areas of cognition, Alzheimer's disease, aging, and stroke management. Evidence from both clinical and preclinical studies indicates a complex and multifaceted impact, with benefits varying among populations and depending on underlying disease conditions, making it an appealing candidate for managing several neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "41030116_0", "pmid": "41030116", "title": "The Eye as a Window to Brain Health: Can Retinal Imaging and AI Modeling Predict Alzheimer's Disease?", "authors": "Awodiya E", "year": "2025", "journal": "Brain and behavior", "keywords": "AI, Alzheimer's, retinal imaging", "chunk": "This is a review article to evaluate clinical evidence for the vascular model of Alzheimer's disease (AD) pathology and elucidate the extent to which retinal imaging with AI modeling can be useful in earlier diagnosis of the condition. I comprehensively reviewed the literature on the current understanding of AD pathology and emerging role of the neurovascular system. I reviewed the evidence for retinal vascular biomarkers that can predict the presence of cognitive impairments seen in AD and AI models that utilize these to diagnose and elucidate pathophysiology for the condition. It is found that retinal imaging offers a non-invasive and cost-effective way to detect AD-related neurovascular changes and, when coupled with AI, holds a transformative role in improving screening, diagnostics, and our understanding of the disease. There is evidence to suggest that retinal imaging can provide an earlier diagnosis of the condition. This can change the practice by encouraging lifestyle", "source": "PubMed"}, {"chunk_id": "41030116_1", "pmid": "41030116", "title": "The Eye as a Window to Brain Health: Can Retinal Imaging and AI Modeling Predict Alzheimer's Disease?", "authors": "Awodiya E", "year": "2025", "journal": "Brain and behavior", "keywords": "AI, Alzheimer's, retinal imaging", "chunk": "and our understanding of the disease. There is evidence to suggest that retinal imaging can provide an earlier diagnosis of the condition. This can change the practice by encouraging lifestyle modification as crucial in modifying the progression of the disease.", "source": "PubMed"}, {"chunk_id": "36276649_0", "pmid": "36276649", "title": "A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies.", "authors": "Wasielewska JM, Chaves JCS, Johnston RL et al.", "year": "2022", "journal": "Theranostics", "keywords": "Aduhelm, Alzheimer's disease, blood-brain barrier, drug delivery, focused ultrasound", "chunk": "<b>Rationale:</b> The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). Focused ultrasound applied together with microbubbles (FUS<sup>+MB</sup>) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS<sup>+MB</sup> is safe, however, the effects of FUS<sup>+MB</sup> on human BBB cells, especially in the context of AD, remain sparsely investigated. In addition, there currently are no cell platforms to test for FUS<sup>+MB</sup>-mediated drug delivery. <b>Methods:</b> Here we generated BBB cells (induced brain endothelial-like cells (iBECs) and astrocytes (iAstrocytes)) from apolipoprotein E gene allele E4 (<i>APOE4</i>, high sporadic AD risk) and allele E3 (<i>APOE3</i>, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We established mono- and co-culture models of human sporadic AD and control BBB cells to investigate the effects of FUS<sup>+MB</sup> on BBB cell phenotype and to screen for the", "source": "PubMed"}, {"chunk_id": "36276649_1", "pmid": "36276649", "title": "A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies.", "authors": "Wasielewska JM, Chaves JCS, Johnston RL et al.", "year": "2022", "journal": "Theranostics", "keywords": "Aduhelm, Alzheimer's disease, blood-brain barrier, drug delivery, focused ultrasound", "chunk": "(iPSCs). We established mono- and co-culture models of human sporadic AD and control BBB cells to investigate the effects of FUS<sup>+MB</sup> on BBB cell phenotype and to screen for the delivery of two potentially therapeutic AD antibodies, an Aducanumab-analogue (Aduhelm<sup>TM</sup>; anti-amyloid-\u03b2) and a novel anti-Tau antibody, RNF5. We then developed a novel hydrogel-based 2.5D BBB model as a step towards a more physiologically relevant FUS<sup>+MB</sup> drug delivery platform. <b>Results:</b> When compared to untreated cells, the delivery of Aducanumab-analogue and RNF5 was significantly increased (up to 1.73 fold), across the Transwell-based BBB models following FUS<sup>+MB</sup> treatment. Our results also demonstrated the safety of FUS<sup>+MB</sup> indicated by minimal changes in iBEC transcriptome as well as little or no changes in iBEC or iAstrocyte viability and inflammatory responses within the first 24 h post FUS<sup>+MB</sup>. Furthermore, we demonstrated successful iBEC barrier formation in our novel 2.5D hydrogel-based BBB model with significantly increased delivery", "source": "PubMed"}, {"chunk_id": "36276649_2", "pmid": "36276649", "title": "A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies.", "authors": "Wasielewska JM, Chaves JCS, Johnston RL et al.", "year": "2022", "journal": "Theranostics", "keywords": "Aduhelm, Alzheimer's disease, blood-brain barrier, drug delivery, focused ultrasound", "chunk": "iAstrocyte viability and inflammatory responses within the first 24 h post FUS<sup>+MB</sup>. Furthermore, we demonstrated successful iBEC barrier formation in our novel 2.5D hydrogel-based BBB model with significantly increased delivery (1.4 fold) of Aducanumab-analogue following FUS<sup>+MB</sup>. <b>Conclusion:</b> Our results demonstrate a robust and reproducible approach to utilize patient cells for FUS<sup>+MB</sup>-mediated drug delivery screening <i>in vitro</i>. With such a cell platform for FUS<sup>+MB</sup> research previously not reported, it has the potential to identify novel FUS<sup>+MB</sup>-deliverable drugs as well as screen for cell- and patient-specific effects of FUS<sup>+MB</sup>, accelerating the use of FUS<sup>+MB</sup> as a therapeutic modality in AD.", "source": "PubMed"}, {"chunk_id": "35603281_0", "pmid": "35603281", "title": "Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain.", "authors": "Sihag S, Naze S, Taghdiri F et al.", "year": "2022", "journal": "Communications medicine", "keywords": "Biological techniques, Dynamical systems", "chunk": "Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects. Graph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions. Here we show that GSP feature from isthmus cingulate in the", "source": "PubMed"}, {"chunk_id": "35603281_1", "pmid": "35603281", "title": "Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain.", "authors": "Sihag S, Naze S, Taghdiri F et al.", "year": "2022", "journal": "Communications medicine", "keywords": "Biological techniques, Dynamical systems", "chunk": "to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions. Here we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes. Our results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits.", "source": "PubMed"}, {"chunk_id": "35603281_2", "pmid": "35603281", "title": "Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain.", "authors": "Sihag S, Naze S, Taghdiri F et al.", "year": "2022", "journal": "Communications medicine", "keywords": "Biological techniques, Dynamical systems", "chunk": "of neurological diseases and studying their impact on personality traits.", "source": "PubMed"}, {"chunk_id": "40720390_0", "pmid": "40720390", "title": "Memory improving effect of silkworm larva on insulin resistance related cognitive impairment model.", "authors": "Hwang J, Choi J, Cha SY et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "Hongjam (HJ) is the steamed and freeze-dried powder of larva-stage silkworm (Bombyx mori) rich in protein, unsaturated fatty acids, and minerals. Silkworm products have traditionally been used for medical purposes, and their effectiveness in diabetic and neurodegenerative diseases has been studied. In particular, the anti-inflammatory-antioxidant, blood sugar-lowering, and neuroprotective effects are expected to be useful for the prevention and treatment of dementia, especially in a model of dementia related to insulin resistance. Most animal models of Alzheimer's disease (AD) are based on genetic factors and research based on these models does not explain the pathophysiology of sporadic AD. Therefore, no drug can effectively delay the progression of AD. We hypothesized that HJ may improve cognitive function in an insulin resistance model which is considered one of the causes of sporadic AD. Insulin resistance was induced by a high-fat diet and streptozotocin injection. Additionally, the effect of HJ was tested in", "source": "PubMed"}, {"chunk_id": "40720390_1", "pmid": "40720390", "title": "Memory improving effect of silkworm larva on insulin resistance related cognitive impairment model.", "authors": "Hwang J, Choi J, Cha SY et al.", "year": "2025", "journal": "PloS one", "keywords": "None", "chunk": "model which is considered one of the causes of sporadic AD. Insulin resistance was induced by a high-fat diet and streptozotocin injection. Additionally, the effect of HJ was tested in in vitro cultured hippocampal slices treated with an N-methyl-D-aspartate antagonist. At the given dose, HJ did not affect on the body weight but lowered blood glucose concentration, improved spatial memory in the Morris water maze and avoidance memory in the passive avoidance tests which was related to hippocampal brain-derived neurotrophic factor. In hippocampal slices, HJ strengthened long-term potentiation, which was suppressed by AP5. Thus, HJ improved cognitive functions in an insulin-resistance related dementia model and may be useful in treating sporadic AD.", "source": "PubMed"}, {"chunk_id": "26084734_0", "pmid": "26084734", "title": "Recent data on Mediterranean diet, cardiovascular disease, cancer, diabetes and life expectancy.", "authors": "Ginter E, Simko V", "year": "2015", "journal": "Bratislavske lekarske listy", "keywords": "cancer, cardiovascular diseases, diabetes, hepatic steatosis, hypertension, life expectancy, mediterranean diet, metabolic syndrome, oleocanthal, resveratrol, sirtuins, telomeres.", "chunk": "Benefits of dietary moderation when on a Mediterranean diet type (MD) have been known for well over half a century. In the past, there has been a vigorous renewal of interest in preventive potential of MD. This review is unique, by focusing on the very recent confirmatory data on the MD, all published within the first half of 2014. Benefits of MD in preventing and reducing cardiovascular disorders (CVD), known before, have been strongly confirmed. While there is little doubt regarding potential benefit of MD for obesity, diabetes type II, metabolic syndrome and fatty liver, critical evaluation has to be aimed at reported benefits of MD in such widely metabolic diverse disorders as cancer, pulmonary disease and cognition defects, including Alzheimer disease (Ref. 20). Text in PDF www.elis.sk.", "source": "PubMed"}, {"chunk_id": "26084734_1", "pmid": "26084734", "title": "Recent data on Mediterranean diet, cardiovascular disease, cancer, diabetes and life expectancy.", "authors": "Ginter E, Simko V", "year": "2015", "journal": "Bratislavske lekarske listy", "keywords": "cancer, cardiovascular diseases, diabetes, hepatic steatosis, hypertension, life expectancy, mediterranean diet, metabolic syndrome, oleocanthal, resveratrol, sirtuins, telomeres.", "chunk": "Alzheimer disease (Ref. 20). Text in PDF www.elis.sk.", "source": "PubMed"}, {"chunk_id": "38654326_0", "pmid": "38654326", "title": "Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy.", "authors": "Rasing I, Voigt S, Koemans EA et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "CAA CSVD score, Cerebral amyloid angiopathy, Glial fibrillary acidic protein (GFAP), MoCA, Neurofilament light chain (NFL)", "chunk": "Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking. We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA. For this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and A\u03b240 and A\u03b242 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and \u226555 years", "source": "PubMed"}, {"chunk_id": "38654326_1", "pmid": "38654326", "title": "Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy.", "authors": "Rasing I, Voigt S, Koemans EA et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "CAA CSVD score, Cerebral amyloid angiopathy, Glial fibrillary acidic protein (GFAP), MoCA, Neurofilament light chain (NFL)", "chunk": "MRI markers (CAA-CSVD-burden) and A\u03b240 and A\u03b242 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and \u226555 years to match the specific groups. We included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls \u2265 55 years (mean age 65 years). In presymptomatic D-CAA, only GFAP in CSF (7.7*10<sup>3</sup>pg/mL vs. 4.4*10<sup>3</sup>pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*10<sup>2</sup>pg/mL vs. 7.8*10<sup>2</sup>pg/mL; P=0.01 and GFAP:11.4*10<sup>3</sup>pg/mL vs. 7.5*10<sup>3</sup>pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only", "source": "PubMed"}, {"chunk_id": "38654326_2", "pmid": "38654326", "title": "Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy.", "authors": "Rasing I, Voigt S, Koemans EA et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "CAA CSVD score, Cerebral amyloid angiopathy, Glial fibrillary acidic protein (GFAP), MoCA, Neurofilament light chain (NFL)", "chunk": "vs. 7.5*10<sup>3</sup>pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*10<sup>2</sup>pg/mL vs 7.8*10<sup>2</sup>pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with A\u03b242 levels (P=0.01/0.02). GFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA.", "source": "PubMed"}, {"chunk_id": "36461035_0", "pmid": "36461035", "title": "Effects of Kami Guibi-tang in patients with mild cognitive impairment: study protocol for a phase III, randomized, double-blind, and placebo-controlled trial.", "authors": "Shin HY, Yim TB, Heo HM et al.", "year": "2022", "journal": "BMC complementary medicine and therapies", "keywords": "Amnestic mild cognitive impairment (aMCI), Functional magnetic resonance imaging (fMRI), Herbal formula, Herbal medicine, Kami Guibi-tang, Korean medicine, Mild cognitive impairment (MCI), Neuropsychological test", "chunk": "Amnestic mild cognitive impairment (aMCI) is often considered a precursor to Alzheimer's disease (AD) and represents a key therapeutic target for early intervention of AD. However, no treatments have been approved for MCI at present. Our previous pilot study has shown that Kami Guibi-tang (KGT), a traditional herbal prescription widely used in Korean medicine for treating amnesia, might be beneficial for improving general cognitive function of aMCI patients. We will conduct a larger-scale clinical trial to validate the findings of our pilot study and further examine the efficacy and safety of KGT in aMCI. This trial is designed as a randomized, double-blind, placebo-controlled clinical trial. A total of 84 aMCI patients will be recruited and randomized into the treatment and control groups. Participants will be administered either KGT or placebo granules for 24 weeks, with a follow-up period of 12 weeks after the last treatment. Primary outcomes will include changes", "source": "PubMed"}, {"chunk_id": "36461035_1", "pmid": "36461035", "title": "Effects of Kami Guibi-tang in patients with mild cognitive impairment: study protocol for a phase III, randomized, double-blind, and placebo-controlled trial.", "authors": "Shin HY, Yim TB, Heo HM et al.", "year": "2022", "journal": "BMC complementary medicine and therapies", "keywords": "Amnestic mild cognitive impairment (aMCI), Functional magnetic resonance imaging (fMRI), Herbal formula, Herbal medicine, Kami Guibi-tang, Korean medicine, Mild cognitive impairment (MCI), Neuropsychological test", "chunk": "control groups. Participants will be administered either KGT or placebo granules for 24 weeks, with a follow-up period of 12 weeks after the last treatment. Primary outcomes will include changes in cognitive performance assessed using a neuropsychological test battery, called the Seoul Neuropsychological Screening Battery, between the baseline, post-intervention visit, and follow-up visit (24th and 36th week, respectively). Secondary outcomes will involve the rate of progression to AD, changes in neuroimaging signals assessed using structural magnetic resonance imaging (MRI), resting-state functional MRI (rs-fMRI), and task-based fMRI, and changes in blood biomarkers measured by the ratio of plasma amyloid-\u03b2 42/40 levels (A\u03b242/A\u03b240) between the baseline and post-intervention visit (24th week). For safety assessments, blood chemistry tests and electrocardiograms (ECG) will also be performed. This study aims to provide confirmatory evidence of the effect of the Korean herbal medicine, KGT, on improving cognitive function in patients with aMCI. We will identify the", "source": "PubMed"}, {"chunk_id": "36461035_2", "pmid": "36461035", "title": "Effects of Kami Guibi-tang in patients with mild cognitive impairment: study protocol for a phase III, randomized, double-blind, and placebo-controlled trial.", "authors": "Shin HY, Yim TB, Heo HM et al.", "year": "2022", "journal": "BMC complementary medicine and therapies", "keywords": "Amnestic mild cognitive impairment (aMCI), Functional magnetic resonance imaging (fMRI), Herbal formula, Herbal medicine, Kami Guibi-tang, Korean medicine, Mild cognitive impairment (MCI), Neuropsychological test", "chunk": "be performed. This study aims to provide confirmatory evidence of the effect of the Korean herbal medicine, KGT, on improving cognitive function in patients with aMCI. We will identify the possible mechanisms underlying the effects of KGT using neuroimaging signals and blood biomarkers. Korean Clinical Trial Registry ( https://cris.nih.go.kr/cris/search/detailSearch.do/16918; Registration number: KCT0007039; Date of registration: February 24, 2022).", "source": "PubMed"}, {"chunk_id": "41304756_0", "pmid": "41304756", "title": "Amodiaquine Modulates Aggregation and Disassembly of Amyloid-\u03b2 and Tau and Attenuates Neuroinflammatory Responses and A\u03b2 Production.", "authors": "Jang S, Kim S, Kim NH et al.", "year": "2025", "journal": "Pharmaceutics", "keywords": "Alzheimer\u2019s disease, aggregation inhibitor, amodiaquine, amyloid beta, tau", "chunk": "<b>Background</b>: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-\u03b2 (A\u03b2) plaques and hyperphosphorylated tau tangles, which synergistically accelerate disease progression. Since A\u03b2 plaques and tau tangles are key factors in the development of AD, dual-targeting of A\u03b2 and tau aggregation represents a promising therapeutic strategy. Amodiaquine (AQ), a quinoline-based antimalarial, has recently attracted attention for its ability to suppress protein aggregation. However, direct effects of AQ on both A\u03b2 and tau aggregation remain unclear. <b>Methods</b>: The effects of AQ on the aggregation and dissociation of A\u03b2 and tau were examined using a thioflavin T (ThT) assays. Molecular docking and molecular dynamics (MD) simulations were performed to examine binding characteristics and structural interactions. The effects of AQ on the expression of pro-inflammatory cytokines induced by A\u03b2 and tau aggregation in BV2 microglial cells were analyzed by qRT-PCR. <b>Results</b>: ThT assay demonstrated a dose-dependent dual effect", "source": "PubMed"}, {"chunk_id": "41304756_1", "pmid": "41304756", "title": "Amodiaquine Modulates Aggregation and Disassembly of Amyloid-\u03b2 and Tau and Attenuates Neuroinflammatory Responses and A\u03b2 Production.", "authors": "Jang S, Kim S, Kim NH et al.", "year": "2025", "journal": "Pharmaceutics", "keywords": "Alzheimer\u2019s disease, aggregation inhibitor, amodiaquine, amyloid beta, tau", "chunk": "of AQ on the expression of pro-inflammatory cytokines induced by A\u03b2 and tau aggregation in BV2 microglial cells were analyzed by qRT-PCR. <b>Results</b>: ThT assay demonstrated a dose-dependent dual effect of AQ on A\u03b2, where 25 \u03bcM inhibited aggregation after 36 h, while 250 \u03bcM markedly accelerated it, reaching a plateau within 12 h. All concentrations of AQ promoted the disassembly of mature A\u03b2 fibrils within 12 h. Molecular docking revealed stronger binding of AQ to aggregated A\u03b2 (-45.17 and -23.32 kcal/mol for pentameric 2BEG and hexameric 2NAO) than to monomeric A\u03b2 (-4.81 and -7.29 kcal/mol for 1Z0Q and 2BEG). MD simulation suggested that AQ disrupted the cross-\u03b2-sheet interactions of A\u03b2 aggregates. In the case of tau, ThT assay showed that all concentrations of AQ inhibited tau aggregation from 6 h, and 350 \u03bcM AQ promoted the disassembly of mature fibrils from 6 h. Molecular docking indicated stronger binding of", "source": "PubMed"}, {"chunk_id": "41304756_2", "pmid": "41304756", "title": "Amodiaquine Modulates Aggregation and Disassembly of Amyloid-\u03b2 and Tau and Attenuates Neuroinflammatory Responses and A\u03b2 Production.", "authors": "Jang S, Kim S, Kim NH et al.", "year": "2025", "journal": "Pharmaceutics", "keywords": "Alzheimer\u2019s disease, aggregation inhibitor, amodiaquine, amyloid beta, tau", "chunk": "that all concentrations of AQ inhibited tau aggregation from 6 h, and 350 \u03bcM AQ promoted the disassembly of mature fibrils from 6 h. Molecular docking indicated stronger binding of AQ to aggregated tau (-27.95 and -12.13 kcal/mol for the pentameric and decameric 5O3L) than to monomeric tau (-3.05 kcal/mol for 8Q96). MD simulations revealed no major structural changes in the aggregates. In BV2 cells, 1 and 10 \u03bcM AQ significantly reduced A\u03b2 and tau-induced TNF-\u03b1 and IL-6 mRNA expressions. In APP-H4 cells, 10 \u03bcM AQ decreased the level of A\u03b2 compared to the control. <b>Conclusions</b>: AQ modulates both A\u03b2 and tau aggregation and attenuates neuroinflammation and reduces A\u03b2 pathology, supporting its potential as a dual-target therapeutic candidate for AD.", "source": "PubMed"}, {"chunk_id": "41425070_0", "pmid": "41425070", "title": "Nomogram to predict 5-year global cognitive impairment in <i>de novo</i> Parkinson disease with normal cognition at baseline.", "authors": "Wang X, Tian L", "year": "2025", "journal": "Frontiers in neuroscience", "keywords": "5-yearfollow-up period, Parkinson disease, global cognitive impairment, nomogram, predictive factors", "chunk": "Cognitive impairment (CI, combing mild cognitive impairment and dementia) seriously affects the quality of life in patients with <i>de novo</i> Parkinson disease (PD). The aim of the present study was to identify the potential predictive factors for 5-year cognitive decline in <i>de novo</i> PD. Parkinson's Progression Marker Initiative (PPMI) database was retrieved and PD patients with normal global cognition at baseline were included. These patients were divided into normal cognitive (NC) group and CI group based on their Montreal Cognitive Assessment (MoCA) scores at the 5-year follow-up period. A total of 66 baseline variables were compared between these two groups. Univariate and multivariate logistic regression analyses were conducted, followed by the development and validation of a nomogram to predict 5-year global cognitive decline in <i>de novo</i> PD patients. A total of 344 PD patients with normal baseline cognition were included, in which 73 individuals developed CI at the 5 year", "source": "PubMed"}, {"chunk_id": "41425070_1", "pmid": "41425070", "title": "Nomogram to predict 5-year global cognitive impairment in <i>de novo</i> Parkinson disease with normal cognition at baseline.", "authors": "Wang X, Tian L", "year": "2025", "journal": "Frontiers in neuroscience", "keywords": "5-yearfollow-up period, Parkinson disease, global cognitive impairment, nomogram, predictive factors", "chunk": "global cognitive decline in <i>de novo</i> PD patients. A total of 344 PD patients with normal baseline cognition were included, in which 73 individuals developed CI at the 5 year follow-up period. Baseline MoCA, Benton Judgment of Line Orientation (BJOLO), Hopkins Verbal Learning Test (HVLT) immediate recall, Letter Number Sequencing (LNS), Symbol-Digit Modalities Test (SDMT), Semantic Fluency Test (SFT) scores, and Scale for Outcomes in Parkinson's disease for Autonomic symptoms (SCOPA-AUT) total, gastrointestinal, and sexual dysfunction scores were selected out from the 66 potential predictors based on logistic regression analysis. These predictors were finally included in the nomogram of the model. The area under the ROC curve of the model was 0.870 (95% CI, 0.825-0.915). Our study constructed a model that predicts 5-year cognitive decline in <i>de novo</i> PD with high accuracy, which may allow for the early risk stratification of future CI in PD patients at baseline.", "source": "PubMed"}, {"chunk_id": "41425070_2", "pmid": "41425070", "title": "Nomogram to predict 5-year global cognitive impairment in <i>de novo</i> Parkinson disease with normal cognition at baseline.", "authors": "Wang X, Tian L", "year": "2025", "journal": "Frontiers in neuroscience", "keywords": "5-yearfollow-up period, Parkinson disease, global cognitive impairment, nomogram, predictive factors", "chunk": "that predicts 5-year cognitive decline in <i>de novo</i> PD with high accuracy, which may allow for the early risk stratification of future CI in PD patients at baseline.", "source": "PubMed"}, {"chunk_id": "40095069_0", "pmid": "40095069", "title": "Biofluid-based staging of Alzheimer's disease.", "authors": "Lantero-Rodriguez J, Montoliu-Gaya L, Ashton NJ et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "Alzheimer, CSF, Plasma, Staging, Tau, p-Tau", "chunk": "Recently, conceptual systems for the in vivo staging of Alzheimer's disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (biomarkers of early, intermediate and late AD pathology, respectively) have potential for biofluid-based staging in cerebrospinal fluid (CSF; n = 219) and plasma (n = 150), and compared them in a paired CSF and plasma subset (n = 76). Our findings suggest a good concordance between biofluid staging and underlying pathology when classifying amyloid-positivity into three categories based on neurofibrillary pathology: minimal/non-existent (p-tau217 positive), early-to-intermediate (p-tau217 and p-tau205 positivity), and advanced tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in", "source": "PubMed"}, {"chunk_id": "40095069_1", "pmid": "40095069", "title": "Biofluid-based staging of Alzheimer's disease.", "authors": "Lantero-Rodriguez J, Montoliu-Gaya L, Ashton NJ et al.", "year": "2025", "journal": "Acta neuropathologica", "keywords": "Alzheimer, CSF, Plasma, Staging, Tau, p-Tau", "chunk": "tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in paired samples). Notably, CSF- and plasma-based staging matched one another in 61.7% of the cases, while approximately 32% of the remaining participants were one to three biofluid stages higher in CSF as compared to plasma. Overall, these exploratory results suggest that biofluid staging of AD holds potential for offering valuable insights into underlying AD hallmarks and disease severity. However, its applicability beyond molecular characterization at research settings has yet to be demonstrated.", "source": "PubMed"}, {"chunk_id": "37703605_0", "pmid": "37703605", "title": "Effects of de-facing software mri_reface on utility of imaging biomarkers used in Alzheimer's disease research.", "authors": "Schwarz CG, Kremers WK, Weigand SD et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Anonymization, De-facing, De-identification, Face recognition", "chunk": "Brain imaging research studies increasingly use \"de-facing\" software to remove or replace facial imagery before public data sharing. Several works have studied the effects of de-facing software on brain imaging biomarkers by directly comparing automated measurements from unmodified vs de-faced images, but most research brain images are used in analyses of correlations with cognitive measurements or clinical statuses, and the effects of de-facing on these types of imaging-to-cognition correlations has not been measured. In this work, we focused on brain imaging measures of amyloid (A), tau (T), neurodegeneration (N), and vascular (V) measures used in Alzheimer's Disease (AD) research. We created a retrospective sample of participants from three age- and sex-matched clinical groups (cognitively unimpaired, mild cognitive impairment, and AD dementia, and we performed region- and voxel-wise analyses of: hippocampal volume (N), white matter hyperintensity volume (V), amyloid PET (A), and tau PET (T) measures, each from multiple software pipelines,", "source": "PubMed"}, {"chunk_id": "37703605_1", "pmid": "37703605", "title": "Effects of de-facing software mri_reface on utility of imaging biomarkers used in Alzheimer's disease research.", "authors": "Schwarz CG, Kremers WK, Weigand SD et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Anonymization, De-facing, De-identification, Face recognition", "chunk": "dementia, and we performed region- and voxel-wise analyses of: hippocampal volume (N), white matter hyperintensity volume (V), amyloid PET (A), and tau PET (T) measures, each from multiple software pipelines, on their ability to separate cognitively defined groups and their degrees of correlation with age and Clinical Dementia Rating (CDR)-Sum of Boxes (CDR-SB). We performed each of these analyses twice: once with unmodified images and once with images de-faced with leading de-facing software mri_reface, and we directly compared the findings and their statistical strengths between the original vs. the de-faced images. Analyses with original and with de-faced images had very high agreement. There were no significant differences between any voxel-wise comparisons. Among region-wise comparisons, only three out of 55 correlations were significantly different between original and de-faced images, and these were not significant after correction for multiple comparisons. Overall, the statistical power of the imaging data for AD biomarkers was", "source": "PubMed"}, {"chunk_id": "37703605_2", "pmid": "37703605", "title": "Effects of de-facing software mri_reface on utility of imaging biomarkers used in Alzheimer's disease research.", "authors": "Schwarz CG, Kremers WK, Weigand SD et al.", "year": "2023", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Anonymization, De-facing, De-identification, Face recognition", "chunk": "were significantly different between original and de-faced images, and these were not significant after correction for multiple comparisons. Overall, the statistical power of the imaging data for AD biomarkers was almost identical between unmodified and de-faced images, and their analyses results were extremely consistent.", "source": "PubMed"}, {"chunk_id": "37661884_0", "pmid": "37661884", "title": "Toward Reagent-Free Discrimination of Alzheimer's Disease Using Blood Plasma Spectral Digital Biomarkers and Machine Learning.", "authors": "Li Z, Wu H, Ji Y et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, blood plasma, discrimination, machine learning, reagent-free, spectral digital biomarkers", "chunk": "Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. The detection of early-stage AD is particularly desirable because it would allow early intervention. However, a minimally invasive, low-cost, and accurate discrimination or diagnostic method for AD is especially difficult in the earliest stage of AD. The aim of this research is to discover blood plasma spectral digital biomarkers of AD, develop a novel intelligent method for the discrimination of AD and accelerate the translation of Fourier transform infrared (FTIR) spectral-based disease discrimination methods from the laboratory to clinical practice. Since vibration spectroscopy can provide the structure and chemical composition information of biological samples at the molecular level, we investigated the potential of FTIR spectral biomarkers of blood plasma to differentiate between AD patients and healthy controls. Combined with machine learning technology, we designed a hierarchical discrimination system that provides reagent-free and accurate AD discrimination based on blood plasma spectral digital", "source": "PubMed"}, {"chunk_id": "37661884_1", "pmid": "37661884", "title": "Toward Reagent-Free Discrimination of Alzheimer's Disease Using Blood Plasma Spectral Digital Biomarkers and Machine Learning.", "authors": "Li Z, Wu H, Ji Y et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, blood plasma, discrimination, machine learning, reagent-free, spectral digital biomarkers", "chunk": "between AD patients and healthy controls. Combined with machine learning technology, we designed a hierarchical discrimination system that provides reagent-free and accurate AD discrimination based on blood plasma spectral digital biomarkers of AD. Accurate segregation between AD patients and healthy controls was achieved with 89.3% sensitivity and 85.7% specificity for early-stage AD patients, 92.8% sensitivity and 87.5% specificity for middle-stage AD patients, and 100% sensitivity and 100% specificity for late-stage AD patients. Our results show that blood plasma spectral digital biomarkers hold great promise as discrimination markers of AD, indicating the potential for the development of an inexpensive, reagent-free, and less laborious clinical test. As a result, our research outcome will accelerate the clinical application of spectral digital biomarkers and machine learning.", "source": "PubMed"}, {"chunk_id": "37661884_2", "pmid": "37661884", "title": "Toward Reagent-Free Discrimination of Alzheimer's Disease Using Blood Plasma Spectral Digital Biomarkers and Machine Learning.", "authors": "Li Z, Wu H, Ji Y et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, blood plasma, discrimination, machine learning, reagent-free, spectral digital biomarkers", "chunk": "machine learning.", "source": "PubMed"}, {"chunk_id": "41317205_0", "pmid": "41317205", "title": "Nomograms integrating cortical morphometric metrics with 3D multi-parametric MRI radiomics for predicting disability progression and cognitive worsening in relapsing-remitting multiple sclerosis: a multi-center validation study.", "authors": "Wang Z, Li S, Liu J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Cognitive worsening, Disability progression, Multiple sclerosis, Radiomics, Surface-based morphometry", "chunk": "To develop individualized nomograms integrating cortical morphometric measures with 3D multi-parametric MRI radiomics to predict disability progression (DP) and cognitive worsening (CW) in patients with relapsing-remitting multiple sclerosis (RRMS). In this multicenter study, 191 RRMS patients from two centers were divided into internal (training and validation sets, n = 158) and external validation (n = 33) sets. All patients underwent clinical and neuropsychological evaluations at both baseline and 2-year follow-up visits. Cortical morphometric metrics were extracted from 3D T1W images, with radiomics features were assessed within MS plaques on 3D DIR, 3D FLAIR, and 3D T1W images. Four models-clinical-only, radiomics-only, cortical morphometric-only, and a combined model-were developed. A nomogram was developed based on a multivariable logistic regression model to provide individualized probability estimates of DP and CW. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The combined nomogram outperformed models using clinical,", "source": "PubMed"}, {"chunk_id": "41317205_1", "pmid": "41317205", "title": "Nomograms integrating cortical morphometric metrics with 3D multi-parametric MRI radiomics for predicting disability progression and cognitive worsening in relapsing-remitting multiple sclerosis: a multi-center validation study.", "authors": "Wang Z, Li S, Liu J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Cognitive worsening, Disability progression, Multiple sclerosis, Radiomics, Surface-based morphometry", "chunk": "individualized probability estimates of DP and CW. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The combined nomogram outperformed models using clinical, radiomic, or cortical morphometric features alone in predicting DP, achieving an area under the curve (AUC) (95% confidence interval [CI]) of 0.950 (0.878-0.994) in the internal cohort and 0.904 (0.781-0.987) in the external cohort. Similarly, the nomogram for CW demonstrated excellent performance, with AUCs of 0.916 (0.831-0.984) and 0.889 (0.752-0.981) in the respective cohorts. Decision curve analysis confirmed the clinical utility of the nomograms. Cortical atrophy, reduced morphological complexity, and high heterogeneity of MS lesions play significant roles in explaining DP and CW in MS. Nomograms integrating clinical indicators, cortical morphometric features, and 3D multi-parametric MRI radiomics, shows potential as a clinical tool for predicting disease progression, facilitating individualized management in RRMS patients.", "source": "PubMed"}, {"chunk_id": "41317205_2", "pmid": "41317205", "title": "Nomograms integrating cortical morphometric metrics with 3D multi-parametric MRI radiomics for predicting disability progression and cognitive worsening in relapsing-remitting multiple sclerosis: a multi-center validation study.", "authors": "Wang Z, Li S, Liu J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Cognitive worsening, Disability progression, Multiple sclerosis, Radiomics, Surface-based morphometry", "chunk": "morphometric features, and 3D multi-parametric MRI radiomics, shows potential as a clinical tool for predicting disease progression, facilitating individualized management in RRMS patients.", "source": "PubMed"}, {"chunk_id": "28572842_0", "pmid": "28572842", "title": "Grid-based stochastic search for hierarchical gene-gene interactions in population-based genetic studies of common human diseases.", "authors": "Moore JH, Andrews PC, Olson RS et al.", "year": "2017", "journal": "BioData mining", "keywords": "Bioinformatics, Common diseases, Epistasis, Genome-wide Association study, Machine learning", "chunk": "Large-scale genetic studies of common human diseases have focused almost exclusively on the independent main effects of single-nucleotide polymorphisms (SNPs) on disease susceptibility. These studies have had some success, but much of the genetic architecture of common disease remains unexplained. Attention is now turning to detecting SNPs that impact disease susceptibility in the context of other genetic factors and environmental exposures. These context-dependent genetic effects can manifest themselves as non-additive interactions, which are more challenging to model using parametric statistical approaches. The dimensionality that results from a multitude of genotype combinations, which results from considering many SNPs simultaneously, renders these approaches underpowered. We previously developed the multifactor dimensionality reduction (MDR) approach as a nonparametric and genetic model-free machine learning alternative. Approaches such as MDR can improve the power to detect gene-gene interactions but are limited in their ability to exhaustively consider SNP combinations in genome-wide association studies (GWAS), due to", "source": "PubMed"}, {"chunk_id": "28572842_1", "pmid": "28572842", "title": "Grid-based stochastic search for hierarchical gene-gene interactions in population-based genetic studies of common human diseases.", "authors": "Moore JH, Andrews PC, Olson RS et al.", "year": "2017", "journal": "BioData mining", "keywords": "Bioinformatics, Common diseases, Epistasis, Genome-wide Association study, Machine learning", "chunk": "Approaches such as MDR can improve the power to detect gene-gene interactions but are limited in their ability to exhaustively consider SNP combinations in genome-wide association studies (GWAS), due to the combinatorial explosion of the search space. We introduce here a stochastic search algorithm called Crush for the application of MDR to modeling high-order gene-gene interactions in genome-wide data. The Crush-MDR approach uses expert knowledge to guide probabilistic searches within a framework that capitalizes on the use of biological knowledge to filter gene sets prior to analysis. Here we evaluated the ability of Crush-MDR to detect hierarchical sets of interacting SNPs using a biology-based simulation strategy that assumes non-additive interactions within genes and additivity in genetic effects between sets of genes within a biochemical pathway. We show that Crush-MDR is able to identify genetic effects at the gene or pathway level significantly better than a baseline random search with the", "source": "PubMed"}, {"chunk_id": "28572842_2", "pmid": "28572842", "title": "Grid-based stochastic search for hierarchical gene-gene interactions in population-based genetic studies of common human diseases.", "authors": "Moore JH, Andrews PC, Olson RS et al.", "year": "2017", "journal": "BioData mining", "keywords": "Bioinformatics, Common diseases, Epistasis, Genome-wide Association study, Machine learning", "chunk": "genes within a biochemical pathway. We show that Crush-MDR is able to identify genetic effects at the gene or pathway level significantly better than a baseline random search with the same number of model evaluations. We then applied the same methodology to a GWAS for Alzheimer's disease and showed base level validation that Crush-MDR was able to identify a set of interacting genes with biological ties to Alzheimer's disease. We discuss the role of stochastic search and cloud computing for detecting complex genetic effects in genome-wide data.", "source": "PubMed"}, {"chunk_id": "40818474_0", "pmid": "40818474", "title": "Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Therriault J, Brum WS, Trudel L et al.", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "Plasma phosphorylated tau (p-tau) biomarkers show promise to transform the clinical management of Alzheimer's disease by providing more accessible and cost-effective diagnostic tools. p-tau biomarkers have emerged as leading contenders for clinical implementation; however, there have been no comprehensive meta-analyses of their diagnostic performance. We aimed to evaluate the diagnostic performance of plasma p-tau biomarkers and individual p-tau assays to identify biologically defined Alzheimer's disease. For this systematic review and meta-analysis, we searched Embase, MEDLINE, PubMed, Scopus, and Web of Science for articles published from July 1, 1984 up to Dec 9, 2024, that reported on the discriminative accuracy of plasma p-tau biomarkers for amyloid-PET, tau-PET, CSF, and neuropathological reference standards. We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited adults from any setting. Articles were excluded if they did not contain data on a p-tau blood biomarker, did not contain an appropriate biological reference standard, did not", "source": "PubMed"}, {"chunk_id": "40818474_1", "pmid": "40818474", "title": "Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Therriault J, Brum WS, Trudel L et al.", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "that recruited adults from any setting. Articles were excluded if they did not contain data on a p-tau blood biomarker, did not contain an appropriate biological reference standard, did not report diagnostic accuracy data, included participants younger than 18 years, or reported duplicate or overlapping data from another publication. Summary data were independently extracted by eight authors. Risk of bias was assessed using QUADAS-2. The primary outcome was the diagnostic performance of plasma p-tau biomarkers for Alzheimer's disease. We used a bivariate random-effects meta-analysis to estimate pooled sensitivity, specificity, diagnostics odds ratio and area under the receiver operating characteristic curve. We assessed the certainty of evidence using GRADE. This study was done following PRISMA-DTA guidelines and is registered with PROSPERO as CRD42023422143. Of the 6429 studies identified by our search, 312 studies were assessed for eligibility, with 113 studies included in the final analysis, comprising 29 625 unique individuals. Plasma", "source": "PubMed"}, {"chunk_id": "40818474_2", "pmid": "40818474", "title": "Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Therriault J, Brum WS, Trudel L et al.", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "as CRD42023422143. Of the 6429 studies identified by our search, 312 studies were assessed for eligibility, with 113 studies included in the final analysis, comprising 29 625 unique individuals. Plasma p-tau217 was the highest-performing biomarker for identifying biologically defined Alzheimer's disease, with pooled sensitivity of 88\u00b71% (95% CI 86\u00b77-89\u00b75, moderate certainty of evidence), specificity of 88\u00b77% (87\u00b74-89\u00b79, moderate certainty of evidence), area under the receiver operating characteristic curve (AUROC) of 91\u00b71% (88\u00b79-92\u00b74, moderate certainty of evidence), and diagnostic odds ratio of 50\u00b77 (40\u00b76-63\u00b74). p-tau181 pooled sensitivity was 80\u00b75% (78\u00b74-82\u00b74, low certainty of evidence), specificity was 76\u00b74% (74\u00b71-78\u00b76, low certainty of evidence), AUROC was 81\u00b75% (80\u00b72-82\u00b79, low certainty of evidence), and diagnostic odds ratio was 13\u00b74 (11\u00b74-16\u00b77). p-tau205 pooled sensitivity was 76\u00b76% (70\u00b77-81\u00b76, moderate certainty of evidence), specificity was 86\u00b70% (78\u00b76-91\u00b72, moderate certainty of evidence), AUROC was 85\u00b71% (80\u00b77-89\u00b76, moderate certainty of evidence), and diagnostic odds ratio was 20\u00b72 (10\u00b75-38\u00b77). p-tau212", "source": "PubMed"}, {"chunk_id": "40818474_3", "pmid": "40818474", "title": "Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Therriault J, Brum WS, Trudel L et al.", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "76\u00b76% (70\u00b77-81\u00b76, moderate certainty of evidence), specificity was 86\u00b70% (78\u00b76-91\u00b72, moderate certainty of evidence), AUROC was 85\u00b71% (80\u00b77-89\u00b76, moderate certainty of evidence), and diagnostic odds ratio was 20\u00b72 (10\u00b75-38\u00b77). p-tau212 pooled sensitivity was 84\u00b75% (75\u00b75-90\u00b76, moderate certainty of evidence), specificity was 87\u00b73% (79\u00b75-92\u00b75, moderate certainty of evidence), AUROC was 90\u00b73% (86\u00b76-94\u00b71, moderate certainty of evidence), and diagnostic odds ratio was 41\u00b72 (22\u00b70-77\u00b73). p-tau231 pooled sensitivity was 75\u00b72% (71\u00b73-78\u00b78, moderate certainty of evidence), specificity was 75\u00b73% (71\u00b72-78\u00b79, moderate certainty of evidence), AUROC was 80\u00b72 (77\u00b76-82\u00b77, moderate certainty of evidence), and diagnostic odds ratio was 9\u00b73 (7\u00b70-12\u00b72). Approximately 90% of studies were rated as high risk of bias for not having used predefined or externally derived thresholds. Plasma p-tau217 is a highly sensitive and specific biomarker for Alzheimer's disease pathology, despite the high risk of bias of many studies. Prospective clinical implementation studies in real-world settings are needed to characterise the effect", "source": "PubMed"}, {"chunk_id": "40818474_4", "pmid": "40818474", "title": "Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.", "authors": "Therriault J, Brum WS, Trudel L et al.", "year": "2025", "journal": "The Lancet. Neurology", "keywords": "None", "chunk": "sensitive and specific biomarker for Alzheimer's disease pathology, despite the high risk of bias of many studies. Prospective clinical implementation studies in real-world settings are needed to characterise the effect of plasma p-tau217 on Alzheimer's disease diagnosis and clinical management. McGill Faculty of Medicine Fellowship.", "source": "PubMed"}, {"chunk_id": "31217131_0", "pmid": "31217131", "title": "Studying the Manifold Structure of Alzheimer's Disease: A Deep Learning Approach Using Convolutional Autoencoders.", "authors": "Martinez-Murcia FJ, Ortiz A, Gorriz JM et al.", "year": "2020", "journal": "IEEE journal of biomedical and health informatics", "keywords": "None", "chunk": "Many classical machine learning techniques have been used to explore Alzheimer's disease (AD), evolving from image decomposition techniques such as principal component analysis toward higher complexity, non-linear decomposition algorithms. With the arrival of the deep learning paradigm, it has become possible to extract high-level abstract features directly from MRI images that internally describe the distribution of data in low-dimensional manifolds. In this work, we try a new exploratory data analysis of AD based on deep convolutional autoencoders. We aim at finding links between cognitive symptoms and the underlying neurodegeneration process by fusing the information of neuropsychological test outcomes, diagnoses, and other clinical data with the imaging features extracted solely via a data-driven decomposition of MRI. The distribution of the extracted features in different combinations is then analyzed and visualized using regression and classification analysis, and the influence of each coordinate of the autoencoder manifold over the brain is estimated. The", "source": "PubMed"}, {"chunk_id": "31217131_1", "pmid": "31217131", "title": "Studying the Manifold Structure of Alzheimer's Disease: A Deep Learning Approach Using Convolutional Autoencoders.", "authors": "Martinez-Murcia FJ, Ortiz A, Gorriz JM et al.", "year": "2020", "journal": "IEEE journal of biomedical and health informatics", "keywords": "None", "chunk": "features in different combinations is then analyzed and visualized using regression and classification analysis, and the influence of each coordinate of the autoencoder manifold over the brain is estimated. The imaging-derived markers could then predict clinical variables with correlations above 0.6 in the case of neuropsychological evaluation variables such as the MMSE or the ADAS11 scores, achieving a classification accuracy over 80% for the diagnosis of AD.", "source": "PubMed"}, {"chunk_id": "40142342_0", "pmid": "40142342", "title": "Morphometric Measurement of Mean Cortical Curvature: Analysis of Alterations in Cognitive Impairment.", "authors": "Apse RR, Zdanovskis N, \u0160neidere K et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "MoCA score, atlas-based segmentation, cognitive impairment, dementia, mean cortical curvature, neuroimaging, structural MRI", "chunk": "<i>Background and Objectives</i>: Cognitive impairment, including mild cognitive impairment (MCI) and Alzheimer's disease (AD), is a growing public health concern. Early detection and an understanding of structural changes are crucial for accurate diagnosis and timely intervention. Cortical curvature, a morphometric measure derived from structural magnetic resonance imaging (MRI), has emerged as a potential biomarker for neurodegenerative processes. This study investigates the relationship between mean cortical curvature and cognitive impairment. <i>Materials and Methods</i>: A cross-sectional study was conducted with 58 participants, categorized into, first, cognitively impaired (CI) and non-cognitively impaired (NC) groups and, second, a normal cognitive group (NC), a mild cognitive performance group (MPG), and a low cognitive performance group (LPG) based on the Montreal Cognitive Assessment (MoCA) score. MRI data were acquired using a 3.0 Tesla scanner, and cortical reconstruction was performed using FreeSurfer 7.2.0. Mean cortical curvature values were extracted for 34 brain regions per hemisphere. <i>Results</i>: Significant", "source": "PubMed"}, {"chunk_id": "40142342_1", "pmid": "40142342", "title": "Morphometric Measurement of Mean Cortical Curvature: Analysis of Alterations in Cognitive Impairment.", "authors": "Apse RR, Zdanovskis N, \u0160neidere K et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "MoCA score, atlas-based segmentation, cognitive impairment, dementia, mean cortical curvature, neuroimaging, structural MRI", "chunk": "data were acquired using a 3.0 Tesla scanner, and cortical reconstruction was performed using FreeSurfer 7.2.0. Mean cortical curvature values were extracted for 34 brain regions per hemisphere. <i>Results</i>: Significant differences in mean cortical curvature were found between the CI and NC groups. In the right hemisphere, statistically significant changes in mean curvature were observed in the isthmus cingulate (U = 188.5, <i>p</i> = 0.006), lingual (U = 202.5, <i>p</i> = 0.013), pars orbitalis (U = 221.5, <i>p</i> = 0.031), and posterior cingulate regions (U = 224.5, <i>p</i> = 0.035). In the left hemisphere, significant differences were detected in the cuneus (U = 226.5, <i>p</i> = 0.038) and posterior cingulate (U = 231.5, <i>p</i> = 0.046) regions. Analysis across three cognitive performance groups (NC, MPG, and LPG) showed significant curvature differences in the right isthmus cingulate (H(2) = 7.492, <i>p</i> = 0.024) and lingual regions (H(2) = 6.250, <i>p</i> =", "source": "PubMed"}, {"chunk_id": "40142342_2", "pmid": "40142342", "title": "Morphometric Measurement of Mean Cortical Curvature: Analysis of Alterations in Cognitive Impairment.", "authors": "Apse RR, Zdanovskis N, \u0160neidere K et al.", "year": "2025", "journal": "Medicina (Kaunas, Lithuania)", "keywords": "MoCA score, atlas-based segmentation, cognitive impairment, dementia, mean cortical curvature, neuroimaging, structural MRI", "chunk": "cognitive performance groups (NC, MPG, and LPG) showed significant curvature differences in the right isthmus cingulate (H(2) = 7.492, <i>p</i> = 0.024) and lingual regions (H(2) = 6.250, <i>p</i> = 0.044). <i>Conclusions</i>: Decreased mean cortical curvature in brain regions associated with cognitive function could be indicative of cognitive impairment and may reflect early neurodegenerative changes. These results highlight cortical curvature as a potential structural sign for cognitive impairment, showing the need for further investigation in longitudinal studies.", "source": "PubMed"}, {"chunk_id": "37280636_0", "pmid": "37280636", "title": "Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate.", "authors": "Nemergut M, Marques SM, Uhrik L et al.", "year": "2023", "journal": "Molecular neurodegeneration", "keywords": "3-sulfopropanoic acid, Aggregation, Alzheimer\u2019s disease, Apolipoprotein E, Cerebral organoids, HDX-MS, Lipidomics, Molecular dynamics, Neurodegeneration, Protein crystallography, Proteomics, Tramiprosate", "chunk": "Apolipoprotein E (ApoE) \u03b54 genotype is the most prevalent risk factor for late-onset Alzheimer's Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown. Here, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE \u03b53/\u03b53 and \u03b54/\u03b54 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level. We found that C112R substitution in ApoE4 induces long-distance (> 15 \u00c5) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis", "source": "PubMed"}, {"chunk_id": "37280636_1", "pmid": "37280636", "title": "Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate.", "authors": "Nemergut M, Marques SM, Uhrik L et al.", "year": "2023", "journal": "Molecular neurodegeneration", "keywords": "3-sulfopropanoic acid, Aggregation, Alzheimer\u2019s disease, Apolipoprotein E, Cerebral organoids, HDX-MS, Lipidomics, Molecular dynamics, Neurodegeneration, Protein crystallography, Proteomics, Tramiprosate", "chunk": "geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis of ApoE \u03b54/\u03b54 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol. Our results connect the ApoE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.", "source": "PubMed"}, {"chunk_id": "38471046_0", "pmid": "38471046", "title": "Nonalcoholic Fatty Liver Disease and Longitudinal Change in Imaging and Plasma Biomarkers of Alzheimer Disease and Vascular Pathology.", "authors": "Lu Y, Pike JR, Hoogeveen R et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "Prospective measures of plasma and cerebral MRI biomarkers of Alzheimer disease (AD) and vascular neuropathology provide an opportunity to investigate possible mechanisms linking liver disease and dementia. We aimed to quantify the association of midlife nonalcoholic fatty liver disease (NAFLD) with change in plasma and brain MRI biomarkers of AD and vascular neuropathology. We included participants from the Atherosclerosis Risk in Communities Study with brain MRI measurements of white matter hyperintensity (WMH) volume and temporal-parietal lobe cortical thickness meta region of interest (ROI) at up to 2 different visits, in 2011-13 and 2016-19, and plasma biomarkers of \u03b2-amyloid (A\u03b2)42:40, phosphorylated tau at threonine 181, and neurofilament light (NfL) were measured up to 3 times in 1993-95, 2011-13, and 2016-19. NAFLD was categorized using the fatty liver index in 1990-92. Multivariate linear regression was performed for associations between midlife NAFLD and change in plasma and brain MRI biomarkers of AD and", "source": "PubMed"}, {"chunk_id": "38471046_1", "pmid": "38471046", "title": "Nonalcoholic Fatty Liver Disease and Longitudinal Change in Imaging and Plasma Biomarkers of Alzheimer Disease and Vascular Pathology.", "authors": "Lu Y, Pike JR, Hoogeveen R et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "was categorized using the fatty liver index in 1990-92. Multivariate linear regression was performed for associations between midlife NAFLD and change in plasma and brain MRI biomarkers of AD and vascular neuropathology. The primary models adjusted for demographics, Apolipoprotein E, alcohol use, and kidney function. Among 1,706 participants (mean age 56 years, 62% female, 28% Black), midlife NAFLD vs no NAFLD was associated with greater late-life WMH volume (difference per SD 0.19, 95% CI 0.06-0.31) and faster late-life WMH increase over 6 years (difference in annual change, SD 0.28, 95% CI 0.05-0.51), suggesting accumulating vascular pathology. Midlife NAFLD vs no NAFLD was also associated with AD biomarkers in midlife (lower A\u03b242:40 [SD -0.21, 95% CI -0.39 to -0.04] measured in 1993-95) and late life (lower A\u03b242:40 [SD -0.13, 95% CI -0.23 to -0.03] and lower temporal-parietal lobe cortical thickness meta ROI [SD -0.16, 95% CI -0.28 to -0.05] measured in", "source": "PubMed"}, {"chunk_id": "38471046_2", "pmid": "38471046", "title": "Nonalcoholic Fatty Liver Disease and Longitudinal Change in Imaging and Plasma Biomarkers of Alzheimer Disease and Vascular Pathology.", "authors": "Lu Y, Pike JR, Hoogeveen R et al.", "year": "2024", "journal": "Neurology", "keywords": "None", "chunk": "1993-95) and late life (lower A\u03b242:40 [SD -0.13, 95% CI -0.23 to -0.03] and lower temporal-parietal lobe cortical thickness meta ROI [SD -0.16, 95% CI -0.28 to -0.05] measured in 2011-13). Although midlife NfL was lower in individuals with vs without midlife NAFLD, those with NAFLD exhibited a faster rate of NfL increase that accelerated over time. Midlife NAFLD shows associations with AD and accumulating vascular pathology, revealing potential pathways linking liver function to dementia. Plasma biomarkers of neuropathology and neuronal injury may serve as easily measurable and dynamic indicators for monitoring the impacts of impaired liver function on brain health.", "source": "PubMed"}, {"chunk_id": "41150017_0", "pmid": "41150017", "title": "Multi-Channel Spectro-Temporal Representations for Speech-Based Parkinson's Disease Detection.", "authors": "Malekroodi HS, Madusanka N, Lee BI et al.", "year": "2025", "journal": "Journal of imaging", "keywords": "Parkinson\u2019s Disease (PD), deep learning, multi-channel spectrograms, speech analysis, speech-based diagnosis", "chunk": "Early, non-invasive detection of Parkinson's Disease (PD) using speech analysis offers promise for scalable screening. In this work, we propose a multi-channel spectro-temporal deep-learning approach for PD detection from sentence-level speech, a clinically relevant yet underexplored modality. We extract and fuse three complementary time-frequency representations-mel spectrogram, constant-Q transform (CQT), and gammatone spectrogram-into a three-channel input analogous to an RGB image. This fused representation is evaluated across CNNs (ResNet, DenseNet, and EfficientNet) and Vision Transformer using the PC-GITA dataset, under 10-fold subject-independent cross-validation for robust assessment. Results showed that fusion consistently improves performance over single representations across architectures. EfficientNet-B2 achieves the highest accuracy (84.39% \u00b1 5.19%) and F1-score (84.35% \u00b1 5.52%), outperforming recent methods using handcrafted features or pretrained models (e.g., Wav2Vec2.0, HuBERT) on the same task and dataset. Performance varies with sentence type, with emotionally salient and prosodically emphasized utterances yielding higher AUC, suggesting that richer prosody enhances discriminability. Our", "source": "PubMed"}, {"chunk_id": "41150017_1", "pmid": "41150017", "title": "Multi-Channel Spectro-Temporal Representations for Speech-Based Parkinson's Disease Detection.", "authors": "Malekroodi HS, Madusanka N, Lee BI et al.", "year": "2025", "journal": "Journal of imaging", "keywords": "Parkinson\u2019s Disease (PD), deep learning, multi-channel spectrograms, speech analysis, speech-based diagnosis", "chunk": "Wav2Vec2.0, HuBERT) on the same task and dataset. Performance varies with sentence type, with emotionally salient and prosodically emphasized utterances yielding higher AUC, suggesting that richer prosody enhances discriminability. Our findings indicate that multi-channel fusion enhances sensitivity to subtle speech impairments in PD by integrating complementary spectral information. Our approach implies that multi-channel fusion could enhance the detection of discriminative acoustic biomarkers, potentially offering a more robust and effective framework for speech-based PD screening, though further validation is needed before clinical application.", "source": "PubMed"}, {"chunk_id": "41027951_0", "pmid": "41027951", "title": "Advanced MRI based Alzheimer's diagnosis through ensemble learning techniques.", "authors": "Sriram S, Nivethitha V, Arun Kaarthic TP et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s Detection, CNN, Deep learning, Ensemble, InceptionResNetV2, ResNet50, Residual Net (ResNet)", "chunk": "Alzheimer's Disease is a condition that affects the brain and causes changes in behavior and memory loss while making it hard to carry out tasks properly. It's vital to spot the illness early, for effective treatment. MRI technology has advanced in detecting Alzheimer's by using machine learning and deep learning models. These models use neural networks to analyze brain MRI results automatically and identify key indicators of Alzheimer's disease. In this study, we used MRI data to train a CNN for diagnosing and categorizing the four stages of Alzheimer's disease with deep learning techniques, offering significant advantages in identifying patterns in medical imaging for this neurodegenerative condition compared to using a CNN exclusively trained for this purpose. They evaluated ResNet50, InceptionResNetv2 as well as a CNN specifically trained for their study and found that combining the models led to highly accurate results. The accuracy rates for the trained CNN model", "source": "PubMed"}, {"chunk_id": "41027951_1", "pmid": "41027951", "title": "Advanced MRI based Alzheimer's diagnosis through ensemble learning techniques.", "authors": "Sriram S, Nivethitha V, Arun Kaarthic TP et al.", "year": "2025", "journal": "Scientific reports", "keywords": "Alzheimer\u2019s Detection, CNN, Deep learning, Ensemble, InceptionResNetV2, ResNet50, Residual Net (ResNet)", "chunk": "InceptionResNetv2 as well as a CNN specifically trained for their study and found that combining the models led to highly accurate results. The accuracy rates for the trained CNN model stood at 90.76%, InceptionResNetv2 at 86.84%, and ResNet50 at 90.27%. In this trial run of the experiment conducted by combining all three models collaboratively resulted in an accuracy rate of 94.27% compared to the accuracy rates of each model working individually.", "source": "PubMed"}, {"chunk_id": "32363230_0", "pmid": "32363230", "title": "Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.", "authors": "Wang PN, Lin KJ, Liu HC et al.", "year": "2020", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "None", "chunk": "Pyroglutamate-modified amyloid \u03b2 (A\u03b2<sub>pE3</sub>) could be a biomarker for A\u03b2 plaque pathology in the brain. An ultra-high-sensitive assay is needed for detecting A\u03b2<sub>pE3-40</sub>. Immunomagnetic reduction was used for quantification of A\u03b2<sub>pE3-40</sub> in plasma from 46 participants. The concentrations of A\u03b2<sub>pE3-40</sub> of these subjects were compared with <sup>18</sup>F-florbetapir positron emission tomography (PET) images. A\u03b2<sub>pE3-40</sub> concentration was 44.1 \u00b1 28.2 fg/mL in PET- (n = 28) and 91.6 \u00b1 54.6 fg/mL in PET+ (n = 18; <i>P</i> < .05). The cutoff value of A\u03b2<sub>pE3-40</sub> for discriminating PET- from PET+ was 55.5 fg/mL, resulting in a sensitivity of 83.3%, a specificity of 71.4%. The concentration of A\u03b2<sub>pE3-40</sub> showed a moderate correlation (r = 0.437) with PET standardized uptake value ratio. We did not enroll pre-clinical AD subject with normal cognition but A\u03b2 PET+. It would be an important issue to explore the feasibility of using A\u03b2<sub>pE3-40</sub> for screening pre-clinical subjects. These results reveal", "source": "PubMed"}, {"chunk_id": "32363230_1", "pmid": "32363230", "title": "Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.", "authors": "Wang PN, Lin KJ, Liu HC et al.", "year": "2020", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "None", "chunk": "enroll pre-clinical AD subject with normal cognition but A\u03b2 PET+. It would be an important issue to explore the feasibility of using A\u03b2<sub>pE3-40</sub> for screening pre-clinical subjects. These results reveal the feasibility of detecting A\u03b2 pathology using quantification of a plaque-derived A\u03b2 molecule in plasma.", "source": "PubMed"}, {"chunk_id": "34008957_0", "pmid": "34008957", "title": "Emerging Application of Nanorobotics and Artificial Intelligence To Cross the BBB: Advances in Design, Controlled Maneuvering, and Targeting of the Barriers.", "authors": "Singh AV, Chandrasekar V, Janapareddy P et al.", "year": "2021", "journal": "ACS chemical neuroscience", "keywords": "Blood\u2212brain barrier, bioengineering, machine learning and artificial intelligence, nanoparticles, nanorobots, transcytosis", "chunk": "The blood-brain barrier (BBB) is a prime focus for clinicians to maintain the homeostatic function in health and deliver the theranostics in brain cancer and number of neurological diseases. The structural hierarchy and in situ biochemical signaling of BBB neurovascular unit have been primary targets to recapitulate into the in vitro modules. The microengineered perfusion systems and development in 3D cellular and organoid culture have given a major thrust to BBB research for neuropharmacology. In this review, we focus on revisiting the nanoparticles based bimolecular engineering to enable them to maneuver, control, target, and deliver the theranostic payloads across cellular BBB as nanorobots or nanobots. Subsequently we provide a brief outline of specific case studies addressing the payload delivery in brain tumor and neurological disorders (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.). In addition, we also address the opportunities and challenges across the nanorobots' development and design. Finally, we", "source": "PubMed"}, {"chunk_id": "34008957_1", "pmid": "34008957", "title": "Emerging Application of Nanorobotics and Artificial Intelligence To Cross the BBB: Advances in Design, Controlled Maneuvering, and Targeting of the Barriers.", "authors": "Singh AV, Chandrasekar V, Janapareddy P et al.", "year": "2021", "journal": "ACS chemical neuroscience", "keywords": "Blood\u2212brain barrier, bioengineering, machine learning and artificial intelligence, nanoparticles, nanorobots, transcytosis", "chunk": "brain tumor and neurological disorders (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.). In addition, we also address the opportunities and challenges across the nanorobots' development and design. Finally, we address how computationally powered machine learning (ML) tools and artificial intelligence (AI) can be partnered with robotics to predict and design the next generation nanorobots to interact and deliver across the BBB without causing damage, toxicity, or malfunctions. The content of this review could be references to multidisciplinary science to clinicians, roboticists, chemists, and bioengineers involved in cutting-edge pharmaceutical design and BBB research.", "source": "PubMed"}, {"chunk_id": "40834628_0", "pmid": "40834628", "title": "Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.", "authors": "Rodr\u00edguez-Fern\u00e1ndez B, Gonz\u00e1lez-Escalante A, Genius P et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Alzheimer's disease, Cortical thickness, Glial biomarkers, Leukocyte telomere length, Preclinical", "chunk": "Short telomere length (TL), a hallmark of biological ageing, has been associated with an increased risk of Alzheimer's disease (AD), but its pathophysiological role remains unclear. This study explored the relationship between blood leukocyte TL (LTL), cerebrospinal fluid (CSF) AD biomarkers changes, and brain structure across early stages of the AD continuum. We included 346 cognitively unimpaired participants (aged 49-71) from the ALFA cohort, enriched for AD risk (53.2% APOE-\u03b54 carriers; 34% amyloid-positive). LTL was measured at baseline (visit 0) using quantitative PCR. Associations were assessed between baseline LTL and CSF biomarkers at visit 1 (mean follow-up from baseline = 3.98 years, SD = 1.02), and with changes in CSF biomarkers between visits 1 and 2 (mean interval = 3.45 years, SD = 0.58). Cortical thickness in ageing- and AD-vulnerable brain regions was evaluated by magnetic resonance imaging (MRI) at visit 1. Analyses were stratified by APOE-\u03b54 status and amyloid-tau", "source": "PubMed"}, {"chunk_id": "40834628_1", "pmid": "40834628", "title": "Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.", "authors": "Rodr\u00edguez-Fern\u00e1ndez B, Gonz\u00e1lez-Escalante A, Genius P et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Alzheimer's disease, Cortical thickness, Glial biomarkers, Leukocyte telomere length, Preclinical", "chunk": "years, SD = 0.58). Cortical thickness in ageing- and AD-vulnerable brain regions was evaluated by magnetic resonance imaging (MRI) at visit 1. Analyses were stratified by APOE-\u03b54 status and amyloid-tau (AT) profiles. Mediation models tested whether CSF biomarkers mediated LTL-cortical thickness associations. Shorter LTL was associated with higher astrocytic reactivity at visit 1 and with increased synaptic dysfunction over time. Among APOE-\u03b54 carriers and AT-positive individuals, shorter LTL was associated with higher p-tau181 and neurodegeneration markers. Shorter LTL was associated with greater cortical thickness in ageing- and AD-vulnerable regions, partially mediated by astrocytic reactivity biomarkers. These findings suggest that shorter telomeres are associated with early AD-related biological changes, potentially via mechanisms involving astrocytic reactivity and brain structural alterations. LTL may serve as an early marker of vulnerability to neurodegenerative processes in at-risk populations. AARG-19-618265; PI19/00119; LCF/PR/GN17/10300004; TriBEKa-17-519007; # SLT002/16/00201.", "source": "PubMed"}, {"chunk_id": "40834628_2", "pmid": "40834628", "title": "Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.", "authors": "Rodr\u00edguez-Fern\u00e1ndez B, Gonz\u00e1lez-Escalante A, Genius P et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Alzheimer's disease, Cortical thickness, Glial biomarkers, Leukocyte telomere length, Preclinical", "chunk": "serve as an early marker of vulnerability to neurodegenerative processes in at-risk populations. AARG-19-618265; PI19/00119; LCF/PR/GN17/10300004; TriBEKa-17-519007; # SLT002/16/00201.", "source": "PubMed"}, {"chunk_id": "41332861_0", "pmid": "41332861", "title": "Development of Alzheimer's Disease Risk Score for Future Primary Care: A White-Box Approach.", "authors": "Wiranto Y, Setiawan DR, Watts A et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s Disease, Cognition, Integrated Primary Care, Interpretable Machine Learning", "chunk": "Interpretable scoring system can contribute to bridge the gap between the timeliness and complexity of diagnosing Alzheimer's disease (AD) and promote early intervention at non-specialist settings. To develop a risk score to predict the likelihood of AD with interpretable machine learning using variables that are obtainable at integrated primary care settings. A secondary data analysis including cohort studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the National Alzheimer's Coordinating Center (NACC) extracted in August 2023 and March 2024. The ADNI and NACC are multi-site cohort studies in North America. Participants with normal cognition or mild cognitive impairment at baseline visit were identified. Participants with the same diagnosis overtime were assigned to the stable group, and those converted to AD were placed in the progressive group. Cognitive tests and daily functioning measured with Functional Assessment Questionnaire (FAQ) at baseline visit. A total of 676 participants from ADNI and 4592 participants", "source": "PubMed"}, {"chunk_id": "41332861_1", "pmid": "41332861", "title": "Development of Alzheimer's Disease Risk Score for Future Primary Care: A White-Box Approach.", "authors": "Wiranto Y, Setiawan DR, Watts A et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s Disease, Cognition, Integrated Primary Care, Interpretable Machine Learning", "chunk": "were placed in the progressive group. Cognitive tests and daily functioning measured with Functional Assessment Questionnaire (FAQ) at baseline visit. A total of 676 participants from ADNI and 4592 participants from NACC were identified. After removing incomplete data, 665 ADNI (mean age [SD]: 73.44 [6.90]; 293 [44.1%] female; 374 stable and 291 progressive) and 3657 NACC participants (mean age [SD]: 70.96 [10.03]; 2405 [65.8%] female; 2445 stable and 1212 progressive) remained. Combinations of 4 measures were selected to generate 10 scorecards using FasterRisk algorithm, showing strong performance (area under the curve [AUC] = 0.868-0.892) in ADNI and remaining robust when validated in NACC (AUC = 0.795). The features were Category Animal \u2264 20 (2 points), Trail Making Test B \u2264 143 (-3 points), Logical Memory Delayed \u2264 3 (4 points), Logical Memory Delayed \u2264 8 (3 points), and FAQ \u2264 2 (-5 points). The probable AD risk corresponded to total", "source": "PubMed"}, {"chunk_id": "41332861_2", "pmid": "41332861", "title": "Development of Alzheimer's Disease Risk Score for Future Primary Care: A White-Box Approach.", "authors": "Wiranto Y, Setiawan DR, Watts A et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s Disease, Cognition, Integrated Primary Care, Interpretable Machine Learning", "chunk": "143 (-3 points), Logical Memory Delayed \u2264 3 (4 points), Logical Memory Delayed \u2264 8 (3 points), and FAQ \u2264 2 (-5 points). The probable AD risk corresponded to total points: 7.4% (-8), 25.3% (-4), 50% (-1), 74.7% (2), and > 90% (\u2265 6). We refer to this model as the (F)unctioning, (LA)nguage, (M)emory, and (E)xecutive functioning or FLAME scorecard. Our findings highlight the potential to predict AD development using obtainable information, allowing for applicability at integrated primary care. While our scope centers on AD, this foundation paves the way for other dementia types.", "source": "PubMed"}, {"chunk_id": "39043341_0", "pmid": "39043341", "title": "Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.", "authors": "Mackey-Alfonso SE, Butler MJ, Taylor AM et al.", "year": "2024", "journal": "Brain, behavior, and immunity", "keywords": "Alzheimer\u2019s disease, Complement cascade, High-fat diet, Memory deficit, Neuroinflammation, Neutrophil inhibitory factor", "chunk": "Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to a role of the diet itself in increasing risk. In AD, the complement system, an arm of the immune system which normally tags redundant or damaged synapses for pruning, becomes pathologically overactivated leading to tagging of healthy synapses. While the unhealthy diet to AD link is strong, the underlying mechanisms are not well understood in part due to confounding variables associated with long-term HFD which can independently influence the brain. Therefore, we experimented with a short-term diet regimen to isolate the diet's impact on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5)", "source": "PubMed"}, {"chunk_id": "39043341_1", "pmid": "39043341", "title": "Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.", "authors": "Mackey-Alfonso SE, Butler MJ, Taylor AM et al.", "year": "2024", "journal": "Brain, behavior, and immunity", "keywords": "Alzheimer\u2019s disease, Complement cascade, High-fat diet, Memory deficit, Neuroinflammation, Neutrophil inhibitory factor", "chunk": "on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5) in vitro microglial synaptic phagocytosis in the 3xTg-AD mouse model. Following the consumption of either standard chow or HFD, 3xTg-AD and non-Tg mice were tested for memory impairments. In a separate cohort of mice, levels of hippocampal inflammatory markers, complement proteins, AD pathology markers, and synaptic markers were measured. For the last set of experiments, BV2 microglial phagocytosis of synapses was evaluated. Synaptoneurosomes isolated from the hippocampus of 3xTg-AD mice fed chow or HFD were incubated with equal numbers of BV2 microglia. The number of BV2 microglia that phagocytosed synaptoneurosomes was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had", "source": "PubMed"}, {"chunk_id": "39043341_2", "pmid": "39043341", "title": "Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.", "authors": "Mackey-Alfonso SE, Butler MJ, Taylor AM et al.", "year": "2024", "journal": "Brain, behavior, and immunity", "keywords": "Alzheimer\u2019s disease, Complement cascade, High-fat diet, Memory deficit, Neuroinflammation, Neutrophil inhibitory factor", "chunk": "was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had significantly impaired long-term contextual and cued fear memory compared to non-Tg mice that was further impaired by HFD. HFD significantly increased inflammatory markers and complement expression while decreasing synaptic marker expression only in 3xTg-AD mice, without altering AD pathology markers. Synaptoneurosomes from HFD-fed 3xTg-AD mice were phagocytosed at a significantly higher rate than those from chow-fed mice, suggesting the synapses were altered by HFD. The complement receptor inhibitor blocked this effect in a dose-dependent manner, demonstrating the HFD-mediated increase in phagocytosis was complement dependent. This study indicates HFD consumption increases neuroinflammation and over-activates the complement cascade in 3xTg-AD mice, resulting in poorer memory. The in vitro data point to complement as a potential mechanistic culprit and therapeutic target underlying HFD's", "source": "PubMed"}, {"chunk_id": "39043341_3", "pmid": "39043341", "title": "Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.", "authors": "Mackey-Alfonso SE, Butler MJ, Taylor AM et al.", "year": "2024", "journal": "Brain, behavior, and immunity", "keywords": "Alzheimer\u2019s disease, Complement cascade, High-fat diet, Memory deficit, Neuroinflammation, Neutrophil inhibitory factor", "chunk": "neuroinflammation and over-activates the complement cascade in 3xTg-AD mice, resulting in poorer memory. The in vitro data point to complement as a potential mechanistic culprit and therapeutic target underlying HFD's influence in increasing cognitive vulnerability to AD.", "source": "PubMed"}, {"chunk_id": "41474988_0", "pmid": "41474988", "title": "Papaverine-Derived Dual-Active Modulator Ameliorates Alzheimer's Disease Pathology in Aged APP/PSEN1 Transgenic Mice.", "authors": "Kumar A, Ramesh M, Bhoi J et al.", "year": "2026", "journal": "Journal of medicinal chemistry", "keywords": "None", "chunk": "Alzheimer's disease (AD) therapeutics remain a challenge due to their complex pathology and multifactorial toxicity. Advanced stages of AD are marked by rapid cognitive decline, driven by amyloid plaques, neurofibrillary tangles, neuroinflammation, synaptic dysfunction, and neuronal loss. We report the design of dual-active, prodrug-like multifunctional modulators by conjugating papaverine with butyrate, a short-chain fatty acid (SCFA) with neuroprotective properties. The lead compound, <b>P4B</b>, undergoes enzymatic hydrolysis to release papaverine derivative <b>P4H</b> and <b>butyrate</b>, collectively inhibiting amyloid aggregation, A\u03b2-oligomer-induced membrane disruption, oxidative stress, and neuroinflammation. In vivo administration of <b>P4B</b> to aged APP/PSEN1 mice significantly reduced the amyloid burden, neuroinflammatory markers, and microglial activation in hippocampal and cortical regions. This work introduces an SCFA-based prodrug strategy to address the multifaceted toxicity of AD, offering a novel therapeutic paradigm with potential applicability to other neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "41474988_1", "pmid": "41474988", "title": "Papaverine-Derived Dual-Active Modulator Ameliorates Alzheimer's Disease Pathology in Aged APP/PSEN1 Transgenic Mice.", "authors": "Kumar A, Ramesh M, Bhoi J et al.", "year": "2026", "journal": "Journal of medicinal chemistry", "keywords": "None", "chunk": "of AD, offering a novel therapeutic paradigm with potential applicability to other neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "40694298_0", "pmid": "40694298", "title": "Development of a nomogram based on METS-IR and SPISE index for predicting mild cognitive impairment in type 2 diabetes mellitus.", "authors": "Tong N, Kunyu L, Xueling Z et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "Insulin resistance, Metabolic score for insulin resistance index, Mild cognitive impairment, Nomogram, Single-point insulin sensitivity estimator index, Type 2 diabetes mellitus", "chunk": "Insulin resistance (IR) is central to metabolic syndrome and contributes to the development of type 2 diabetes mellitus (T2DM) as well as mild cognitive impairment (MCI). Several low-cost surrogate markers have been proposed to assess IR, such as the triglyceride-glucose (TyG) index, TyG-BMI, TG/HDL-C, metabolic score for insulin resistance (METS-IR), and single-point insulin sensitivity estimator (SPISE). This study aimed to develop nomogram models integrating these indices with clinical data to predict MCI in patients with T2DM. A total of 600 patients diagnosed with T2DM were recruited. Demographic, clinical, and biochemical parameters were documented, and cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Logistic regression analyses identified predictors of MCI, and receiver operating characteristic (ROC) curves evaluated their predictive accuracy. Two nomogram models were constructed: Model 1 included METS-IR, age, sex, education level, and hypertension; Model 2 substituted SPISE for METS-IR, retaining other clinical", "source": "PubMed"}, {"chunk_id": "40694298_1", "pmid": "40694298", "title": "Development of a nomogram based on METS-IR and SPISE index for predicting mild cognitive impairment in type 2 diabetes mellitus.", "authors": "Tong N, Kunyu L, Xueling Z et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "Insulin resistance, Metabolic score for insulin resistance index, Mild cognitive impairment, Nomogram, Single-point insulin sensitivity estimator index, Type 2 diabetes mellitus", "chunk": "(ROC) curves evaluated their predictive accuracy. Two nomogram models were constructed: Model 1 included METS-IR, age, sex, education level, and hypertension; Model 2 substituted SPISE for METS-IR, retaining other clinical variables. All IR surrogate indices were significantly associated with MCI and reduced MMSE scores (P < 0.001). METS-IR and SPISE exhibited higher predictive accuracy (AUC: METS-IR = 0.809, SPISE = 0.805) compared to TyG, TyG-BMI, and TG/HDL-C, particularly among female participants. Nomogram models demonstrated robust predictive performance (AUC: Model 1 = 0.846; Model 2 = 0.838). Nomogram models incorporating METS-IR or SPISE alongside key clinical parameters effectively predicted the risk of MCI among patients with T2DM. These indices notably outperformed other surrogate markers, highlighting their clinical value for early assessment of cognitive risk.", "source": "PubMed"}, {"chunk_id": "40694298_2", "pmid": "40694298", "title": "Development of a nomogram based on METS-IR and SPISE index for predicting mild cognitive impairment in type 2 diabetes mellitus.", "authors": "Tong N, Kunyu L, Xueling Z et al.", "year": "2025", "journal": "Journal of endocrinological investigation", "keywords": "Insulin resistance, Metabolic score for insulin resistance index, Mild cognitive impairment, Nomogram, Single-point insulin sensitivity estimator index, Type 2 diabetes mellitus", "chunk": "of cognitive risk.", "source": "PubMed"}, {"chunk_id": "27038867_0", "pmid": "27038867", "title": "[Alzheimer's disease and diabetes - the common pathogenesis].", "authors": "Halmos T, Suba I", "year": "2016", "journal": "Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology", "keywords": "None", "chunk": "Epidemiological studies presented evidence that Alzheimer's disease and type 2 diabetes share common features in their pathophysiology and clinical patterns. Insulin resistance is a characteristic feature of both diseases. According to the pathomechanism, inflammatory, metabolic, and an atypical form based on the deficiency of zinc ions can be distinguished. Glucose metabolic disorders, related to Alzheimer's disease, are type 2 diabetes, and prediabetes/metabolic syndrome. Based on the common pathophysiological patterns of these two diseases, Alzheimer's disease is customary called type 3 diabetes. In the research on dementias, insulin resistance stands in the highlight for its documented harmful effects on cognitive function and causes dementia. Insulin-like growth factor also influences cognitive functions. Reduced input of this hormone into the brain may also cause dementia, however literary data are controversial. In Alzheimer's disease, deposition of amyloid \u00df in the brain, hyperphosphorylation of tau proteins and dysruption of neurofibrilles are characteristic. Amyloid \u00df is", "source": "PubMed"}, {"chunk_id": "27038867_1", "pmid": "27038867", "title": "[Alzheimer's disease and diabetes - the common pathogenesis].", "authors": "Halmos T, Suba I", "year": "2016", "journal": "Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology", "keywords": "None", "chunk": "cause dementia, however literary data are controversial. In Alzheimer's disease, deposition of amyloid \u00df in the brain, hyperphosphorylation of tau proteins and dysruption of neurofibrilles are characteristic. Amyloid \u00df is co-secreted in the \u00df-cells of the pancreas with insulin. Amyloid \u00df and hyperphosphorylated tau protein were detected in the Langerhans islets by autopsy. Amyloid deposits, found in the pancreas and brain presented similarities. As a consequence of hyperglycemia, glycation endproducts cause the development of amyloid plaques, dysruption of neurofibrilles, and activated microglia, all are typical to Alzheimer's disease. Continuous hyperglycemia leads to oxidative stress, which used to play significant role in the development of both diseases. Low-grade inflammation is also a significant pathophysiological factor in both disorders. The sources of inflammation are proinflammatorical adipocytokines, dysbacteriosis, metabolic endotoxaemia, caused by lipopolysaccharides, and high fat diet which also lead to insulin resistance. Based on recent data, microbial amyloid, the main product of", "source": "PubMed"}, {"chunk_id": "27038867_2", "pmid": "27038867", "title": "[Alzheimer's disease and diabetes - the common pathogenesis].", "authors": "Halmos T, Suba I", "year": "2016", "journal": "Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology", "keywords": "None", "chunk": "inflammation are proinflammatorical adipocytokines, dysbacteriosis, metabolic endotoxaemia, caused by lipopolysaccharides, and high fat diet which also lead to insulin resistance. Based on recent data, microbial amyloid, the main product of bacteria, is also contributing to the pathophysiology of the human central nervous system. Alzheimer's disease is a heterogeneous disorder, and as yet there is no effective therapy. Encouraging results have emerged by using intranasal insulin spray. Insulin sensitizers like metformin, thiazolidines have also resulted in improvements in cognitive functions, mainly in animal experiments. Glucagon-like peptide-1, beyond its insulin-stimulating effect, also has central pleiotropic influences. Research results with the application of these molecules seem to be enouraging. More recently, glucagon-like peptide-1, and glucose-dependent insulinotropic peptide were administered together, with promising early results. The real breakthrough has not yet arrived. For the time being we have to endeavour to the prevention of both chronic diseases via a more healthy life-style.", "source": "PubMed"}, {"chunk_id": "27038867_3", "pmid": "27038867", "title": "[Alzheimer's disease and diabetes - the common pathogenesis].", "authors": "Halmos T, Suba I", "year": "2016", "journal": "Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology", "keywords": "None", "chunk": "results. The real breakthrough has not yet arrived. For the time being we have to endeavour to the prevention of both chronic diseases via a more healthy life-style.", "source": "PubMed"}, {"chunk_id": "40691577_0", "pmid": "40691577", "title": "Inhibition of FAM19A5 reverses synaptic loss and cognitive decline in mouse models of Alzheimer's disease.", "authors": "Kim HB, Yoo S, Kwak H et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, FAM19A5, LRRC4B, Mushroom spine, NS101, Synapse restoration", "chunk": "FAM19A5 is a secretory protein primarily expressed in neurons. Although its role in synaptic function has been suggested, the precise molecular mechanisms underlying its effects at the synapse remain unclear. Given that synaptic loss is a critical hallmark of Alzheimer's disease (AD), elucidating the mechanisms involving FAM19A5 could provide valuable insights into reversing synaptic loss in AD. The binding partner of FAM19A5 was identified through co-immunoprecipitation experiments of mouse brain tissue. The effect of FAM19A5 on spine density in hippocampal neurons was evaluated using immunocytochemistry by overexpressing FAM19A5, treating neurons with FAM19A5 protein, and/or an anti-FAM19A5 antibody NS101. Target engagement of NS101 was determined by measuring FAM19A5 levels in mouse, rat, and human plasma at specific time points post NS101 injection using ELISA. Changes in spine density and dynamics in P301S tauopathy mice were assessed via Golgi staining and two-photon microscopy after NS101 administration. The synaptic strengthening of hippocampal neurons", "source": "PubMed"}, {"chunk_id": "40691577_1", "pmid": "40691577", "title": "Inhibition of FAM19A5 reverses synaptic loss and cognitive decline in mouse models of Alzheimer's disease.", "authors": "Kim HB, Yoo S, Kwak H et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, FAM19A5, LRRC4B, Mushroom spine, NS101, Synapse restoration", "chunk": "injection using ELISA. Changes in spine density and dynamics in P301S tauopathy mice were assessed via Golgi staining and two-photon microscopy after NS101 administration. The synaptic strengthening of hippocampal neurons in APP/PS1 amyloidopathy mice after NS101 treatment was assessed by measuring miniature excitatory postsynaptic currents (mEPSCs) and field excitatory postsynaptic potentials (fEPSPs). Cognitive performance in AD mice after NS101 treatment was measured using the Y-maze and Morris water maze tests. FAM19A5 binds to LRRC4B, a postsynaptic adhesion molecule, leading to reductions in spine density in mouse hippocampal neurons. Inhibiting FAM19A5 function with NS101 increased spine density. Intravenous administration of NS101 increased spine density in the prefrontal cortex of P301S mice, which initially showed reduced spine density compared to wild-type (WT) mice. NS101 normalized the spine elimination rate in P301S mice, restoring the net spine count to levels comparable to WT mice. NS101 treatment enhanced the frequency of mEPSCs and fEPSPs", "source": "PubMed"}, {"chunk_id": "40691577_2", "pmid": "40691577", "title": "Inhibition of FAM19A5 reverses synaptic loss and cognitive decline in mouse models of Alzheimer's disease.", "authors": "Kim HB, Yoo S, Kwak H et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, FAM19A5, LRRC4B, Mushroom spine, NS101, Synapse restoration", "chunk": "mice. NS101 normalized the spine elimination rate in P301S mice, restoring the net spine count to levels comparable to WT mice. NS101 treatment enhanced the frequency of mEPSCs and fEPSPs in the hippocampal synapses of APP/PS1 mice, leading to improved cognitive function. The increases in plasma FAM19A5 levels upon systemic NS101 administration suggest that the antibody effectively engages its target and facilitates the transport of FAM19A5 from the brain. This study demonstrated that inhibiting FAM19A5 function with an anti-FAM19A5 antibody restores synaptic integrity and enhances cognitive function in AD, suggesting a novel therapeutic strategy for AD. https://clinicaltrials.gov/study/NCT05143463 , Identifier: NCT05143463, Release date: 3 December 2021.", "source": "PubMed"}, {"chunk_id": "41435531_0", "pmid": "41435531", "title": "Dual glymphatic roles in first-episode schizophrenia and clinical high-risk for psychosis: Evidence from diffusion tensor image analysis along the perivascular space index.", "authors": "Peng S, Geng X, Huen WWK et al.", "year": "2026", "journal": "Schizophrenia research", "keywords": "At-risk mental state, Clinical high-risk for psychosis, DTI-ALPS, First-episode schizophrenia, Glymphatic system", "chunk": "Emerging evidence has implicated glymphatic dysfunction in schizophrenia-spectrum disorders (SSD), yet its role during early stages of the disease remains unclear. To clarify its involvement in pathophysiological mechanisms in the early illness course, we evaluated glymphatic function in first-episode SSD (FES) and clinical high-risk for psychosis (CHR-P) populations using diffusion-tensor image analysis along perivascular space (DTI-ALPS) index, testing whether it would exhibit progressive deterioration or transient compensatory adaptation. We examined 55 FES patients, 23 individuals with CHR-P and 30 healthy controls (HCs). ANCOVAs were conducted on the global and bilateral DTI-ALPS indices across the three groups, adjusting for age, sex, and head motion. Partial correlation analyses further examined associations between DTI-ALPS index and measures on severity of various symptom dimensions, functioning, and cognitive performance of FES and CHR-P samples. After controlling for covariates, group comparisons revealed that FES patients showed significantly lower global and bilateral DTI-ALPS indices than HCs, while", "source": "PubMed"}, {"chunk_id": "41435531_1", "pmid": "41435531", "title": "Dual glymphatic roles in first-episode schizophrenia and clinical high-risk for psychosis: Evidence from diffusion tensor image analysis along the perivascular space index.", "authors": "Peng S, Geng X, Huen WWK et al.", "year": "2026", "journal": "Schizophrenia research", "keywords": "At-risk mental state, Clinical high-risk for psychosis, DTI-ALPS, First-episode schizophrenia, Glymphatic system", "chunk": "functioning, and cognitive performance of FES and CHR-P samples. After controlling for covariates, group comparisons revealed that FES patients showed significantly lower global and bilateral DTI-ALPS indices than HCs, while CHR-P did not differ from HCs. Antipsychotic dosage and FES diagnostic subtypes showed no significant differences in DTI-ALPS indices. Correlation analyses showed that, after correction for multiple comparisons, ALPS indices showed no significant correlations with symptoms or cognitive performance. But in the uncorrected analyses, the FES and CHR-P groups showed opposite patterns of correlations with symptoms and cognition. These findings indicate that glymphatic dysfunction is a prominent feature of FES, while early signs of dysfunction may already be present during the prodromal stage. DTI-ALPS index show potential as a stage-specific marker pending longitudinal validation and replication.", "source": "PubMed"}, {"chunk_id": "41435531_2", "pmid": "41435531", "title": "Dual glymphatic roles in first-episode schizophrenia and clinical high-risk for psychosis: Evidence from diffusion tensor image analysis along the perivascular space index.", "authors": "Peng S, Geng X, Huen WWK et al.", "year": "2026", "journal": "Schizophrenia research", "keywords": "At-risk mental state, Clinical high-risk for psychosis, DTI-ALPS, First-episode schizophrenia, Glymphatic system", "chunk": "marker pending longitudinal validation and replication.", "source": "PubMed"}, {"chunk_id": "36551947_0", "pmid": "36551947", "title": "Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation.", "authors": "Choi HJ, Han M, Jung B et al.", "year": "2022", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s disease, aquaporin-4, blood\u2013brain barrier, focused ultrasound, methylene blue", "chunk": "Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. Despite the small molecular size of MB, which can cross the BBB, the therapeutic effective dosage using a BBB-permeable delivery system in a specific brain localization remains unclear. In this study, we presented magnetic resonance-guided focused ultrasound (MRgFUS) as a delivery system to enhance BBB permeability for the effective treatment of AD. MRgFUS using two ultrasound intensities (0.25 and 0.32 MPa) was used to intravenously deliver MB to the hippocampal region. Compared with treatment with 0.25 MPa FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-\u03b2 (A\u03b2) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore,", "source": "PubMed"}, {"chunk_id": "36551947_1", "pmid": "36551947", "title": "Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood-Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation.", "authors": "Choi HJ, Han M, Jung B et al.", "year": "2022", "journal": "Biomedicines", "keywords": "Alzheimer\u2019s disease, aquaporin-4, blood\u2013brain barrier, focused ultrasound, methylene blue", "chunk": "FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-\u03b2 (A\u03b2) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore, aquaporin-4 expression increased significantly in the 0.32 MPa FUS and 0.32 MPa FUS/MB groups without glial fibrillary acidic protein activation. The results from this study demonstrate that FUS improved MB delivery to the brain, and FUS/MB combination treatment reduced the number of A\u03b2 plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD.", "source": "PubMed"}, {"chunk_id": "38167971_0", "pmid": "38167971", "title": "Palmitic Acid Induces Posttranslational Modifications of Tau Protein in Alzheimer's Disease-Related Epitopes and Increases Intraneuronal Tau Levels.", "authors": "Garc\u00eda-Cruz VM, Arias C", "year": "2024", "journal": "Molecular neurobiology", "keywords": "GSK3\u03b2, PP2A, Palmitic acid, Tau acetylation, Tau phosphorylation, mTORC1", "chunk": "Metabolic diseases derived from an unhealthy lifestyle have been linked with an increased risk for developing cognitive impairment and even Alzheimer's disease (AD). Although high consumption of saturated fatty acids such as palmitic acid (PA) has been associated with the development of obesity and type II diabetes, the mechanisms connecting elevated neuronal PA levels and increased AD marker expression remain unclear. Among other effects, PA induces insulin resistance, increases intracellular calcium and reactive oxygen species (ROS) production, and reduces the NAD+/NADH ratio, resulting in decreased activity of the deacetylase Sirtuin1 (SIRT1) in neurons. These mechanisms may affect signaling pathways that impact the posttranslational modifications (PTMs) of the tau protein. To analyze the role played by PA in inducing the phosphorylation and acetylation of tau, we examined PTM changes in human tau in differentiated neurons from human neuroblastoma cells. We found changes in the phosphorylation state of several AD-related sites, namely,", "source": "PubMed"}, {"chunk_id": "38167971_1", "pmid": "38167971", "title": "Palmitic Acid Induces Posttranslational Modifications of Tau Protein in Alzheimer's Disease-Related Epitopes and Increases Intraneuronal Tau Levels.", "authors": "Garc\u00eda-Cruz VM, Arias C", "year": "2024", "journal": "Molecular neurobiology", "keywords": "GSK3\u03b2, PP2A, Palmitic acid, Tau acetylation, Tau phosphorylation, mTORC1", "chunk": "and acetylation of tau, we examined PTM changes in human tau in differentiated neurons from human neuroblastoma cells. We found changes in the phosphorylation state of several AD-related sites, namely, S199/202 and S214, that were mediated by a mechanism associated with the dysregulated activity of the kinases GSK3\u03b2 and mTOR. PA also increased the acetylation of residue K280 and elevated total tau level after long exposure time. These findings provide information about the mechanisms by which saturated fatty acids cause tau PTMs that are similar to those observed in association with AD biochemical changes.", "source": "PubMed"}, {"chunk_id": "41491073_0", "pmid": "41491073", "title": "NLRP3 inflammasome and Alzheimer's disease: bridging inflammation and neurodegeneration.", "authors": "Wasim R, Azmi S, Ahmad A et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Mitochondrial dysfunction, NLRP3 inflammasome, Neuroinflammation, Therapeutic targets", "chunk": "The progressive neurodegenerative disease known as Alzheimer's disease (AD) is characterized by widespread neuronal death, memory loss, and cognitive decline. The NLRP3 inflammasome has emerged as a key modulator of neuroinflammation, which is increasingly implicated in the pathophysiology of AD. In response to endogenous and pathogenic danger signals, the innate immune system's multiprotein complex known as the NLRP3 inflammasome is activated. Pyroptosis and neuroinflammatory cascades are eventually triggered by its activation, which causes caspase-1 to be cleaved and pro-inflammatory cytokines like interleukin-1\u03b2 and interleukin-18 to be released. NLRP3 activation is strongly stimulated by tau aggregation and \u03b2-amyloid plaques in AD, which accelerates neuronal damage and prolongs chronic inflammation. The control and activation of inflammasomes are involved in both canonical and non-canonical pathways as well as mitochondrial dysfunction. Significantly, animal models indicate that NLRP3's therapeutic potential is highlighted by the reduction of amyloid burden and amelioration of cognitive decline that results", "source": "PubMed"}, {"chunk_id": "41491073_1", "pmid": "41491073", "title": "NLRP3 inflammasome and Alzheimer's disease: bridging inflammation and neurodegeneration.", "authors": "Wasim R, Azmi S, Ahmad A et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Amyloid-\u03b2, Mitochondrial dysfunction, NLRP3 inflammasome, Neuroinflammation, Therapeutic targets", "chunk": "non-canonical pathways as well as mitochondrial dysfunction. Significantly, animal models indicate that NLRP3's therapeutic potential is highlighted by the reduction of amyloid burden and amelioration of cognitive decline that results from its inhibition or genetic deletion. Small-molecule inhibitors and natural substances that can alter NLRP3 activity have been discovered recently, providing intriguing approaches to AD treatment. Despite tremendous advancements, issues with medication selectivity and blood-brain barrier penetration still need to be resolved before these discoveries can be used in clinical settings. Comprehending the complex relationship between NLRP3 activation and Alzheimer's pathology may open the door to new, focused treatments meant to slow or stop the progression of the illness.", "source": "PubMed"}, {"chunk_id": "38927020_0", "pmid": "38927020", "title": "Crystal Violet Selectively Detects A\u03b2 Oligomers but Not Fibrils In Vitro and in Alzheimer's Disease Brain Tissue.", "authors": "Karunarathne K, Kee TR, Jeon H et al.", "year": "2024", "journal": "Biomolecules", "keywords": "Alzheimer\u2019s Disease, Crystal Violet, Thioflavin T, amyloid beta, amyloid oligomers, fluorescence, tissue staining", "chunk": "Deposition of extracellular Amyloid Beta (A\u03b2) and intracellular tau fibrils in post-mortem brains remains the only way to conclusively confirm cases of Alzheimer's Disease (AD). Substantial evidence, though, implicates small globular oligomers instead of fibrils as relevant biomarkers of, and critical contributors to, the clinical symptoms of AD. Efforts to verify and utilize amyloid oligomers as AD biomarkers in vivo have been limited by the near-exclusive dependence on conformation-selective antibodies for oligomer detection. While antibodies have yielded critical evidence for the role of both A\u03b2 and tau oligomers in AD, they are not suitable for imaging amyloid oligomers in vivo. Therefore, it would be desirable to identify a set of oligomer-selective small molecules for subsequent development into Positron Emission Tomography (PET) probes. Using a kinetics-based screening assay, we confirm that the triarylmethane dye Crystal Violet (CV) is oligomer-selective for A\u03b242 oligomers (A\u03b2Os) grown under near-physiological solution conditions in vitro. In", "source": "PubMed"}, {"chunk_id": "38927020_1", "pmid": "38927020", "title": "Crystal Violet Selectively Detects A\u03b2 Oligomers but Not Fibrils In Vitro and in Alzheimer's Disease Brain Tissue.", "authors": "Karunarathne K, Kee TR, Jeon H et al.", "year": "2024", "journal": "Biomolecules", "keywords": "Alzheimer\u2019s Disease, Crystal Violet, Thioflavin T, amyloid beta, amyloid oligomers, fluorescence, tissue staining", "chunk": "(PET) probes. Using a kinetics-based screening assay, we confirm that the triarylmethane dye Crystal Violet (CV) is oligomer-selective for A\u03b242 oligomers (A\u03b2Os) grown under near-physiological solution conditions in vitro. In postmortem brains of an AD mouse model and human AD patients, we demonstrate that A11 antibody-positive oligomers but not Thioflavin S (ThioS)-positive fibrils colocalize with CV staining, confirming in vitro results. Therefore, our kinetic screen represents a robust approach for identifying new classes of small molecules as candidates for oligomer-selective dyes (OSDs). Such OSDs, in turn, provide promising starting points for the development of PET probes for pre-mortem imaging of oligomer deposits in humans.", "source": "PubMed"}, {"chunk_id": "39811969_0", "pmid": "39811969", "title": "Tungsten disulphide nanosheet modulated fluorescent gold nanocluster immunoprobe for the detection of tau peptide: Alzheimer's disease biomarker.", "authors": "Abraham MK, Madanan AS, Varghese S et al.", "year": "2025", "journal": "Analytical methods : advancing methods and applications", "keywords": "None", "chunk": "The neuronal tau peptide serves as a key biomarker for neurodegenerative diseases, specifically, Alzheimer's disease, a condition that currently has no cure or definitive diagnosis. The methodology to noninvasively detect tau levels from body fluids remains a major hurdle for a rapid and simple diagnostic approach. Thus, developing new detection methods for sensing tau protein levels is crucial. In this work, we report an immunoprobe based on anti-tau antibody (mAb-tau)-conjugated fluorescent gold nanoclusters (AuNCs) quenched with tungsten disulphide nanosheets (WS<sub>2</sub> NS) for the detection of tau protein in human serum samples. The mAb-tau conjugated probe is designed to provide a specific binding site for the tau peptide by strong antigen-antibody interface. The WS<sub>2</sub> NS surface quenches the fluorescence of mAb-tau@AuNCs, which is subsequently recovered by the addition of tau peptide in a linear concentration range (63.3-615.38 pg mL<sup>-1</sup>). The enhancement in fluorescence of WS<sub>2</sub> NS@mAb-tau@AuNCs enables the quantification of tau", "source": "PubMed"}, {"chunk_id": "39811969_1", "pmid": "39811969", "title": "Tungsten disulphide nanosheet modulated fluorescent gold nanocluster immunoprobe for the detection of tau peptide: Alzheimer's disease biomarker.", "authors": "Abraham MK, Madanan AS, Varghese S et al.", "year": "2025", "journal": "Analytical methods : advancing methods and applications", "keywords": "None", "chunk": "which is subsequently recovered by the addition of tau peptide in a linear concentration range (63.3-615.38 pg mL<sup>-1</sup>). The enhancement in fluorescence of WS<sub>2</sub> NS@mAb-tau@AuNCs enables the quantification of tau peptide in concentrations pertinent to human serum tau levels in Alzheimer's patients. The developed probe achieves a limit of detection (LOD) and limit of quantification (LOQ) of 6.54 pg mL<sup>-1</sup> and 21.8 pg mL<sup>-1</sup> for tau peptide in PBS buffer. The study is further extended in spiked human serum samples, with satisfactory recovery percentages in the range of 94.37-117.53%. The technique holds promise as an immunoprobe for tau peptide detection and has potential in developing an economically viable probe for the clinical diagnosis of tau-related neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "41830497_0", "pmid": "41830497", "title": "Late-life methionine restriction attenuates neuroinflammation in Alzheimer's disease mice via FGF21 activation in a metabolism-independent manner.", "authors": "Zhang Y, Li Y, Wang Q et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's Disease, fibroblast growth factor 21, metabolism, methionine restriction, neuroinflammation", "chunk": "Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear. Fourteen-month-old male APP/PS1 mice received 17 weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno-associated virus. Late-life MR improved peripheral glucose/lipid profiles, reduced A\u03b2 deposition, preserved synaptic markers, and suppressed neuroinflammation. MR-induced hepatic FGF21 and brain FGFR1-AMPK\u03b1 signaling to inhibit NF\u03baB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact. Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21-brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation.", "source": "PubMed"}, {"chunk_id": "41830497_1", "pmid": "41830497", "title": "Late-life methionine restriction attenuates neuroinflammation in Alzheimer's disease mice via FGF21 activation in a metabolism-independent manner.", "authors": "Zhang Y, Li Y, Wang Q et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's Disease, fibroblast growth factor 21, metabolism, methionine restriction, neuroinflammation", "chunk": "FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation.", "source": "PubMed"}, {"chunk_id": "41571430_0", "pmid": "41571430", "title": "Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [<sup>18</sup>F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.", "authors": "Ngam PI, Anzai Y, Cliatt Brown CJ et al.", "year": "2026", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "AD, LATE, MRI volumetry, [18F]FDG PET", "chunk": "Limbic-predominant age-related transactive response DNA-binding protein 43 kDa encephalopathy (LATE) is emerging as a prevalent neurodegenerative disorder in aging populations, mimicking the clinical presentation of Alzheimer disease (AD). This study investigates in vivo [<sup>18</sup>F]FDG PET and MRI biomarkers in detecting probable LATE neuropathologic change. <b>Methods:</b> We retrospectively analyzed 944 [<sup>18</sup>F]FDG PET cases referred from cognitive disorder clinics in a tertiary care center. To characterize the LATE and AD findings objectively and quantitatively, we created 3-dimensional stereotactic surface projection PET templates for LATE neuropathologic change (<i>n</i> = 6) and AD neuropathologic change (<i>n</i> = 32) from autopsy-confirmed Alzheimer's Disease Neuroimaging Initiative and University of Utah datasets, respectively. All 3-dimensional stereotactic surface projection <i>z</i> score [<sup>18</sup>F]FDG maps were created in comparison to normal PET scans from 20 control cases whose amyloid PET scans were negative. Using the autopsy-derived <i>z</i> score maps, <i>z</i> score product indices (the individual <i>z</i> score map multiplied by", "source": "PubMed"}, {"chunk_id": "41571430_1", "pmid": "41571430", "title": "Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [<sup>18</sup>F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.", "authors": "Ngam PI, Anzai Y, Cliatt Brown CJ et al.", "year": "2026", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "AD, LATE, MRI volumetry, [18F]FDG PET", "chunk": "normal PET scans from 20 control cases whose amyloid PET scans were negative. Using the autopsy-derived <i>z</i> score maps, <i>z</i> score product indices (the individual <i>z</i> score map multiplied by the <i>z</i> scores of autopsy-confirmed cohorts) were generated for each subject, stratifying participants into probable LATE, probable LATE and AD (LATE+AD), and probable AD. Clinical and quantitative MRI volumetry data were compared across the groups using 1-way or Welch ANOVA and Fisher exact tests, depending on the assessed variables. <b>Results:</b> Of the 944 clinical cases, 13.0% were characterized as probable LATE (2.4% pure LATE and 10.6% LATE+AD) and 23.7% were characterized as probable AD without LATE. MRI volumetry revealed that the medial temporal lobe was most affected in pure LATE cases (<i>P</i> < 0.001), whereas the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE+AD cases (<i>P</i> = 0.001; <i>P</i> < 0.001). Post hoc analysis identified the", "source": "PubMed"}, {"chunk_id": "41571430_2", "pmid": "41571430", "title": "Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [<sup>18</sup>F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.", "authors": "Ngam PI, Anzai Y, Cliatt Brown CJ et al.", "year": "2026", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "AD, LATE, MRI volumetry, [18F]FDG PET", "chunk": "cases (<i>P</i> < 0.001), whereas the orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE+AD cases (<i>P</i> = 0.001; <i>P</i> < 0.001). Post hoc analysis identified the entorhinal cortex and amygdala as key regions for distinguishing mixed LATE+AD cases from pure LATE and pure AD cases, respectively (<i>P</i> = 0.05; <i>P</i> < 0.001). Subgroup analysis of the probable LATE+AD group demonstrated additive or synergistic effects of both pathologies, with three quarters of cases exhibiting concordant lateralized metabolic brain changes, predominantly left-sided, based on LATE and AD <i>z</i> score products (<i>P</i> < 0.001). A similar pattern of left-dominant brain atrophy was observed in MRI volumetry. <b>Conclusion:</b> Substantial numbers of our patients exhibited LATE features that were characterized objectively using scans from autopsy-proven cases. These LATE cases were associated with specific regional atrophy measured by quantitative MRI. Cases with LATE+AD copathologies demonstrated synergistic hemispheric involvement. Further investigations of such", "source": "PubMed"}, {"chunk_id": "41571430_3", "pmid": "41571430", "title": "Copathologies of Limbic-Predominant Age-Related TDP-43 Encephalopathy and Alzheimer Disease: [<sup>18</sup>F]FDG PET Statistical Mapping and Quantitative MRI Volumetry.", "authors": "Ngam PI, Anzai Y, Cliatt Brown CJ et al.", "year": "2026", "journal": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "keywords": "AD, LATE, MRI volumetry, [18F]FDG PET", "chunk": "using scans from autopsy-proven cases. These LATE cases were associated with specific regional atrophy measured by quantitative MRI. Cases with LATE+AD copathologies demonstrated synergistic hemispheric involvement. Further investigations of such synergistic changes between LATE and AD are warranted.", "source": "PubMed"}, {"chunk_id": "36905719_0", "pmid": "36905719", "title": "Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia.", "authors": "Chen C, Kowahl NR, Rainaldi E et al.", "year": "2023", "journal": "Parkinsonism & related disorders", "keywords": "Digital biomarkers in Parkinson's, Digital-based endpoints in Parkinson's, Pharmacodynamic response biomarkers in Parkinson's, Wearable sensors", "chunk": "Few late-stage clinical trials in Parkinson's disease (PD) have produced evidence on the clinical validity of sensor-based digital measurements of daily life activities to detect responses to treatment. The objective of this study was to assess whether digital measures from patients with mild-to-moderate Lewy Body Dementia demonstrate treatment effects during a randomized Phase 2 trial. Substudy within a 12-week trial of mevidalen (placebo vs 10, 30, or 75 mg), where 70/344 patients (comparable to the overall population) wore a wrist-worn multi-sensor device. Treatment effects were statistically significant by conventional clinical assessments (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] sum of Parts I-III and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC] scores) in the full study cohort at Week 12, but not in the substudy. However, digital measurements detected significant effects in the substudy cohort at week 6, persisting to week 12. Digital measurements detected treatment effects in", "source": "PubMed"}, {"chunk_id": "36905719_1", "pmid": "36905719", "title": "Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia.", "authors": "Chen C, Kowahl NR, Rainaldi E et al.", "year": "2023", "journal": "Parkinsonism & related disorders", "keywords": "Digital biomarkers in Parkinson's, Digital-based endpoints in Parkinson's, Pharmacodynamic response biomarkers in Parkinson's, Wearable sensors", "chunk": "Week 12, but not in the substudy. However, digital measurements detected significant effects in the substudy cohort at week 6, persisting to week 12. Digital measurements detected treatment effects in a smaller cohort over a shorter period than conventional clinical assessments. clinicaltrials.gov, NCT03305809.", "source": "PubMed"}, {"chunk_id": "41405782_0", "pmid": "41405782", "title": "Vision and convolutional transformers for Alzheimer's disease diagnosis: a systematic review of architectures, multimodal fusion and critical gaps.", "authors": "Afifi I, Elgendy M, Abdelfatah M et al.", "year": "2025", "journal": "Brain informatics", "keywords": "Alzheimer\u2019s disease (AD), Convolutional vision transformers (CViTs), Deep learning (DL), Disease progression prediction, Explainable AI (XAI), Large vision models (LVMs), Mild cognitive impairment (MCI), Multimodal fusion, Systematic review, Vision transformers (ViTs)", "chunk": "Alzheimer's disease (AD), a significant public health challenge, requires accurate early diagnosis to improve patient outcomes. Vision Transformers (ViTs) and Convolutional Vision Transformers (CViTs) have emerged as powerful Deep Learning architectures for this task. Following PRISMA guidelines, this systematic review analyzes 68 studies selected from 564 publications (2021-2025) across five major databases: Scopus, Web of Science, ScienceDirect, IEEE Xplore, and PubMed. We introduce novel taxonomies to systematically categorize these works by model architecture, data modality, fusion strategy, and diagnostic objective. Our analysis reveals key trends, such as the rise of hybrid CViT frameworks, and critical gaps, including a limited focus on Mild Cognitive Impairment-to-AD progression. Critically, we also assess practical implementation details, revealing widespread challenges in algorithmic reproducibility. The discussion culminates in a forward-looking analysis of Large Vision Models and proposes future directions emphasizing the need for robust multimodal integration, lightweight transformer designs, and Explainable AI to advance AD research", "source": "PubMed"}, {"chunk_id": "41405782_1", "pmid": "41405782", "title": "Vision and convolutional transformers for Alzheimer's disease diagnosis: a systematic review of architectures, multimodal fusion and critical gaps.", "authors": "Afifi I, Elgendy M, Abdelfatah M et al.", "year": "2025", "journal": "Brain informatics", "keywords": "Alzheimer\u2019s disease (AD), Convolutional vision transformers (CViTs), Deep learning (DL), Disease progression prediction, Explainable AI (XAI), Large vision models (LVMs), Mild cognitive impairment (MCI), Multimodal fusion, Systematic review, Vision transformers (ViTs)", "chunk": "culminates in a forward-looking analysis of Large Vision Models and proposes future directions emphasizing the need for robust multimodal integration, lightweight transformer designs, and Explainable AI to advance AD research and bridge the critical gap between high-performance modeling and clinical applicability.", "source": "PubMed"}, {"chunk_id": "38108349_0", "pmid": "38108349", "title": "A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.", "authors": "Na S, Lee C, Ho S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cohort study, improvement, memory, subject cognitive decline", "chunk": "Subjective cognitive decline (SCD) refers to the self-reported persistent cognitive decline despite normal objective testing, increasing the risk of dementia compared to cognitively normal individuals. This study aims to investigate the attributes of SCD patients who demonstrated memory function improvement. In this prospective study of SCD, a total of 120 subjects were enrolled as part of a multicenter cohort study aimed at identifying predictors for the clinical progression to mild cognitive impairment or dementia (CoSCo study). All subjects underwent 18F-florbetaben PET and brain MRI scans at baseline and annual neuropsychological tests. At the 24-month follow-up, we classified SCD patients based on changes in memory function, the z-score of the Seoul verbal learning test delayed recall. Of the 120 enrolled patients, 107 successfully completed the 24-month follow-up assessment. Among these, 80 patients (74.8%) with SCD exhibited memory function improvements. SCD patients with improved memory function had a lower prevalence of coronary", "source": "PubMed"}, {"chunk_id": "38108349_1", "pmid": "38108349", "title": "A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.", "authors": "Na S, Lee C, Ho S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cohort study, improvement, memory, subject cognitive decline", "chunk": "107 successfully completed the 24-month follow-up assessment. Among these, 80 patients (74.8%) with SCD exhibited memory function improvements. SCD patients with improved memory function had a lower prevalence of coronary artery disease at baseline and performed better in the trail-making test part B compared to those without improvement. Anatomical and biomarker analysis showed a lower frequency of amyloid PET positivity and larger volumes in the left and right superior parietal lobes in subjects with improved memory function. Our prospective study indicates that SCD patients experiencing memory improvement over a 24-month period had a lower amyloid burden, fewer cardiovascular risk factors, and superior executive cognitive function. Identifying these key factors associated with cognitive improvement may assist clinicians in predicting future memory function improvements in SCD patients.", "source": "PubMed"}, {"chunk_id": "38108349_2", "pmid": "38108349", "title": "A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.", "authors": "Na S, Lee C, Ho S et al.", "year": "2024", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, cohort study, improvement, memory, subject cognitive decline", "chunk": "function improvements in SCD patients.", "source": "PubMed"}, {"chunk_id": "25932362_0", "pmid": "25932362", "title": "A review of sleep deprivation studies evaluating the brain transcriptome.", "authors": "Elliott AS, Huber JD, O'Callaghan JP et al.", "year": "2014", "journal": "SpringerPlus", "keywords": "Rodent, Sleep deprivation, Sleep disruption, Transcriptome", "chunk": "Epidemiological studies show a positive association between adequate sleep and good health. Further, disrupted sleep may increase the risk for CNS diseases, such as stroke and Alzheimer's disease. However, there has been limited progress in determining how sleep is linked to brain health or how sleep disruption may increase susceptibility to brain insult and disease. Animal studies can aid in understanding these links. In reviewing the animal literature related to the effects of sleep disruption on the brain, we found most of the work was directed toward investigating and characterizing the role of various brain areas or structures in initiating and regulating sleep. In contrast, limited effort has been directed towards understanding how sleep disruption alters the brain's health or susceptibility to insult. We also note many current studies have determined the changes in the brain following compromised sleep by examining, for example, the brain transcriptome or to a more", "source": "PubMed"}, {"chunk_id": "25932362_1", "pmid": "25932362", "title": "A review of sleep deprivation studies evaluating the brain transcriptome.", "authors": "Elliott AS, Huber JD, O'Callaghan JP et al.", "year": "2014", "journal": "SpringerPlus", "keywords": "Rodent, Sleep deprivation, Sleep disruption, Transcriptome", "chunk": "susceptibility to insult. We also note many current studies have determined the changes in the brain following compromised sleep by examining, for example, the brain transcriptome or to a more limited extent the proteome. However, these studies have utilized almost exclusively total sleep deprivation (e.g., 24 out of 24 hours) paradigms or single short periods of limited acute sleep deprivation (e.g., 3 out of 24 hours). While such strategies are beneficial in understanding how sleep is controlled, they may not have much translational value for determining links between sleep and brain health or for determining how sleep disruption may increase brain susceptibility to insult. Surprisingly, few studies have determined how the duration and recurrence of sleep deprivation influence the effects seen after sleep deprivation. Our aim in this review was to identify relevant rodent studies from 1980 through 2012 and analyze those that use varying durations of sleep deprivation or", "source": "PubMed"}, {"chunk_id": "25932362_2", "pmid": "25932362", "title": "A review of sleep deprivation studies evaluating the brain transcriptome.", "authors": "Elliott AS, Huber JD, O'Callaghan JP et al.", "year": "2014", "journal": "SpringerPlus", "keywords": "Rodent, Sleep deprivation, Sleep disruption, Transcriptome", "chunk": "seen after sleep deprivation. Our aim in this review was to identify relevant rodent studies from 1980 through 2012 and analyze those that use varying durations of sleep deprivation or restriction in their effort to evaluate the effects of sleep deprivation on the brain transcriptome and to a more limited extent the proteome. We examined how differences in the duration of sleep deprivation affect gene and protein expression to better understand the full consequences of repeated sleep disruption on the brain. Future research needs to consider and emphasize how the type and extent of the sleep deprivation exposure impacts the conclusions reached concerning the influence of sleep disruption on the brain. We identified relevant studies between 1980 and 2012 by searching the electronic databases of PubMed, Medline (Ovid), Embase (Ovid), and Web of Science using the terms \"sleep\" AND \"disrupt\", \"deprivation\", \"restrict\", \"fragment\", \"loss\", \"disturb\", \"disorder\", \"dysfunction\", \"brain\", \"cortex\", striatum\",", "source": "PubMed"}, {"chunk_id": "25932362_3", "pmid": "25932362", "title": "A review of sleep deprivation studies evaluating the brain transcriptome.", "authors": "Elliott AS, Huber JD, O'Callaghan JP et al.", "year": "2014", "journal": "SpringerPlus", "keywords": "Rodent, Sleep deprivation, Sleep disruption, Transcriptome", "chunk": "searching the electronic databases of PubMed, Medline (Ovid), Embase (Ovid), and Web of Science using the terms \"sleep\" AND \"disrupt\", \"deprivation\", \"restrict\", \"fragment\", \"loss\", \"disturb\", \"disorder\", \"dysfunction\", \"brain\", \"cortex\", striatum\", hypothalamus\", \"hippocampus\", \"gene\", \"protein\", \"genomics\", \"proteomics\", \"polymerase chain reaction\", \"pcr\", \"microarray\", \"molecular\", \"rodent\" \"rat\", \"rats\", \"mouse\", \"mice\". All searches were limited to rodent studies in English and the reference lists of retrieved articles were searched for additional pertinent studies.", "source": "PubMed"}, {"chunk_id": "41494649_0", "pmid": "41494649", "title": "Synergistic potential of TREM2 agonists and exercise training in Alzheimer's disease.", "authors": "Zhang J, St Pierre Schneider B, Muguerza E et al.", "year": "2026", "journal": "American journal of physiology. Endocrinology and metabolism", "keywords": "efferocytosis, exercise, macrophage, metabolism, phagocytosis", "chunk": "Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-enriched receptor that regulates phagocytosis, lipid metabolism, and inflammation resolution in the brain. Loss or mutation of TREM2, including the R47H variant, impairs amyloid-\u03b2 clearance and lipid handling, thereby increasing the risk and accelerating the progression of Alzheimer's disease (AD). TREM2 signaling couples debris recognition with mitochondrial activation and fatty acid oxidation, maintaining microglial energy balance and promoting a reparative phenotype. Pharmacologic TREM2 agonists, such as AL002, DNL919, and VG-3927, enhance microglial survival, plaque compaction, and mitochondrial respiration in AD models, although clinical efficacy may depend on disease stage and metabolic fitness. Exercise training represents a complementary strategy that similarly enhances TREM2 expression, restores microglial homeostasis, and improves mitochondrial metabolism. Both aerobic and resistance exercise activate TREM2-dependent signaling pathways to reduce neuroinflammation and support synaptic integrity. Collectively, these findings highlight TREM2 as a central immunometabolic regulator and suggest that combining", "source": "PubMed"}, {"chunk_id": "41494649_1", "pmid": "41494649", "title": "Synergistic potential of TREM2 agonists and exercise training in Alzheimer's disease.", "authors": "Zhang J, St Pierre Schneider B, Muguerza E et al.", "year": "2026", "journal": "American journal of physiology. Endocrinology and metabolism", "keywords": "efferocytosis, exercise, macrophage, metabolism, phagocytosis", "chunk": "Both aerobic and resistance exercise activate TREM2-dependent signaling pathways to reduce neuroinflammation and support synaptic integrity. Collectively, these findings highlight TREM2 as a central immunometabolic regulator and suggest that combining TREM2-targeted therapeutics with exercise may offer a synergistic strategy to slow neurodegeneration in AD.", "source": "PubMed"}, {"chunk_id": "36961472_0", "pmid": "36961472", "title": "Exosomes, microvesicles, and other extracellular vesicles-a Keystone Symposia report.", "authors": "Cable J, Witwer KW, Coffey RJ et al.", "year": "2023", "journal": "Annals of the New York Academy of Sciences", "keywords": "exomere, exosome, extracellular RNA, extracellular vesicle, mitovesicle, supermere", "chunk": "Extracellular vesicles (EVs) are small, lipid-bilayer-bound particles released by cells that can contain important bioactive molecules, including lipids, RNAs, and proteins. Once released in the extracellular environment, EVs can act as messengers locally as well as to distant tissues to coordinate tissue homeostasis and systemic responses. There is a growing interest in not only understanding the physiology of EVs as signaling particles but also leveraging them as minimally invasive diagnostic and prognostic biomarkers (e.g., they can be found in biofluids) and drug-delivery vehicles. On October 30-November 2, 2022, researchers in the EV field convened for the Keystone symposium \"Exosomes, Microvesicles, and Other Extracellular Vesicles\" to discuss developing standardized language and methodology, new data on the basic biology of EVs and potential clinical utility, as well as novel technologies to isolate and characterize EVs.", "source": "PubMed"}, {"chunk_id": "36961472_1", "pmid": "36961472", "title": "Exosomes, microvesicles, and other extracellular vesicles-a Keystone Symposia report.", "authors": "Cable J, Witwer KW, Coffey RJ et al.", "year": "2023", "journal": "Annals of the New York Academy of Sciences", "keywords": "exomere, exosome, extracellular RNA, extracellular vesicle, mitovesicle, supermere", "chunk": "potential clinical utility, as well as novel technologies to isolate and characterize EVs.", "source": "PubMed"}, {"chunk_id": "33202751_0", "pmid": "33202751", "title": "<i>Porphyromonas gingivalis</i> and Its Systemic Impact: Current Status.", "authors": "Mei F, Xie M, Huang X et al.", "year": "2020", "journal": "Pathogens (Basel, Switzerland)", "keywords": "Porphyromonas gingivalis, periodontitis, systemic diseases", "chunk": "The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. <i>Porphyromonas gingivalis</i>, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of <i>Porphyromonas gingivalis</i> in atherosclerosis, Alzheimer's disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about <i>Porphyromonas gingivalis</i> and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which <i>Porphyromonas gingivalis</i> is involved in the onset or exacerbation", "source": "PubMed"}, {"chunk_id": "33202751_1", "pmid": "33202751", "title": "<i>Porphyromonas gingivalis</i> and Its Systemic Impact: Current Status.", "authors": "Mei F, Xie M, Huang X et al.", "year": "2020", "journal": "Pathogens (Basel, Switzerland)", "keywords": "Porphyromonas gingivalis, periodontitis, systemic diseases", "chunk": "aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which <i>Porphyromonas gingivalis</i> is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that <i>Porphyromonas gingivalis</i> should be regarded as a modifiable factor for several diseases.", "source": "PubMed"}, {"chunk_id": "35173015_0", "pmid": "35173015", "title": "Cerebrospinal Fluid Biomarkers in Autopsy-Confirmed Alzheimer Disease and Frontotemporal Lobar Degeneration.", "authors": "Mattsson-Carlgren N, Grinberg LT, Boxer A et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "To determine how fully automated Elecsys CSF immunoassays for \u03b2-amyloid (A\u03b2) and tau biomarkers and an ultrasensitive Simoa assay for neurofilament light chain (NFL) correlate with neuropathologic changes of Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). We studied 101 patients with antemortem CSF and neuropathology data. CSF samples were collected a mean of 2.9 years before death (range 0.2-7.5 years). CSF was analyzed for A\u03b2<sub>40</sub>, A\u03b2<sub>42</sub>, total tau (T-tau), tau phosphorylated at amino acid residue 181 (P-tau), P-tau/A\u03b2<sub>42</sub> and A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratios, and NFL. Neuropathology measures included Thal phases, Braak stages, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores, AD neuropathologic change (ADNC), and primary and contributory pathologic diagnoses. Associations between CSF biomarkers and neuropathologic features were tested in regression models adjusted for age, sex, and time from sampling to death. CSF biomarkers were associated with neuropathologic measures of A\u03b2 (Thal, CERAD score), tau (Braak stage), and overall", "source": "PubMed"}, {"chunk_id": "35173015_1", "pmid": "35173015", "title": "Cerebrospinal Fluid Biomarkers in Autopsy-Confirmed Alzheimer Disease and Frontotemporal Lobar Degeneration.", "authors": "Mattsson-Carlgren N, Grinberg LT, Boxer A et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "in regression models adjusted for age, sex, and time from sampling to death. CSF biomarkers were associated with neuropathologic measures of A\u03b2 (Thal, CERAD score), tau (Braak stage), and overall ADNC. The CSF P-tau/A\u03b2<sub>42</sub> and A\u03b2<sub>42</sub>/A\u03b2<sub>40</sub> ratios had high sensitivity, specificity, and overall diagnostic performance for intermediate-high ADNC (area under the curve range 0.95-0.96). Distinct biomarker patterns were seen in different FTLD subtypes, with increased NFL and reduced P-tau/T-tau in FTLD-TAR DNA-binding protein 43 and reduced T-tau in progressive supranuclear palsy compared to other FTLD variants. CSF biomarkers, including P-tau, T-tau, A\u03b2<sub>42</sub>, A\u03b2<sub>40</sub>, and NFL, support in vivo identification of AD neuropathology and correlate with FTLD neuropathology. This study provides Class II evidence that distinct CSF biomarker patterns, including for P-tau, T-tau, A\u03b2<sub>42</sub>, A\u03b2<sub>40</sub>, and NFL, are associated with AD and FTLD neuropathology.", "source": "PubMed"}, {"chunk_id": "35173015_2", "pmid": "35173015", "title": "Cerebrospinal Fluid Biomarkers in Autopsy-Confirmed Alzheimer Disease and Frontotemporal Lobar Degeneration.", "authors": "Mattsson-Carlgren N, Grinberg LT, Boxer A et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "P-tau, T-tau, A\u03b2<sub>42</sub>, A\u03b2<sub>40</sub>, and NFL, are associated with AD and FTLD neuropathology.", "source": "PubMed"}, {"chunk_id": "40536997_0", "pmid": "40536997", "title": "Deep brain stimulation for the treatment of Alzheimer's disease: A safer and more effective strategy.", "authors": "Zhang F, Meng Y, Zhang W", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, cholinergic system, deep brain stimulation, entorhinal cortex, fornix, hippocampus, mechanisms, nucleus basalis of Meynert, therapy", "chunk": "Alzheimer's disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit", "source": "PubMed"}, {"chunk_id": "40536997_1", "pmid": "40536997", "title": "Deep brain stimulation for the treatment of Alzheimer's disease: A safer and more effective strategy.", "authors": "Zhang F, Meng Y, Zhang W", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, cholinergic system, deep brain stimulation, entorhinal cortex, fornix, hippocampus, mechanisms, nucleus basalis of Meynert, therapy", "chunk": "research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms, including reducing the deposition of amyloid-\u03b2, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer's disease biomarkers. Researchers must also", "source": "PubMed"}, {"chunk_id": "40536997_2", "pmid": "40536997", "title": "Deep brain stimulation for the treatment of Alzheimer's disease: A safer and more effective strategy.", "authors": "Zhang F, Meng Y, Zhang W", "year": "2026", "journal": "Neural regeneration research", "keywords": "Alzheimer\u2019s disease, amyloid-\u03b2, cholinergic system, deep brain stimulation, entorhinal cortex, fornix, hippocampus, mechanisms, nucleus basalis of Meynert, therapy", "chunk": "evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer's disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer's disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41225656_0", "pmid": "41225656", "title": "Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration.", "authors": "Parker TD, Bethlehem RAI, Seidlitz J et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, BrainChart, Dementia, Frontotemporal lobar degeneration, MRI, Neurodegeneration, Normative modelling", "chunk": "Determining whether MRI brain scans demonstrate atrophy that is beyond \"normal for age\" is challenging. Automated measurements of structural metrics in individual brain regions have shown promise as biomarkers of neurodegeneration, yet widely available reference standards that aid interpretation at the individual level are lacking. Normative modelling, enabling standardized \"brain charts\", represents a significant step in addressing this challenge by generating individualized age- and sex- adjusted centile scores derived from large, aggregated datasets for MRI-derived quantitative metrics. Using normative data from 56,173 participants across the life course, we have developed regional cortical thickness and amygdala/hippocampal volume brain charts (adjusted for total intracranial volume) that can be applied at the individual level. At the group level, we investigate whether regional centile scores relate to cognitive performance (mini-mental state examination) and discriminate individuals with neuropathological evidence of Alzheimer's disease (n = 351) from propensity-matched controls from the National Alzheimer's Coordinating Center (NACC)", "source": "PubMed"}, {"chunk_id": "41225656_1", "pmid": "41225656", "title": "Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration.", "authors": "Parker TD, Bethlehem RAI, Seidlitz J et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, BrainChart, Dementia, Frontotemporal lobar degeneration, MRI, Neurodegeneration, Normative modelling", "chunk": "scores relate to cognitive performance (mini-mental state examination) and discriminate individuals with neuropathological evidence of Alzheimer's disease (n = 351) from propensity-matched controls from the National Alzheimer's Coordinating Center (NACC) dataset. In addition, we explored the relationships between disease stage, cognition, regional tau deposition and regional centile scores in amyloid-\u03b2-PET-positive individuals with Alzheimer's disease dementia (n = 39) and mild cognitive impairment (n = 71) from the Alzheimer's Disease Neuroimaging Initiative-3 (ADNI-3). We then extended this approach to phenotypes of frontotemporal lobar degeneration using the Neuroimaging in Frontotemporal Dementia dataset (n = 113). We demonstrate BrainChart's application to illustrative individual cases. At the group level, we show that in Alzheimer's disease, regional centile scores from brain charting predicted cognitive performance, temporal lobe tau PET tracer uptake and discriminated disease groups from propensity matched cognitively normal controls in independent cohorts. Distinct patterns of age-inappropriate cortical atrophy were also evident in different", "source": "PubMed"}, {"chunk_id": "41225656_2", "pmid": "41225656", "title": "Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration.", "authors": "Parker TD, Bethlehem RAI, Seidlitz J et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, BrainChart, Dementia, Frontotemporal lobar degeneration, MRI, Neurodegeneration, Normative modelling", "chunk": "temporal lobe tau PET tracer uptake and discriminated disease groups from propensity matched cognitively normal controls in independent cohorts. Distinct patterns of age-inappropriate cortical atrophy were also evident in different clinical phenotypes of frontotemporal lobar degeneration from the Neuroimaging in Frontotemporal Dementia dataset. Regional centile scores derived from an extensive normative dataset represent a generalizable method for objectively identifying atrophy in neurodegenerative diseases and can be applied to determine neurodegenerative atrophy at the individual level.", "source": "PubMed"}, {"chunk_id": "38304322_0", "pmid": "38304322", "title": "Performance of the Lumipulse plasma A\u03b242/40 and pTau181 immunoassays in the detection of amyloid pathology.", "authors": "Figdore DJ, Wiste HJ, Bornhorst JA et al.", "year": "2024", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease blood biomarkers, A\u03b242/A\u03b240, amyloid beta, amyloid\u2010PET, pTau181, plasma pTau", "chunk": "This study evaluated the performance of the Lumipulse plasma beta-amyloid (A\u03b2) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid-positron emission tomography (PET). Plasma samples from cognitively unimpaired (<i>N</i> = 179) and MCI/AD dementia (<i>N</i> = 36) individuals were retrospectively evaluated. Plasma A\u03b242/40 and pTau181 were measured using the Lumipulse and Simoa immunoassays. An immunoprecipitation mass spectrometry (IP-MS) assay for plasma A\u03b242/40 was also evaluated. Amyloid-PET status was the outcome measure. Lumipulse and IP-MS A\u03b242/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid-PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa A\u03b242/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining A\u03b242/40 and pTau181 did not significantly improve performance over A\u03b242/40 alone for Lumipulse (AUC 0.83) or over pTau181 alone for Simoa (AUC 0.71). The Lumipulse", "source": "PubMed"}, {"chunk_id": "38304322_1", "pmid": "38304322", "title": "Performance of the Lumipulse plasma A\u03b242/40 and pTau181 immunoassays in the detection of amyloid pathology.", "authors": "Figdore DJ, Wiste HJ, Bornhorst JA et al.", "year": "2024", "journal": "Alzheimer's & dementia (Amsterdam, Netherlands)", "keywords": "Alzheimer's disease blood biomarkers, A\u03b242/A\u03b240, amyloid beta, amyloid\u2010PET, pTau181, plasma pTau", "chunk": "diagnostic accuracy (AUC 0.57). Combining A\u03b242/40 and pTau181 did not significantly improve performance over A\u03b242/40 alone for Lumipulse (AUC 0.83) or over pTau181 alone for Simoa (AUC 0.71). The Lumipulse A\u03b242/40 assay showed similar performance to the IP-MS A\u03b242/40 assay for detection of an abnormal amyloid-PET; and both assays performed better than the two p-tau181 immunoassays. The Simoa A\u03b242/A\u03b240 assay was the least accurate at predicting an abnormal amyloid-PET status. Lumipulse plasma A\u03b242/A\u03b240 AUC for abnormal amyloid-PET detection was 0.81.This performance was comparable to previously reported IP-MS and higher than Simoa.Performance of Alzheimer's disease blood biomarkers varies between assays.", "source": "PubMed"}, {"chunk_id": "12515900_0", "pmid": "12515900", "title": "The glucagon-like peptides: a new genre in therapeutic targets for intervention in Alzheimer's disease.", "authors": "Perry T, Greig NH", "year": "2002", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an insulinotropic hormone, secreted from the enteroendocrine L cells of the intestinal tract in response to nutrient ingestion. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose in patients with type 2 diabetes mellitus. GLP-1 receptors, which are coupled to the cyclic AMP second messenger pathway, are expressed throughout the brains of rodents and humans. The chemoarchitecture of receptor distribution in the brain correlates well with a central role for GLP-1 in the regulation of food intake and response to aversive stress. We have recently reported that GLP-1 and several longer acting analogs that bind at the GLP-1 receptor, possess neurotrophic properties, and offer protection against glutamate-induced apoptosis and oxidative injury in cultured neuronal cells. Furthermore, GLP-1 can modify processing of the amyloid beta- protein precursor in cell culture and dose-dependently reduces amyloid beta-peptide levels in the brain in vivo.", "source": "PubMed"}, {"chunk_id": "12515900_1", "pmid": "12515900", "title": "The glucagon-like peptides: a new genre in therapeutic targets for intervention in Alzheimer's disease.", "authors": "Perry T, Greig NH", "year": "2002", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "injury in cultured neuronal cells. Furthermore, GLP-1 can modify processing of the amyloid beta- protein precursor in cell culture and dose-dependently reduces amyloid beta-peptide levels in the brain in vivo. As such, this review discusses the known role of GLP-1 within the central nervous system, and considers the potential of GLP-1 and analogs as novel therapeutic targets for intervention in Alzheimer's disease (AD) and potentially other central and peripheral neurodegenerative conditions.", "source": "PubMed"}, {"chunk_id": "41383948_0", "pmid": "41383948", "title": "The role of gut microbiota-derived metabolites in neuroinflammation.", "authors": "Mu L, Wang Y", "year": "2025", "journal": "Neuroprotection (Chichester, England)", "keywords": "TMAO, bile acids, indoles, microbiota\u2010gut\u2013brain axis, neuroinflammation", "chunk": "Neuroinflammation, a key defense mechanism of the nervous system, is associated with changes in inflammatory markers and stimulation of neuroimmune cells such as microglia and astrocytes. Growing evidence indicates that the gut microbiota and its metabolites directly or indirectly regulate host health. According to recent studies, bacterial dysbiosis in the gut is closely linked to several central nervous system disorders that cause neuroinflammation, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, sepsis-associated encephalopathy, and ischemic stroke. Recent findings indicate a bidirectional communication network between the gut microbiota and central nervous system that influences neuroinflammation and cognitive function. Dysregulation of this system can affect the generation of cytotoxic metabolites, promote neuroinflammation, and impair cognition. This review explores the lesser-studied microbiota-derived metabolites involved in neuroinflammation-bile acids, trimethylamine-N-oxide, and indole derivatives-as targets for creating new treatment tools for neuroinflammatory illnesses, as well as possible biomarkers for early diagnosis and prognosis.", "source": "PubMed"}, {"chunk_id": "41383948_1", "pmid": "41383948", "title": "The role of gut microbiota-derived metabolites in neuroinflammation.", "authors": "Mu L, Wang Y", "year": "2025", "journal": "Neuroprotection (Chichester, England)", "keywords": "TMAO, bile acids, indoles, microbiota\u2010gut\u2013brain axis, neuroinflammation", "chunk": "in neuroinflammation-bile acids, trimethylamine-N-oxide, and indole derivatives-as targets for creating new treatment tools for neuroinflammatory illnesses, as well as possible biomarkers for early diagnosis and prognosis.", "source": "PubMed"}, {"chunk_id": "41069044_0", "pmid": "41069044", "title": "Storage-dependent variability in Alzheimer disease-related plasma biomarker results using the Fujirebio Lumipulse G1200 platform.", "authors": "Choucair I, Lee TL, Van Eldik LJ et al.", "year": "2025", "journal": "Journal of neuropathology and experimental neurology", "keywords": "Alzheimer disease, A\u03b242), amyloid-beta (A\u03b240, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), pTau217), phosphorylated tau (pTau181, plasma biomarker, pre-analytical stability", "chunk": "Alzheimer disease plasma biomarkers have emerged as minimally invasive, cost-effective tools for early diagnosis and disease monitoring yet their stability under common \"real world\" pre-analytical conditions remains incompletely characterized. We evaluated the stability of six plasma biomarkers, A\u03b240, A\u03b242, pTau181, pTau217, NfL, and glial fibrillary acidic protein (GFAP) using the Fujirebio Lumipulse G1200 platform. Plasma samples were initially collected from four healthy and cognitively unimpaired volunteers. Samples were stored under four conditions: room temperature (0-4 h), +4 \u00b0C (1-10 days), -20 \u00b0C (1-3 weeks), and -80 \u00b0C (4-8 weeks). In this pilot study, A\u03b240 and A\u03b242 remained generally stable. In contrast, pTau181 readings exhibited marked elevations in frozen samples, while pTau217 showed modest early fluctuations followed by significant decreases with prolonged storage. Next, we recruited 12 additional participants (six cognitively normal and six with mild cognitive impairment [MCI]), and their plasma samples were analyzed both fresh and after 4 weeks", "source": "PubMed"}, {"chunk_id": "41069044_1", "pmid": "41069044", "title": "Storage-dependent variability in Alzheimer disease-related plasma biomarker results using the Fujirebio Lumipulse G1200 platform.", "authors": "Choucair I, Lee TL, Van Eldik LJ et al.", "year": "2025", "journal": "Journal of neuropathology and experimental neurology", "keywords": "Alzheimer disease, A\u03b242), amyloid-beta (A\u03b240, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), pTau217), phosphorylated tau (pTau181, plasma biomarker, pre-analytical stability", "chunk": "prolonged storage. Next, we recruited 12 additional participants (six cognitively normal and six with mild cognitive impairment [MCI]), and their plasma samples were analyzed both fresh and after 4 weeks of storage at -80 \u00b0C. Among these participants, pTau181 readouts were significantly higher, and pTau217 were lower, in -80 \u00b0C frozen in comparison to never-frozen samples. These findings underscore the critical need for biomarker-specific sample workup and handling protocols and indicate that results for fresh plasma cannot be assumed to be the same as for frozen samples.", "source": "PubMed"}, {"chunk_id": "10850738_0", "pmid": "10850738", "title": "Early diagnosis of Alzheimer disease with positron emission tomography.", "authors": "Jelic V, Nordberg A", "year": "2000", "journal": "Alzheimer disease and associated disorders", "keywords": "None", "chunk": "The emergence of drugs that may slow progression of Alzheimer disease, if administered early during its course, has necessitated early diagnosis of the disease itself. Among the functional imaging methods that could assist in early diagnosis, positron emission tomography has an important role in providing quantitative measures of various aspects of brain function affected by the disease. Positron emission tomography studies in patients with Alzheimer disease have revealed a typical pattern of metabolic deficits in the temporal and parietal lobes. Additionally, converging evidence from numerous studies indicates that a similar pattern of deficits can be observed in nondemented subjects who are at risk of developing the disease, such as those with recognized genetic traits such as familial Alzheimer disease with mutations in chromosomes 21 and 14, Down syndrome, subjects with the epsilon4 allele of the apolipoprotein E gene, and individuals with mild cognitive impairment. These findings might have implications for", "source": "PubMed"}, {"chunk_id": "10850738_1", "pmid": "10850738", "title": "Early diagnosis of Alzheimer disease with positron emission tomography.", "authors": "Jelic V, Nordberg A", "year": "2000", "journal": "Alzheimer disease and associated disorders", "keywords": "None", "chunk": "mutations in chromosomes 21 and 14, Down syndrome, subjects with the epsilon4 allele of the apolipoprotein E gene, and individuals with mild cognitive impairment. These findings might have implications for the selection of patients for clinical trials, defining the outcome measures and evaluation of treatment efficacy and responder characteristics, but should be confirmed by prospective studies comprising larger samples and include clinicopathologic correlations.", "source": "PubMed"}, {"chunk_id": "41396614_0", "pmid": "41396614", "title": "Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clinical Mismatch.", "authors": "Brown CA, Mundada NS, Cousins KAQ et al.", "year": "2026", "journal": "JAMA neurology", "keywords": "None", "chunk": "Even within individuals who are amyloid positive, clinical symptoms can be impacted by Alzheimer pathology, other pathologic proteins, and cognitive reserve or resilience. Understanding how each of these factors contributes to a patient's clinical presentation is crucial for prognosis and treatment decisions in the era of disease-modifying therapies. To evaluate tau-clinical mismatch as a means to identify those more likely to harbor copathology and/or exhibit resilience to Alzheimer pathology. This was a longitudinal, observational cohort study conducted from 2004 to 2024. The setting included multiple academic medical centers in the US participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) or Penn Alzheimer's Disease Research Center (Penn-ADRC). Included in the analysis were individuals with clinical assessment and measures of either tau positron emission tomography (tau-PET) or phosphorylated tau 217 (p-tau217) who were selected from individuals positive for amyloid \u03b2 (A\u03b2+) in the ADNI cohort (aged 55-95 years) and the Penn-ADRC cohort", "source": "PubMed"}, {"chunk_id": "41396614_1", "pmid": "41396614", "title": "Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clinical Mismatch.", "authors": "Brown CA, Mundada NS, Cousins KAQ et al.", "year": "2026", "journal": "JAMA neurology", "keywords": "None", "chunk": "positron emission tomography (tau-PET) or phosphorylated tau 217 (p-tau217) who were selected from individuals positive for amyloid \u03b2 (A\u03b2+) in the ADNI cohort (aged 55-95 years) and the Penn-ADRC cohort (aged 54-92 years). Clinical assessment (Clinical Dementia Rating Sum of Boxes [CDR-SB]) and tau burden (tau-PET or p-tau217) for mismatch group classification. Cross-sectional measures of neurodegeneration (medial temporal lobe volume and thickness, cortical thickness, TAR DNA-binding protein 43 [TDP-43] imaging signature), \u03b1-synuclein cerebrospinal fluid seed-amplification assay, and longitudinal CDR-SB. A total of 365 participants (mean [SD] age, 75.4 [7.9] years; 192 female [52.6%]) in the ADNI tau-PET group and 524 participants (mean [SD] age, 77.1 [7.9] years; 268 male [51.1%]) in the ADNI p-tau217 group were selected from the 998 individuals who were A\u03b2+ in the ADNI cohort and used to generate tau-clinical mismatch models with 55.6% to 57.1% classified as canonical (CDR-SB commensurate to tau), 23.7% to 24.7% as", "source": "PubMed"}, {"chunk_id": "41396614_2", "pmid": "41396614", "title": "Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clinical Mismatch.", "authors": "Brown CA, Mundada NS, Cousins KAQ et al.", "year": "2026", "journal": "JAMA neurology", "keywords": "None", "chunk": "individuals who were A\u03b2+ in the ADNI cohort and used to generate tau-clinical mismatch models with 55.6% to 57.1% classified as canonical (CDR-SB commensurate to tau), 23.7% to 24.7% as resilient (CDR-SB < tau), and 19.3% to 19.7% as vulnerable (CDR-SB > tau). Vulnerable groups had evidence of greater likelihood of copathology, with TDP-43 neurodegeneration patterns and \u03b1-synuclein positivity. Mismatch groups showed diverging clinical trajectories with earlier cognitive impairment in vulnerable groups and later impairment in resilient individuals. Similar findings were seen when applied to an independent dataset of 244 individuals (mean [SD] age, 73.7 [6.8] years; 139 female [57.0%]) of the 248 who were A\u03b2+ in Penn-ADRC cohort. Finally, these models were applied to a cohort receiving antiamyloid therapy to show the utility of this method for predicting individual cognitive trajectories during therapy. Results of this cohort study suggest that tau-clinical mismatch identified individuals more likely to have an", "source": "PubMed"}, {"chunk_id": "41396614_3", "pmid": "41396614", "title": "Evaluation of Copathology and Clinical Trajectories in Individuals With Tau-Clinical Mismatch.", "authors": "Brown CA, Mundada NS, Cousins KAQ et al.", "year": "2026", "journal": "JAMA neurology", "keywords": "None", "chunk": "to show the utility of this method for predicting individual cognitive trajectories during therapy. Results of this cohort study suggest that tau-clinical mismatch identified individuals more likely to have an accelerated disease course due to the presence of copathology and those exhibiting greater cognitive resilience to disease pathology. These models provide an important tool that can be implemented in clinical practice to provide improved individualized prognosis and, potentially, monitoring of response to disease-modifying therapy.", "source": "PubMed"}, {"chunk_id": "37699957_0", "pmid": "37699957", "title": "Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.", "authors": "Yang D, Xie H, Wu S et al.", "year": "2023", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson's disease (iPD). To examine the baseline and longitudinal changes in NfL levels in GBA-PD, SNCA-PD, and LRRK2-PD and further investigate the association between these genetic mutations, NfL, and dementia in PD. We analyzed data from the Parkinson's Progression Markers Initiative (PPMI), including 184 healthy controls (HC) and 617 PD categorized as iPD (n = 381), LRRK2-PD (n = 142), GBA-PD (n = 76) and SNCA-PD (n = 18). Analysis of covariance (ANCOVA) or linear mixed-effect models were used to compare the baseline or dynamic NfL levels between groups. We then explored the relationship between genetic mutations, serum NfL levels, and conversion to dementia using mediation analysis. After adjusting for confounding factors, SNCA-PD exhibited higher baseline serum NfL levels than iPD. Regarding longitudinal changes, SNCA-PD showed the highest increase rate in estimated NfL levels (2.43 pg/mL per", "source": "PubMed"}, {"chunk_id": "37699957_1", "pmid": "37699957", "title": "Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.", "authors": "Yang D, Xie H, Wu S et al.", "year": "2023", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "After adjusting for confounding factors, SNCA-PD exhibited higher baseline serum NfL levels than iPD. Regarding longitudinal changes, SNCA-PD showed the highest increase rate in estimated NfL levels (2.43 pg/mL per year), while LRRK2-PD experienced the slowest increase rate (0.52 pg/mL per year). Mediation analysis indicated that higher estimated NfL level changes were associated with faster cognitive decline (\u03b2 = 0.591, p = 0.026). Specifically, the relationship between LRRK2 and dementia was mediated by the estimated NfL level change (\u03b2 = -0.717, p < 0.05). Longitudinal changes in serum NfL levels may serve as a biomarker for cognitive decline in Parkinson's disease. Moreover, compared to iPD, the slower progression of dementia in LRRK2-PD may be partially attributed to a slower increase in NfL levels.", "source": "PubMed"}, {"chunk_id": "37699957_2", "pmid": "37699957", "title": "Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.", "authors": "Yang D, Xie H, Wu S et al.", "year": "2023", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "in NfL levels.", "source": "PubMed"}, {"chunk_id": "34091443_0", "pmid": "34091443", "title": "MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.", "authors": "Liu W, Au LWC, Abrigo J et al.", "year": "2021", "journal": "Aging", "keywords": "MRI, amyloid and tau PET, preclinical Alzheimer\u2019s disease, prodromal Alzheimer's disease, volumetric segmentation tool", "chunk": "Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (\u22650.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET (<sup>11</sup>C-PIB, <sup>18</sup>F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other", "source": "PubMed"}, {"chunk_id": "34091443_1", "pmid": "34091443", "title": "MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.", "authors": "Liu W, Au LWC, Abrigo J et al.", "year": "2021", "journal": "Aging", "keywords": "MRI, amyloid and tau PET, preclinical Alzheimer\u2019s disease, prodromal Alzheimer's disease, volumetric segmentation tool", "chunk": "AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.", "source": "PubMed"}, {"chunk_id": "41770504_0", "pmid": "41770504", "title": "Semi-quantitative tau PET approaches for Braak staging: concordance of CenTauRz and STOC with visual assessment.", "authors": "Wachi K, Yamao T, Miwa K et al.", "year": "2026", "journal": "Annals of nuclear medicine", "keywords": "18F-flortaucipir, Alzheimer\u2019s disease, Braak staging, CenTauRz, STOC, Tau PET", "chunk": "The progression of tau pathology in Alzheimer's disease (AD) is closely linked to cognitive decline. Visual Braak staging of tau PET reflects neurofibrillary tangle distribution but requires expertise in interpretation. The present study aimed to evaluate agreement between Braak stages and semi-quantitative CenTauRz and Simplified Temporal-Occipital Classification (STOC). We collected data from 112 persons with normal cognition (NC), as well as 103 patients with mild cognitive impairment (MCI), and 48 with AD who were assessed by <sup>1</sup>\u2078F-flortaucipir PET and MRI in the ADNI3 study. A board-certified nuclear medicine physician visually assessed Braak stages on PET images. CenTauRz scores were derived by converting standardized uptake value ratios (SUVRs) from five predefined regions. STOC stages was based on SUVRs from four regions, and classified cognitive impairment into five stages of typical tau progression or atypical patterns. Tau positivity was defined as Braak stage \u2265 IV, CenTauRz \u2265 2.0, or STOC stage \u2265", "source": "PubMed"}, {"chunk_id": "41770504_1", "pmid": "41770504", "title": "Semi-quantitative tau PET approaches for Braak staging: concordance of CenTauRz and STOC with visual assessment.", "authors": "Wachi K, Yamao T, Miwa K et al.", "year": "2026", "journal": "Annals of nuclear medicine", "keywords": "18F-flortaucipir, Alzheimer\u2019s disease, Braak staging, CenTauRz, STOC, Tau PET", "chunk": "and classified cognitive impairment into five stages of typical tau progression or atypical patterns. Tau positivity was defined as Braak stage \u2265 IV, CenTauRz \u2265 2.0, or STOC stage \u2265 2/atypical. Concordance (Cohen's \u03ba) and Spearman's correlations (rho, \u03c1) with Braak stages were calculated. The accuracy of CenTauRz compared to Braak stages was 0.84-0.90, \u03ba = 0.61-0.77, and \u03c1 = 0.67-0.83 and that of STOC was 0.87; \u03ba = 0.71, and \u03c1 = 0.81. CenTauRz captured the regional heterogeneity of tau accumulation, whereas STOC provided a staging framework aligned with Braak progression. The agreement of CenTauRz and STOC with visually assessed Braak stages was strong. Combinations of semi-quantitative methods might serve as complementary tools for tau PET images and improve interpretive reliability and objectivity.", "source": "PubMed"}, {"chunk_id": "41770504_2", "pmid": "41770504", "title": "Semi-quantitative tau PET approaches for Braak staging: concordance of CenTauRz and STOC with visual assessment.", "authors": "Wachi K, Yamao T, Miwa K et al.", "year": "2026", "journal": "Annals of nuclear medicine", "keywords": "18F-flortaucipir, Alzheimer\u2019s disease, Braak staging, CenTauRz, STOC, Tau PET", "chunk": "interpretive reliability and objectivity.", "source": "PubMed"}, {"chunk_id": "41557460_0", "pmid": "41557460", "title": "Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.", "authors": "Prescott M, Collinson M, Hall AJ et al.", "year": "2026", "journal": "Health technology assessment (Winchester, England)", "keywords": "ACUTE DISEASE, AGED, COST\u2013BENEFIT ANALYSIS, EXERCISE THERAPY, FOLLOW-UP STUDIES, FRAIL ELDERLY, FRAILTY, FUNCTIONAL STATUS, HOSPITALS, HUMANS, INTENTION-TO-TREAT ANALYSIS, PATIENT DISCHARGE, PATIENT RE-ADMISSION, QUALITY OF LIFE, RANDOMISED CONTROLLED TRIAL, SELF-REPORT, SUBACUTE CARE", "chunk": "Half of older people in hospital have frailty and are at increased risk of re-admission or death following discharge. Although short-term rehabilitation can reduce early re-admissions, benefits are attenuated over time. It is unknown whether extended rehabilitation for older people with frailty can improve outcomes. Pragmatic, multicentre, individually randomised controlled parallel-group superiority trial with economic evaluation and embedded process evaluation. Participants: Eligible participants were 65 years or older with mild/moderate/severe frailty (score of 5-7 on Clinical Frailty Scale) admitted to hospital with acute illness or injury, then discharged home directly or from intermediate care (post-acute care) rehabilitation services. People with significant cognitive impairment and care home residents were among those ineligible. Recruitment took place from December 2017 to August 2021, with follow-up till August 2022. Interventions: Participants were randomly assigned (1.28 : 1) to the Home-based Older People's Exercise programme - a 24-week home-based manualised, progressive exercise intervention delivered by", "source": "PubMed"}, {"chunk_id": "41557460_1", "pmid": "41557460", "title": "Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.", "authors": "Prescott M, Collinson M, Hall AJ et al.", "year": "2026", "journal": "Health technology assessment (Winchester, England)", "keywords": "ACUTE DISEASE, AGED, COST\u2013BENEFIT ANALYSIS, EXERCISE THERAPY, FOLLOW-UP STUDIES, FRAIL ELDERLY, FRAILTY, FUNCTIONAL STATUS, HOSPITALS, HUMANS, INTENTION-TO-TREAT ANALYSIS, PATIENT DISCHARGE, PATIENT RE-ADMISSION, QUALITY OF LIFE, RANDOMISED CONTROLLED TRIAL, SELF-REPORT, SUBACUTE CARE", "chunk": "with follow-up till August 2022. Interventions: Participants were randomly assigned (1.28 : 1) to the Home-based Older People's Exercise programme - a 24-week home-based manualised, progressive exercise intervention delivered by National Health Service therapists as extended rehabilitation, or usual care (control). Randomisation occurred after the participant had been discharged from hospital or intermediate care. Participants were not masked to allocation. Main outcome measures: The primary outcome was physical health-related quality of life, measured using the physical component score of the modified Short Form 36-item health questionnaire at 12 months. Secondary outcomes at 6 and 12 months included physical and mental health-related quality of life, functional independence, death, hospitalisations and care home admissions. Researchers involved in data collection were masked to allocation. Data sources: Primary and secondary outcomes were obtained via self-report questionnaire at 6 and 12 months. Hospitalisations and deaths were collected from routine healthcare data. We randomised 740 participants", "source": "PubMed"}, {"chunk_id": "41557460_2", "pmid": "41557460", "title": "Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.", "authors": "Prescott M, Collinson M, Hall AJ et al.", "year": "2026", "journal": "Health technology assessment (Winchester, England)", "keywords": "ACUTE DISEASE, AGED, COST\u2013BENEFIT ANALYSIS, EXERCISE THERAPY, FOLLOW-UP STUDIES, FRAIL ELDERLY, FRAILTY, FUNCTIONAL STATUS, HOSPITALS, HUMANS, INTENTION-TO-TREAT ANALYSIS, PATIENT DISCHARGE, PATIENT RE-ADMISSION, QUALITY OF LIFE, RANDOMISED CONTROLLED TRIAL, SELF-REPORT, SUBACUTE CARE", "chunk": "allocation. Data sources: Primary and secondary outcomes were obtained via self-report questionnaire at 6 and 12 months. Hospitalisations and deaths were collected from routine healthcare data. We randomised 740 participants (410 Home-based Older People's Exercise, 330 control) across 15 sites. Four hundred and seventy-nine (64.7%) participants completed 12-month follow-up. One hundred and eighty-eight Home-based Older People's Exercise participants (45.9%) completed 24 weeks of intervention delivery. Over half of participants completed more than 75% of prescribed exercises. Intention-to-treat analyses (258 Home-based Older People's Exercise participants, 208 control participants for primary outcome) showed no evidence that Home-based Older People's Exercise was superior to control for 12-month physical component score (adjusted mean difference -0.22, 95% confidence interval -1.47 to 1.03; <i>p</i> = 0.73). There was some evidence of a higher rate of all-cause hospitalisations in the control arm (incidence rate ratio 1.12, 95% confidence interval 1.00 to 1.25; <i>p</i> = 0.05), but no", "source": "PubMed"}, {"chunk_id": "41557460_3", "pmid": "41557460", "title": "Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.", "authors": "Prescott M, Collinson M, Hall AJ et al.", "year": "2026", "journal": "Health technology assessment (Winchester, England)", "keywords": "ACUTE DISEASE, AGED, COST\u2013BENEFIT ANALYSIS, EXERCISE THERAPY, FOLLOW-UP STUDIES, FRAIL ELDERLY, FRAILTY, FUNCTIONAL STATUS, HOSPITALS, HUMANS, INTENTION-TO-TREAT ANALYSIS, PATIENT DISCHARGE, PATIENT RE-ADMISSION, QUALITY OF LIFE, RANDOMISED CONTROLLED TRIAL, SELF-REPORT, SUBACUTE CARE", "chunk": "There was some evidence of a higher rate of all-cause hospitalisations in the control arm (incidence rate ratio 1.12, 95% confidence interval 1.00 to 1.25; <i>p</i> = 0.05), but no evidence of differences in other outcomes. The process evaluation found the intervention was largely delivered as intended and proved acceptable to most participants. The economic analysis showed incremental costs of Home-based Older People's Exercise plus usual care of GB\u00a31401 (mean per participant), compared with usual care alone. There was a 0.024 quality-adjusted life-year improvement in Home-based Older People's Exercise compared to control. The incremental cost-effectiveness ratio was \u00a358,375. This trial was delivered during especially challenging circumstances that included the COVID-19 pandemic. We examined outcomes taking account of this but detected no difference in primary or secondary outcomes, providing reassurance that COVID-19 was unlikely to have influenced trial results. Based on our findings, we do not recommend routine commissioning of extended", "source": "PubMed"}, {"chunk_id": "41557460_4", "pmid": "41557460", "title": "Home-based extended rehabilitation for older people with frailty (HERO): a multicentre randomised controlled trial with health economic analysis and process evaluation.", "authors": "Prescott M, Collinson M, Hall AJ et al.", "year": "2026", "journal": "Health technology assessment (Winchester, England)", "keywords": "ACUTE DISEASE, AGED, COST\u2013BENEFIT ANALYSIS, EXERCISE THERAPY, FOLLOW-UP STUDIES, FRAIL ELDERLY, FRAILTY, FUNCTIONAL STATUS, HOSPITALS, HUMANS, INTENTION-TO-TREAT ANALYSIS, PATIENT DISCHARGE, PATIENT RE-ADMISSION, QUALITY OF LIFE, RANDOMISED CONTROLLED TRIAL, SELF-REPORT, SUBACUTE CARE", "chunk": "no difference in primary or secondary outcomes, providing reassurance that COVID-19 was unlikely to have influenced trial results. Based on our findings, we do not recommend routine commissioning of extended rehabilitation for older people with frailty after discharge home from hospital or intermediate care, following an acute admission with illness or injury. Future work should consider how existing core intermediate care and community rehabilitation services should be best organised and delivered to ensure that older people with frailty feel ready for discharge from rehabilitation, and are enabled to maintain their independence. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/43/07.", "source": "PubMed"}, {"chunk_id": "27107571_0", "pmid": "27107571", "title": "Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes.", "authors": "Ninkovic VM, Ninkovic SM, Miloradovic V et al.", "year": "2016", "journal": "Acta diabetologica", "keywords": "ECG, QT dispersion, QT interval, Type 2 diabetes", "chunk": "Prolonged QT interval is associated with cardiac arrhythmias and sudden death. The present study determined the prevalence of prolonged QT interval and QT dispersion and defined their clinical and metabolic predictors in patients with type 2 diabetes. Cross-sectional study included 501 patients with type 2 diabetes. A standard 12-lead electrocardiogram was recorded. QT corrected for heart rate (QTc) >440 ms and QT dispersion (QTd) >80 ms were considered abnormally prolonged. QTc \u2265 500 ms was considered a high-risk QTc prolongation. Demographic, clinical and laboratory data were collected. Independent risk factors for prolonged QTc and QTd were assessed using logistic regression analysis. Prevalence of QTc > 440 ms and QTd > 80 ms were 44.1 and 3.6 %, respectively. Prevalence of high-risk QTc (\u2265500 ms) was 2 % only. Independent risk factors for QTc prolongation >440 ms were mean blood glucose (\u03b2 = 2.192, p < 0.001), treatment with sulphonylurea (\u03b2", "source": "PubMed"}, {"chunk_id": "27107571_1", "pmid": "27107571", "title": "Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes.", "authors": "Ninkovic VM, Ninkovic SM, Miloradovic V et al.", "year": "2016", "journal": "Acta diabetologica", "keywords": "ECG, QT dispersion, QT interval, Type 2 diabetes", "chunk": "high-risk QTc (\u2265500 ms) was 2 % only. Independent risk factors for QTc prolongation >440 ms were mean blood glucose (\u03b2 = 2.192, p < 0.001), treatment with sulphonylurea (\u03b2 = 5.198, p = 0.027), female gender (\u03b2 = 8.844, p < 0.001), and coronary heart disease (\u03b2 = 8.636, p = 0.001). Independent risk factors for QTc \u2265 500 ms were coronary heart disease (\u03b2 = 4.134, p < 0.001) and mean blood glucose level (\u03b2 = 1.735, p < 0.001). The independent risk factor for prolonged QTd was only coronary heart disease (\u03b2 = 5.354, p < 0.001). Although the prevalence of prolonged QTc > 440 ms is significant, the prevalence of high-risk QTc (\u2265500 ms) and QTd > 80 ms is very low in patients with type 2 diabetes. Hyperglycaemia and coronary heart disease are strong predictors of high-risk QTc.", "source": "PubMed"}, {"chunk_id": "27107571_2", "pmid": "27107571", "title": "Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes.", "authors": "Ninkovic VM, Ninkovic SM, Miloradovic V et al.", "year": "2016", "journal": "Acta diabetologica", "keywords": "ECG, QT dispersion, QT interval, Type 2 diabetes", "chunk": "> 80 ms is very low in patients with type 2 diabetes. Hyperglycaemia and coronary heart disease are strong predictors of high-risk QTc.", "source": "PubMed"}, {"chunk_id": "37862101_0", "pmid": "37862101", "title": "Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.", "authors": "Kim SY, Park J, Choi H et al.", "year": "2023", "journal": "Journal of medical Internet research", "keywords": "Alzheimer disease, biomarkers, dementia, digital markers, eye movement, hand movement, machine learning, mild cognitive impairment, screening, virtual reality", "chunk": "With the global rise in Alzheimer disease (AD), early screening for mild cognitive impairment (MCI), which is a preclinical stage of AD, is of paramount importance. Although biomarkers such as cerebrospinal fluid amyloid level and magnetic resonance imaging have been studied, they have limitations, such as high cost and invasiveness. Digital markers to assess cognitive impairment by analyzing behavioral data collected from digital devices in daily life can be a new alternative. In this context, we developed a \"virtual kiosk test\" for early screening of MCI by analyzing behavioral data collected when using a kiosk in a virtual environment. We aimed to investigate key behavioral features collected from a virtual kiosk test that could distinguish patients with MCI from healthy controls with high statistical significance. Also, we focused on developing a machine learning model capable of early screening of MCI based on these behavioral features. A total of 51 participants", "source": "PubMed"}, {"chunk_id": "37862101_1", "pmid": "37862101", "title": "Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.", "authors": "Kim SY, Park J, Choi H et al.", "year": "2023", "journal": "Journal of medical Internet research", "keywords": "Alzheimer disease, biomarkers, dementia, digital markers, eye movement, hand movement, machine learning, mild cognitive impairment, screening, virtual reality", "chunk": "controls with high statistical significance. Also, we focused on developing a machine learning model capable of early screening of MCI based on these behavioral features. A total of 51 participants comprising 20 healthy controls and 31 patients with MCI were recruited by 2 neurologists from a university hospital. The participants performed a virtual kiosk test-developed by our group-where we recorded various behavioral data such as hand and eye movements. Based on these time series data, we computed the following 4 behavioral features: hand movement speed, proportion of fixation duration, time to completion, and the number of errors. To compare these behavioral features between healthy controls and patients with MCI, independent-samples 2-tailed t tests were used. Additionally, we used these behavioral features to train and validate a machine learning model for early screening of patients with MCI from healthy controls. In the virtual kiosk test, all 4 behavioral features showed statistically", "source": "PubMed"}, {"chunk_id": "37862101_2", "pmid": "37862101", "title": "Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.", "authors": "Kim SY, Park J, Choi H et al.", "year": "2023", "journal": "Journal of medical Internet research", "keywords": "Alzheimer disease, biomarkers, dementia, digital markers, eye movement, hand movement, machine learning, mild cognitive impairment, screening, virtual reality", "chunk": "features to train and validate a machine learning model for early screening of patients with MCI from healthy controls. In the virtual kiosk test, all 4 behavioral features showed statistically significant differences between patients with MCI and healthy controls. Compared with healthy controls, patients with MCI had slower hand movement speed (t<sub>49</sub>=3.45; P=.004), lower proportion of fixation duration (t<sub>49</sub>=2.69; P=.04), longer time to completion (t<sub>49</sub>=-3.44; P=.004), and a greater number of errors (t<sub>49</sub>=-3.77; P=.001). All 4 features were then used to train a support vector machine to distinguish between healthy controls and patients with MCI. Our machine learning model achieved 93.3% accuracy, 100% sensitivity, 83.3% specificity, 90% precision, and 94.7% F<sub>1</sub>-score. Our research preliminarily suggests that analyzing hand and eye movements in the virtual kiosk test holds potential as a digital marker for early screening of MCI. In contrast to conventional biomarkers, this digital marker in virtual reality is advantageous", "source": "PubMed"}, {"chunk_id": "37862101_3", "pmid": "37862101", "title": "Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.", "authors": "Kim SY, Park J, Choi H et al.", "year": "2023", "journal": "Journal of medical Internet research", "keywords": "Alzheimer disease, biomarkers, dementia, digital markers, eye movement, hand movement, machine learning, mild cognitive impairment, screening, virtual reality", "chunk": "movements in the virtual kiosk test holds potential as a digital marker for early screening of MCI. In contrast to conventional biomarkers, this digital marker in virtual reality is advantageous as it can collect ecologically valid data at an affordable cost and in a short period (5-15 minutes), making it a suitable means for early screening of MCI. We call for further studies to confirm the reliability and validity of this approach.", "source": "PubMed"}, {"chunk_id": "26240147_0", "pmid": "26240147", "title": "All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor \u03baB (NF\u03baB) signaling.", "authors": "Wang R, Chen S, Liu Y et al.", "year": "2015", "journal": "The Journal of biological chemistry", "keywords": "Alzheimer disease, NFkappa B (NFKB), beta-secretase 1 (BACE1), gene transcription, retinoic acid, retinoid signaling", "chunk": "Insulin resistance and neuroinflammation have emerged as two likely key contributors in the pathogenesis of Alzheimer disease (AD), especially in those sporadic AD cases compromised by diabetes or cardiovascular disease. Amyloid-\u03b2 (A\u03b2) deposition and its associated inflammatory response are hallmarks in sporadic AD brains. Elevated expression and activity of \u03b2-secretase 1 (BACE1), the rate-limiting enzyme responsible for the \u03b2-cleavage of amyloid precursor proteins to A\u03b2 peptides, are also observed in sporadic AD brains. Previous studies have suggested that there is therapeutic potential for retinoic acid in treating neurodegeneration based on decreased A\u03b2. Here we discovered that BACE1 expression is elevated in the brains of both Tg2576 transgenic mice and mice on high fat diets. These conditions are associated with a neuroinflammatory response. We found that administration of all-trans-retinoic acid (atRA) down-regulated the expression of BACE1 in the brains of Tg2576 mice and in mice fed a high fat diet. Moreover,", "source": "PubMed"}, {"chunk_id": "26240147_1", "pmid": "26240147", "title": "All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor \u03baB (NF\u03baB) signaling.", "authors": "Wang R, Chen S, Liu Y et al.", "year": "2015", "journal": "The Journal of biological chemistry", "keywords": "Alzheimer disease, NFkappa B (NFKB), beta-secretase 1 (BACE1), gene transcription, retinoic acid, retinoid signaling", "chunk": "neuroinflammatory response. We found that administration of all-trans-retinoic acid (atRA) down-regulated the expression of BACE1 in the brains of Tg2576 mice and in mice fed a high fat diet. Moreover, in LPS-treated mice and cultured neurons, BACE1 expression was repressed by the addition of atRA, correlating with the anti-inflammatory efficacy of atRA. Mutations of the NF\u03baB binding site in BACE1 promoter abolished the suppressive effect of atRA. Furthermore, atRA disrupted LPS-induced nuclear translocation of NF\u03baB and its binding to BACE1 promoter as well as promoting the recruitment of the corepressor NCoR. Our findings indicate that atRA represses BACE1 gene expression under inflammatory conditions via the modulation of NF\u03baB signaling.", "source": "PubMed"}, {"chunk_id": "41822652_0", "pmid": "41822652", "title": "Potential Synergistic Roles of Ketogenic Diet and Stem Cell Therapy in Parkinson's Disease: A Narrative Review.", "authors": "Sindurakar P, Gorantla VR, Ponnoth D", "year": "2026", "journal": "Cureus", "keywords": "ketogenic diet therapy, levodopa, neurodegeneration, parkinson's disease, stem cell therapy", "chunk": "Parkinson's disease (PD) is a complex neurodegenerative disorder and is the second most common, after Alzheimer's disease. Marked by the gradual loss of dopaminergic signaling and accumulation of abnormal protein aggregates, this condition presents in patients with a combination of motor and non-motor symptoms. While first-line treatments often include exogenous dopamine therapy, such as levodopa-carbidopa, and surgical procedures or deep brain stimulation, these mainstream therapeutics often fail to improve disabling symptoms of PD, induce serious side effects, and have no effect in controlling disease progression. An alternative approach of cell-based therapies has shown to be an effective therapeutic in reducing neurodegeneration. Additionally, diet and exercise modifications have played crucial roles in the management of the condition. Given that certain dietary regimens may be associated with stem cell renewal and regeneration, specifically in the context of tumors and cancer, a potential combination of a ketogenic diet, a high-fat and low-carbohydrate strict", "source": "PubMed"}, {"chunk_id": "41822652_1", "pmid": "41822652", "title": "Potential Synergistic Roles of Ketogenic Diet and Stem Cell Therapy in Parkinson's Disease: A Narrative Review.", "authors": "Sindurakar P, Gorantla VR, Ponnoth D", "year": "2026", "journal": "Cureus", "keywords": "ketogenic diet therapy, levodopa, neurodegeneration, parkinson's disease, stem cell therapy", "chunk": "regimens may be associated with stem cell renewal and regeneration, specifically in the context of tumors and cancer, a potential combination of a ketogenic diet, a high-fat and low-carbohydrate strict dietary regimen, and stem cell therapy with dopaminergic neurons could serve as a beneficial therapeutic option for PD patients, altering the underlying neurodegeneration. Based on several processes of PD pathophysiology, mainly mitochondrial dysfunction, defective protein clearance mechanisms, and neuroinflammation, treating patients with current therapeutics and implementing a ketogenic diet alongside stem cell therapy may significantly improve PD symptoms and progression. This narrative review was conducted using a structured literature search from PubMed and Google Scholar using terms such as PD, stem cell therapy, ketogenic diet, mitochondrial dysfunction, and neuroinflammation. Given the central roles of mitochondrial dysfunction, impaired protein clearance, and neuroinflammation in PD pathophysiology, the combined use of metabolic interventions and stem cell-based strategies represents an avenue for future investigation.", "source": "PubMed"}, {"chunk_id": "41822652_2", "pmid": "41822652", "title": "Potential Synergistic Roles of Ketogenic Diet and Stem Cell Therapy in Parkinson's Disease: A Narrative Review.", "authors": "Sindurakar P, Gorantla VR, Ponnoth D", "year": "2026", "journal": "Cureus", "keywords": "ketogenic diet therapy, levodopa, neurodegeneration, parkinson's disease, stem cell therapy", "chunk": "the central roles of mitochondrial dysfunction, impaired protein clearance, and neuroinflammation in PD pathophysiology, the combined use of metabolic interventions and stem cell-based strategies represents an avenue for future investigation. Currently, there are no clinical trials using human models to establish the safety, feasibility, or efficacy of the combined therapy using the ketogenic diet and stem cell therapy in PD. Rigorous preclinical validation and well-designed clinical trials are required before such strategies can be considered viable disease-modifying options for PD.", "source": "PubMed"}, {"chunk_id": "41121344_0", "pmid": "41121344", "title": "Neurobiological correlates of Mild Behavioral Impairment: a systematic review and meta-analysis.", "authors": "Remelli F, Barbieri MG, Ferrighi E et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Brain imaging, Cerebrospinal fluid, Dementia, Mild behavioral impairment, Neurodegeneration, Neuroinflammation, Plasma, Positron emission tomography", "chunk": "Although individuals with Mild Behavioral Impairment (MBI) show an increased rate of developing dementia, it remains uncertain whether MBI should be considered a risk factor or an actual early sign of neurocognitive disease. This systematic review and meta-analysis aimed to explore the association between MBI and neurobiological correlates of dementia. The study protocol followed PRISMA guidelines and was registered in PROSPERO (CRD42024589059). Five databases and gray literature were systematically searched from inception to January 31, 2025 to identify studies that explored the relationship between MBI and brain imaging findings or neurodegenerative and neuroinflammatory fluid biomarker levels. When studies employed comparable methodologies, a random-effects meta-analysis was performed to summarize the results; conversely, a qualitative synthesis was conducted. The Newcastle-Ottawa Quality Assessment Scale was used to assess the study quality. Of the 834 records, 27 studies were included. Most studies were cross-sectional and examined the presence of structural or functional abnormalities through", "source": "PubMed"}, {"chunk_id": "41121344_1", "pmid": "41121344", "title": "Neurobiological correlates of Mild Behavioral Impairment: a systematic review and meta-analysis.", "authors": "Remelli F, Barbieri MG, Ferrighi E et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Brain imaging, Cerebrospinal fluid, Dementia, Mild behavioral impairment, Neurodegeneration, Neuroinflammation, Plasma, Positron emission tomography", "chunk": "Scale was used to assess the study quality. Of the 834 records, 27 studies were included. Most studies were cross-sectional and examined the presence of structural or functional abnormalities through brain imaging in individuals with MBI. Six studies, 4 of which were longitudinal, focused on MBI and cerebrospinal fluid or plasma biomarkers of neurodegeneration and neuroinflammation. Due to the high methodological heterogeneity across studies, five random-effects meta-analyses were conducted, each including two studies. These analyses reported a positive, cross-sectional correlation between MBI burden and brain deposition of amyloid-beta (A\u03b2) or tau. Conversely, MBI was not significantly associated with either plasma phosphorylated-tau181 levels or Magnetic Resonance Imaging (MRI) brain atrophy markers. Nevertheless, based on the qualitative synthesis of the 27 included studies, MBI was frequently linked to Alzheimer's disease (AD) abnormalities - both in biomarkers and brain imaging studies. Across studies, MBI appears to be linked to specific neurobiological markers of", "source": "PubMed"}, {"chunk_id": "41121344_2", "pmid": "41121344", "title": "Neurobiological correlates of Mild Behavioral Impairment: a systematic review and meta-analysis.", "authors": "Remelli F, Barbieri MG, Ferrighi E et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Biomarkers, Brain imaging, Cerebrospinal fluid, Dementia, Mild behavioral impairment, Neurodegeneration, Neuroinflammation, Plasma, Positron emission tomography", "chunk": "studies, MBI was frequently linked to Alzheimer's disease (AD) abnormalities - both in biomarkers and brain imaging studies. Across studies, MBI appears to be linked to specific neurobiological markers of AD, including A\u03b2 and tau brain deposition, as well as alterations in the mesolimbic pathway and neurodegenerative and neuroinflammatory fluid biomarker levels. Although emerging evidence supports MBI as a potential early clinical sign of AD, heterogeneity across studies precludes definitive conclusions regarding its precise role in the onset and progression of the disease.", "source": "PubMed"}, {"chunk_id": "38253362_0", "pmid": "38253362", "title": "NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study.", "authors": "Linnemann C, Wilke C, Mengel D et al.", "year": "2024", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "COGNITION, FRONTOTEMPORAL DEMENTIA, NEUROPSYCHIATRY", "chunk": "Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites. Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in <i>C9orf72</i>, <i>GRN</i> or <i>MAPT</i>; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer. NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12\u00b11.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across", "source": "PubMed"}, {"chunk_id": "38253362_1", "pmid": "38253362", "title": "NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study.", "authors": "Linnemann C, Wilke C, Mengel D et al.", "year": "2024", "journal": "Journal of neurology, neurosurgery, and psychiatry", "keywords": "COGNITION, FRONTOTEMPORAL DEMENTIA, NEUROPSYCHIATRY", "chunk": "(pg/mL) in Bland-Altman analysis: 1.12\u00b11.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model. Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.", "source": "PubMed"}, {"chunk_id": "40859843_0", "pmid": "40859843", "title": "The association of umbilical cord blood neurofilament light with non-reassuring fetal status: A prospective observational study.", "authors": "Zalcberg D, Kramer K, Payne E et al.", "year": "2026", "journal": "International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics", "keywords": "HIE, asphyxia, hypoxic\u2013ischemic encephalopathy, neurofilament light, umbilical cord blood", "chunk": "Early detection of hypoxic-ischemic encephalopathy (HIE) in neonates is critical. We conducted a pilot cohort study to determine the feasibility of collecting umbilical cord blood samples for neurofilament light (NfL) and to assess the association of NfL with non-reassuring fetal status and other cord biomarkers. We aimed to address (1) Feasibility of cord NfL sample collection and analysis; (2) Association of NfL with non-reassuring fetal status (CTG changes and/or documented non-reassuring fetal status), neonatal intensive care unit (NICU) admission and length of stay; (3) Correlation of NfL with other cord biomarkers. This was a prospective cohort study performed in a single, large tertiary and quaternary referral hospital. A total of 108 maternal participants consented to donate cord blood. Umbilical cord blood NfL levels were measured via single molecule array (Simoa) analysis. Cord NfL was higher in preterm neonates and was correlated with cord lactate, pH, and base excess. After controlling", "source": "PubMed"}, {"chunk_id": "40859843_1", "pmid": "40859843", "title": "The association of umbilical cord blood neurofilament light with non-reassuring fetal status: A prospective observational study.", "authors": "Zalcberg D, Kramer K, Payne E et al.", "year": "2026", "journal": "International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics", "keywords": "HIE, asphyxia, hypoxic\u2013ischemic encephalopathy, neurofilament light, umbilical cord blood", "chunk": "blood NfL levels were measured via single molecule array (Simoa) analysis. Cord NfL was higher in preterm neonates and was correlated with cord lactate, pH, and base excess. After controlling for mode of delivery and gestational age, NfL (odds ratio [OR] = 2.29, 95% confidence interval [CI]: 1.15-5.57), but not pH (OR = 0.78, 95% CI: 0.42-1.41), base excess (OR = 0.83, 95% CI: 0.37-1.86), or lactate (OR = 1.06, 95% CI: 0.51-2.12) was associated with non-reassuring fetal status. NfL levels were higher in neonates admitted to NICU (median [IQR]: 11.3 [7] vs 8.5 [5.1]). Cord blood NfL analysis was feasible and provided correlates of adverse outcomes. Higher venous cord blood NfL levels were associated with non-reassuring fetal status. Further research is needed to validate these findings and establish the role of NfL, if any, in clinical practice.", "source": "PubMed"}, {"chunk_id": "40859843_2", "pmid": "40859843", "title": "The association of umbilical cord blood neurofilament light with non-reassuring fetal status: A prospective observational study.", "authors": "Zalcberg D, Kramer K, Payne E et al.", "year": "2026", "journal": "International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics", "keywords": "HIE, asphyxia, hypoxic\u2013ischemic encephalopathy, neurofilament light, umbilical cord blood", "chunk": "research is needed to validate these findings and establish the role of NfL, if any, in clinical practice.", "source": "PubMed"}, {"chunk_id": "41260015_0", "pmid": "41260015", "title": "Cerebral phosphorus metabolite as imaging biomarkers in Alzheimer's disease: a <sup>31</sup>P magnetic resonance spectroscopy study.", "authors": "Zhao S, Dong Y, Jiang B et al.", "year": "2025", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Amnestic mild cognitive impairment, Cognitive, Phosphorus-31 magnetic resonance spectroscopic imaging", "chunk": "This study employed phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) to characterize hippocampal and frontal metabolic alterations in Alzheimer's disease (AD) and to evaluate their associations with cognitive decline. We enrolled 30 patients with AD, 26 with amnestic mild cognitive impairment (aMCI), and 25 healthy controls (HC), all of whom underwent <sup>31</sup>P-MRSI using a 3.0 T MRI scanner with a dual-tuned <sup>1</sup>H/<sup>31</sup>P head coil. Spectroscopic data were acquired from the hippocampus, prefrontal gray matter, and prefrontal white matter regions for subsequent analysis.The results of this study indicate that compared to the HC groups, patients with AD showed a significantly reduced phosphocreatine to inorganic phosphate ratio in the hippocampal region (p = 0.018). Meanwhile, the phosphomonoesters to phosphodiesters (PME/PDE) ratio in both the hippocampus and prefrontal gray matter exhibited a progressive increase along the HC-aMCI-AD disease continuum(all p < 0.001), although the difference between the aMCI and HC groups did not reach", "source": "PubMed"}, {"chunk_id": "41260015_1", "pmid": "41260015", "title": "Cerebral phosphorus metabolite as imaging biomarkers in Alzheimer's disease: a <sup>31</sup>P magnetic resonance spectroscopy study.", "authors": "Zhao S, Dong Y, Jiang B et al.", "year": "2025", "journal": "NeuroImage. Clinical", "keywords": "Alzheimer\u2019s disease, Amnestic mild cognitive impairment, Cognitive, Phosphorus-31 magnetic resonance spectroscopic imaging", "chunk": "the hippocampus and prefrontal gray matter exhibited a progressive increase along the HC-aMCI-AD disease continuum(all p < 0.001), although the difference between the aMCI and HC groups did not reach statistical significance in the frontal gray matter. Further analysis revealed a association between the elevated PME/PDE ratios in these brain regions and the decline in cognitive function. These findings support the potential of <sup>31</sup>P-MRSI as a noninvasive imaging tool for detecting metabolic alterations associated with Alzheimer's disease, providing important insights for future clinical research and early diagnosis.", "source": "PubMed"}, {"chunk_id": "37102466_0", "pmid": "37102466", "title": "Don't forget primary progressive aphasia for anti-amyloid drugs: An estimation of eligible patients from the Lausanne Memory Center registry.", "authors": "Hausmann A, Chiabotti PS, Nasuti M et al.", "year": "2023", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "None", "chunk": "The study recently published on the clinical effect of lecanemab in early Alzheimer's disease (AD) only includes patients with amnestic presentation. However, a significant portion of AD patients presents a non-amnestic phenotype of AD, such as primary progressive aphasia (PPA) and could benefit of rather than on lecanemab. Therefore, we conducted a 10-year retrospective study at the Leenaards Memory Center in Lausanne (Switzerland) to identify how many PPA patients would be eligible for lecanemab. Among 54 patients with PPA, we identified 11 (20%) eligible patients. Furthermore, almost half of the 18 patients with logopenic variant would be eligible for lecanemab treatment.", "source": "PubMed"}, {"chunk_id": "35264925_0", "pmid": "35264925", "title": "Pathological Human Tau Induces Alterations in the Brain Insulin Signaling Cascade.", "authors": "El Idrissi A, Alonso ADC", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, brain waves, glucose tolerance test, hyperphosphorylated tau, insulin resistance, seizures, tau transgenic mouse model", "chunk": "The process of neurodegeneration in Alzheimer's disease has been associated with a disruption of insulin signaling cascade in neurons, and to insulin resistance. T2DM correlates with Alzheimer's disease, but mechanisms of interaction are unknown. We have developed a mouse model of tau induced neurodegeneration expressing pseudo-phosphorylated tau [Pathological Human Tau (PH-Tau)] in neurons. This model (PH-Tau-Tg) recapitulated cognitive decline and neurodegeneration observed in AD. In this study we examined if expression of PH-Tau could affect neuronal excitability and insulin receptor signaling. Neuronal excitability was investigated using intracerebral recordings of extracellular field potentials from prefrontal cortex after insulin and kainic acid (KA) injection. Analysis of baseline recordings indicated an increased excitability of PH-Tau-Tg as evidenced by higher spectrum densities (PSDs) of high frequencies brain waves. Injection of insulin (1IU, s.c) led to a decrease of fast ripples PSDs, more pronounced in PH-Tau-Tg mice than controls. Subsequent injection of kainic acid (KA,", "source": "PubMed"}, {"chunk_id": "35264925_1", "pmid": "35264925", "title": "Pathological Human Tau Induces Alterations in the Brain Insulin Signaling Cascade.", "authors": "El Idrissi A, Alonso ADC", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, brain waves, glucose tolerance test, hyperphosphorylated tau, insulin resistance, seizures, tau transgenic mouse model", "chunk": "high frequencies brain waves. Injection of insulin (1IU, s.c) led to a decrease of fast ripples PSDs, more pronounced in PH-Tau-Tg mice than controls. Subsequent injection of kainic acid (KA, 5 mg/kg, s.c) led to significant increase in firing rate, amplitude of extracellular field potentials and PSDs of high frequency brain waves in control mice only. To further investigate the role of insulin in PH-Tau-Tg mice, we subjected mice to a glucose tolerance test. We found that PH-Tau-Tg mice were significantly hyperglycemic prior to glucose injection. Interestingly, the PH-Tau-Tg mice showed a moderate increase at 30 min due to the higher baseline, indicating a low sensitivity of insulin receptor in these mice. This is consistent with increased levels of activated insulin receptors in the brain and the inhibitory effect of insulin on ictal activity post KA injection in PH-Tau-Tg mice. We suggest that these mice have reduced insulin sensitivity (hyperglycemia)", "source": "PubMed"}, {"chunk_id": "35264925_2", "pmid": "35264925", "title": "Pathological Human Tau Induces Alterations in the Brain Insulin Signaling Cascade.", "authors": "El Idrissi A, Alonso ADC", "year": "2022", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, brain waves, glucose tolerance test, hyperphosphorylated tau, insulin resistance, seizures, tau transgenic mouse model", "chunk": "insulin receptors in the brain and the inhibitory effect of insulin on ictal activity post KA injection in PH-Tau-Tg mice. We suggest that these mice have reduced insulin sensitivity (hyperglycemia) and as a compensatory mechanism there is overactivation/expression of insulin receptor in the brain rendering neuronal circuits resistant to seizure induction after injection of insulin. These data indicate that insulin signal transduction pathway is altered in PH-Tau-Tg mice, and that injection of exogenous insulin reduces hypersynchronous bursting activity of field potentials recorded from cortical neuronal circuits. We propose that the appearance of abnormal tau might potentiate the toxic environment by interfering with the insulin signaling cascade in the brain of patients with Alzheimer's disease.", "source": "PubMed"}, {"chunk_id": "41825292_0", "pmid": "41825292", "title": "A deep clustering Gaussian process algorithm for motor progression prediction of Parkinson's disease.", "authors": "Pan C, Tian Y, Zhou T et al.", "year": "2026", "journal": "Computer methods and programs in biomedicine", "keywords": "Disease heterogeneity, Disease progression prediction, Gaussian process, Parkinson\u2019s disease", "chunk": "Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by significant spatial and temporal heterogeneity in symptom presentation and progression, which poses a major challenge for accurate motor progression prediction. Developing a highly individualized model for predicting PD motor progression that can reflect the heterogeneity may lead to better management. To address this issue, we propose a novel Deep Clustering Gaussian process (DCGP) algorithm to predict PD motor progression using readily available clinical statistics and scales. The algorithm consists of three modules: a pretraining module to obtain valuable latent representations, a clustering module to capture heterogeneity among different progression patterns, and an adaptive module to fine-tune models for specific patient clusters. Experiments conducted on 342 patients from the Parkinson's Progression Markers Initiative (PPMI) and 336 patients from the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarkers Program (PDBP) demonstrated that our proposed DCGP significantly outperforms existing state-of-the-art", "source": "PubMed"}, {"chunk_id": "41825292_1", "pmid": "41825292", "title": "A deep clustering Gaussian process algorithm for motor progression prediction of Parkinson's disease.", "authors": "Pan C, Tian Y, Zhou T et al.", "year": "2026", "journal": "Computer methods and programs in biomedicine", "keywords": "Disease heterogeneity, Disease progression prediction, Gaussian process, Parkinson\u2019s disease", "chunk": "Progression Markers Initiative (PPMI) and 336 patients from the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarkers Program (PDBP) demonstrated that our proposed DCGP significantly outperforms existing state-of-the-art predictive models (PPMI: RMSE = 4.607 \u00b1 0.218, MAE = 3.504 \u00b1 0.138, R\u00b2 = 0.890 \u00b1 0.012; PDBP: RMSE = 7.486 \u00b1 0.208, MAE = 5.477 \u00b1 0.157, R\u00b2 = 0.652 \u00b1 0.020). The ablation experiments show that our proposed algorithm improves predictive performance by capturing heterogeneity among different progression patterns. Based on the proposed DCGP, the magnitude of this disease progression heterogeneity was quantified as the difference between average levels and the variation over time and results reveal that the PDBP cohort exhibits greater heterogeneity in average disease levels, whereas the PPMI cohort shows greater heterogeneity in progression rate, trend, and smoothness. This study proposes a novel DCGP algorithm to predict PD motor progression, which can enhance predictive", "source": "PubMed"}, {"chunk_id": "41825292_2", "pmid": "41825292", "title": "A deep clustering Gaussian process algorithm for motor progression prediction of Parkinson's disease.", "authors": "Pan C, Tian Y, Zhou T et al.", "year": "2026", "journal": "Computer methods and programs in biomedicine", "keywords": "Disease heterogeneity, Disease progression prediction, Gaussian process, Parkinson\u2019s disease", "chunk": "levels, whereas the PPMI cohort shows greater heterogeneity in progression rate, trend, and smoothness. This study proposes a novel DCGP algorithm to predict PD motor progression, which can enhance predictive performance by quantitatively capturing heterogeneity, thereby aiding doctors in making accurate predictions and providing tailored management plans for PD patients.", "source": "PubMed"}, {"chunk_id": "34585215_0", "pmid": "34585215", "title": "Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.", "authors": "Lowe SL, Duggan Evans C, Shcherbinin S et al.", "year": "2021", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid plaque, donanemab, florbetapir PET, immunogenicity", "chunk": "Donanemab (LY3002813) is an IgG1 antibody directed at an N\u2011terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques. To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity. Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study. Patients recruited at clinical research sites in the United States and Japan. 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer's disease and mild-to-moderate Alzheimer's disease dementia. Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15). Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse", "source": "PubMed"}, {"chunk_id": "34585215_1", "pmid": "34585215", "title": "Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.", "authors": "Lowe SL, Duggan Evans C, Shcherbinin S et al.", "year": "2021", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid plaque, donanemab, florbetapir PET, immunogenicity", "chunk": "72 weeks (N=18) or placebo (N = 15). Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse events, magnetic resonance imaging, electrocardiogram, vital signs, laboratory testing, neurological monitoring, and immunogenicity. Treatment with donanemab resulted in rapid reduction of amyloid, even after a single dose. By 24 weeks, amyloid positron emission tomography mean changes from baseline for single donanemab doses in Centiloids were: -16.5 (standard error 11.22) 10-mg/kg intravenous; 40.0 (standard error 11.23) 20 mg/kg intravenous; and -49.6 (standard error 15.10) 40-mg/kg intravenous. Mean reduction of amyloid plaque in multiple dose cohorts by 24 weeks in Centiloids were: 55.8 (standard error 9.51) 10-mg/kg every 2 weeks; -50.2 (standard error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose", "source": "PubMed"}, {"chunk_id": "34585215_2", "pmid": "34585215", "title": "Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.", "authors": "Lowe SL, Duggan Evans C, Shcherbinin S et al.", "year": "2021", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid plaque, donanemab, florbetapir PET, immunogenicity", "chunk": "error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose of donanemab. Repeated dosing resulted in continued florbetapir positron emission tomography reductions over time compared to single dosing with 6 out of 28 patients attaining complete amyloid clearance within 24 weeks. Within these, 5 out of 10 patients in the 20 mg/kg every 4 weeks cohort attained complete amyloid clearance within 36 weeks. When dosing with donanemab was stopped after 24 weeks of repeat dosing in the 10 mg every 2 weeks cohort, florbetapir positron emission tomography reductions were sustained up to 72 weeks. For the single dose cohorts on day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose", "source": "PubMed"}, {"chunk_id": "34585215_3", "pmid": "34585215", "title": "Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.", "authors": "Lowe SL, Duggan Evans C, Shcherbinin S et al.", "year": "2021", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid plaque, donanemab, florbetapir PET, immunogenicity", "chunk": "day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose cohorts. Donanemab clearance was comparable across the dose levels. Mean donanemab elimination-half-life following 20 mg/kg single dose was 9.3 days with range of 5.6 to 16.2 days. Greater than 90% of patients had positive treatment-emergent antidrug antibodies with donanemab. However, overall, the treatment-emergent antidrug antibodies did not have a significant impact on pharmacokinetics. Donanemab was generally well tolerated. Amongst the 46 participants treated with donanemab, the following amyloid-related imaging abnormalities, common to the drug class, were observed: 12 vasogenic cerebral edema events (12 [19.7%] patients), 10 cerebral microhemorrhage events (6 [13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid", "source": "PubMed"}, {"chunk_id": "34585215_4", "pmid": "34585215", "title": "Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.", "authors": "Lowe SL, Duggan Evans C, Shcherbinin S et al.", "year": "2021", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, amyloid plaque, donanemab, florbetapir PET, immunogenicity", "chunk": "[13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid plaque despite treatment-emergent antidrug antibodies detected in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent event.", "source": "PubMed"}, {"chunk_id": "33602086_0", "pmid": "33602086", "title": "Association of Red Blood Cell Indices with Mild Cognitive Impairment in Chinese Elderly Individuals: A Matched Case-control Study.", "authors": "Du Y, Jin M, Liu Q et al.", "year": "2020", "journal": "Current Alzheimer research", "keywords": "Mild cognitive impairment, ROC curve, biomarker, dementia, elderly, matched case-control study", "chunk": "Mild cognitive impairment (MCI) represents an intermediate and modifiable stage between normal aging and dementia. There is an urgent need for simple, non-invasive testing of MCI by blood biomarkers. This study aimed to retrospectively evaluate the association of red blood cell (RBC) indices with MCI, and select the best hematologic characteristic for detection of MCI in elderly Chinese. Matched case-control study was carried out with 85 pairs of MCI subjects and healthy controls. The matching criteria was age, gender and education attainment. All samples were analyzed for RBC indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD). A conditional logistic regression model was used to evaluate the association between RBC indices and MCI. The diagnostic efficacy of the biomarkers was evaluated by receiver operating characteristics (ROC). Among all RBC indices, there were significant differences in HGB (124.82", "source": "PubMed"}, {"chunk_id": "33602086_1", "pmid": "33602086", "title": "Association of Red Blood Cell Indices with Mild Cognitive Impairment in Chinese Elderly Individuals: A Matched Case-control Study.", "authors": "Du Y, Jin M, Liu Q et al.", "year": "2020", "journal": "Current Alzheimer research", "keywords": "Mild cognitive impairment, ROC curve, biomarker, dementia, elderly, matched case-control study", "chunk": "association between RBC indices and MCI. The diagnostic efficacy of the biomarkers was evaluated by receiver operating characteristics (ROC). Among all RBC indices, there were significant differences in HGB (124.82 \u00b1 7.89 vs. 133.93 \u00b1 4.52, P < 0.001) and RDW-SD (45.29 \u00b1 2.03 vs. 41.34 \u00b1 4.41, P < 0.001) between two groups. In the logistic regression model, after adjustment for lifestyle factors and comorbidities, significant statistically associations have been found between higher HGB and lower risk of MCI (adjusted OR: 0.831; 95% CI: 0.773-0.893), higher RDW-SD and a higher risk of MCI (adjusted OR: 1.575; 95% CI: 1.326- 1.872). ROC analysis suggested that the largest area under the ROC curve (AUC) was found with the combination of HGB and RDW-SD (AUC = 0.842), followed by HGB(AUC = 0.795), and finally by modest RDW-SD (AUC = 0.777). Combination of HGB <131 g/L and RDW-SD >43.4 fL yielded a sensitivity", "source": "PubMed"}, {"chunk_id": "33602086_2", "pmid": "33602086", "title": "Association of Red Blood Cell Indices with Mild Cognitive Impairment in Chinese Elderly Individuals: A Matched Case-control Study.", "authors": "Du Y, Jin M, Liu Q et al.", "year": "2020", "journal": "Current Alzheimer research", "keywords": "Mild cognitive impairment, ROC curve, biomarker, dementia, elderly, matched case-control study", "chunk": "and RDW-SD (AUC = 0.842), followed by HGB(AUC = 0.795), and finally by modest RDW-SD (AUC = 0.777). Combination of HGB <131 g/L and RDW-SD >43.4 fL yielded a sensitivity of 92% and a specificity of 89%, overall diagnosis efficiency of which were better than HBG and RDW-SD alone. Lower HGB and higher RDW-SD alone were significantly found to be associated with increased risk of MCI, and offered modest sensitivity and specificity as a diagnostic marker. The combination of HGB and RDW-SD was more sensitive and had higher classification accuracy for differentiating MCI from healthy controls. Further prospective research is needed to clarify whether HGB in combination with RDW-SD may be a potential diagnostic tool for early diagnosis of AD.", "source": "PubMed"}, {"chunk_id": "40801297_0", "pmid": "40801297", "title": "Comparison of plasma p-tau217/A\u03b242, p-tau217, and A\u03b242/A\u03b240 biomarkers by race to detect Alzheimer's disease.", "authors": "Cousins KAQ, Korecka M, Wan Y et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, A\u03b242/A\u03b240, cognition, differential diagnosis, plasma biomarkers, p\u2010tau217, p\u2010tau217/A\u03b242, race, test\u2013retest", "chunk": "In clinically and racially diverse training and test sets, we evaluated and validated Alzheimer's disease (AD) plasma biomarkers: phosphorylated tau-217 (p-tau217), amyloid beta 1-42/1-40 (A\u03b242/A\u03b240), and p-tau217/A\u03b242. Inclusion criteria were available plasma, race (people who self-identified as Black/African American [pBlack] or White [pWhite]), cognitive status (normal, mild cognitive impairment [MCI], dementia), and <sup>18</sup>F-florbetaben or <sup>18</sup>F-florbetapir positron emission tomography (PET) data. In the training set (n = 289; 28% pBlack), we used receiver-operating characteristic (ROC) analysis to calculate two cut points (0.95 sensitivity and specificity) to detect amyloid PET positivity. Cut points were validated in an independent test set (n = 846; 12% pBlack). In the test set, plasma p-tau217/A\u03b242 had the highest accuracy (pBlack: 0.88, pWhite: 0.91) and lowest proportion of intermediate classifications (\u22640.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33). False negatives were more likely to", "source": "PubMed"}, {"chunk_id": "40801297_1", "pmid": "40801297", "title": "Comparison of plasma p-tau217/A\u03b242, p-tau217, and A\u03b242/A\u03b240 biomarkers by race to detect Alzheimer's disease.", "authors": "Cousins KAQ, Korecka M, Wan Y et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, A\u03b242/A\u03b240, cognition, differential diagnosis, plasma biomarkers, p\u2010tau217, p\u2010tau217/A\u03b242, race, test\u2013retest", "chunk": "of intermediate classifications (\u22640.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33). False negatives were more likely to be cognitively normal (vs mild cognitive impairment [MCI]; OR = 7.79, 95% CI = 2.33-40.81, p = 5.1e-05) than correct classifications. Plasma p-tau217/A\u03b242 had high accuracy to detect AD, with comparable performance across race. We tested plasma phosphorylated tau-217 (p-tau217)/amyloid beta (A\u03b2)<sub>42</sub>, p-tau217, and A\u03b242/A\u03b240 in diverse training and test sets. In models, race \u00d7 amyloid PET interactions were not significant. Plasma p-tau217/A\u03b242 had the highest accuracy in people who self-identified as Black/African American (pBlack; 0.88) and people who self-identified as White (pWhite; 0.91). Plasma p-tau217/A\u03b242 had the lowest proportion of intermediate cases (range = 0.09-0.16). False negatives were more likely to have normal cognition, female sex, and high body mass index.", "source": "PubMed"}, {"chunk_id": "40801297_2", "pmid": "40801297", "title": "Comparison of plasma p-tau217/A\u03b242, p-tau217, and A\u03b242/A\u03b240 biomarkers by race to detect Alzheimer's disease.", "authors": "Cousins KAQ, Korecka M, Wan Y et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, A\u03b242/A\u03b240, cognition, differential diagnosis, plasma biomarkers, p\u2010tau217, p\u2010tau217/A\u03b242, race, test\u2013retest", "chunk": "of intermediate cases (range = 0.09-0.16). False negatives were more likely to have normal cognition, female sex, and high body mass index.", "source": "PubMed"}, {"chunk_id": "36240668_0", "pmid": "36240668", "title": "Diabetes and dementia: Clinical perspective, innovation, knowledge gaps.", "authors": "Savelieff MG, Chen KS, Elzinga SE et al.", "year": "2022", "journal": "Journal of diabetes and its complications", "keywords": "Alzheimer's disease, Cognitive impairment, Dementia, Metabolic syndrome, Obesity, Type 2 diabetes", "chunk": "The world faces a pandemic-level prevalence of type 2 diabetes. In parallel with this massive burden of metabolic disease is the growing prevalence of dementia as the population ages. The two health issues are intertwined. The Lancet Commission on dementia prevention, intervention, and care was convened to tackle the growing global concern of dementia by identifying risk factors. It concluded, along with other studies, that diabetes as well as obesity and the metabolic syndrome more broadly, which are frequently comorbid, raise the risk of developing dementia. Type 2 diabetes is a modifiable risk factor; however, it is uncertain whether anti-diabetic drugs mitigate risk of developing dementia. Reasons are manifold but constitute a critical knowledge gap in the field. This review outlines studies of type 2 diabetes on risk of dementia, illustrating key concepts. Moreover, it identifies knowledge gaps, reviews strategies to help fill these gaps, and concludes with a series", "source": "PubMed"}, {"chunk_id": "36240668_1", "pmid": "36240668", "title": "Diabetes and dementia: Clinical perspective, innovation, knowledge gaps.", "authors": "Savelieff MG, Chen KS, Elzinga SE et al.", "year": "2022", "journal": "Journal of diabetes and its complications", "keywords": "Alzheimer's disease, Cognitive impairment, Dementia, Metabolic syndrome, Obesity, Type 2 diabetes", "chunk": "outlines studies of type 2 diabetes on risk of dementia, illustrating key concepts. Moreover, it identifies knowledge gaps, reviews strategies to help fill these gaps, and concludes with a series of recommendations to mitigate risk and advance understanding of type 2 diabetes and dementia.", "source": "PubMed"}, {"chunk_id": "40525100_0", "pmid": "40525100", "title": "Underexplored Connections Between Diabetes, Hypomanic States and Insecure Attachment.", "authors": "Bogdanova D, Maes M, Stoyanov D", "year": "2025", "journal": "Psychology research and behavior management", "keywords": "attachment style, bipolar disorder, diabetes \u2013 type 1 and type 2, dopamine, hypomania, mania", "chunk": "Diabetes, dopamine, attachment style disorders, and hypomania share complex interrelations involving neuroinflammation, dysfunction in brain networks (DMN, CEN, SAL), and emotional regulation. Both Type 1 and Type 2 diabetes induce cognitive and structural changes in the brain through mechanisms such as hyperglycemia, insulin resistance, and chronic inflammation. These processes can affect the dopaminergic system, which plays a pivotal role in motivation, emotional regulation, and the manifestation of hypomania. Dopamine is directly linked to attachment styles, with disturbances in this system increasing vulnerability to emotional disorders, including bipolar disorder and schizophrenia. Hypomania, a hallmark of the bipolar spectrum, is associated with dopaminergic imbalances, often observed in diabetes.", "source": "PubMed"}, {"chunk_id": "35098974_0", "pmid": "35098974", "title": "Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults \u2265 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.", "authors": "Avgerinos KI, Mullins RJ, Egan JM et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Ketosis, cognition, extracellular vesicles, ketone ester, magnetic resonance spectroscopy, metabolic syndrome", "chunk": "Ketone bodies have been proposed as an \"energy rescue\" for the Alzheimer's disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce. To investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD. Double-blinded randomized placebo-controlled clinical trial. Clinical Unit of the National Institute on Aging, Baltimore, US. Fifty cognitively intact adults \u2265 55 years old, with metabolic syndrome. Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance", "source": "PubMed"}, {"chunk_id": "35098974_1", "pmid": "35098974", "title": "Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults \u2265 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.", "authors": "Avgerinos KI, Mullins RJ, Egan JM et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Ketosis, cognition, extracellular vesicles, ketone ester, magnetic resonance spectroscopy, metabolic syndrome", "chunk": "with metabolic syndrome. Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer's effects in humans.", "source": "PubMed"}, {"chunk_id": "35098974_2", "pmid": "35098974", "title": "Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults \u2265 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.", "authors": "Avgerinos KI, Mullins RJ, Egan JM et al.", "year": "2022", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Ketosis, cognition, extracellular vesicles, ketone ester, magnetic resonance spectroscopy, metabolic syndrome", "chunk": "between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer's effects in humans.", "source": "PubMed"}, {"chunk_id": "41751251_0", "pmid": "41751251", "title": "Rapid Profiling of EEG Responses to Non-Invasive Brain Stimulation in Parkinson's Disease: A Biomarker-Driven Screening Framework.", "authors": "Hajipour Sardouie S, Babaei M, Naseri M et al.", "year": "2026", "journal": "Biomedicines", "keywords": "EEG biomarkers, Parkinson\u2019s disease (PD), galvanic vestibular stimulation (GVS), multi-criteria decision analysis (MCDA), neuromodulation, resting-state", "chunk": "<b>Background/Objectives</b>: Parkinson's disease (PD) is associated with alterations in resting-state Electroencephalogram (EEG) biomarkers. Identifying stimulation protocols that reliably shift these biomarkers toward healthy-like patterns is essential for developing personalized neuromodulation strategies. This study introduces a rapid, biomarker-driven framework for screening the EEG effects of diverse Galvanic Vestibular Stimulation (GVS) waveforms in PD. <b>Methods</b>: More than 300 subthreshold GVS stimuli were delivered during resting-state EEG to PD (<i>n</i> = 5) subjects and Healthy Controls (<i>n</i> = 5). A composite biomarker score that included spectral, cross-frequency, aperiodic, and complexity measures quantified stimulation-related changes. A linear classifier and multi-criteria decision analysis were used to evaluate and rank stimuli. <b>Results</b>: Stimulation produced consistent improvements in the composite biomarker score, with the strongest effects observed for beta-range sinusoids, multisine waveforms, frequency-modulated stimuli with a 75 Hz carrier, and PAC-modulated signals. No significant post-stimulation carryover effects were detected. <b>Conclusions</b>: While preliminary, this exploratory framework enables rapid,", "source": "PubMed"}, {"chunk_id": "41751251_1", "pmid": "41751251", "title": "Rapid Profiling of EEG Responses to Non-Invasive Brain Stimulation in Parkinson's Disease: A Biomarker-Driven Screening Framework.", "authors": "Hajipour Sardouie S, Babaei M, Naseri M et al.", "year": "2026", "journal": "Biomedicines", "keywords": "EEG biomarkers, Parkinson\u2019s disease (PD), galvanic vestibular stimulation (GVS), multi-criteria decision analysis (MCDA), neuromodulation, resting-state", "chunk": "for beta-range sinusoids, multisine waveforms, frequency-modulated stimuli with a 75 Hz carrier, and PAC-modulated signals. No significant post-stimulation carryover effects were detected. <b>Conclusions</b>: While preliminary, this exploratory framework enables rapid, interpretable profiling of EEG responses to non-invasive stimulation in PD. By prioritizing candidate GVS protocols based on biomarker shifts rather than behavioural endpoints, the approach provides a practical foundation for future personalized neuromodulation strategies.", "source": "PubMed"}, {"chunk_id": "38007652_0", "pmid": "38007652", "title": "PICALM Variation Moderates the Relationships of APOE \u025b4 with Alzheimer's Disease Cerebrospinal Biomarkers and Memory Function Among Non-Demented Population.", "authors": "Liu YB, Wang XJ, Tan L et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE \u025b4, Alzheimer\u2019s disease, PICALM, amyloid, cognition, interaction, memory, tau protein", "chunk": "APOE \u025b4 and PICALM are established genes associated with risk of late-onset Alzheimer's disease (AD). Previous study indicated interaction of PICALM with APOE \u025b4 in AD patients. To explore whether PICALM variation could moderate the influences of APOE \u025b4 on AD pathology biomarkers and cognition in pre-dementia stage. A total of 1,034 non-demented participants (mean age 74 years, 56% females, 40% APOE \u025b4 carriers) were genotyped for PICALM rs3851179 and APOE \u025b4 at baseline and were followed for influences on changes of cognition and cerebrospinal fluid (CSF) AD markers in six years. The interaction effects were examined via regression models adjusting for age, gender, education, and cognitive diagnosis. The interaction term of rs3851179\u00d7APOE \u025b4 accounted for a significant amount of variance in baseline general cognition (p = 0.039) and memory function (p = 0.002). The relationships of APOE \u025b4 with trajectory of CSF A\u03b242 (p = 0.007), CSF P-tau181 (p", "source": "PubMed"}, {"chunk_id": "38007652_1", "pmid": "38007652", "title": "PICALM Variation Moderates the Relationships of APOE \u025b4 with Alzheimer's Disease Cerebrospinal Biomarkers and Memory Function Among Non-Demented Population.", "authors": "Liu YB, Wang XJ, Tan L et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "APOE \u025b4, Alzheimer\u2019s disease, PICALM, amyloid, cognition, interaction, memory, tau protein", "chunk": "variance in baseline general cognition (p = 0.039) and memory function (p = 0.002). The relationships of APOE \u025b4 with trajectory of CSF A\u03b242 (p = 0.007), CSF P-tau181 (p = 0.003), CSF T-tau (p = 0.001), and memory function (p = 0.017) were also moderated by rs3851179 variation. APOE \u025b4 carriers experienced slower clinical and pathological progression when they had more protective A alleles of PICALM rs3851179. These findings firstly revealed the gene-gene interactive effects of PICALM with APOE \u025b4 in pre-dementia stage.", "source": "PubMed"}, {"chunk_id": "34921102_0", "pmid": "34921102", "title": "Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study.", "authors": "Fohner AE, Bartz TM, Tracy RP et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "Neurofilament light chain (NfL) in blood is a sensitive but nonspecific marker of brain injury. This study sought to evaluate associations between NfL concentration and MRI findings of vascular brain injury in older adults. A longitudinal cohort study included 2 cranial MRI scans performed about 5 years apart and assessed for white matter hyperintensities (WMH) and infarcts. About 1 year before their second MRI, 1,362 participants (median age 77 years, 61.4% women) without a history of TIA or stroke had measurement of 4 biomarkers: NfL, total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L1. Most (n = 1,279) also had the first MRI scan, and some (n = 633) had quantitative measurements of hippocampal and WMH. In primary analyses, we assessed associations of NfL with a 10-point white matter grade (WMG) and prevalent infarcts on second MRI and with worsening WMG and incident infarct comparing the 2", "source": "PubMed"}, {"chunk_id": "34921102_1", "pmid": "34921102", "title": "Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study.", "authors": "Fohner AE, Bartz TM, Tracy RP et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "primary analyses, we assessed associations of NfL with a 10-point white matter grade (WMG) and prevalent infarcts on second MRI and with worsening WMG and incident infarct comparing the 2 scans. A <i>p</i> value <0.0125 (0.05/4) was considered significant for these analyses. We also assessed associations with hippocampal and WMH volume. In fully adjusted models, log<sub>2</sub>(NfL) concentration was associated with WMG (\u03b2 = 0.27; <i>p</i> = 2.3 \u00d7 10<sup>-4</sup>) and worsening WMG (relative risk [RR] 1.24; <i>p</i> = 0.0022), but less strongly with prevalent brain infarcts (RR 1.18; <i>p</i> = 0.013) and not with incident brain infarcts (RR 1.18; <i>p</i> = 0.18). Associations were also present with WMH volume (\u03b2 = 2,242.9, <i>p</i> = 0.0036). For the other 3 biomarkers, the associations for log<sub>2</sub> (GFAP) concentration with WMG and worsening WMG were significant. Among older adults without a history of stroke, higher serum NfL concentration was associated with covert MRI", "source": "PubMed"}, {"chunk_id": "34921102_2", "pmid": "34921102", "title": "Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study.", "authors": "Fohner AE, Bartz TM, Tracy RP et al.", "year": "2022", "journal": "Neurology", "keywords": "None", "chunk": "the associations for log<sub>2</sub> (GFAP) concentration with WMG and worsening WMG were significant. Among older adults without a history of stroke, higher serum NfL concentration was associated with covert MRI findings of vascular brain injury, especially the burden of WMH and its worsening. Whether these results offer opportunities for the use of NfL as a noninvasive biomarker of WMH or to control vascular risk factors remains to be determined.", "source": "PubMed"}, {"chunk_id": "41008329_0", "pmid": "41008329", "title": "Transcranial Magnetic Stimulation as a Diagnostic Tool in Mild Cognitive Impairment: A Systematic Review.", "authors": "Dognini E, Finazzi S, Campana E et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer disease, ICF, LICI, MCI, SAI, SICI, TMS, diagnostic markers, frontotemporal dementia, intracortical facilitation, long-interval intracortical inhibition, mild cognitive impairment, short latency afferent inhibition, short-interval intracortical inhibition, transcranial magnetic stimulation", "chunk": "<b>Background/Objective</b>: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. <b>Methods</b>: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. <b>Results</b>: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI", "source": "PubMed"}, {"chunk_id": "41008329_1", "pmid": "41008329", "title": "Transcranial Magnetic Stimulation as a Diagnostic Tool in Mild Cognitive Impairment: A Systematic Review.", "authors": "Dognini E, Finazzi S, Campana E et al.", "year": "2025", "journal": "Brain sciences", "keywords": "Alzheimer disease, ICF, LICI, MCI, SAI, SICI, TMS, diagnostic markers, frontotemporal dementia, intracortical facilitation, long-interval intracortical inhibition, mild cognitive impairment, short latency afferent inhibition, short-interval intracortical inhibition, transcranial magnetic stimulation", "chunk": "in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians' diagnostic confidence when TMS data were incorporated. <b>Conclusions</b>: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability.", "source": "PubMed"}, {"chunk_id": "41238324_0", "pmid": "41238324", "title": "Artificial intelligence in presymptomatic neurological diseases: Bridging normal variation and prodromal signatures.", "authors": "Soulier T, Burgos N, Hassanaly R et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "Anomaly detection, Artificial intelligence, Presymptomatic neurological diseases, Pseudo healthy digital twins", "chunk": "Presymptomatic neurological diseases are marked by early pathological changes that occur before overt clinical symptoms. These stages, which include prodromes such as REM sleep behavior disorder in Parkinson's or mild cognitive impairment in Alzheimer's, offer critical opportunities for early intervention. However, their detection remains challenging due to the subtlety of changes and the overlap with normal interindividual variability. Artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), offers new tools to uncover hidden signatures in complex biomedical data. First, we explore how supervised ML models can detect known prodromal patterns across diverse modalities, including EEG, cognitive scores, and structural imaging. Depending on the input, various model types - such as tree-based algorithms for structured data and convolutional or transformer networks for images and signals - can extract predictive features of early neurodegeneration. These approaches have demonstrated success in identifying at-risk individuals before clinical thresholds are reached. Yet, detecting", "source": "PubMed"}, {"chunk_id": "41238324_1", "pmid": "41238324", "title": "Artificial intelligence in presymptomatic neurological diseases: Bridging normal variation and prodromal signatures.", "authors": "Soulier T, Burgos N, Hassanaly R et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "Anomaly detection, Artificial intelligence, Presymptomatic neurological diseases, Pseudo healthy digital twins", "chunk": "transformer networks for images and signals - can extract predictive features of early neurodegeneration. These approaches have demonstrated success in identifying at-risk individuals before clinical thresholds are reached. Yet, detecting only known patterns limits the scope of early intervention. Many individuals who will go on to develop neurological disease may not yet exhibit any recognized prodromal syndrome. Bridging this gap requires moving beyond predefined labels toward models capable of identifying subtle, unknown anomalies in individuals still considered healthy. Second, we address the detection of latent anomalies among individuals not yet considered at risk without identifiable known prodromal patterns. By mining clinical records, free-text medical notes, and population-level health databases (e.g., UK Biobank, EDS-AP-HP), and by analyzing sensor data from smartphones or wearables, AI can flag deviations from healthy patterns long before symptom onset or formal diagnosis. This approach holds promise for scalable, low-burden, ecological screening. Finally, we introduce the concept", "source": "PubMed"}, {"chunk_id": "41238324_2", "pmid": "41238324", "title": "Artificial intelligence in presymptomatic neurological diseases: Bridging normal variation and prodromal signatures.", "authors": "Soulier T, Burgos N, Hassanaly R et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "Anomaly detection, Artificial intelligence, Presymptomatic neurological diseases, Pseudo healthy digital twins", "chunk": "or wearables, AI can flag deviations from healthy patterns long before symptom onset or formal diagnosis. This approach holds promise for scalable, low-burden, ecological screening. Finally, we introduce the concept of pseudo-healthy twins - synthetic, personalized baselines generated from structural data such as MRI, to improve anomaly detection. These models predict a patient's expected healthy signal in another modality, such as PET, enabling the subtraction of normal anatomical and physiological variability to isolate disease-specific effects. Generative models like GANs and VAEs have shown promise in producing these cross-modal references, enhancing early anomaly detection in diseases like Alzheimer's and multiple sclerosis. Together, these approaches show how AI can bridge the gap between normal variation and early pathology, enabling more sensitive, personalized, and population-scalable detection of presymptomatic neurological disease.", "source": "PubMed"}, {"chunk_id": "41238324_3", "pmid": "41238324", "title": "Artificial intelligence in presymptomatic neurological diseases: Bridging normal variation and prodromal signatures.", "authors": "Soulier T, Burgos N, Hassanaly R et al.", "year": "2025", "journal": "Revue neurologique", "keywords": "Anomaly detection, Artificial intelligence, Presymptomatic neurological diseases, Pseudo healthy digital twins", "chunk": "and population-scalable detection of presymptomatic neurological disease.", "source": "PubMed"}, {"chunk_id": "38431614_0", "pmid": "38431614", "title": "An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD.", "authors": "Miller MW, Wolf EJ, Zhao X et al.", "year": "2024", "journal": "Clinical epigenetics", "keywords": "African ancestry, Alzheimer\u2019s disease, A\u03b240, A\u03b242, Biomarkers, Dementia, EWAS, GFAP, NfL, PTSD, Plasma, Structural equation model, pTau-181", "chunk": "Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE \u03b54 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers A\u03b240, A\u03b242, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers. Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which identified a two-factor solution. Drawing from the ATN research framework, we termed the first factor, defined by A\u03b240 and A\u03b242, \"Factor A\" and the second factor, defined by GFAP, NfL and pTau-181, \"Factor TN.\" Next, we performed epigenome-wide association analyses (EWAS) of the two-factor scores. Finally, using structural equation modeling (SEM), we", "source": "PubMed"}, {"chunk_id": "38431614_1", "pmid": "38431614", "title": "An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD.", "authors": "Miller MW, Wolf EJ, Zhao X et al.", "year": "2024", "journal": "Clinical epigenetics", "keywords": "African ancestry, Alzheimer\u2019s disease, A\u03b240, A\u03b242, Biomarkers, Dementia, EWAS, GFAP, NfL, PTSD, Plasma, Structural equation model, pTau-181", "chunk": "and the second factor, defined by GFAP, NfL and pTau-181, \"Factor TN.\" Next, we performed epigenome-wide association analyses (EWAS) of the two-factor scores. Finally, using structural equation modeling (SEM), we evaluated (a) the influence of PTSD, age, APOE \u03b54 genotype and other covariates on levels of the ATN factors, and (b) tested the mediating influence of the EWAS-significant DNAm loci on these associations. The Factor A EWAS identified one significant locus, cg13053408, in FANCD2OS. The Factor TN analysis identified 3 EWAS-significant associations: cg26033520 near ASCC1, cg23156469 in FAM20B, and cg15356923 in FAM19A4. The SEM showed age to be related to both factors, more so with Factor TN (\u03b2 = 0.581, p < 0.001) than Factor A (\u03b2 = 0.330, p < 0.001). Genotype-determined African ancestry was associated with lower Factor A (\u03b2 = 0.196, p < 0.001). Contrary to our primary hypothesis, we found a modest negative bivariate correlation between", "source": "PubMed"}, {"chunk_id": "38431614_2", "pmid": "38431614", "title": "An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD.", "authors": "Miller MW, Wolf EJ, Zhao X et al.", "year": "2024", "journal": "Clinical epigenetics", "keywords": "African ancestry, Alzheimer\u2019s disease, A\u03b240, A\u03b242, Biomarkers, Dementia, EWAS, GFAP, NfL, PTSD, Plasma, Structural equation model, pTau-181", "chunk": "< 0.001). Genotype-determined African ancestry was associated with lower Factor A (\u03b2 = 0.196, p < 0.001). Contrary to our primary hypothesis, we found a modest negative bivariate correlation between PTSD and the TN factor scores (r = - 0.133, p < 0.001) attributable primarily to reduced levels of GFAP (r = - 0.128, p < 0.001). This study identified novel epigenetic associations with ATN biomarkers and demonstrated robust age and ancestral associations that will be essential to consider in future efforts to develop the clinical applications of these tests. The association between PTSD and reduced GFAP, which has been reported previously, warrants further investigation.", "source": "PubMed"}, {"chunk_id": "34087249_0", "pmid": "34087249", "title": "Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease.", "authors": "Zhang S, Asghar S, Zhu C et al.", "year": "2021", "journal": "Journal of controlled release : official journal of the Controlled Release Society", "keywords": "Alzheimer's disease, Amyloid-\u03b2, Apolipoprotein E, Peptide, Self-assmbly", "chunk": "Targeting a single molecule or a single pathway and poor drug delivery to the brain hamper the therapy of Alzheimer's disease (AD) based on abnormal metabolism of amyloid-\u03b2 (A\u03b2). To solve these problems, we designed and synthesized a multi - strategy peptide (MOP), an ingenious apolipoprotein E mimetic peptide, which could reduce A\u03b2 deposition via inhibiting A\u03b2 aggregation and at the same time accelerate A\u03b2 clearance. Meanwhile, MOP could be self-assembled into different nanostructure, thus we constructed a multifunctional delivery system (APND-3) based on MOP self-assembled nanorods (aspect ratios of 3) that was a favorable morphology to enhance the permeation across the blood brain barrier (BBB) to address the poor delivery to brain issues. Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the", "source": "PubMed"}, {"chunk_id": "34087249_1", "pmid": "34087249", "title": "Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease.", "authors": "Zhang S, Asghar S, Zhu C et al.", "year": "2021", "journal": "Journal of controlled release : official journal of the Controlled Release Society", "keywords": "Alzheimer's disease, Amyloid-\u03b2, Apolipoprotein E, Peptide, Self-assmbly", "chunk": "polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing A\u03b2 deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment.", "source": "PubMed"}, {"chunk_id": "37858252_0", "pmid": "37858252", "title": "A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice.", "authors": "Balu D, Valencia-Olvera AC, Nguyen A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E, EFAD, Female sex, IAXO-101, Neuroinflammation, TLR4, Treatment paradigms", "chunk": "APOE genotype is the greatest genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 increases AD risk up to 12-fold compared to APOE3, an effect that is greater in females. Evidence suggests that one-way APOE could modulate AD risk and progression through neuroinflammation. Indeed, APOE4 is associated with higher glial activation and cytokine levels in AD patients and mice. Therefore, identifying pathways that contribute to APOE4-associated neuroinflammation is an important approach for understanding and treating AD. Human and in vivo evidence suggests that TLR4, one of the key receptors involved in the innate immune system, could be involved in APOE-modulated neuroinflammation. Consistent with that idea, we previously demonstrated that the TLR4 antagonist IAXO-101 can reduce LPS- and A\u03b2-induced cytokine secretion in APOE4 glial cultures. Therefore, the goal of this study was to advance these findings and determine whether IAXO-101 can modulate neuroinflammation, A\u03b2 pathology, and behavior in mice that express", "source": "PubMed"}, {"chunk_id": "37858252_1", "pmid": "37858252", "title": "A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice.", "authors": "Balu D, Valencia-Olvera AC, Nguyen A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E, EFAD, Female sex, IAXO-101, Neuroinflammation, TLR4, Treatment paradigms", "chunk": "in APOE4 glial cultures. Therefore, the goal of this study was to advance these findings and determine whether IAXO-101 can modulate neuroinflammation, A\u03b2 pathology, and behavior in mice that express APOE4. We used mice that express five familial AD mutations and human APOE3 (E3FAD) or APOE4 (E4FAD). Female and male E4FAD mice and female E3FAD mice were treated with vehicle or IAXO-101 in two treatment paradigms: prevention from 4 to 6 months of age or reversal from 6 to 7 months of age. Learning and memory were assessed by modified Morris water maze. A\u03b2 deposition, fibrillar amyloid deposition, astrogliosis, and microgliosis were assessed by immunohistochemistry. Soluble levels of A\u03b2 and apoE, insoluble levels of apoE and A\u03b2, and IL-1\u03b2 were measured by ELISA. IAXO-101 treatment resulted in lower Iba-1 coverage, lower number of reactive microglia, and improved memory in female E4FAD mice in both prevention and reversal paradigms. IAXO-101-treated male", "source": "PubMed"}, {"chunk_id": "37858252_2", "pmid": "37858252", "title": "A small-molecule TLR4 antagonist reduced neuroinflammation in female E4FAD mice.", "authors": "Balu D, Valencia-Olvera AC, Nguyen A et al.", "year": "2023", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer\u2019s disease, Apolipoprotein E, EFAD, Female sex, IAXO-101, Neuroinflammation, TLR4, Treatment paradigms", "chunk": "measured by ELISA. IAXO-101 treatment resulted in lower Iba-1 coverage, lower number of reactive microglia, and improved memory in female E4FAD mice in both prevention and reversal paradigms. IAXO-101-treated male E4FAD mice also had lower Iba-1 coverage and reactivity in the RVS paradigm, but there was no effect on behavior. There was also no effect of IAXO-101 treatment on neuroinflammation and behavior in female E3FAD mice. Our data supports that TLR4 is a potential mechanistic therapeutic target for modulating neuroinflammation and cognition in APOE4 females.", "source": "PubMed"}, {"chunk_id": "41219570_0", "pmid": "41219570", "title": "Deep transcranial magnetic stimulation in progressive supranuclear palsy: a randomized double-blind, cross-over study.", "authors": "Radicati FG, Vacca L, Casali M et al.", "year": "2025", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Deep transcranial magnetic stimulation, Dorsolateral prefrontal cortex, Motor cortex, Motor symptoms, Non-motor symptoms, Progressive supranuclear palsy", "chunk": "Progressive supranuclear palsy (PSP) is a rare neuro-degenerative disease. The Deep Transcranial Magnetic Stimulation (DTMS) has been proposed as a therapeutic approach in Parkinson's Disease but there are few studies that have evaluated its efficacy in PSP. This was a pilot, randomized, cross-over, double blind trial, with the aim to evaluate the effect of DTMS on motor functions, freezing of gait, and cognitive performance in patients with PSP. Nineteen subjects were recruited and randomly assigned to one of the study sequences: real-sham or sham-real. Each cycle consisted of 12 sessions of high frequency DTMS over a 4-week period, separated by a 5-week wash-out period. The targets were the motor cortex and the dorsolateral prefrontal cortex. After adjusting for baseline scores, an interaction effect between DTMS and period of administration emerged for the PSP scale; it was estimated that the real treatment applied to the first period induced a decrease of", "source": "PubMed"}, {"chunk_id": "41219570_1", "pmid": "41219570", "title": "Deep transcranial magnetic stimulation in progressive supranuclear palsy: a randomized double-blind, cross-over study.", "authors": "Radicati FG, Vacca L, Casali M et al.", "year": "2025", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Deep transcranial magnetic stimulation, Dorsolateral prefrontal cortex, Motor cortex, Motor symptoms, Non-motor symptoms, Progressive supranuclear palsy", "chunk": "an interaction effect between DTMS and period of administration emerged for the PSP scale; it was estimated that the real treatment applied to the first period induced a decrease of about 0.79 points (p=0.41) and 4 point (p=0.01) when administered in the second period. Improvement in gait and be relevant since early falls and gait dysfunction have a great impact on disability. Patients and caregivers appreciated the improvements but for a short period of time (about a week). This is the first crossover, double blind, randomized clinical trial to use DTMS in patients with PSP. DMTS was associated with a motor and non-motor improvement in PSP patients. clinicaltrial.gov: NCT02734485.", "source": "PubMed"}, {"chunk_id": "40380000_0", "pmid": "40380000", "title": "Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.", "authors": "Saloner R, Staffaroni AM, Dammer EB et al.", "year": "2025", "journal": "Nature aging", "keywords": "None", "chunk": "The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic signatures was tested and confirmed in independent cohorts of (1) sporadic progressive supranuclear palsy-Richardson syndrome and (2) frontotemporal dementia spectrum clinical syndromes. Network-based proteomics hold promise for identifying replicable molecular pathways in adults living with FTLD. 'Hub' proteins driving co-expression of affected modules warrant further attention as candidate biomarkers and therapeutic", "source": "PubMed"}, {"chunk_id": "40380000_1", "pmid": "40380000", "title": "Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.", "authors": "Saloner R, Staffaroni AM, Dammer EB et al.", "year": "2025", "journal": "Nature aging", "keywords": "None", "chunk": "syndromes. Network-based proteomics hold promise for identifying replicable molecular pathways in adults living with FTLD. 'Hub' proteins driving co-expression of affected modules warrant further attention as candidate biomarkers and therapeutic targets.", "source": "PubMed"}, {"chunk_id": "37248903_0", "pmid": "37248903", "title": "Chiral Amino Acid Profiling in Serum Reveals Potential Biomarkers for Alzheimer's Disease.", "authors": "Liu M, Li M, He J et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, biomarker, chiral amino acid, serum", "chunk": "Alzheimer's disease (AD) is a complex neurodegenerative disease, and increasing evidence has linked dysregulation of amino acids to AD pathogenesis. However, the existing studies often ignore the chirality of amino acids, and some results are inconsistent and controversial. The changes of amino acid profiles in AD from the perspective of enantiomers remain elusive. The purpose of this study is to investigate whether the levels of amino acids, especially D-amino acids, are deregulated in the peripheral serum of AD patients, with the ultimate goal of discovering novel biomarkers for AD. The chiral amino acid profiles were determined by HPLC-MS/MS with a pre-column derivatization method. Experimental data obtained from 37 AD patients and 34 healthy controls (HC) were statistically analyzed. Among the 35 amino acids detected, D-proline, D/total-proline ratio, D-aspartate, and D/total-aspartate ratio were decreased, while D-phenylalanine was elevated in AD compared to HC. Significant age-dependent increases in D-proline, D/total-proline ratio, and", "source": "PubMed"}, {"chunk_id": "37248903_1", "pmid": "37248903", "title": "Chiral Amino Acid Profiling in Serum Reveals Potential Biomarkers for Alzheimer's Disease.", "authors": "Liu M, Li M, He J et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, biomarker, chiral amino acid, serum", "chunk": "35 amino acids detected, D-proline, D/total-proline ratio, D-aspartate, and D/total-aspartate ratio were decreased, while D-phenylalanine was elevated in AD compared to HC. Significant age-dependent increases in D-proline, D/total-proline ratio, and D-phenylalanine were observed in HC, but not in AD. Receiver operator characteristic analyses of the combination of D-proline, D-aspartate, D-phenylalanine, and age for discriminating AD from HC provided satisfactory area under the curve (0.87), specificity (97.0%), and sensitivity (83.8%). Furthermore, the D-aspartate level was significantly decreased with the progression of AD, as assessed by the Clinical Dementia Rating Scale and Mini-Mental State Examination. The panels of D-proline, D-phenylalanine, and D-aspartate in peripheral serum may serve as novel biomarker candidates for AD. The latter parameter is further associated with the severity of AD.", "source": "PubMed"}, {"chunk_id": "37248903_2", "pmid": "37248903", "title": "Chiral Amino Acid Profiling in Serum Reveals Potential Biomarkers for Alzheimer's Disease.", "authors": "Liu M, Li M, He J et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, biomarker, chiral amino acid, serum", "chunk": "of AD.", "source": "PubMed"}, {"chunk_id": "41577565_0", "pmid": "41577565", "title": "Associations between contralesional neuroplasticity and motor impairment through deep learning-derived MRI regional brain age in chronic stroke (ENIGMA): a multicohort, retrospective, observational study.", "authors": "Park G, Khan MH, Andrushko JW et al.", "year": "2026", "journal": "The Lancet. Digital health", "keywords": "None", "chunk": "Stroke leads to complex chronic structural and functional brain changes that specifically affect motor outcomes. The brain predicted age difference (PAD) has emerged as a sensitive biomarker of both sensorimotor and cognitive function after stroke. Our previous study showed a higher global brain PAD associated with poorer motor function after stroke. However, the association between local stroke lesion load, regional brain age, and motor impairment is unclear. This study aimed to investigate the associations between focal lesion damage, regional brain PAD in both hemispheres, and motor outcomes in chronic stroke, and to identify key predictors of motor impairment. In this multicohort, retrospective, observational study, we included individuals with chronic unilateral stroke (>180 days post stroke) from the ENIGMA Stroke Recovery Working Group dataset and used individuals from the UK Biobank cohort to train the regional brain age prediction model. Structural T1-weighted MRI scans were used to estimate regional brain PAD", "source": "PubMed"}, {"chunk_id": "41577565_1", "pmid": "41577565", "title": "Associations between contralesional neuroplasticity and motor impairment through deep learning-derived MRI regional brain age in chronic stroke (ENIGMA): a multicohort, retrospective, observational study.", "authors": "Park G, Khan MH, Andrushko JW et al.", "year": "2026", "journal": "The Lancet. Digital health", "keywords": "None", "chunk": "Working Group dataset and used individuals from the UK Biobank cohort to train the regional brain age prediction model. Structural T1-weighted MRI scans were used to estimate regional brain PAD in 18 predefined functional subregions via a graph convolutional network algorithm. Lesion load for each region was calculated on the basis of lesion overlap. Linear mixed-effects models assessed associations between lesion size, local lesion load, and regional brain PAD. Machine learning classifiers predicted motor outcomes using lesion loads and regional brain PADs. Structural equation modelling examined directional relationships among corticospinal tract lesion load, ipsilesional brain PAD, motor outcomes, and contralesional brain PAD. We included 501 individuals from the ENIGMA Stroke Recovery Working Group dataset (34 cohorts in eight countries) and 17 791 individuals from the UK Biobank dataset. Larger total lesion size was positively associated with higher ipsilesional regional brain PADs (older brain age) across most regions (\u03b2=0\u00b75420 to 0\u00b79458", "source": "PubMed"}, {"chunk_id": "41577565_2", "pmid": "41577565", "title": "Associations between contralesional neuroplasticity and motor impairment through deep learning-derived MRI regional brain age in chronic stroke (ENIGMA): a multicohort, retrospective, observational study.", "authors": "Park G, Khan MH, Andrushko JW et al.", "year": "2026", "journal": "The Lancet. Digital health", "keywords": "None", "chunk": "17 791 individuals from the UK Biobank dataset. Larger total lesion size was positively associated with higher ipsilesional regional brain PADs (older brain age) across most regions (\u03b2=0\u00b75420 to 0\u00b79458 across significantly correlated regions, false discovery rate [FDR]-corrected p<0\u00b705), and with lower brain PAD in the contralesional ventral attention and language network region (\u03b2=-0\u00b73747, 95% CI -0\u00b76961 to -0\u00b70534, FDR-corrected p<0\u00b705). Higher local lesion loads showed similar patterns. Specifically, lesion load in the salience network significantly influenced regional brain PADs across both hemispheres. Machine learning models identified corticospinal tract lesion load (adjusted mean difference -0\u00b70905, 95% CI -0\u00b71221 to -0\u00b70589, p<0\u00b70001), salience network lesion load (-0\u00b70632, -0\u00b70906 to -0\u00b70358, p<0\u00b70001), and regional brain PAD in the contralesional frontoparietal network (0\u00b79939, 0\u00b74929 to 1\u00b74950, p=0\u00b70001) as the top three predictors of motor outcomes. Structural equation modelling revealed that higher corticospinal tract lesion load was associated with poorer motor outcomes (\u03b2=-0\u00b7355, 95%", "source": "PubMed"}, {"chunk_id": "41577565_3", "pmid": "41577565", "title": "Associations between contralesional neuroplasticity and motor impairment through deep learning-derived MRI regional brain age in chronic stroke (ENIGMA): a multicohort, retrospective, observational study.", "authors": "Park G, Khan MH, Andrushko JW et al.", "year": "2026", "journal": "The Lancet. Digital health", "keywords": "None", "chunk": "0\u00b74929 to 1\u00b74950, p=0\u00b70001) as the top three predictors of motor outcomes. Structural equation modelling revealed that higher corticospinal tract lesion load was associated with poorer motor outcomes (\u03b2=-0\u00b7355, 95% CI -0\u00b7446 to -0\u00b7267, p<0\u00b70001), which were further linked to younger contralesional brain age (0\u00b7204, 0\u00b7111 to 0\u00b7295, p<0\u00b70001), suggesting that severe motor impairment is linked to compensatory decreases in contralesional brain age. Our findings reveal that larger stroke lesions are associated with accelerated ageing in the ipsilesional hemisphere and paradoxically decelerated brain ageing in the contralesional hemisphere, suggesting compensatory neural mechanisms. Assessing regional brain age might serve as a biomarker for neuroplasticity and inform targeted interventions to enhance motor recovery after stroke. US National Institutes of Health.", "source": "PubMed"}, {"chunk_id": "41698978_0", "pmid": "41698978", "title": "Synaptic and cytoskeletal CSF signatures of motor neuron disease: the role of cyclase-associated protein 2.", "authors": "Pilotto A, Pelucchi S, Trasciatti C et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Cerebrospinal fluid (CSF), Motor neuron disease (MND), Neurofilament light chain (NfL), Synaptic biomarkers", "chunk": "Cyclase-associated protein 2 (CAP2) is a synaptic actin-binding protein involved in cofilin-mediated spine remodelling, Alzheimer\u2019s Disease synaptic failure and myofibril maintenance, indicating its potential involvement in motor neuron disease (MND). This study examined cerebrospinal fluid (CSF) levels of CAP2 in 60 patients with MND and 40 healthy controls (HC) to assess its diagnostic and prognostic value and its relationship with neuronal, glial and synaptic markers. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated and total tau (p-Tau 181, t-Tau), CAP2 and synaptosomal-associated protein 25 (SNAP-25) were quantified using ELISA, Lumipulse and SIMOA platforms. MND patients displayed increased GFAP, NfL, t-Tau, p-Tau 181 levels and CAP2 while SNAP-25 was reduced. CAP2 correlated with tau markers, but not with NfL or GFAP. Unlike NfL, which was higher in upper motor neuron\u2013predominant cases and predicted faster progression and poorer survival, CAP2 did not vary with disease subtypes or severity. The study", "source": "PubMed"}, {"chunk_id": "41698978_1", "pmid": "41698978", "title": "Synaptic and cytoskeletal CSF signatures of motor neuron disease: the role of cyclase-associated protein 2.", "authors": "Pilotto A, Pelucchi S, Trasciatti C et al.", "year": "2026", "journal": "Scientific reports", "keywords": "Cerebrospinal fluid (CSF), Motor neuron disease (MND), Neurofilament light chain (NfL), Synaptic biomarkers", "chunk": "or GFAP. Unlike NfL, which was higher in upper motor neuron\u2013predominant cases and predicted faster progression and poorer survival, CAP2 did not vary with disease subtypes or severity. The study showed that CAP2 is associated with MND independently from neuronal, glial and presynaptic dysfunction. Integrating CAP2 into multi-marker panels could enhance understanding of synaptic pathology in MND. The online version contains supplementary material available at 10.1038/s41598-026-39274-0.", "source": "PubMed"}, {"chunk_id": "40167925_0", "pmid": "40167925", "title": "Inspecting Biological Deregulation, Putative Markers, and Therapeutic Targets for Neurodegenerative Diseases Through an Integrative Bioinformatics Analysis of the Human Cerebrospinal Fluid Proteome: A Tutorial.", "authors": "Trindade F, Nogueira-Ferreira R, Bastos P et al.", "year": "2025", "journal": "Methods in molecular biology (Clifton, N.J.)", "keywords": "CSF proteome, Candidate biomarkers, Gene ontology enrichment analysis, Neurodegenerative diseases, Protein-protein interaction, Therapeutic targets", "chunk": "Cerebrospinal fluid (CSF) is a source of valuable information concerning brain disorders. The technical advances of high throughput omics platforms to analyze body fluids can generate a huge amount of data, whose translation of the biological meaning can be a challenge. Several bioinformatics tools have emerged to help handle this data from a systems biology perspective. Herein, we describe a step-by-step tutorial for CSF proteome data analysis in the set of neurodegenerative diseases using: (i) ShinyGO webtool to perform functional enrichment analysis envisioning the characterization of the biological pathways and processes deregulated in neurodegenerative diseases including Alzheimer's and Parkinson's diseases; (ii) Cytoscape to map disease-specific proteins based on evidence from proteomics; (iii) DisGeNET to identify the proteins more strongly and more specifically associated with neurodegenerative diseases to date; (iv) STRING to identify putative therapeutic targets through a combined protein-protein interaction and network topological analyses. This step-by-step guide might help researchers", "source": "PubMed"}, {"chunk_id": "40167925_1", "pmid": "40167925", "title": "Inspecting Biological Deregulation, Putative Markers, and Therapeutic Targets for Neurodegenerative Diseases Through an Integrative Bioinformatics Analysis of the Human Cerebrospinal Fluid Proteome: A Tutorial.", "authors": "Trindade F, Nogueira-Ferreira R, Bastos P et al.", "year": "2025", "journal": "Methods in molecular biology (Clifton, N.J.)", "keywords": "CSF proteome, Candidate biomarkers, Gene ontology enrichment analysis, Neurodegenerative diseases, Protein-protein interaction, Therapeutic targets", "chunk": "more specifically associated with neurodegenerative diseases to date; (iv) STRING to identify putative therapeutic targets through a combined protein-protein interaction and network topological analyses. This step-by-step guide might help researchers to better characterize disease pathogenesis and to identify putative disease biomarkers and therapeutic targets.", "source": "PubMed"}, {"chunk_id": "39169442_0", "pmid": "39169442", "title": "Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.", "authors": "Bader I, Groot C, Tan HS et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Age-related eye disorder, Alzheimer\u2019s disease, Blood-based biomarkers, Eye clinic, Hyperspectral retinal imaging, Plasma p-tau, Retinal imaging, Screening, Visual impairment", "chunk": "Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups. The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being \u2265 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial", "source": "PubMed"}, {"chunk_id": "39169442_1", "pmid": "39169442", "title": "Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.", "authors": "Bader I, Groot C, Tan HS et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Age-related eye disorder, Alzheimer\u2019s disease, Blood-based biomarkers, Eye clinic, Hyperspectral retinal imaging, Plasma p-tau, Retinal imaging, Screening, Visual impairment", "chunk": "longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being \u2265 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo A\u03b2-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments. We aim to implement the current protocol between April 2024 until March", "source": "PubMed"}, {"chunk_id": "39169442_2", "pmid": "39169442", "title": "Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.", "authors": "Bader I, Groot C, Tan HS et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Age-related eye disorder, Alzheimer\u2019s disease, Blood-based biomarkers, Eye clinic, Hyperspectral retinal imaging, Plasma p-tau, Retinal imaging, Screening, Visual impairment", "chunk": "hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments. We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using A\u03b2- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding. We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection. The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.", "source": "PubMed"}, {"chunk_id": "39169442_3", "pmid": "39169442", "title": "Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.", "authors": "Bader I, Groot C, Tan HS et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Age-related eye disorder, Alzheimer\u2019s disease, Blood-based biomarkers, Eye clinic, Hyperspectral retinal imaging, Plasma p-tau, Retinal imaging, Screening, Visual impairment", "chunk": "is approved by the ethical review board of the Amsterdam UMC.", "source": "PubMed"}, {"chunk_id": "33003562_0", "pmid": "33003562", "title": "<i>Mens Sana in Corpore Sano</i>: Does the Glycemic Index Have a Role to Play?", "authors": "Carneiro L, Leloup C", "year": "2020", "journal": "Nutrients", "keywords": "cognition, glycemia, ketone bodies, metabolism, neurodegeneration, nutrition, nutrition therapy", "chunk": "Although diet interventions are mostly related to metabolic disorders, nowadays they are used in a wide variety of pathologies. From diabetes and obesity to cardiovascular diseases, to cancer or neurological disorders and stroke, nutritional recommendations are applied to almost all diseases. Among such disorders, metabolic disturbances and brain function and/or diseases have recently been shown to be linked. Indeed, numerous neurological functions are often associated with perturbations of whole-body energy homeostasis. In this regard, specific diets are used in various neurological conditions, such as epilepsy, stroke, or seizure recovery. In addition, Alzheimer's disease and Autism Spectrum Disorders are also considered to be putatively improved by diet interventions. Glycemic index diets are a novel developed indicator expected to anticipate the changes in blood glucose induced by specific foods and how they can affect various physiological functions. Several results have provided indications of the efficiency of low-glycemic index diets in weight management", "source": "PubMed"}, {"chunk_id": "33003562_1", "pmid": "33003562", "title": "<i>Mens Sana in Corpore Sano</i>: Does the Glycemic Index Have a Role to Play?", "authors": "Carneiro L, Leloup C", "year": "2020", "journal": "Nutrients", "keywords": "cognition, glycemia, ketone bodies, metabolism, neurodegeneration, nutrition, nutrition therapy", "chunk": "in blood glucose induced by specific foods and how they can affect various physiological functions. Several results have provided indications of the efficiency of low-glycemic index diets in weight management and insulin sensitivity, but also cognitive function, epilepsy treatment, stroke, and neurodegenerative diseases. Overall, studies involving the glycemic index can provide new insights into the relationship between energy homeostasis regulation and brain function or related disorders. Therefore, in this review, we will summarize the main evidence on glycemic index involvement in brain mechanisms of energy homeostasis regulation.", "source": "PubMed"}, {"chunk_id": "39932872_0", "pmid": "39932872", "title": "Machine learning reveals connections between preclinical type 2 diabetes subtypes and brain health.", "authors": "Yi F, Yuan J, Han F et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "brain health, machine learning, preclinical-T2DM, subtype and stage inference", "chunk": "Previous research has established type 2 diabetes mellitus as a significant risk factor for various disorders, adversely impacting human health. While evidence increasingly links type 2 diabetes to cognitive impairment and brain disorders, understanding the causal effects of its preclinical stage on brain health is yet to be fully known. This knowledge gap hinders advancements in screening and preventing neurological and psychiatric diseases. To address this gap, we employed a robust machine learning algorithm (Subtype and Stage Inference, SuStaIn) with cross-sectional clinical data from the UK Biobank (20 277 preclinical type 2 diabetes participants and 20 277 controls) to identify underlying subtypes and stages for preclinical type 2 diabetes. Our analysis revealed one subtype distinguished by elevated circulating leptin levels and decreased leptin receptor levels, coupled with increased body mass index, diminished lipid metabolism, and heightened susceptibility to psychiatric conditions such as anxiety disorder, depression disorder, and bipolar disorder. Conversely,", "source": "PubMed"}, {"chunk_id": "39932872_1", "pmid": "39932872", "title": "Machine learning reveals connections between preclinical type 2 diabetes subtypes and brain health.", "authors": "Yi F, Yuan J, Han F et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "brain health, machine learning, preclinical-T2DM, subtype and stage inference", "chunk": "and decreased leptin receptor levels, coupled with increased body mass index, diminished lipid metabolism, and heightened susceptibility to psychiatric conditions such as anxiety disorder, depression disorder, and bipolar disorder. Conversely, individuals in the second subtype manifested typical abnormalities in glucose metabolism, including rising glucose and haemoglobin A1c levels, with observed correlations with neurodegenerative disorders. A >10-year follow-up of these individuals revealed differential declines in brain health and significant clinical outcome disparities between subtypes. The first subtype exhibited faster progression and higher risk for psychiatric conditions, while the second subtype was associated with more severe progression of Alzheimer's disease and Parkinson's disease and faster progression to type 2 diabetes. Our findings highlight that monitoring and addressing the brain health needs of individuals in the preclinical stage of type 2 diabetes is imperative.", "source": "PubMed"}, {"chunk_id": "39932872_2", "pmid": "39932872", "title": "Machine learning reveals connections between preclinical type 2 diabetes subtypes and brain health.", "authors": "Yi F, Yuan J, Han F et al.", "year": "2025", "journal": "Brain : a journal of neurology", "keywords": "brain health, machine learning, preclinical-T2DM, subtype and stage inference", "chunk": "individuals in the preclinical stage of type 2 diabetes is imperative.", "source": "PubMed"}, {"chunk_id": "39550564_0", "pmid": "39550564", "title": "Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort.", "authors": "Castilla-Mart\u00ed L, Garc\u00eda-S\u00e1nchez A, Mart\u00ednez J et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer's disease, Biomarkers, Choroidal thickness, NORFACE cohort, Optical coherence tomography, Vascular dementia", "chunk": "Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer's disease dementia (ADD), and vascular dementia (VaD). Clinical, demographical, ophthalmological and OCT data from the Neuro-ophthalmological Research at Fundaci\u00f3 ACE (NORFACE) project were analyzed. CT was assessed in the macula across nine Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, average thickness, total volume, and subfoveal choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison", "source": "PubMed"}, {"chunk_id": "39550564_1", "pmid": "39550564", "title": "Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort.", "authors": "Castilla-Mart\u00ed L, Garc\u00eda-S\u00e1nchez A, Mart\u00ednez J et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer's disease, Biomarkers, Choroidal thickness, NORFACE cohort, Optical coherence tomography, Vascular dementia", "chunk": "choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison between manual and automatic CT measurements in a subset of participants was also performed. The study cohort comprised 1,280 participants: 301 CU, 196 MCI-AD, 112 MCI-Va, 578 ADD, and 93 VaD. CT was significantly increased in individuals with cognitive impairment compared to those CU, particularly in the VaD and MCI-Va groups and in the peripheral ETDRS regions. No significant differences were found in inner superior, center and subfoveal choroidal thickness. The interaction of sex and diagnosis had no effect in differentiating CT. Mini-Mental State Examination (MMSE) scores were not correlated to CT. Manual and automated CT measurements showed good reliability. Our findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker", "source": "PubMed"}, {"chunk_id": "39550564_2", "pmid": "39550564", "title": "Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort.", "authors": "Castilla-Mart\u00ed L, Garc\u00eda-S\u00e1nchez A, Mart\u00ednez J et al.", "year": "2024", "journal": "Alzheimer's research & therapy", "keywords": "Alzheimer's disease, Biomarkers, Choroidal thickness, NORFACE cohort, Optical coherence tomography, Vascular dementia", "chunk": "to CT. Manual and automated CT measurements showed good reliability. Our findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker for cognitive decline and suggest different pathogenic pathways in AD and VaD. Further research is required to explore CT as a reliable ocular biomarker for cognitive impairment.", "source": "PubMed"}, {"chunk_id": "41710117_0", "pmid": "41710117", "title": "The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer's Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment.", "authors": "Sergio J, Price A, Snyder PJ et al.", "year": "2026", "journal": "Clinical interventions in aging", "keywords": "blood biomarkers, gait metrics, pTau181, pTau217, timed up and go", "chunk": "The Timed Up and Go (TUG) is a 20-foot gait assessment, with TUG-dual task (DT) serial subtractions to determine dual-task cost. Alzheimer's disease (AD) risk is established using plasma biomarkers and APOE genotyping. We investigated: 1) TUG/TUG-DT differences between AD low-risk cognitively unimpaired (CU) older adults (N = 74), AD high-risk CU older adults (N = 87), and mild cognitively impaired (MCI) older adults (N = 33) and 2) the relationship between TUG/TUG-DT performance and plasma biomarkers. One hundred and ninety-four older adults ages 55-80 completed TUG/TUG-DT, a fasting blood draw, and APOE genotyping. Scores on the Clinical Dementia Rating Scale (CU = 0; CI = \u22650.5) and Montreal Cognitive Assessment (CU \u2265 24; CI = \u226423) determined whether participants were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of", "source": "PubMed"}, {"chunk_id": "41710117_1", "pmid": "41710117", "title": "The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer's Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment.", "authors": "Sergio J, Price A, Snyder PJ et al.", "year": "2026", "journal": "Clinical interventions in aging", "keywords": "blood biomarkers, gait metrics, pTau181, pTau217, timed up and go", "chunk": "were placed into the CU low-risk, CU high-risk, or MCI groups. Risk level for CU participants were assessed by APOE genotyping. Those participants who carried at least one copy of the APOE \u03b54 allele were designated to the high-risk group (n = 87). Participants with no APOE \u03b54 allele were assigned to the low-risk group (n = 75). MCI participants took longer to perform the TUG than CU participants (<i>p</i> < 0.001). CU high-risk and MCI group performed similarly on step counts, while the CU low-risk took significantly fewer steps (<i>p</i><0.001). Speed predicted whether someone was below an AD-risk threshold for pTau217 in CU participants (n = 150). Exploratory generalized additive models showed plasma biomarkers predicted gait metrics in CU groups. Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical", "source": "PubMed"}, {"chunk_id": "41710117_2", "pmid": "41710117", "title": "The Relationship Between Gait Task Performance and Plasma Biomarkers for Alzheimer's Disease in Cognitively Unimpaired Older Adults and Patients with Mild Cognitive Impairment.", "authors": "Sergio J, Price A, Snyder PJ et al.", "year": "2026", "journal": "Clinical interventions in aging", "keywords": "blood biomarkers, gait metrics, pTau181, pTau217, timed up and go", "chunk": "groups. Step count may be more sensitive, compared to speed alone, in identifying those in preclinical AD stages. Gait metrics (speed and efficiency) played a key role as a clinical manifestation of early AD pathophysiology determined by blood-based biomarker concentration. Combining these assessments offers a multidimensional, cost-effective approach for preclinical-AD screening and potential early intervention.", "source": "PubMed"}, {"chunk_id": "38033552_0", "pmid": "38033552", "title": "Lipids and lipoproteins may play a role in the neuropathology of Alzheimer's disease.", "authors": "Akyol O, Akyol S, Chou MC et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, LDLR, LOX-1, cholesterol, electronegative LDL, lipids", "chunk": "Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the pathophysiology of AD. Although changes in cholesterol, triglyceride, LDL, and glucose levels are seen in AD, the cause remains unknown. We believe that L5-the most electronegative subfraction of LDL-may be a crucial factor in understanding the involvement of lipids in AD pathology. LDL and L5 are internalized by cells through", "source": "PubMed"}, {"chunk_id": "38033552_1", "pmid": "38033552", "title": "Lipids and lipoproteins may play a role in the neuropathology of Alzheimer's disease.", "authors": "Akyol O, Akyol S, Chou MC et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, LDLR, LOX-1, cholesterol, electronegative LDL, lipids", "chunk": "We believe that L5-the most electronegative subfraction of LDL-may be a crucial factor in understanding the involvement of lipids in AD pathology. LDL and L5 are internalized by cells through different receptors and mechanisms that trigger separate intracellular pathways. One of the receptors involved in L5 internalization, LOX-1, triggers apoptotic pathways. Aging is associated with dysregulation of lipid homeostasis, and it is believed that alterations in lipid metabolism contribute to the pathogenesis of AD. Proposed mechanisms of lipid dysregulation in AD include mitochondrial dysfunction, blood-brain barrier disease, neuronal signaling, inflammation, and oxidative stress, all of which lead ultimately to memory loss through deficiency of synaptic integration. Several lipid species and their receptors have essential functions in AD pathogenesis and may be potential biomarkers.", "source": "PubMed"}, {"chunk_id": "38033552_2", "pmid": "38033552", "title": "Lipids and lipoproteins may play a role in the neuropathology of Alzheimer's disease.", "authors": "Akyol O, Akyol S, Chou MC et al.", "year": "2023", "journal": "Frontiers in neuroscience", "keywords": "Alzheimer\u2019s disease, LDLR, LOX-1, cholesterol, electronegative LDL, lipids", "chunk": "be potential biomarkers.", "source": "PubMed"}, {"chunk_id": "41303517_0", "pmid": "41303517", "title": "Mild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes.", "authors": "Oporto-Colicoi V, Sep\u00falveda-Lara A, Marzuca-Nassr GN et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "dementia prevention, hippocampus, mild cognitive impairment, neuroinflammation, neuroplasticity, resistance exercise, sarcopenia", "chunk": "Mild cognitive impairment (MCI) and sarcopenia are prevalent age-related conditions that often coexist and share common mechanisms such as chronic inflammation, reduced neuroplasticity, and impaired muscle function. Resistance exercise training (RET) has emerged as a promising non-pharmacological strategy capable of addressing both physical and cognitive decline. The aim of this narrative review is to synthesize preclinical and clinical evidence on the effects of RET in older adults with MCI and sarcopenia, with a specific focus on its impact on neuroinflammation, cognitive performance and structural brain changes. At the molecular level, RET activates anabolic pathways, including PI3K/Akt/mTOR, enhances neurotrophic support via BDNF, NT-3, and IGF-1, and promotes hippocampal neurogenesis through exercise-induced myokines such as irisin and cathepsin B. RET also exerts immunomodulatory actions by shifting microglia toward anti-inflammatory M2 phenotypes, attenuating reactive astrogliosis, and supporting oligodendrocyte precursor cell differentiation, thereby improving myelin integrity. Neuroimaging studies consistently report preservation of hippocampal and", "source": "PubMed"}, {"chunk_id": "41303517_1", "pmid": "41303517", "title": "Mild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes.", "authors": "Oporto-Colicoi V, Sep\u00falveda-Lara A, Marzuca-Nassr GN et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "dementia prevention, hippocampus, mild cognitive impairment, neuroinflammation, neuroplasticity, resistance exercise, sarcopenia", "chunk": "immunomodulatory actions by shifting microglia toward anti-inflammatory M2 phenotypes, attenuating reactive astrogliosis, and supporting oligodendrocyte precursor cell differentiation, thereby improving myelin integrity. Neuroimaging studies consistently report preservation of hippocampal and precuneus gray matter, as well as improved white matter connectivity following RET. Clinically, RET has demonstrated significant and sustained improvements in executive function, memory, and global cognition, with effects persisting for up to 18 months. Collectively, RET represents a multifaceted intervention with the potential to delay progression from MCI to Alzheimer's disease by integrating neuroprotective, anti-inflammatory, and anabolic effects. Standardization of RET protocols and identification of biomarkers of responsiveness are needed to optimize its role within multimodal dementia-prevention strategies.", "source": "PubMed"}, {"chunk_id": "40678042_0", "pmid": "40678042", "title": "Progression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.", "authors": "Berger M, Garcia-Moreno H, Ferreira M et al.", "year": "2025", "journal": "The Lancet regional health. Europe", "keywords": "ATXN3, Biomarker, Disease modelling, MRI, NfL, Spinocerebellar ataxia, Staging model", "chunk": "Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited adult-onset disease. We aimed to describe longitudinal changes in clinical and biological findings and to identify predictors for clinical progression. We used data from participants enrolled in the ESMI cohort collected between Nov 09, 2016 and July 18, 2023. The data freeze included data from 14 sites in five European countries and the United States. We assessed ataxia with the Scale for the Assessment and Rating of Ataxia (SARA). We measured disease-specific mutant ataxin-3 protein (ATXN3) and neurofilament light chain (NfL) in plasma and performed MRIs. Data were analysed by regression modelling on a timescale defined by onset. The onset of abnormality of a marker was defined as the time at which its value, as determined by modelling, exceeded the mean \u00b1 2 SD of healthy controls. To study responsiveness of markers, we determined the sensitivity to change ratios (SCSs).", "source": "PubMed"}, {"chunk_id": "40678042_1", "pmid": "40678042", "title": "Progression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.", "authors": "Berger M, Garcia-Moreno H, Ferreira M et al.", "year": "2025", "journal": "The Lancet regional health. Europe", "keywords": "ATXN3, Biomarker, Disease modelling, MRI, NfL, Spinocerebellar ataxia, Staging model", "chunk": "at which its value, as determined by modelling, exceeded the mean \u00b1 2 SD of healthy controls. To study responsiveness of markers, we determined the sensitivity to change ratios (SCSs). Data from 291 SCA3 mutation carriers before and after clinical onset and 121 healthy controls were included. NfL levels became abnormal in SCA3 mutation carriers more than 20 years (-21.5 years [95% CI n.d.-9.5]) before onset. The earliest MRI abnormality was volume loss of medulla oblongata (-4.7 years [95% CI n.d.-3.3]). The responsiveness of markers depended on the disease stage. Across all stages, pons volume had the highest responsiveness with an SCS of 1.35 [95% CI 1.11-1.78] exceeding that of SARA (0.99 [95% CI 0.88-1.11]). In SCA3, lower age (p = 0.0459 [95% CI of slope change -0.0018 to 0.0000]) and lower medulla oblongata volume (p < 0.0001 [95% CI of slope change -0.0298 to -0.0115]) were predictors of SARA", "source": "PubMed"}, {"chunk_id": "40678042_2", "pmid": "40678042", "title": "Progression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.", "authors": "Berger M, Garcia-Moreno H, Ferreira M et al.", "year": "2025", "journal": "The Lancet regional health. Europe", "keywords": "ATXN3, Biomarker, Disease modelling, MRI, NfL, Spinocerebellar ataxia, Staging model", "chunk": "= 0.0459 [95% CI of slope change -0.0018 to 0.0000]) and lower medulla oblongata volume (p < 0.0001 [95% CI of slope change -0.0298 to -0.0115]) were predictors of SARA progression. Our study provides quantitative information on the progression of biological markers in SCA3 mutation carriers before and after onset of ataxia, and allowed the identification of predictors for clinical progression. Our data could prove useful for the design of future clinical trials. HEU Joint Programme - Neurodegenerative Disease Research (JPND) (Federal Ministry of Education and Research, Germany; The Netherlands Organisation for Health Research and Development; Foundation for Science and Technology, Portugal; Medical Research Council, Regional Fund for Science and Technology, Azores), and Servier. At the US sites this work was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS080816.", "source": "PubMed"}, {"chunk_id": "40678042_3", "pmid": "40678042", "title": "Progression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.", "authors": "Berger M, Garcia-Moreno H, Ferreira M et al.", "year": "2025", "journal": "The Lancet regional health. Europe", "keywords": "ATXN3, Biomarker, Disease modelling, MRI, NfL, Spinocerebellar ataxia, Staging model", "chunk": "was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS080816.", "source": "PubMed"}, {"chunk_id": "34741576_0", "pmid": "34741576", "title": "Improving Sensitivity of Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease Using Transfer Learning of Deep Learning-Based ASL Denoising.", "authors": "Zhang L, Xie D, Li Y et al.", "year": "2022", "journal": "Journal of magnetic resonance imaging : JMRI", "keywords": "Alzheimer's disease, arterial spin labeling perfusion MRI, deep learning, denoising, transfer learning", "chunk": "Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) denoising through deep learning (DL) often faces insufficient training data from patients. One solution is to train DL models using healthy subjects' data which are more widely available and transfer them to patients' data. To evaluate the transferability of a DL-based ASL MRI denoising method (DLASL). Retrospective. Four hundred and twenty-eight subjects (189 females) from three cohorts. 3 T two-dimensional (2D) echo-planar imaging (EPI)-based pseudo-continuous ASL (PCASL) and 2D EPI-based pulsed ASL (PASL) sequences. DLASL was trained using young healthy adults' PCASL data (Dataset 1: 250/30 subjects as training/validation set) and was directly transferred (DTF) to PCASL data from Dataset 2 (45 subjects test set) of normal controls (NC) and Alzheimer's disease (AD) groups. DLASL was fine-tuned (DLASLFT) and tested on PASL data from Dataset 3 (103 subjects test set) of NC and AD. An existing non-DL method (NonDL) was used", "source": "PubMed"}, {"chunk_id": "34741576_1", "pmid": "34741576", "title": "Improving Sensitivity of Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease Using Transfer Learning of Deep Learning-Based ASL Denoising.", "authors": "Zhang L, Xie D, Li Y et al.", "year": "2022", "journal": "Journal of magnetic resonance imaging : JMRI", "keywords": "Alzheimer's disease, arterial spin labeling perfusion MRI, deep learning, denoising, transfer learning", "chunk": "disease (AD) groups. DLASL was fine-tuned (DLASLFT) and tested on PASL data from Dataset 3 (103 subjects test set) of NC and AD. An existing non-DL method (NonDL) was used for comparison. Cerebral blood flow (CBF) images from ASL MRI were compared between NC and AD to assess characteristic hypoperfusion (lower CBF) patterns in AD. CBF image quality and CBF map sensitivity for detecting hypoperfusion using peak t-value and suprathreshold cluster size are outcome measures. Paired t-test, two-sample t-test, one-way analysis of variance, and Tukey honestly significant difference, and linear mixed-effects models were used. P < 0.05 was considered statistically significant. Mean contrast-to-noise ratio (CNR) of Dataset 2 showed that DTF outperformed NonDL (AD: 3.38 vs. 2.64, NC: 3.80 vs. 3.36). On Dataset 3, DLASLFT outperformed NonDL measured by mean CNR (AD: 2.45 vs. 1.87, NC: 2.54 vs. 2.17) and mean radiologic score (2.86 vs. 2.44). Image quality improvement was", "source": "PubMed"}, {"chunk_id": "34741576_2", "pmid": "34741576", "title": "Improving Sensitivity of Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease Using Transfer Learning of Deep Learning-Based ASL Denoising.", "authors": "Zhang L, Xie D, Li Y et al.", "year": "2022", "journal": "Journal of magnetic resonance imaging : JMRI", "keywords": "Alzheimer's disease, arterial spin labeling perfusion MRI, deep learning, denoising, transfer learning", "chunk": "3.36). On Dataset 3, DLASLFT outperformed NonDL measured by mean CNR (AD: 2.45 vs. 1.87, NC: 2.54 vs. 2.17) and mean radiologic score (2.86 vs. 2.44). Image quality improvement was significant on both test sets. DTF and DLASLFT improved sensitivity for detecting AD-related hypoperfusion patterns compared with NonDL. We demonstrated the DLASL's transferability across different ASL sequences and different populations. 3 TECHNICAL EFFICACY: Stage 2.", "source": "PubMed"}, {"chunk_id": "40801241_0", "pmid": "40801241", "title": "Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models.", "authors": "Jin Z, Lu Y, Tang H et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, early diagnosis, models, neuroinflammation, non\u2010human primates, therapy", "chunk": "The amyloid/tau/neurodegeneration (ATN) biomarker framework has greatly progressed the diagnosis and staging of Alzheimer's disease (AD). However, recent research highlights neuroinflammation as an equally critical factor in AD pathology across humans, rodents, and non-human primates (NHPs). This review evaluates the combined use of ATN and neuroinflammatory biomarkers-such as glial fibrillary acidic protein (GFAP) (astrocytic marker) and triggering receptor expressed on myeloid cells 2 (TREM2)/ ionized calcium-binding adapter molecule 1 (IBA-1) (microglial markers)-in elucidating AD mechanisms, promoting early diagnosis, and shaping therapeutic strategies. It also summarizes the key features and translational potential of NHP models that closely mimic human AD pathology, highlighting the promising prospects of integrating these models with the ATN(X) biomarker system. These insights strengthen the link between biomarkers, NHP research, and clinical practice, opening new avenues for the early detection and treatment strategies of AD. HIGHLIGHTS: Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on", "source": "PubMed"}, {"chunk_id": "40801241_1", "pmid": "40801241", "title": "Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models.", "authors": "Jin Z, Lu Y, Tang H et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, biomarkers, early diagnosis, models, neuroinflammation, non\u2010human primates, therapy", "chunk": "NHP research, and clinical practice, opening new avenues for the early detection and treatment strategies of AD. HIGHLIGHTS: Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2)/sTREM2, and YKL-40, show strong clinical potential in Alzheimer's disease (AD). Incorporating neuroinflammation biomarkers into the ATN(X) framework may enhance diagnostic precision. Advanced non-human primate (NHP) models closely replicate human brain pathology, addressing key limitations of mouse models. Measuring ATN(X) biomarkers in NHPs may improve clinical translation and support early diagnosis of AD. Optimizing NHP models-including ApoE4 status, injection protocols, and gene-editing approaches-is crucial for reproducibility and efficiency.", "source": "PubMed"}, {"chunk_id": "41519179_0", "pmid": "41519179", "title": "The impact of sleep deprivation on dynamic functional connectivity of the brain: Based on alertness task performance.", "authors": "Ouyang A, Lin X, Zhang T et al.", "year": "2026", "journal": "Brain research bulletin", "keywords": "Cognitive impairment, Dynamical functional connectivity analysis, Functional magnetic resonance imaging, Psychomotor vigilance task, Sleep deprivation", "chunk": "Sleep deprivation (SD) impairs mood and cognition, yet its dynamic neural mechanisms remain unclear. Forty healthy adults (30-h SD) completed mood assessments, resting-state fMRI (rs-fMRI), and psychomotor vigilance task (PVT) tests at baseline and post-SD. Using dynamic functional connectivity (dFC) with sliding windows and k-means clustering, we identified two recurrent whole-brain states: (i) an economical state with sparse, weaker global coupling and (ii) a maladaptive compensatory state with globally strengthened synchronization. SD increased both the fraction of windows and mean dwell time (MDT) of the maladaptive state. Across participants, PVT lapses correlated positively with the maladaptive state's MDT and fraction of windows and negatively with those of the economical state. Finally, we built an interpretable predictive model of PVT lapses using competitive adaptive reweighted sampling partial least-squares regression (CARS-PLSR), which highlighted connections within the dorsal attention network (DAN) as key predictors. These findings link behavioral impairment to altered brain-state dynamics", "source": "PubMed"}, {"chunk_id": "41519179_1", "pmid": "41519179", "title": "The impact of sleep deprivation on dynamic functional connectivity of the brain: Based on alertness task performance.", "authors": "Ouyang A, Lin X, Zhang T et al.", "year": "2026", "journal": "Brain research bulletin", "keywords": "Cognitive impairment, Dynamical functional connectivity analysis, Functional magnetic resonance imaging, Psychomotor vigilance task, Sleep deprivation", "chunk": "using competitive adaptive reweighted sampling partial least-squares regression (CARS-PLSR), which highlighted connections within the dorsal attention network (DAN) as key predictors. These findings link behavioral impairment to altered brain-state dynamics and provide a sparse, testable feature set that can support early risk stratification and intervention for SD-related cognitive decline.", "source": "PubMed"}, {"chunk_id": "36076944_0", "pmid": "36076944", "title": "Dysfunctional Glucose Metabolism in Alzheimer's Disease Onset and Potential Pharmacological Interventions.", "authors": "Kumar V, Kim SH, Bishayee K", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "Alzheimer\u2019s disease, ROS, diabetes, genetic mutation, glycolysis, therapy", "chunk": "Alzheimer's disease (AD) is the most common age-related dementia. The alteration in metabolic characteristics determines the prognosis. Patients at risk show reduced glucose uptake in the brain. Additionally, type 2 diabetes mellitus increases the risk of AD with increasing age. Therefore, changes in glucose uptake in the cerebral cortex may predict the histopathological diagnosis of AD. The shifts in glucose uptake and metabolism, insulin resistance, oxidative stress, and abnormal autophagy advance the pathogenesis of AD syndrome. Here, we summarize the role of altered glucose metabolism in type 2 diabetes for AD prognosis. Additionally, we discuss diagnosis and potential pharmacological interventions for glucose metabolism defects in AD to encourage the development of novel therapeutic methods.", "source": "PubMed"}, {"chunk_id": "40856863_0", "pmid": "40856863", "title": "Blueberries for brainpower: A systematic review and meta-analysis with Bayesian post hoc analysis of RCTS exploring cognitive function in the elderly with prior cognitive decline.", "authors": "da Silva ABN, de Oliveira GM, Gallo Ruelas M et al.", "year": "2025", "journal": "Biogerontology", "keywords": "Alzheimer\u2019s, Blueberries, Cognitive decline, Dementia, Elderly population, Supplementation", "chunk": "Blueberries are anthocyanin-rich fruits widely consumed by the general population, with well-established health benefits on the endocrine and cardiovascular systems attributed to their potent anti-inflammatory properties. However, the potential impact of blueberry consumption on cognitive function in elderly individuals with prior cognitive decline, such as Alzheimer's disease and dementia, remains insufficiently explored in the literature. Therefore, we aimed to evaluate the potential effects of chronic blueberry consumption on cognitive performance in this population through various memory assessment tools. We searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) evaluating the effect of chronic blueberry consumption on cognitive function. We pooled standard mean differences (SMD) and 95% confidence interval (CI) using a random-effects model. We identified nine eligible RCTs involving 513 patients. In elderly individuals with mild cognitive impairment (MCI) and subjective cognitive decline, blueberry intake showed a statistically significant improvement in episodic memory. (SMD = 0.34; 95% CI 0.11", "source": "PubMed"}, {"chunk_id": "40856863_1", "pmid": "40856863", "title": "Blueberries for brainpower: A systematic review and meta-analysis with Bayesian post hoc analysis of RCTS exploring cognitive function in the elderly with prior cognitive decline.", "authors": "da Silva ABN, de Oliveira GM, Gallo Ruelas M et al.", "year": "2025", "journal": "Biogerontology", "keywords": "Alzheimer\u2019s, Blueberries, Cognitive decline, Dementia, Elderly population, Supplementation", "chunk": "513 patients. In elderly individuals with mild cognitive impairment (MCI) and subjective cognitive decline, blueberry intake showed a statistically significant improvement in episodic memory. (SMD = 0.34; 95% CI 0.11 to 0.57; p < 0.05). The subgroup analysis revealed that diagnostic objetivity was not a statistically significant effect modifier. Blueberry intake was also associated with improved language memory in MCI patients (SMD = 0.30; 95% CI 0.01 to 0.60; p < 0.05). No improvements were seen in processing speed (SMD = - 0.33; 95% CI - 0.85 to 0.19, p > 0.05), recognition memory (SMD = 0.14; 95% CI - 0.17 to 0.46, p > 0.05), visuospatial learning (SMD = 0.32; 95% CI - 0.16 to 0.79, p > 0.05) and working memory (SMD = 0.09; 95% CI - 0.21 to 0.39, p > 0.05). Chronic blueberry intake may improve episodic memory in the elderly with MCI and subjective cognitive", "source": "PubMed"}, {"chunk_id": "40856863_2", "pmid": "40856863", "title": "Blueberries for brainpower: A systematic review and meta-analysis with Bayesian post hoc analysis of RCTS exploring cognitive function in the elderly with prior cognitive decline.", "authors": "da Silva ABN, de Oliveira GM, Gallo Ruelas M et al.", "year": "2025", "journal": "Biogerontology", "keywords": "Alzheimer\u2019s, Blueberries, Cognitive decline, Dementia, Elderly population, Supplementation", "chunk": "and working memory (SMD = 0.09; 95% CI - 0.21 to 0.39, p > 0.05). Chronic blueberry intake may improve episodic memory in the elderly with MCI and subjective cognitive decline, and also language in the elderly with MCI. These findings should be confirmed in further multicenter trials to confirm generalizability and long-term impact.", "source": "PubMed"}, {"chunk_id": "40065919_0", "pmid": "40065919", "title": "Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies.", "authors": "Sato K, Niimi Y, Ihara R et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, blood\u2010based biomarker, clinical trial, cost\u2010effectiveness, predictive performance, prescreening", "chunk": "Blood-based biomarkers (BBBMs), including plasma amyloid beta (A\u03b2) or phosphorylated tau (p-tau), combined with apolipoprotein E (<i>APOE</i>) testing, are anticipated to serve as prescreening tools before amyloid positron emission tomography (PET) for recruiting participants for Alzheimer's disease (AD) prevention studies. The predictive efficacy and cost-effectiveness of prescreening may vary with different testing combinations, sequences, and cutoff levels. We conducted a simulation study utilizing data from our ongoing Japanese Trial-Ready Cohort (J-TRC) onsite study (<i>n</i> = 202) recruited online. We included cognitively unimpaired individuals who had undergone amyloid PET, <i>APOE</i> genotyping, and evaluation of BBBMs (i.e., plasma A\u03b242/A\u03b240 ratio, plasma p-tau217, and plasma p-tau217/A\u03b242 ratio). We examined 14 different prescreening models incorporating <i>APOE</i> genotype and/or BBBMs with varied combinations and cutoff levels. Models were evaluated for predictive performance (sensitivity, specificity, and positive predictive value [PPV]) and cost-effectiveness (cost per identified amyloid-positive case) across varied testing costs and the prevalence of amyloid", "source": "PubMed"}, {"chunk_id": "40065919_1", "pmid": "40065919", "title": "Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies.", "authors": "Sato K, Niimi Y, Ihara R et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, blood\u2010based biomarker, clinical trial, cost\u2010effectiveness, predictive performance, prescreening", "chunk": "levels. Models were evaluated for predictive performance (sensitivity, specificity, and positive predictive value [PPV]) and cost-effectiveness (cost per identified amyloid-positive case) across varied testing costs and the prevalence of amyloid positivity. Applying BBBM prescreening significantly decreased sensitivity and increased specificity and PPV compared to the no-prescreening scenario. Although no single model was superior in all performance metrics, a trade-off between sensitivity and specificity was observed. Generalized linear models (GLMs) simultaneously incorporating plasma A\u03b242/A\u03b240 ratio and p-tau217 showed a balanced efficacy (the best level of improvement in number needed to screen (NNS) but modest worsening in sensitivity) and the best level of cost-effectiveness compared to other models, although there were substantial overlaps in their 95% confidence intervals (CIs). The minimum-required PET/BBBM cost ratio to achieve improved cost-effectiveness by employing the prescreening process was negatively associated with the background prevalence of amyloid positivity. The choice of prescreening strategy in AD prevention studies/trials", "source": "PubMed"}, {"chunk_id": "40065919_2", "pmid": "40065919", "title": "Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies.", "authors": "Sato K, Niimi Y, Ihara R et al.", "year": "2025", "journal": "Alzheimer's & dementia (New York, N. Y.)", "keywords": "Alzheimer's disease, blood\u2010based biomarker, clinical trial, cost\u2010effectiveness, predictive performance, prescreening", "chunk": "cost ratio to achieve improved cost-effectiveness by employing the prescreening process was negatively associated with the background prevalence of amyloid positivity. The choice of prescreening strategy in AD prevention studies/trials should be tailored to specific trial requirements, considering the relative importance of sensitivity versus cost-effectiveness, local testing cost environments, and background population characteristics. We investigated different models of blood-based biomarker (BBBM) prescreening.Data from Japanese Trial-Ready Cohort Study were used for simulation.BBBM reduced the number needed to screen with positron emission tomography (PET) but decreased the sensitivity.The cost-effectiveness improved with a higher PET/BBBM cost ratio.No single model was optimal for all scenarios.", "source": "PubMed"}, {"chunk_id": "36949311_0", "pmid": "36949311", "title": "Glial-Neuronal Interaction in Synapses: A Possible Mechanism of the Pathophysiology of Bipolar Disorder.", "authors": "Wartchow KM, Scaini G, Quevedo J", "year": "2023", "journal": "Advances in experimental medicine and biology", "keywords": "Astrocytes, Bipolar disorder, Glial cells, Microglia, Neurons, Tripartite synapses", "chunk": "Bipolar disorder (BD) is a severe and chronic psychiatric disorder that affects approximately 1-4% of the world population and is characterized by recurrent episodes of mania or hypomania and depression. BD is also associated with illnesses marked by immune activation, such as metabolic syndrome, obesity, type 2 diabetes mellitus, and cardiovascular diseases. Indeed, a connection has been suggested between neuroinflammation and peripheral inflammatory markers in the pathophysiology of BD, which can be associated with the modulation of many dysfunctional processes, including synaptic plasticity, neurotransmission, neurogenesis, neuronal survival, apoptosis, and even cognitive/behavioral functioning. Rising evidence suggests that synaptic dysregulations, especially glutamatergic system dysfunction, are directly involved in mood disorders. It is becoming clear that dysregulations in connection and structural changes of glial cells play a central role in the BD pathophysiology. This book chapter highlighted the latest findings that support the theory of synaptic dysfunction in BD, providing an overview of", "source": "PubMed"}, {"chunk_id": "36949311_1", "pmid": "36949311", "title": "Glial-Neuronal Interaction in Synapses: A Possible Mechanism of the Pathophysiology of Bipolar Disorder.", "authors": "Wartchow KM, Scaini G, Quevedo J", "year": "2023", "journal": "Advances in experimental medicine and biology", "keywords": "Astrocytes, Bipolar disorder, Glial cells, Microglia, Neurons, Tripartite synapses", "chunk": "glial cells play a central role in the BD pathophysiology. This book chapter highlighted the latest findings that support the theory of synaptic dysfunction in BD, providing an overview of the alterations in neurotransmitters release, astrocytic uptake, and receptor signaling, as well as the role of inflammation on glial cells in mood disorders. Particular emphasis is given to the alterations in presynaptic and postsynaptic neurons and glial cells, all cellular elements of the \"tripartite synapse,\" compromising the neurotransmitters system, excitatory-inhibitory balance, and neurotrophic states of local networks in mood disorders. Together, these studies provide a foundation of knowledge about the exact role of the glial-neuronal interaction in mood disorders.", "source": "PubMed"}, {"chunk_id": "31466398_0", "pmid": "31466398", "title": "A Deep Learning approach for Diagnosis of Mild Cognitive Impairment Based on MRI Images.", "authors": "Gorji HT, Kaabouch N", "year": "2019", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, convolutional neural network, deep learning, mild cognitive impairment", "chunk": "Mild cognitive impairment (MCI) is an intermediary stage condition between healthy people and Alzheimer's disease (AD) patients and other dementias. AD is a progressive and irreversible neurodegenerative disorder, which is a significant threat to people, age 65 and older. Although MCI does not always lead to AD, an early diagnosis at the stage of MCI can be very helpful in identifying people who are at risk of AD. Moreover, the early diagnosis of MCI can lead to more effective treatment, or at least, significantly delay the disease's progress, and can lead to social and financial benefits. Magnetic resonance imaging (MRI), which has become a significant tool for the diagnosis of MCI and AD, can provide neuropsychological data for analyzing the variance in brain structure and function. MCI is divided into early and late MCI (EMCI and LMCI) and sadly, there is no clear differentiation between the brain structure of healthy", "source": "PubMed"}, {"chunk_id": "31466398_1", "pmid": "31466398", "title": "A Deep Learning approach for Diagnosis of Mild Cognitive Impairment Based on MRI Images.", "authors": "Gorji HT, Kaabouch N", "year": "2019", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, convolutional neural network, deep learning, mild cognitive impairment", "chunk": "variance in brain structure and function. MCI is divided into early and late MCI (EMCI and LMCI) and sadly, there is no clear differentiation between the brain structure of healthy people and MCI patients, especially in the EMCI stage. This paper aims to use a deep learning approach, which is one of the most powerful branches of machine learning, to discriminate between healthy people and the two types of MCI groups based on MRI results. The convolutional neural network (CNN) with an efficient architecture was used to extract high-quality features from MRIs to classify people into healthy, EMCI, or LMCI groups. The MRIs of 600 individuals used in this study included 200 control normal (CN) people, 200 EMCI patients, and 200 LMCI patients. This study randomly selected 70 percent of the data to train our model and 30 percent for the test set. The results showed the best overall classification", "source": "PubMed"}, {"chunk_id": "31466398_2", "pmid": "31466398", "title": "A Deep Learning approach for Diagnosis of Mild Cognitive Impairment Based on MRI Images.", "authors": "Gorji HT, Kaabouch N", "year": "2019", "journal": "Brain sciences", "keywords": "Alzheimer\u2019s disease, convolutional neural network, deep learning, mild cognitive impairment", "chunk": "200 LMCI patients. This study randomly selected 70 percent of the data to train our model and 30 percent for the test set. The results showed the best overall classification between CN and LMCI groups in the sagittal view with an accuracy of 94.54 percent. In addition, 93.96 percent and 93.00 percent accuracy were reached for the pairs of EMCI/LMCI and CN/EMCI, respectively.", "source": "PubMed"}, {"chunk_id": "41620604_0", "pmid": "41620604", "title": "Dynamic brain synergy uncovers functional neural coordination in Parkinson's disease under dopaminergic modulation.", "authors": "Lu J, Cheng Y, Zhang X et al.", "year": "2026", "journal": "Journal of neuroengineering and rehabilitation", "keywords": "Dopaminergic modulation, Dynamic brain synergy, Dynamic information decomposition, Parkinson\u2019s disease", "chunk": "Brain synergy and redundancy are emerging as pivotal aspects to understand neural functions, providing insights into high-order information that traditional functional connectivity (FC) methods cannot access. Despite their significance, these aspects have not been investigated in Parkinson's disease (PD). This paper advances the understanding of synergy and redundancy by integrating them with dynamic analysis, which is essential in the investigation of PD. Dynamic brain synergy and redundancy were developed and quantified by the constructed dynamic information decomposition framework, and was applied to walking-state functional near-infrared spectroscopy (fNIRS) signals of 63 PD patients undergoing dopaminergic treatment and 36 healthy controls. Dynamic brain synergy was restored to normal levels following dopaminergic treatment. Dynamic FC could not access high-order neural information and had insignificant variations in dopaminergic modulation among PD patients, and dynamic brain redundancy also exhibited insignificant treatment-induced variations. Dynamic brain synergy offers an advancing perspective on neural dynamics and promises to", "source": "PubMed"}, {"chunk_id": "41620604_1", "pmid": "41620604", "title": "Dynamic brain synergy uncovers functional neural coordination in Parkinson's disease under dopaminergic modulation.", "authors": "Lu J, Cheng Y, Zhang X et al.", "year": "2026", "journal": "Journal of neuroengineering and rehabilitation", "keywords": "Dopaminergic modulation, Dynamic brain synergy, Dynamic information decomposition, Parkinson\u2019s disease", "chunk": "insignificant variations in dopaminergic modulation among PD patients, and dynamic brain redundancy also exhibited insignificant treatment-induced variations. Dynamic brain synergy offers an advancing perspective on neural dynamics and promises to uncover high-order functional biomarkers for PD early diagnosis and individualized treatment. This study has been registered in Chinese Clinical Trial Registry (ChiCTR1900022655).", "source": "PubMed"}, {"chunk_id": "41291820_0", "pmid": "41291820", "title": "Lateral weight transfer deficits reveal balance vulnerability in early-stage Parkinson's disease during trip-perturbed walking.", "authors": "Hua A, Akinlosotu RY, Westlake KP", "year": "2025", "journal": "Journal of neuroengineering and rehabilitation", "keywords": "Balance, Falls, Gait, Parkinson\u2019s Disease", "chunk": "Individuals with early-stage Parkinson's disease (PD) typically do not exhibit impaired balance during clinical assessments; but subtle impairments may exist during challenging dynamic tasks that are not immediately apparent. This study investigates reactive balance responses to trip perturbations during walking in early-stage PD compared to age-matched controls. Sixteen individuals with early-stage PD (Hoehn & Yahr 2-2.5) and sixteen age-matched controls walked on a treadmill, experiencing an unpredictable trip perturbation. Whole-body kinematics were analyzed to compute margin of stability (MoS) and lateral body center of mass (COM) displacement trajectories across four reactive steps. Statistical comparisons evaluated group differences in MoS and COM displacement, while correlation analyses assessed relationships between stability and lateral COM displacement. By the third recovery step, controls had regained stability, while PD participants displayed significant variability. Half of the PD group exhibited negative MoS values, indicating instability, while the other half maintained stability comparable to controls. Moderate correlations", "source": "PubMed"}, {"chunk_id": "41291820_1", "pmid": "41291820", "title": "Lateral weight transfer deficits reveal balance vulnerability in early-stage Parkinson's disease during trip-perturbed walking.", "authors": "Hua A, Akinlosotu RY, Westlake KP", "year": "2025", "journal": "Journal of neuroengineering and rehabilitation", "keywords": "Balance, Falls, Gait, Parkinson\u2019s Disease", "chunk": "regained stability, while PD participants displayed significant variability. Half of the PD group exhibited negative MoS values, indicating instability, while the other half maintained stability comparable to controls. Moderate correlations between third-step MoS and lateral COM displacement (r > 0.56, p < 0.01) suggest impaired lateral weight transfer contributes to balance failure in PD. This study reveals variability in reactive balance capacity among early-stage PD participants, with nearly half showing subclinical deficits in lateral COM control. Trip-perturbed walking could serve as a promising biomarker for early balance impairments, potentially guiding proactive fall prevention strategies in PD management.", "source": "PubMed"}, {"chunk_id": "41452714_0", "pmid": "41452714", "title": "A Combination of Low-Dose \u0394<sup>9</sup>-THC and Celecoxib as a Therapeutic Strategy for Alzheimer's Disease.", "authors": "Zhang J, Zhu D, Hu M et al.", "year": "2025", "journal": "Aging and disease", "keywords": "None", "chunk": "Alzheimer's disease (AD) is the leading cause of dementia in the elderly, and no effective therapies are currently available to prevent, treat, or halt its progression. \u0394<sup>9</sup>-Tetrahydrocannabinol (\u0394<sup>9</sup>-THC), the primary psychoactive compound in marijuana, has been considered a potential therapeutic agent, but clear evidence for its ability to prevent cognitive decline is lacking. Previous studies have demonstrated that \u0394<sup>9</sup>-THC-induced cognitive impairments are associated with the induction of cyclooxygenase-2 (COX-2). In this study, we aimed to evaluate whether \u0394<sup>9</sup>-THC alone or in combination with Celecoxib, a selective COX-2 inhibitor, could reduce neuropathology and improve cognitive function in AD model animals. We observed that \u0394<sup>9</sup>-THC (3.0 mg/kg), either alone or with Celecoxib (1.0 mg/kg), significantly reduced A\u03b2 and tau pathologies, enhanced synaptic marker expression, and prevented the onset of cognitive decline. Notably, the combination treatment produced greater improvements in spatial learning and effectively mitigated \u0394<sup>9</sup>-THC-induced neuroinflammatory responses. Furthermore, \u0394<sup>9</sup>-THC reversed or attenuated", "source": "PubMed"}, {"chunk_id": "41452714_1", "pmid": "41452714", "title": "A Combination of Low-Dose \u0394<sup>9</sup>-THC and Celecoxib as a Therapeutic Strategy for Alzheimer's Disease.", "authors": "Zhang J, Zhu D, Hu M et al.", "year": "2025", "journal": "Aging and disease", "keywords": "None", "chunk": "marker expression, and prevented the onset of cognitive decline. Notably, the combination treatment produced greater improvements in spatial learning and effectively mitigated \u0394<sup>9</sup>-THC-induced neuroinflammatory responses. Furthermore, \u0394<sup>9</sup>-THC reversed or attenuated the dysregulated expression of synaptic and immune/inflammation-related genes and restored the downregulated expression of genes linked to AD observed in both AD patients and AD animal models, with greater efficacy when combined with Celecoxib in AD model mice. These findings suggest that the combination of low-dose \u0394<sup>9</sup>-THC and Celecoxib holds promise as an early intervention strategy for preventing AD onset or treating mild cognitive impairment (MCI). Importantly, both \u0394<sup>9</sup>-THC (in the form of Dronabinol and Nabilone) and Celecoxib are FDA-approved medications already in clinical use, supporting the strong translational potential of this combination therapy and its feasibility for rapid advancement to clinical trials to assess its efficacy in preventing or delaying AD onset in humans.", "source": "PubMed"}, {"chunk_id": "41452714_2", "pmid": "41452714", "title": "A Combination of Low-Dose \u0394<sup>9</sup>-THC and Celecoxib as a Therapeutic Strategy for Alzheimer's Disease.", "authors": "Zhang J, Zhu D, Hu M et al.", "year": "2025", "journal": "Aging and disease", "keywords": "None", "chunk": "of this combination therapy and its feasibility for rapid advancement to clinical trials to assess its efficacy in preventing or delaying AD onset in humans.", "source": "PubMed"}, {"chunk_id": "36284489_0", "pmid": "36284489", "title": "Recent advances in arterial spin labeling perfusion MRI in patients with vascular cognitive impairment.", "authors": "Huang D, Guo Y, Guan X et al.", "year": "2023", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Vascular cognitive impairment, arterial spin labeling, cerebral blood flow, neuroimaging, neurovascular unit, perfusion MRI, vascular dementia", "chunk": "Cognitive impairment (CI) is a major health concern in aging populations. It impairs patients' independent life and may progress to dementia. Vascular cognitive impairment (VCI) encompasses all cerebrovascular pathologies that contribute to cognitive impairment (CI). Moreover, the majority of CI subtypes involve various aspects of vascular dysfunction. Recent research highlights the critical role of reduced cerebral blood flow (CBF) in the progress of VCI, and the detection of altered CBF may help to detect or even predict the onset of VCI. Arterial spin labeling (ASL) is a non-invasive, non-ionizing perfusion MRI technique for assessing CBF qualitatively and quantitatively. Recent methodological advances enabling improved signal-to-noise ratio (SNR) and data acquisition have led to an increase in the use of ASL to assess CBF in VCI patients. Combined with other imaging modalities and biomarkers, ASL has great potential for identifying early VCI and guiding prediction and prevention strategies. This review focuses on", "source": "PubMed"}, {"chunk_id": "36284489_1", "pmid": "36284489", "title": "Recent advances in arterial spin labeling perfusion MRI in patients with vascular cognitive impairment.", "authors": "Huang D, Guo Y, Guan X et al.", "year": "2023", "journal": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism", "keywords": "Vascular cognitive impairment, arterial spin labeling, cerebral blood flow, neuroimaging, neurovascular unit, perfusion MRI, vascular dementia", "chunk": "assess CBF in VCI patients. Combined with other imaging modalities and biomarkers, ASL has great potential for identifying early VCI and guiding prediction and prevention strategies. This review focuses on recent advances in ASL-based perfusion MRI for identifying patients at high risk of VCI.", "source": "PubMed"}, {"chunk_id": "41256153_0", "pmid": "41256153", "title": "Cross-cohort validation and cutpoint estimation of the Janssen plasma p-tau217+ assay in predominantly cognitively normal community cohorts.", "authors": "Balogun WG, Zeng X, Triana-Baltzer G et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, amyloid beta pathology, blood-based biomarker, community-based cohort, p-tau217, p-tau217+, tau pathology", "chunk": "Cross-cohort validation studies for plasma p-tau217 are limited. We evaluated the Janssen plasma p-tau217+ assay and proposed a cutpoint value in three independent community-based cohorts. We included n=441 participants (age=70.3\u00b17.3), with A\u03b2-PET, tau-PET, clinical and cognitive information. The cohorts had low pre-test probability (%A\u03b2 positivity=14.9-24.7) and were predominantly cognitively normal (>73%). Plasma p-tau217+ had high accuracy for abnormal A\u03b2 PET (AUCs=81-86%), good correlation with A\u03b2-PET burden (0.336-0.397) that was highest in the cohort with the most A\u03b2-PET-positive participants, and the biomarker concentrations were highest in the joint A\u03b2-PET and tau-PET positive group. NPV was high across cohorts (\u226493%) but PPV was consistently poor (<57%). Sensitivity and specificity averaged 75% and 84% respectively. A combined cohort cutpoint of 0.05pg/ml gave AUC=84.5%, NPV=94%, PPV=50%, sensitivity=75%, and specificity=84%. Plasma p-tau217+ can rule out A\u03b2 pathophysiology due to Alzheimer's disease at the population level. Cohort-level %A\u03b2-PET positivity influences accuracies.", "source": "PubMed"}, {"chunk_id": "41256153_1", "pmid": "41256153", "title": "Cross-cohort validation and cutpoint estimation of the Janssen plasma p-tau217+ assay in predominantly cognitively normal community cohorts.", "authors": "Balogun WG, Zeng X, Triana-Baltzer G et al.", "year": "2025", "journal": "medRxiv : the preprint server for health sciences", "keywords": "Alzheimer\u2019s disease, amyloid beta pathology, blood-based biomarker, community-based cohort, p-tau217, p-tau217+, tau pathology", "chunk": "NPV=94%, PPV=50%, sensitivity=75%, and specificity=84%. Plasma p-tau217+ can rule out A\u03b2 pathophysiology due to Alzheimer's disease at the population level. Cohort-level %A\u03b2-PET positivity influences accuracies.", "source": "PubMed"}, {"chunk_id": "36585167_0", "pmid": "36585167", "title": "Androgen Deprivation Therapy Unrelated to Alzheimer's Disease in the UK Biobank Cohort.", "authors": "Lehrer S, Rheinstein PH", "year": "2023", "journal": "Anticancer research", "keywords": "Alzheimer\u2019s disease, Neurodegeneration, androgen deprivation therapy, prostate cancer", "chunk": "In a meta-analysis of 14 studies, men who received androgen deprivation therapy (ADT) for prostate cancer had a higher risk of dementia and/or Alzheimer disease (AD) than men who did not receive ADT. The effect was more pronounced when ADT was given for more than 12 months. However, in all these analyses, two of the strongest AD risk factors after age, family history of AD and the apolipoprotein e4 allele, were not included. In the current study, we have used data from the UK Biobank (UKB) that incorporates these two factors. Our analysis included all subjects with prostate cancer and AD. Prostate cancer diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD10), C61. AD diagnosis was ascertained using the 10<sup>th</sup> Revision of the International Classification of Diseases (ICD10) G30. Single nucleotide polymorphism (SNP) data for rs429358 and rs7412 were used to determine ApoE genotypes. ADT", "source": "PubMed"}, {"chunk_id": "36585167_1", "pmid": "36585167", "title": "Androgen Deprivation Therapy Unrelated to Alzheimer's Disease in the UK Biobank Cohort.", "authors": "Lehrer S, Rheinstein PH", "year": "2023", "journal": "Anticancer research", "keywords": "Alzheimer\u2019s disease, Neurodegeneration, androgen deprivation therapy, prostate cancer", "chunk": "was ascertained using the 10<sup>th</sup> Revision of the International Classification of Diseases (ICD10) G30. Single nucleotide polymorphism (SNP) data for rs429358 and rs7412 were used to determine ApoE genotypes. ADT was in UKB field 20003, Treatment/medication code, Medications. Family history of AD was in UKB data fields 20107, Illnesses of father; 20110, Illnesses of mother; 20111, Illnesses of siblings. We studied 13,203 men with prostate cancer. The age of 132 subjects that received ADT was 64\u00b15.6 (mean\u00b1standard deviation), and the age of 13,071 subjects that did not receive ADT was 62\u00b15.6 (p<0.001). ADT was not associated with AD, but Apoe3e3 was significantly associated with diminished risk of AD when compared to e4e4. Moreover, every year of age was associated with increased risk of AD. ADT was unrelated to AD (p=0.997). Our UK Biobank data analysis does not confirm that ADT causes AD in men with prostate cancer. Large studies that", "source": "PubMed"}, {"chunk_id": "36585167_2", "pmid": "36585167", "title": "Androgen Deprivation Therapy Unrelated to Alzheimer's Disease in the UK Biobank Cohort.", "authors": "Lehrer S, Rheinstein PH", "year": "2023", "journal": "Anticancer research", "keywords": "Alzheimer\u2019s disease, Neurodegeneration, androgen deprivation therapy, prostate cancer", "chunk": "increased risk of AD. ADT was unrelated to AD (p=0.997). Our UK Biobank data analysis does not confirm that ADT causes AD in men with prostate cancer. Large studies that include family history of AD and ApoeE genotype are needed. Mendelian randomization would also be desirable for a more definitive result.", "source": "PubMed"}, {"chunk_id": "40191788_0", "pmid": "40191788", "title": "An imaging and genetic-based deep learning network for Alzheimer's disease diagnosis.", "authors": "Li Y, Niu D, Qi K et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, MRI, SNP, multi-scale deep convolutional networks, transformer", "chunk": "Conventional computer-aided diagnostic techniques for Alzheimer's disease (AD) predominantly rely on magnetic resonance imaging (MRI) in isolation. Genetic imaging methods, by establishing the link between genes and brain structures in disease progression, facilitate early prediction of AD development. While deep learning methods based on MRI have demonstrated promising results for early AD diagnosis, the limited dataset size has led most AD studies to lean on statistical approaches within the realm of imaging genetics. Existing deep-learning approaches typically utilize pre-defined regions of interest and risk variants from known susceptibility genes, employing relatively straightforward feature fusion methods that fail to fully capture the relationship between images and genes. To address these limitations, we proposed a multi-modal deep learning classification network based on MRI and single nucleotide polymorphism (SNP) data for AD diagnosis and mild cognitive impairment (MCI) progression prediction. Our model leveraged a convolutional neural network (CNN) to extract whole-brain structural features,", "source": "PubMed"}, {"chunk_id": "40191788_1", "pmid": "40191788", "title": "An imaging and genetic-based deep learning network for Alzheimer's disease diagnosis.", "authors": "Li Y, Niu D, Qi K et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer's disease, MRI, SNP, multi-scale deep convolutional networks, transformer", "chunk": "MRI and single nucleotide polymorphism (SNP) data for AD diagnosis and mild cognitive impairment (MCI) progression prediction. Our model leveraged a convolutional neural network (CNN) to extract whole-brain structural features, a Transformer network to capture genetic features, and employed a cross-transformer-based network for comprehensive feature fusion. Furthermore, we incorporated an attention-map-based interpretability method to analyze and elucidate the structural and risk variants associated with AD and their interrelationships. The proposed model was trained and evaluated using 1,541 subjects from the ADNI database. Experimental results underscored the superior performance of our model in effectively integrating and leveraging information from both modalities, thus enhancing the accuracy of AD diagnosis and prediction.", "source": "PubMed"}, {"chunk_id": "40755109_0", "pmid": "40755109", "title": "Integration of Neuroimaging and Molecular Biomarkers in the Diagnosis of Alzheimer's Disease and Frontotemporal Dementia: The Promise of fMRI.", "authors": "Poszwa J, S\u0142owikowski B, Owecki W et al.", "year": "2025", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease, FTD, Molecular parameters, dementia, fMRI. *, neuroimaging factors", "chunk": "Dementia is a set of acquired and progressive neuropsychiatric disorders. The most common types of dementia include Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD). Early intravital diagnosis of both types of dementia is difficult. Both molecular and neuroimaging markers are important for the diagnosis of different types of dementia. This review employed freely accessible databases, including PubMed, Google Scholar, and ScienceDirect, using keywords such as molecular parameters, neuroimaging factors, dementia, FTD, Alzheimer's disease, and fMRI. Among the molecular markers of dementia, there are parameters common to its various types and enabling their differentiation. These parameters include both genetic and biochemical factors. Markers include genetic factors that help differentiate AD <i>(APP, PSEN1, PSEN2)</i> from FTD (e.g., <i>TARDBP, FUS, MAPT)</i>. Simultaneously, there are important biochemical parameters differentiating AD (amyloid-beta (A\u03b2), neurofibrillary tangles) from FTD (TDP-43, FUS, and different forms of tau protein aggregates). Currently, there is growing interest in neuroimaging studies in", "source": "PubMed"}, {"chunk_id": "40755109_1", "pmid": "40755109", "title": "Integration of Neuroimaging and Molecular Biomarkers in the Diagnosis of Alzheimer's Disease and Frontotemporal Dementia: The Promise of fMRI.", "authors": "Poszwa J, S\u0142owikowski B, Owecki W et al.", "year": "2025", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease, FTD, Molecular parameters, dementia, fMRI. *, neuroimaging factors", "chunk": "are important biochemical parameters differentiating AD (amyloid-beta (A\u03b2), neurofibrillary tangles) from FTD (TDP-43, FUS, and different forms of tau protein aggregates). Currently, there is growing interest in neuroimaging studies in the differential diagnosis of dementia. Positron Emission Tomography (PET) imaging enables the quantification and localization of A\u03b2 deposits in the brain through the selective binding of the Pittsburgh Compound-B (PiB) ligand. This method has become the standard in AD diagnostics. In the context of magnetic resonance imaging studies, it is worth noting the search for structural differences between AD (mainly affecting the temporal lobe, including the hippocampus and entorhinal cortex, and the parietal lobe) and FTD (primarily involving the prefrontal cortex, anterior temporal lobes, and subcortical structures, as well as exhibiting an anteroposterior gradient of atrophy). However, the method of the future appears to be functional Magnetic Resonance Imaging (fMRI), especially since functional changes precede structural changes in the development", "source": "PubMed"}, {"chunk_id": "40755109_2", "pmid": "40755109", "title": "Integration of Neuroimaging and Molecular Biomarkers in the Diagnosis of Alzheimer's Disease and Frontotemporal Dementia: The Promise of fMRI.", "authors": "Poszwa J, S\u0142owikowski B, Owecki W et al.", "year": "2025", "journal": "Current Alzheimer research", "keywords": "Alzheimer\u2019s disease, FTD, Molecular parameters, dementia, fMRI. *, neuroimaging factors", "chunk": "exhibiting an anteroposterior gradient of atrophy). However, the method of the future appears to be functional Magnetic Resonance Imaging (fMRI), especially since functional changes precede structural changes in the development of dementia. The review encompasses the basic diagnostic criteria for AD and FTD dementia, as well as molecular and neuroimaging parameters important for the intravital diagnosis of these dementias. It seems that the use of fMRI can contribute to both early diagnosis and early introduction of targeted treatment in developing dementia. Although it is not yet widely used clinically, its diagnostic value is increasingly recognized. The benefits of fMRI studies complementing molecular markers in the diagnosis of dementia were highlighted.", "source": "PubMed"}, {"chunk_id": "40042435_0", "pmid": "40042435", "title": "Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.", "authors": "Leuzy A, Bollack A, Pellegrino D et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer, A\u03b2\u2010PET, CSF, biomarkers, diagnosis", "chunk": "Amyloid-\u03b2 (A\u03b2) positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarkers are now established tools in the diagnostic workup of patients with Alzheimer's disease (AD), and their use is anticipated to increase with the introduction of new disease-modifying therapies. Although these biomarkers are comparable alternatives in research settings to determine A\u03b2 status, biomarker testing in clinical practice requires careful consideration of the strengths and limitations of each modality, as well as the specific clinical context, to identify which test is best suited for each patient. This article provides a comprehensive review of the pathologic processes reflected by A\u03b2-PET and CSF biomarkers, their performance, and their current and future applications and contexts of use. The primary aim is to assist clinicians in making better-informed decisions about the suitability of each biomarker in different clinical situations, thereby reducing the risk of misdiagnosis or incorrect interpretation of biomarker results. HIGHLIGHTS: Recent advances", "source": "PubMed"}, {"chunk_id": "40042435_1", "pmid": "40042435", "title": "Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.", "authors": "Leuzy A, Bollack A, Pellegrino D et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer, A\u03b2\u2010PET, CSF, biomarkers, diagnosis", "chunk": "clinicians in making better-informed decisions about the suitability of each biomarker in different clinical situations, thereby reducing the risk of misdiagnosis or incorrect interpretation of biomarker results. HIGHLIGHTS: Recent advances have positioned A\u03b2 PET and CSF biomarkers as pivotal in AD diagnosis. It is crucial to understand the differences in the clinical use of these biomarkers. A team of experts reviewed the state of A\u03b2 PET and CSF markers in clinical settings. Differential features in the clinical application of these biomarkers were reviewed. We discussed the role of A\u03b2 PET and CSF in the context of novel plasma biomarkers.", "source": "PubMed"}, {"chunk_id": "36232368_0", "pmid": "36232368", "title": "Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia.", "authors": "Linh TTD, Hsieh YC, Huang LK et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "clinical trial, vascular cognitive impairment, vascular dementia", "chunk": "Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer's disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword \"vascular dementia\" was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer's dementia. Drug trials on vascular", "source": "PubMed"}, {"chunk_id": "36232368_1", "pmid": "36232368", "title": "Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia.", "authors": "Linh TTD, Hsieh YC, Huang LK et al.", "year": "2022", "journal": "International journal of molecular sciences", "keywords": "clinical trial, vascular cognitive impairment, vascular dementia", "chunk": "in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer's dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies' investment in new drugs targeting VCI and vascular dementia remains insufficient.", "source": "PubMed"}, {"chunk_id": "41732800_0", "pmid": "41732800", "title": "Rising energetic cost of walking predicts cognitive impairment.", "authors": "Dougherty RJ, Wang J, Tian Q et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, cognition, cognitive health, dementia, gait, metabolic cost of walking, motor control, walking economy", "chunk": "The energetic cost of walking increases with age and is linked to physical function impairment, but its relation to cognitive impairment is unknown. A total of 687 initially cognitively normal older adults (mean age 74.0 \u00b1 7.2 years, 52% women) underwent repeated walking energy expenditure assessments (V\u0307O<sub>2</sub>) and adjudicated cognitive diagnoses over 7.6 \u00b1 3.8 years. We examined (1) trajectories in the energetic cost of walking prior to any clinical diagnosis of cognitive impairment, comparing adults who later developed cognitive impairment versus those who did not, and (2) the baseline energetic cost and future risk of cognitive impairment using linear mixed-effects and Cox regression models. Ninety-one participants (13%) progressed to cognitive impairment. Progressors exhibited a steeper increase in energetic cost than non-progressors (B = 0.13; p = 0.003). Higher baseline cost predicted impairment among adults \u226575 years (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.00 to 1.20,", "source": "PubMed"}, {"chunk_id": "41732800_1", "pmid": "41732800", "title": "Rising energetic cost of walking predicts cognitive impairment.", "authors": "Dougherty RJ, Wang J, Tian Q et al.", "year": "2026", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, cognition, cognitive health, dementia, gait, metabolic cost of walking, motor control, walking economy", "chunk": "than non-progressors (B = 0.13; p = 0.003). Higher baseline cost predicted impairment among adults \u226575 years (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.00 to 1.20, p = 0.039), but not those aged 65 to 74 (HR = 0.91, 95% CI = 0.81 to 1.01, p = 0.089). Walking efficiency provides a physiological link between mobility and cognitive health; preserving efficiency may reduce risk of Alzheimer's disease and related dementias.", "source": "PubMed"}, {"chunk_id": "22850315_0", "pmid": "22850315", "title": "The imbalance of vascular molecules in Alzheimer's disease.", "authors": "Bell RD", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "The vascular system plays an integral role during Alzheimer's disease (AD). Both systemic circulatory changes and alterations directly within the brain vasculature have been suggested to contribute to both the onset and progression of neurological conditions such as AD. It is now well established that vascular risk factors including hypertension, diabetes, obesity, atherosclerosis, metabolic syndrome, and stroke significantly increase one's risk of later developing AD. Research within the last decade has begun to identify specific vascular molecules associated with such risk factors as well as elucidate the biological role they may play in the pathological processes linked to AD. This review aims to provide an overview of some of the key molecules within vascular cells and circulating in blood that have been identified to be altered in AD pathogenesis. In particular, the vascular-specific transcription factors MEOX2, MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and circulating", "source": "PubMed"}, {"chunk_id": "22850315_1", "pmid": "22850315", "title": "The imbalance of vascular molecules in Alzheimer's disease.", "authors": "Bell RD", "year": "2012", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "None", "chunk": "have been identified to be altered in AD pathogenesis. In particular, the vascular-specific transcription factors MEOX2, MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and circulating molecules such as sLRP1, homocysteine, and albumin are discussed. I aim to clarify how these identified vascular molecules may help to predict, explain, and influence the incidence AD. A strong emphasis is placed on the concept that these molecules play overlapping roles in cardiovascular disease progression, neurovascular dysfunction, and amyloid-\u03b2 pathology. The studies reviewed here have identified vascular-based molecular targets in AD and thus provide new therapeutic avenues for the treatment of this devastating disease.", "source": "PubMed"}, {"chunk_id": "41105529_0", "pmid": "41105529", "title": "Blood pressure dynamic instability and neurodegeneration in older adults.", "authors": "Lohman T, Shenasa F, Sible I et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, arterial stiffness, blood pressure variability, medial temporal lobe, neurodegeneration, plasma neurofilament light, voxel-based morphometry", "chunk": "BackgroundBlood pressure variability (BPV) is an age-related hemodynamic risk factor for neurodegeneration, but it remains unclear whether distinct forms of BPV display independent or interactive effects on brain health.ObjectiveInvestigate whether high beat-to-beat BPV, when combined with increased pulse pressure variability, a form of BPV associated with arterial stiffness, exacerbates markers of neurodegeneration.MethodsOlder adults (N = 105) without major neurological or systemic disease were recruited for brain magnetic resonance imaging and continuous blood pressure (BP) monitoring to quantify beat-to-beat BPV through systolic average real variability (ARV) and pulse pressure variability using arterial stiffness index (ASI). The interactive effect of ARV and ASI on medial temporal lobe atrophy, plasma neurofilament light chain (NfL), and plasma glial fibrillary acidic protein (GFAP) was studied using hierarchical linear regression in older adults<i>.</i> Voxel-based morphometry was used to confirm region-of-interest analysis findings.ResultsThe interaction between higher ARV and higher ASI was significantly associated with left-sided medial temporal", "source": "PubMed"}, {"chunk_id": "41105529_1", "pmid": "41105529", "title": "Blood pressure dynamic instability and neurodegeneration in older adults.", "authors": "Lohman T, Shenasa F, Sible I et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, arterial stiffness, blood pressure variability, medial temporal lobe, neurodegeneration, plasma neurofilament light, voxel-based morphometry", "chunk": "using hierarchical linear regression in older adults<i>.</i> Voxel-based morphometry was used to confirm region-of-interest analysis findings.ResultsThe interaction between higher ARV and higher ASI was significantly associated with left-sided medial temporal lobe atrophy in both the region-of-interest (left hippocampus \u03b2 = -252.79, p = 0.0002, right hippocampus \u03b2 = -193.56, p = 0.001, left entorhinal cortex \u03b2 = -0.13, p = 0.007), and false discovery rate-corrected voxel-based morphometry analysis (p = 0.03). The interactive effect was also significantly associated with increased plasma NfL (\u03b2 = 3.88, p = 0.01), but not GFAP.ConclusionsThe interaction between ARV and ASI is independently associated with neurodegenerative markers, including medial temporal lobe atrophy and plasma NfL, in older adults. These findings suggest that greater hemodynamic instability is associated with increased risk for neurodegenerative processes.", "source": "PubMed"}, {"chunk_id": "41105529_2", "pmid": "41105529", "title": "Blood pressure dynamic instability and neurodegeneration in older adults.", "authors": "Lohman T, Shenasa F, Sible I et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, arterial stiffness, blood pressure variability, medial temporal lobe, neurodegeneration, plasma neurofilament light, voxel-based morphometry", "chunk": "is associated with increased risk for neurodegenerative processes.", "source": "PubMed"}, {"chunk_id": "41561142_0", "pmid": "41561142", "title": "PyCaret machine learning library with three preprocessing steps after eLORETA source estimation predicts Alzheimer's disease.", "authors": "Aoki Y, Takahashi R, Pascual-Marqui RD et al.", "year": "2026", "journal": "Neuroimage. Reports", "keywords": "Alzheimer's disease, Electroencephalography (EEG), Exact low-resolution electromagnetic tomography (eLORETA), Linear discriminant analysis, Machine learning, PyCaret", "chunk": "Alzheimer's disease (AD) -the most common form of dementia- begins with mild memory loss and gradually progresses, eventually resulting in a generalized loss of brain function. The pathological changes of AD in the brain cortex begin decades before the onset of symptoms. Improvements in lifestyle habits and disease-modifying treatments before the onset of the disease have been shown to help prevent or delay the onset of AD. However, diagnosis of AD is difficult at the early stage -or even at the prodromal stage [i.e., mild cognitive impairment due to AD (MCIAD)]- since normal aging and other types of dementia also involve memory impairment. Therefore, there is an urgent need to identify markers for the detection of AD at the early stage or pre-onset stage. In this study, we applied exact low-resolution brain electromagnetic tomography (eLORETA) as the source estimation method to electroencephalography (EEG) data. We obtained cortical electrical activity in", "source": "PubMed"}, {"chunk_id": "41561142_1", "pmid": "41561142", "title": "PyCaret machine learning library with three preprocessing steps after eLORETA source estimation predicts Alzheimer's disease.", "authors": "Aoki Y, Takahashi R, Pascual-Marqui RD et al.", "year": "2026", "journal": "Neuroimage. Reports", "keywords": "Alzheimer's disease, Electroencephalography (EEG), Exact low-resolution electromagnetic tomography (eLORETA), Linear discriminant analysis, Machine learning, PyCaret", "chunk": "stage or pre-onset stage. In this study, we applied exact low-resolution brain electromagnetic tomography (eLORETA) as the source estimation method to electroencephalography (EEG) data. We obtained cortical electrical activity in 96 drug-free AD patients and 147 healthy subjects to train the final model, in addition to activity for 21 MCIAD patients and seven healthy subjects for the purpose of its evaluation. We then applied the low-code machine learning library of PyCaret, with three preprocessing steps (subject-wise normalization, age-difference correction, and log-transformation) to the eLORETA data of AD and healthy subjects. Of the many machine learning classification models used, the linear discriminant analysis (LDA) model showed the highest accuracy, identifying 10 AD patients and 15 healthy subjects with an accuracy of 100.0 %. The LDA model of eLORETA has high transparency and we visualized the discriminant function of the LDA final model using Viewer in eLORETA. Cortical electrical activities in the", "source": "PubMed"}, {"chunk_id": "41561142_2", "pmid": "41561142", "title": "PyCaret machine learning library with three preprocessing steps after eLORETA source estimation predicts Alzheimer's disease.", "authors": "Aoki Y, Takahashi R, Pascual-Marqui RD et al.", "year": "2026", "journal": "Neuroimage. Reports", "keywords": "Alzheimer's disease, Electroencephalography (EEG), Exact low-resolution electromagnetic tomography (eLORETA), Linear discriminant analysis, Machine learning, PyCaret", "chunk": "100.0 %. The LDA model of eLORETA has high transparency and we visualized the discriminant function of the LDA final model using Viewer in eLORETA. Cortical electrical activities in the delta, theta and alpha frequency bands increased in the right dorsolateral prefrontal cortex (DLPFC) regions, as the degree of AD increased (Figs. 2-4). Cortical electrical activity in the beta frequency band decreased in the posterior cingulate cortex (PCC) regions, as the degree of AD increased (Fig. 5) Furthermore, the LDA final model correctly identified 21 MCIAD patients and seven healthy subjects with an accuracy of 96.4 %. Our findings indicate that the LDA final model of eLORETA had the capacity to detect physiological features of AD in EEG data, even before the onset of the disease. Overall, PyCaret with three preprocessing steps after eLORETA source estimation can create an accurate EEG classification model, which makes a significant contribution to the", "source": "PubMed"}, {"chunk_id": "41561142_3", "pmid": "41561142", "title": "PyCaret machine learning library with three preprocessing steps after eLORETA source estimation predicts Alzheimer's disease.", "authors": "Aoki Y, Takahashi R, Pascual-Marqui RD et al.", "year": "2026", "journal": "Neuroimage. Reports", "keywords": "Alzheimer's disease, Electroencephalography (EEG), Exact low-resolution electromagnetic tomography (eLORETA), Linear discriminant analysis, Machine learning, PyCaret", "chunk": "before the onset of the disease. Overall, PyCaret with three preprocessing steps after eLORETA source estimation can create an accurate EEG classification model, which makes a significant contribution to the early detection of AD among the many individuals in the general population who remain undiagnosed.", "source": "PubMed"}, {"chunk_id": "37478886_0", "pmid": "37478886", "title": "Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.", "authors": "Lin FR, Pike JR, Albert MS et al.", "year": "2023", "journal": "Lancet (London, England)", "keywords": "None", "chunk": "Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was", "source": "PubMed"}, {"chunk_id": "37478886_1", "pmid": "37478886", "title": "Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.", "authors": "Lin FR, Pike JR, Albert MS et al.", "year": "2023", "journal": "Lancet (London, England)", "keywords": "None", "chunk": "aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32\u00b75%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76\u00b78 years (SD 4\u00b70), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de", "source": "PubMed"}, {"chunk_id": "37478886_2", "pmid": "37478886", "title": "Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.", "authors": "Lin FR, Pike JR, Albert MS et al.", "year": "2023", "journal": "Lancet (London, England)", "keywords": "None", "chunk": "male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0\u00b7200 [95% CI -0\u00b7256 to -0\u00b7144] in the hearing intervention group and -0\u00b7202 [-0\u00b7258 to -0\u00b7145] in the control group; difference 0\u00b7002 [-0\u00b7077 to 0\u00b7081]; p=0\u00b796). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (p<sub>interaction</sub>=0\u00b7010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention", "source": "PubMed"}, {"chunk_id": "37478886_3", "pmid": "37478886", "title": "Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.", "authors": "Lin FR, Pike JR, Albert MS et al.", "year": "2023", "journal": "Lancet (London, England)", "keywords": "None", "chunk": "that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. US National Institutes of Health.", "source": "PubMed"}, {"chunk_id": "41131028_0", "pmid": "41131028", "title": "Neural signatures of turn-induced freezing of gait in Parkinson's disease: insights from phase-specific cortico-subthalamic dynamics.", "authors": "Zhang Q, Xie H, Zhao B et al.", "year": "2025", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "Freezing of gait (FOG), particularly during turning, is common in Parkinson's disease (PD), but its phase-specific neural mechanisms remain unclear. This study investigated cortico-subthalamic dynamics underlying turning-induced FOG and their modulation by dopaminergic medication. Local field potentials from primary motor cortex (M1), premotor cortex (PMC), bilateral subthalamic nucleus (STN), and kinematic data were recorded from 19 PD patients during timed up-and-go tasks in medication-off and medication-on states. Turns were segmented into four phases: TurnPre, TurnStart, TurnEnd, and TurnPost. During freezing episodes, alpha power in M1 and PMC significantly decreased in early turning phases. Enhanced PMC-STN coherence appeared during TurnPre in normal turning and TurnStart in freezing turning, with TurnPre alpha suppression and coherence predicting freezing duration. Medication normalized these abnormal oscillations and improved turning. These findings reveal phase-specific cortico-subthalamic disruptions in FOG and suggest novel electrophysiological biomarkers for intervention. Trial Registration: ChiCTR1900026601, registered October 15, 2019.", "source": "PubMed"}, {"chunk_id": "41131028_1", "pmid": "41131028", "title": "Neural signatures of turn-induced freezing of gait in Parkinson's disease: insights from phase-specific cortico-subthalamic dynamics.", "authors": "Zhang Q, Xie H, Zhao B et al.", "year": "2025", "journal": "NPJ Parkinson's disease", "keywords": "None", "chunk": "oscillations and improved turning. These findings reveal phase-specific cortico-subthalamic disruptions in FOG and suggest novel electrophysiological biomarkers for intervention. Trial Registration: ChiCTR1900026601, registered October 15, 2019.", "source": "PubMed"}, {"chunk_id": "37822109_0", "pmid": "37822109", "title": "Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.", "authors": "Izuo N, Watanabe N, Noda Y et al.", "year": "2023", "journal": "Aging cell", "keywords": "Alzheimer's disease, cerebral blood flow, cholinergic system, cognitive dysfunction, insulin resistance, nicotinic acetylcholine receptor \u03b17", "chunk": "Although insulin resistance increases the risk of Alzheimer's disease (AD), the mechanisms remain unclear, partly because no animal model exhibits the insulin-resistant phenotype without persistent hyperglycemia. Here we established an AD model with whole-body insulin resistance without persistent hyperglycemia (APP/IR-dKI mice) by crossbreeding constitutive knock-in mice with P1195L-mutated insulin receptor (IR-KI mice) and those with mutated amyloid precursor protein (App<sup>NL-G-F</sup> mice: APP-KI mice). APP/IR-dKI mice exhibited cognitive impairment at an earlier age than APP-KI mice. Since cholinergic dysfunction is a major characteristic of AD, pharmacological interventions on the cholinergic system were performed to investigate the mechanism. Antagonism to a nicotinic acetylcholine receptor \u03b17 (nAChR\u03b17) suppressed cognitive function and cortical blood flow (CBF) response to cholinergic-regulated peripheral stimulation in APP-KI mice but not APP/IR-dKI mice. Cortical expression of Chrna7, encoding nAChR\u03b17, was downregulated in APP/IR-dKI mice compared with APP-KI. Amyloid \u03b2 burden did not differ between APP-KI and APP/IR-dKI mice. Therefore,", "source": "PubMed"}, {"chunk_id": "37822109_1", "pmid": "37822109", "title": "Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.", "authors": "Izuo N, Watanabe N, Noda Y et al.", "year": "2023", "journal": "Aging cell", "keywords": "Alzheimer's disease, cerebral blood flow, cholinergic system, cognitive dysfunction, insulin resistance, nicotinic acetylcholine receptor \u03b17", "chunk": "but not APP/IR-dKI mice. Cortical expression of Chrna7, encoding nAChR\u03b17, was downregulated in APP/IR-dKI mice compared with APP-KI. Amyloid \u03b2 burden did not differ between APP-KI and APP/IR-dKI mice. Therefore, insulin resistance, not persistent hyperglycemia, induces the earlier onset of cognitive dysfunction and CBF deregulation mediated by nAChR\u03b17 downregulation. Our mouse model will help clarify the association between type 2 diabetes mellitus and AD.", "source": "PubMed"}, {"chunk_id": "34022637_0", "pmid": "34022637", "title": "Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.", "authors": "Cecchini MA, Yassuda MS, Squarzoni P et al.", "year": "2021", "journal": "Brain and cognition", "keywords": "Alzheimer\u2019s disease, Amyloid, Biomarkers, Mild cognitive impairment, PET, Short-term memory binding", "chunk": "The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([<sup>11</sup>C]PIB) assessing amyloid beta (A\u03b2) aggregation (A) and 18fluorine-fluorodeoxyglucose ([<sup>18</sup>F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT", "source": "PubMed"}, {"chunk_id": "34022637_1", "pmid": "34022637", "title": "Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.", "authors": "Cecchini MA, Yassuda MS, Squarzoni P et al.", "year": "2021", "journal": "Brain and cognition", "keywords": "Alzheimer\u2019s disease, Amyloid, Biomarkers, Mild cognitive impairment, PET, Short-term memory binding", "chunk": "N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.", "source": "PubMed"}, {"chunk_id": "41345970_0", "pmid": "41345970", "title": "Telomere dynamics are influenced by sleep, sleep variability and circadian rhythms in older adults with or without alzheimer's risk.", "authors": "Lehodey A, Montagne B, Rehel S et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Ageing, Alzheimer\u2019s disease, Circadian rhythms, Sleep, Sleep variability, Telomeres", "chunk": "Sleep and circadian rhythm disturbances have been related to cognitive decline and increased risk of Alzheimer's disease (AD). These disruptions are also closely associated with biological ageing processes. Telomere shortening, a key marker of cellular ageing, has been implicated in various age-related diseases, including AD. Although sleep disturbances have been linked to shorter telomere length (TL), the effects of sleep, its variability, and circadian rhythms on telomere dynamics (over 18 months) remain unknown. Furthermore, the interplay between these factors and AD risk has yet to be investigated in healthy older adults. Therefore, the objective of this study was to explore how sleep, sleep variability, and circadian rhythms affect telomere dynamics in healthy older adults and the influence of AD risk on these relationships. Data from 124 healthy older adults (mean age \u00b1 SD: 69.27 \u00b1 3.73y) from the Age-Well interventional trial (NCT02977819) were analyzed. Blood samples were collected to determine", "source": "PubMed"}, {"chunk_id": "41345970_1", "pmid": "41345970", "title": "Telomere dynamics are influenced by sleep, sleep variability and circadian rhythms in older adults with or without alzheimer's risk.", "authors": "Lehodey A, Montagne B, Rehel S et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Ageing, Alzheimer\u2019s disease, Circadian rhythms, Sleep, Sleep variability, Telomeres", "chunk": "on these relationships. Data from 124 healthy older adults (mean age \u00b1 SD: 69.27 \u00b1 3.73y) from the Age-Well interventional trial (NCT02977819) were analyzed. Blood samples were collected to determine three TL metrics (50th and 20th percentile TL, and percentage of critically short telomeres (%CST) at baseline and after 18-month follow-up). Sleep and its variability were assessed using the Somno-Art<sup>\u00ae</sup> device over 5 nights (n = 77), and circadian rhythms using actigraphy for 1 week (n = 123). Multiple linear regressions examined whether baseline sleep and circadian rhythm measures predicted TL changes over time. Interaction analyses assessed the modulatory effects of amyloid (A\u03b2) status, assessed using Forbetapir-PET imaging, and APOE4 status on these relationships. Age, sex, education, BMI, and intervention group were included as covariates. Poor sleep quality (characterized by lower sleep efficiency and higher wake after sleep onset) and greater variability in sleep efficiency predicted an increase in %CST.", "source": "PubMed"}, {"chunk_id": "41345970_2", "pmid": "41345970", "title": "Telomere dynamics are influenced by sleep, sleep variability and circadian rhythms in older adults with or without alzheimer's risk.", "authors": "Lehodey A, Montagne B, Rehel S et al.", "year": "2025", "journal": "Alzheimer's research & therapy", "keywords": "Ageing, Alzheimer\u2019s disease, Circadian rhythms, Sleep, Sleep variability, Telomeres", "chunk": "group were included as covariates. Poor sleep quality (characterized by lower sleep efficiency and higher wake after sleep onset) and greater variability in sleep efficiency predicted an increase in %CST. Greater regularity in sleep/wake patterns was associated with a decrease in 50th and 20th percentile TL and an increase in %CST. In A\u03b2-positive individuals, longer latency of rapid eye movement sleep predicted a reduction in 20th percentile TL and an increase in %CST. This study suggests that poor sleep quality, sleep variability and circadian rhythm disturbances may accelerate cellular ageing through telomere shortening in older adults. Our results highlight the potential value of sleep interventions in mitigating biological ageing and reducing vulnerability to age-related diseases.", "source": "PubMed"}, {"chunk_id": "39711105_0", "pmid": "39711105", "title": "Sex and APOE \u03b54 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.", "authors": "Peterson A, Sathe A, Zaras D et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, aging, sex differences, white matter disease", "chunk": "The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized. Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 \u00b1 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA<sub>FWcorr</sub>) were used to assess differences in white matter microstructure by sex and APOE \u03b54 carrier status. Sex differences in FA<sub>FWcorr</sub> in projection tracts and APOE \u03b54 differences in FW limbic and occipital transcallosal tracts were most pronounced. There are prominent differences in white matter microstructure by sex and APOE \u03b54 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Sex and apolipoprotein E (APOE) \u03b54 carrier status relate to white matter microstructural integrity. Females generally have lower", "source": "PubMed"}, {"chunk_id": "39711105_1", "pmid": "39711105", "title": "Sex and APOE \u03b54 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.", "authors": "Peterson A, Sathe A, Zaras D et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, aging, sex differences, white matter disease", "chunk": "AD. Additional work to understand the etiology of these differences is warranted. Sex and apolipoprotein E (APOE) \u03b54 carrier status relate to white matter microstructural integrity. Females generally have lower free water-corrected fractional anisotropy compared to males. APOE \u03b54 carriers tended to have higher free water than non-carriers.", "source": "PubMed"}, {"chunk_id": "41278800_0", "pmid": "41278800", "title": "lncRNA <i>3222401L13Rik</i>/<i>ENSG00000272070</i> modulates microglial inflammatory programs in association with PU.1.", "authors": "Pradhan R, Sadman Sakib M, Kaurani L et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, PU.1 (SPI1), long non-coding RNA (lncRNA), microglia, neuroinflammation, non-coding RNAome", "chunk": "Long non-coding RNAs (lncRNAs) are emerging as key regulators of brain function, but their contribution to microglial aging and neurodegenerative disease remains largely unknown. Because only 1.5% of the human genome encodes proteins, whereas the vast majority of transcripts belong to the largely unexplored non-coding RNAome, elucidating the functions of non-coding RNAs provides an unprecedented opportunity to expand the space for therapeutic discovery. We recently identified the glia-enriched lncRNA <i>3222401L13Rik</i> as upregulated in the aging mouse hippocampus. Here, we investigated its function in microglia and its human homolog <i>ENSG00000272070</i>. We found that <i>3222401L13Rik</i> is expressed in both astrocytes and microglia and increases with age. Knockdown of <i>3222401L13Rik</i> in primary microglia led to enhanced expression of pro-inflammatory cytokines, including TNF\u03b1, and increased phagocytic activity. RNA-sequencing revealed widespread transcriptional changes enriched for TNF and complement signaling pathways. The human homolog <i>ENSG00000272070</i> showed conserved functions in iPSC-derived microglia, where its loss similarly promoted", "source": "PubMed"}, {"chunk_id": "41278800_1", "pmid": "41278800", "title": "lncRNA <i>3222401L13Rik</i>/<i>ENSG00000272070</i> modulates microglial inflammatory programs in association with PU.1.", "authors": "Pradhan R, Sadman Sakib M, Kaurani L et al.", "year": "2025", "journal": "bioRxiv : the preprint server for biology", "keywords": "Alzheimer\u2019s disease, PU.1 (SPI1), long non-coding RNA (lncRNA), microglia, neuroinflammation, non-coding RNAome", "chunk": "increased phagocytic activity. RNA-sequencing revealed widespread transcriptional changes enriched for TNF and complement signaling pathways. The human homolog <i>ENSG00000272070</i> showed conserved functions in iPSC-derived microglia, where its loss similarly promoted inflammatory gene expression and phagocytosis. Mechanistically, <i>3222401L13Rik</i> interacts with the microglial transcription factor PU.1, and its depletion overlapped with PU.1-driven transcriptional programs. Consistent with these findings, <i>ENSG00000272070</i> expression was significantly reduced in postmortem Alzheimer's disease (AD) brains, and AD-associated genes were enriched among <i>3222401L13Rik</i>-regulated targets. Together, our results identify <i>3222401L13Rik</i>/<i>ENSG00000272070</i> as a conserved, aging-associated lncRNA that modulates microglial inflammatory states through interaction with PU.1. This work links glial lncRNA regulation to AD-related neuroinflammation and suggests <i>3222401L13Rik</i> as a potential molecular target to fine-tune microglial activity in neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "41608987_0", "pmid": "41608987", "title": "Multi-platform integration of brain and CSF proteomes reveals biomarker panels for Alzheimer's disease.", "authors": "Tsai WY, Giesbertz P, Breimann S et al.", "year": "2026", "journal": "Briefings in bioinformatics", "keywords": "CSF, biomarkers, brain tissue, data integration, machine learning, proteomics", "chunk": "Alzheimer's disease (AD) is the leading cause of dementia and represents a progressive, irreversible neurodegenerative disorder. Given the complexity and heterogeneity of AD, which involves numerous interrelated molecular pathways, large-scale proteomics datasets are essential for robust biomarker discovery. Comprehensive proteomic profiling enables the unbiased identification of novel biomarkers across diverse biological processes, thereby increasing the likelihood of finding sensitive and specific candidates for early diagnosis and therapeutic targeting. In this study, we analyzed 28 large-scale proteomics datasets obtained from the AD Knowledge Portal and published studies. The data comprise tandem mass tag, label-free quantification, and proximity extension assay measurements from brain tissue and cerebrospinal fluid. To enhance analytical power, we integrated these proteomic profiles with corresponding clinical information to construct comprehensive feature sets for subsequent machine learning analysis. Using Random Forest and Logistic Regression models, we identified a panel of proteins capable of distinguishing AD patients from healthy controls. Several", "source": "PubMed"}, {"chunk_id": "41608987_1", "pmid": "41608987", "title": "Multi-platform integration of brain and CSF proteomes reveals biomarker panels for Alzheimer's disease.", "authors": "Tsai WY, Giesbertz P, Breimann S et al.", "year": "2026", "journal": "Briefings in bioinformatics", "keywords": "CSF, biomarkers, brain tissue, data integration, machine learning, proteomics", "chunk": "comprehensive feature sets for subsequent machine learning analysis. Using Random Forest and Logistic Regression models, we identified a panel of proteins capable of distinguishing AD patients from healthy controls. Several of these biomarkers have been previously validated in the context of AD, while others represent novel candidates not yet reported as AD-associated. These newly identified biomarkers warrant further experimental validation and hold promise for improving early diagnosis as well as guiding the development of targeted therapies for AD.", "source": "PubMed"}, {"chunk_id": "40951978_0", "pmid": "40951978", "title": "Rates of clinical progression according to biological Alzheimer's disease stages.", "authors": "Trudel L, Therriault J, Macedo AC et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, prognostic value, risk of progression, tau\u2010PET imaging", "chunk": "Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings. We assessed progression to mild cognitive impairment (MCI) and all-cause dementia in 492 individuals from the TRIAD, ADNI, and HABS-HD cohorts followed for an average of 2.49 years. Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T<sub>2</sub>-/A+T<sub>2MTL</sub>+/A+T<sub>2MOD</sub>+/A+T<sub>2HIGH</sub>+). Cognitively unimpaired (CU) individuals in the A+T<sub>2MTL</sub>+, A+T<sub>2MOD</sub>+, and A+T<sub>2HIGH</sub>+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T<sub>2HIGH</sub>+ stage showing", "source": "PubMed"}, {"chunk_id": "40951978_1", "pmid": "40951978", "title": "Rates of clinical progression according to biological Alzheimer's disease stages.", "authors": "Trudel L, Therriault J, Macedo AC et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, prognostic value, risk of progression, tau\u2010PET imaging", "chunk": "to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T<sub>2HIGH</sub>+ stage showing the steepest rate of decline (p < 0.001). Our results highlight the prognostic value of biological AD staging. Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)-positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD. In individuals with mild cognitive impairment (MCI), only the A+T<sub>2HIGH</sub>+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T<sub>2HIGH</sub>+ stage showing the steepest rate of decline.", "source": "PubMed"}, {"chunk_id": "40951978_2", "pmid": "40951978", "title": "Rates of clinical progression according to biological Alzheimer's disease stages.", "authors": "Trudel L, Therriault J, Macedo AC et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, prognostic value, risk of progression, tau\u2010PET imaging", "chunk": "demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T<sub>2HIGH</sub>+ stage showing the steepest rate of decline.", "source": "PubMed"}, {"chunk_id": "38755275_0", "pmid": "38755275", "title": "A ResNet mini architecture for brain age prediction.", "authors": "Zhang X, Duan SY, Wang SQ et al.", "year": "2024", "journal": "Scientific reports", "keywords": "Brain age prediction, Deep learning, Lightweight network, MRI, ResNet", "chunk": "The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that", "source": "PubMed"}, {"chunk_id": "38755275_1", "pmid": "38755275", "title": "A ResNet mini architecture for brain age prediction.", "authors": "Zhang X, Duan SY, Wang SQ et al.", "year": "2024", "journal": "Scientific reports", "keywords": "Brain age prediction, Deep learning, Lightweight network, MRI, ResNet", "chunk": "consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.", "source": "PubMed"}, {"chunk_id": "41012331_0", "pmid": "41012331", "title": "Effects of Dioxin Exposure on Brain Regional Volumes of Fathers from Birth Cohorts in Herbicide-Sprayed and Unsprayed Areas in Vietnam.", "authors": "Nguyen HM, Vu HT, Pham TN et al.", "year": "2025", "journal": "Toxics", "keywords": "Agent Orange, Vietnamese men, biological equivalency, brain regional volume, dioxins, neuro imaging analysis, residency", "chunk": "We previously reported that the fathers of the Bien Hoa birth cohort in Vietnam showed altered brain regional gray matter volumes, as measured by magnetic resonance imaging, and social anxiety traits associated with perinatal dioxin exposure. In the present study, we aimed to compare gray matter volumes and social anxiety scale scores between dioxin-exposed fathers in Bien Hoa and unexposed controls in an unsprayed area. Fat-based bioassay-toxic equivalency levels in serum were used to indicate dioxin exposure in adulthood. Results indicated that the longer Bien Hoa residency group (\u226530 years) exposed to dioxins during the perinatal period and early childhood showed higher gray matter volumes in the right and left temporal lobes than controls. However, no significant differences in temporal lobe gray matter volumes were found between the shorter Bien Hoa residency group (<30 years) and controls. Furthermore, the longer, but not shorter, Bien Hoa residency group showed higher social-emotional", "source": "PubMed"}, {"chunk_id": "41012331_1", "pmid": "41012331", "title": "Effects of Dioxin Exposure on Brain Regional Volumes of Fathers from Birth Cohorts in Herbicide-Sprayed and Unsprayed Areas in Vietnam.", "authors": "Nguyen HM, Vu HT, Pham TN et al.", "year": "2025", "journal": "Toxics", "keywords": "Agent Orange, Vietnamese men, biological equivalency, brain regional volume, dioxins, neuro imaging analysis, residency", "chunk": "lobe gray matter volumes were found between the shorter Bien Hoa residency group (<30 years) and controls. Furthermore, the longer, but not shorter, Bien Hoa residency group showed higher social-emotional subscale scores than controls. Additionally, fat-based bioassay-toxic equivalency levels were inversely correlated with gray matter volumes in several right temporal gyri. These findings suggest biphasic life stage-dependent adverse effects of dioxin exposure: perinatal dioxin exposure increases gray matter volumes, especially in the temporal lobe, which leads to neurodevelopmental disorders with socio-emotional disturbances, whereas dioxin exposure after brain development decreases cortical gray matter volumes, possibly leading to cognitive dysfunction.", "source": "PubMed"}, {"chunk_id": "39609257_0", "pmid": "39609257", "title": "Sex differences in the trajectories of plasma biomarkers, brain atrophy, and cognitive decline relative to amyloid onset.", "authors": "Joynes CM, Bilgel M, An Y et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, brain volume loss, cognitive decline, longitudinal study, plasma biomarkers, sex differences", "chunk": "The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid-positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid-\u03b2. Linear mixed-effects modeling investigated overall and sex-specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to the estimated age of amyloid onset in a cohort of 78 amyloid-positive Baltimore Longitudinal Study of Aging (BLSA) participants (n = 45 male; follow-up time: 6.8 years [SD 3.31]). Amyloid status was ascertained with <sup>11</sup>C-Pittsburgh compound B (PiB) PET imaging. After amyloid onset, men displayed steeper increases in pTau181, pTau231, and neurofilament light (NfL) compared to women. In this same period, men demonstrated steeper declines in brain volume and cognitive performance. These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become", "source": "PubMed"}, {"chunk_id": "39609257_1", "pmid": "39609257", "title": "Sex differences in the trajectories of plasma biomarkers, brain atrophy, and cognitive decline relative to amyloid onset.", "authors": "Joynes CM, Bilgel M, An Y et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "Alzheimer's disease, brain volume loss, cognitive decline, longitudinal study, plasma biomarkers, sex differences", "chunk": "period, men demonstrated steeper declines in brain volume and cognitive performance. These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become amyloid-positive. Steeper rates of increase in pTau and GFAP among amyloid-positive individuals. After amyloid onset, steeper increases in pTau and NfL concentrations in men than in women. Steeper declines in brain volume and cognition in men corroborate biomarker results.", "source": "PubMed"}, {"chunk_id": "40438598_0", "pmid": "40438598", "title": "Nanocarrier-based targeted drug delivery for Alzheimer's disease: addressing neuroinflammation and enhancing clinical translation.", "authors": "Wang K, Yang R, Li J et al.", "year": "2025", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, blood-brain barrier, clinical translation, drug delivery, nanocarriers, nanotechnology, neuroinflammation", "chunk": "Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-beta (A\u03b2) aggregation, tau pathology, and chronic neuroinflammation. Among these, neuroinflammation plays a crucial role in exacerbating disease progression, making it an attractive therapeutic target. However, the presence of the blood-brain barrier (BBB) significantly limits the effective delivery of therapeutic agents to the brain, necessitating novel drug delivery strategies. Nanocarrier-based delivery systems have emerged as a promising solution to these challenges, offering targeted drug transport, enhanced BBB penetration, and improved bioavailability while minimizing systemic toxicity. This review explores the current advancements in nanocarrier-mediated drug delivery for AD, focusing on the mechanisms of neuroinflammation, the role of nanocarriers in overcoming the BBB, and their ability to modulate inflammatory pathways. Furthermore, the review discusses preclinical validation strategies and key challenges, including safety concerns, large-scale production limitations, and regulatory hurdles that must be addressed to enable clinical translation. Future perspectives emphasize", "source": "PubMed"}, {"chunk_id": "40438598_1", "pmid": "40438598", "title": "Nanocarrier-based targeted drug delivery for Alzheimer's disease: addressing neuroinflammation and enhancing clinical translation.", "authors": "Wang K, Yang R, Li J et al.", "year": "2025", "journal": "Frontiers in pharmacology", "keywords": "Alzheimer\u2019s disease, blood-brain barrier, clinical translation, drug delivery, nanocarriers, nanotechnology, neuroinflammation", "chunk": "Furthermore, the review discusses preclinical validation strategies and key challenges, including safety concerns, large-scale production limitations, and regulatory hurdles that must be addressed to enable clinical translation. Future perspectives emphasize the integration of nanotechnology with precision medicine, gene therapy, and artificial intelligence to optimize nanocarrier design for individualized AD treatment. By overcoming these obstacles, nanocarriers hold the potential to revolutionize therapeutic approaches for AD and other neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "40325262_0", "pmid": "40325262", "title": "Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer's disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress.", "authors": "Abdel-Lah ES, Sherkawy HS, Mohamed WH et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Empagliflozin, Heavy metal mixtures, Memantine, Oxidative stress, Pro-inflammatory cytokines, Scopolamine", "chunk": "One of the major consequences of diabetes mellitus that has gained attention due to its rising incidence is cognitive impairment. Recent research suggested that sodium-glucose cotransporter-2 (SGLT-2) inhibitors can mitigate memory impairment linked to Alzheimer's disease and are now being explored for their cognitive benefits. However, their mechanisms were not thoroughly studied. This research investigates the hypothesis of the neuroprotective effect of empagliflozin administration against scopolamine-heavy metal mixture (SCO + HMM)-treated Alzheimer's rat models in comparison with memantine as a reference drug and the impact of their combination. Yet, the neuroprotective effects of memantine and empagliflozin combination against cognitive impairment have not been previously explored. This study employed adult male albino rats categorized into five groups. The impact of empagliflozin, memantine, and their concomitant administration on cognitive performance was assessed in a scopolamine and heavy metal mixture-treated Alzheimer's disease model in rats. The assessment of rats' cognitive behavior, memory, and", "source": "PubMed"}, {"chunk_id": "40325262_1", "pmid": "40325262", "title": "Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer's disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress.", "authors": "Abdel-Lah ES, Sherkawy HS, Mohamed WH et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Empagliflozin, Heavy metal mixtures, Memantine, Oxidative stress, Pro-inflammatory cytokines, Scopolamine", "chunk": "memantine, and their concomitant administration on cognitive performance was assessed in a scopolamine and heavy metal mixture-treated Alzheimer's disease model in rats. The assessment of rats' cognitive behavior, memory, and spatial learning was conducted, followed by an evaluation of hippocampal brain-derived neurotrophic factor (BDNF), beta-secretase (BACE-1), oxidative stress (OS), and inflammatory marker activity. And, a western blot analysis was conducted to detect phosphorylated 5' AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of rapamycin (p-mTOR), and heme oxygenase-1 (HO-1). Hippocampal and cerebellar histopathology were thoroughly examined, in addition to the expressions of amyloid \u03b2 (A\u03b2). The current data demonstrate the involvement of the pAMPK/mTOR/HO-1 signaling pathway in empagliflozin neuroprotection against SCO + HMM-induced AD. In addition, it reduces AD hallmarks (A\u03b2 and BACE1), neuro-inflammation, and oxidative stress sequelae, and enhances neurogenesis and synaptic density via BDNF. This study proposes that EMPA, especially when co-administered with other conventional anti-Alzheimer therapy, may be", "source": "PubMed"}, {"chunk_id": "40325262_2", "pmid": "40325262", "title": "Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer's disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress.", "authors": "Abdel-Lah ES, Sherkawy HS, Mohamed WH et al.", "year": "2025", "journal": "Inflammopharmacology", "keywords": "Alzheimer\u2019s disease, Empagliflozin, Heavy metal mixtures, Memantine, Oxidative stress, Pro-inflammatory cytokines, Scopolamine", "chunk": "and BACE1), neuro-inflammation, and oxidative stress sequelae, and enhances neurogenesis and synaptic density via BDNF. This study proposes that EMPA, especially when co-administered with other conventional anti-Alzheimer therapy, may be formulated into an innovative therapeutic strategy for the enhancement of cognitive impairments associated with neurodegenerative disorders.", "source": "PubMed"}, {"chunk_id": "32310173_0", "pmid": "32310173", "title": "Plasma Neurofilament Light and Longitudinal Progression of White Matter Hyperintensity in Elderly Persons Without Dementia.", "authors": "Sun Y, Tan L, Xu W et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease neuroimaging initiative, cognitively decline, non-dementia elders, noninvasive biomarker, plasma neurofilament light protein, white matter hyperintensity", "chunk": "White matter hyperintensities (WMH) is mainly caused by cerebrovascular injury and may also increase the possibilities of progression to Alzheimer's disease. The present study aims to determine whether plasma neurofilament light (NFL) protein levels could predict the progression of WMH volume in elderly persons without dementia. The present study enrolled 1029 non-dementia participants from the Alzheimer's Disease Neuroimaging Initiative in which all had measurements of plasma NFL and WMH at baseline and 589 had longitudinal measurements during follow-up. Spearman correlation analyses and regression models were used to assess cross-sectional and longitudinal associations between plasma NFL and WMH. Plasma NFL concentration had a moderately strong correlation with WMH at baseline (r = 0.17, p < 0.001). Longitudinal analyses showed that higher baseline plasma NFL concentration was associated with accelerated progression of WMH (\u03b2=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the", "source": "PubMed"}, {"chunk_id": "32310173_1", "pmid": "32310173", "title": "Plasma Neurofilament Light and Longitudinal Progression of White Matter Hyperintensity in Elderly Persons Without Dementia.", "authors": "Sun Y, Tan L, Xu W et al.", "year": "2020", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease neuroimaging initiative, cognitively decline, non-dementia elders, noninvasive biomarker, plasma neurofilament light protein, white matter hyperintensity", "chunk": "baseline plasma NFL concentration was associated with accelerated progression of WMH (\u03b2=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the future (\u03b2=0.581, p = 0.002). The results of the study suggest that plasma NFL level might be used as a noninvasive biomarker to track variation trend in WMH in elderly persons without dementia.", "source": "PubMed"}, {"chunk_id": "37355896_0", "pmid": "37355896", "title": "Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.", "authors": "Caillaud M, Maltezos S, Hudon C et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, hippocampal volume, mild cognitive impairment, neuropsychology, subjective cognitive decline", "chunk": "Subjective cognitive decline (SCD) was proposed to identify older adults who complain about their memory but perform within a normal range on standard neuropsychological tests. Persons with SCD are at increased risk of dementia meaning that some SCD individuals experience subthreshold memory decline due to an underlying progression of Alzheimer's disease (AD). Our main goal was to determine whether hippocampal volume and APOE4, which represent typical AD markers, predict inter-individual differences in memory performance among SCD individuals and can be used to identify a meaningful clinical subgroup. Neuropsychological assessment, structural MRI, and genetic testing for APOE4 were administered to one hundred and twenty-five older adults over the age of 65 from the CIMAQ cohort: 66 SCD, 29 individuals with mild cognitive impairment (MCI), and 30 cognitively intact controls (CTRLS). Multiple regression models were first used to identify which factor (hippocampal volume, APOE4 allele, or cognitive reserve) best predicted inter-individual differences", "source": "PubMed"}, {"chunk_id": "37355896_1", "pmid": "37355896", "title": "Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.", "authors": "Caillaud M, Maltezos S, Hudon C et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, hippocampal volume, mild cognitive impairment, neuropsychology, subjective cognitive decline", "chunk": "cognitive impairment (MCI), and 30 cognitively intact controls (CTRLS). Multiple regression models were first used to identify which factor (hippocampal volume, APOE4 allele, or cognitive reserve) best predicted inter-individual differences in a Face-name association memory task within the SCD group. Hippocampal volume was found to be the only and best predictor of memory performance. We then compared the demographic, clinical and cognitive characteristics of two SCD subgroups, one with small hippocampal volume (SCD/SH) and another with normal hippocampal volume (SCD/NH), with MCI and CTRLS. SCD/SH were comparable to MCI on neuropsychological tasks evaluating memory (i.e., test of delayed word recall), whereas SCD/NH were comparable to CTRLS. Thus, using hippocampal volume allows identification of an SCD subgroup with a cognitive profile consistent with a higher risk of conversion to AD.", "source": "PubMed"}, {"chunk_id": "37355896_2", "pmid": "37355896", "title": "Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.", "authors": "Caillaud M, Maltezos S, Hudon C et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, hippocampal volume, mild cognitive impairment, neuropsychology, subjective cognitive decline", "chunk": "consistent with a higher risk of conversion to AD.", "source": "PubMed"}, {"chunk_id": "40690160_0", "pmid": "40690160", "title": "Advancing clinical trial readiness in white matter disease and related dementias: key steps for future research progress.", "authors": "Sompol P, Jicha GA, Hinman JD et al.", "year": "2026", "journal": "GeroScience", "keywords": "Alzheimer, Dementia, White matter disease", "chunk": "White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer's disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate new knowledge and guidelines for studying white matter in dementia. The 4th annual ARIWMC workshop was held on May 31-June 2, 2023, where researchers met to set strategies for clinical trial readiness. Significant discussion by participants advocated research on multiple levels, including molecular, cellular, metabolic, behavioral, and risk factors that", "source": "PubMed"}, {"chunk_id": "40690160_1", "pmid": "40690160", "title": "Advancing clinical trial readiness in white matter disease and related dementias: key steps for future research progress.", "authors": "Sompol P, Jicha GA, Hinman JD et al.", "year": "2026", "journal": "GeroScience", "keywords": "Alzheimer, Dementia, White matter disease", "chunk": "2, 2023, where researchers met to set strategies for clinical trial readiness. Significant discussion by participants advocated research on multiple levels, including molecular, cellular, metabolic, behavioral, and risk factors that contribute to disease etiology and regeneration processes. Moreover, participants also addressed identifying and validating biomarkers and functional studies in animal models and human trials that are key steps for treatment development. Other areas that were discussed included epidemiological studies and pragmatic clinical trials where health care researchers and everyday medical practice support risk factor management or healthy lifestyle, and prevention trials could mitigate the incident of the disease. In summary, this workshop fostered a better understanding of how white matter lesions contribute to cognitive impairment from bench-to-biomarker-to-bedside-to-translational approaches which will facilitate and support the discovery and development of therapies and prevention strategies that facilitate a healthy brain and reduce white matter-related pathologies associated with and contributing to VCID and ADRD.", "source": "PubMed"}, {"chunk_id": "40690160_2", "pmid": "40690160", "title": "Advancing clinical trial readiness in white matter disease and related dementias: key steps for future research progress.", "authors": "Sompol P, Jicha GA, Hinman JD et al.", "year": "2026", "journal": "GeroScience", "keywords": "Alzheimer, Dementia, White matter disease", "chunk": "facilitate and support the discovery and development of therapies and prevention strategies that facilitate a healthy brain and reduce white matter-related pathologies associated with and contributing to VCID and ADRD.", "source": "PubMed"}, {"chunk_id": "41208852_0", "pmid": "41208852", "title": "Aligning with regulatory agencies for the use of digital health technologies in drug development: a case study from Parkinson's disease.", "authors": "Hill DL, Carroll C, Belfiore-Oshan R et al.", "year": "2025", "journal": "Frontiers in digital health", "keywords": "Parkinson's disease, data sharing, digital health technologies, drug development, neurological disorders, regulatory framework", "chunk": "Digital Health Technologies (DHTs) have been under investigation for many years as innovative tools for Parkinson's disease motor symptoms given their inherent high-frequency, sensitive, and objective measurement properties. DHTs used in drug development, can be defined as Drug Development Tools (DDT), though some DHTs may also be categorized as medical devices. The recent rapid increase in use of DHTs in clinical trials has been accompanied by a rapidly evolving regulatory landscape, resulting in a challenging environment for widespread implementation of DHTs in applications that will provide clear impact on pharmaceutical company drug development pipelines. Parkinson's disease represents a disease of escalating burden with high unmet need for therapies that are disease modifying. Early intervention is a key area of focus, yet the heterogeneity of symptoms and lack of biomarkers poses challenges for drug development. Furthermore, the technologies and device platforms, both hardware and software, are rapidly evolving, and the companies", "source": "PubMed"}, {"chunk_id": "41208852_1", "pmid": "41208852", "title": "Aligning with regulatory agencies for the use of digital health technologies in drug development: a case study from Parkinson's disease.", "authors": "Hill DL, Carroll C, Belfiore-Oshan R et al.", "year": "2025", "journal": "Frontiers in digital health", "keywords": "Parkinson's disease, data sharing, digital health technologies, drug development, neurological disorders, regulatory framework", "chunk": "yet the heterogeneity of symptoms and lack of biomarkers poses challenges for drug development. Furthermore, the technologies and device platforms, both hardware and software, are rapidly evolving, and the companies developing the underlying devices frequently have objectives and timelines that may not align with those of the pharmaceutical industry. DHTs therefore have a unique set of challenges in terms of devising meaningful measures, standardization of data collected, responding to evolving regulatory expectations, and ensuring alignment across stakeholders. There is a growing need for new models of collaboration to bring together diverse stakeholders required to achieve regulatory endorsement of DHTs for use as DDTs. Collaborations between stakeholders working on DHTs need to be firmly anchored in the regulatory ecosystem as many regulatory challenges in DHTs have parallels in other technologies. Furthermore, there is an especially urgent need to define the pre-competitive space in which DHT data can be shared, data collection", "source": "PubMed"}, {"chunk_id": "41208852_2", "pmid": "41208852", "title": "Aligning with regulatory agencies for the use of digital health technologies in drug development: a case study from Parkinson's disease.", "authors": "Hill DL, Carroll C, Belfiore-Oshan R et al.", "year": "2025", "journal": "Frontiers in digital health", "keywords": "Parkinson's disease, data sharing, digital health technologies, drug development, neurological disorders, regulatory framework", "chunk": "regulatory challenges in DHTs have parallels in other technologies. Furthermore, there is an especially urgent need to define the pre-competitive space in which DHT data can be shared, data collection standards devised, and novel analysis approaches that are robust to residual variability developed. Critical Path for Parkinson's Consortium's (CPP) Digital Drug Development Tool (3DT) initiative is highlighted as a case example to illustrate how pre-competitive public private partnerships can advance the regulatory maturity of digital health technology measures for use in clinical trials.", "source": "PubMed"}, {"chunk_id": "32597244_0", "pmid": "32597244", "title": "Engineering of fluorescent or photoactive Trojan probes for detection and eradication of \u03b2-Amyloids.", "authors": "Aziz AA, Siddiqui RA, Amtul Z", "year": "2020", "journal": "Drug delivery", "keywords": "Alzheimer\u2019s disease, Trojan horse, blood-brain barrier, photosensitizer, quantum dots, smart drugs, \u03b2\u2009\u2212\u2009amyloid", "chunk": "Trojan horse technology institutes a potentially promising strategy to bring together a diagnostic or cell-based drug design and a delivery platform. It provides the opportunity to re-engineer a novel multimodal, neurovascular detection probe, or medicine to fuse with blood-brain barrier (BBB) molecular Trojan horse. In Alzheimer's disease (AD) this could allow the targeted delivery of detection or therapeutic probes across the BBB to the sites of plaques and tangles development to image or decrease amyloid load, enhance perivascular A\u03b2 clearance, and improve cerebral blood flow, owing principally to the significantly improved cerebral permeation. A Trojan horse can also be equipped with photosensitizers, nanoparticles, quantum dots, or fluorescent molecules to function as multiple targeting theranostic compounds that could be activated following changes in disease-specific processes of the diseased tissue such as pH and protease activity, or exogenous stimuli such as, light. This concept review theorizes the use of receptor-mediated transport-based platforms", "source": "PubMed"}, {"chunk_id": "32597244_1", "pmid": "32597244", "title": "Engineering of fluorescent or photoactive Trojan probes for detection and eradication of \u03b2-Amyloids.", "authors": "Aziz AA, Siddiqui RA, Amtul Z", "year": "2020", "journal": "Drug delivery", "keywords": "Alzheimer\u2019s disease, Trojan horse, blood-brain barrier, photosensitizer, quantum dots, smart drugs, \u03b2\u2009\u2212\u2009amyloid", "chunk": "changes in disease-specific processes of the diseased tissue such as pH and protease activity, or exogenous stimuli such as, light. This concept review theorizes the use of receptor-mediated transport-based platforms to transform such novel ideas to engineer systemic and smart Trojan detection or therapeutic probes to advance the neurodegenerative field.", "source": "PubMed"}, {"chunk_id": "35833655_0", "pmid": "35833655", "title": "Urinary AD7c-NTP Evaluates Cognition Impairment and Differentially Diagnoses AD and MCI.", "authors": "Xu MR, Dai RF, Wei QQ et al.", "year": "2022", "journal": "American journal of Alzheimer's disease and other dementias", "keywords": "AD7c-NTP, Alzheimer\u2019s disease, mild cognitive impairment, neuropsychology, urine", "chunk": "The AD7c-NTP is a promising biomarker for AD diagnosis. However, the exact urinary AD7c-NTP concentration to differentiate AD from the mild cognitive impairment (MCI) remains inconclusive. We enrolled 98 and 90 clinical defined AD and MCI patients, respectively, and access their cognition impairment with Neuropsychiatric Inventory (NPI) and Mental State Examination (MMSE) along with their urinary AD7c-NTP. We demonstrated that urinary AD7c-NTP level in sequence from high to low was AD, MCI, and healthy groups (<i>P</i> < .01), and the AD7c-NTP was positively and negatively correlated with the NPI and MMSE scores, respectively. Additionally, AD7c-NTP well-matched NPI subscale scores, including agitation, depression, and apathy (<i>P</i> < .05). Importantly, the optimal cut-off AD7c-NTP level to distinguish the AD and MCI was .94 ng/mL (sensitivity 85.71% & specificity 73.91%). Conclusively, urinary AD7c-NTP could be used for cognition impairment evaluation and differentiated diagnosis of AD and MCI.", "source": "PubMed"}, {"chunk_id": "35833655_1", "pmid": "35833655", "title": "Urinary AD7c-NTP Evaluates Cognition Impairment and Differentially Diagnoses AD and MCI.", "authors": "Xu MR, Dai RF, Wei QQ et al.", "year": "2022", "journal": "American journal of Alzheimer's disease and other dementias", "keywords": "AD7c-NTP, Alzheimer\u2019s disease, mild cognitive impairment, neuropsychology, urine", "chunk": ".94 ng/mL (sensitivity 85.71% & specificity 73.91%). Conclusively, urinary AD7c-NTP could be used for cognition impairment evaluation and differentiated diagnosis of AD and MCI.", "source": "PubMed"}, {"chunk_id": "39291165_0", "pmid": "39291165", "title": "Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.", "authors": "Rennie A, Ekman U, Shams S et al.", "year": "2024", "journal": "Brain communications", "keywords": "atrophy, imaging, multi-cohort, naturalistic cohort", "chunk": "Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of", "source": "PubMed"}, {"chunk_id": "39291165_1", "pmid": "39291165", "title": "Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.", "authors": "Rennie A, Ekman U, Shams S et al.", "year": "2024", "journal": "Brain communications", "keywords": "atrophy, imaging, multi-cohort, naturalistic cohort", "chunk": "dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of \u03b2-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample (<i>N</i> = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger", "source": "PubMed"}, {"chunk_id": "39291165_2", "pmid": "39291165", "title": "Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.", "authors": "Rennie A, Ekman U, Shams S et al.", "year": "2024", "journal": "Brain communications", "keywords": "atrophy, imaging, multi-cohort, naturalistic cohort", "chunk": "than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when \u03b2-amyloid was included in the model. Instead, \u03b2-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of \u03b2-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on", "source": "PubMed"}, {"chunk_id": "39291165_3", "pmid": "39291165", "title": "Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.", "authors": "Rennie A, Ekman U, Shams S et al.", "year": "2024", "journal": "Brain communications", "keywords": "atrophy, imaging, multi-cohort, naturalistic cohort", "chunk": "matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on \u03b2-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of the other diagnostic groups.", "source": "PubMed"}, {"chunk_id": "40829101_0", "pmid": "40829101", "title": "Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging.", "authors": "Brown TM, James SN, Nicholas JM et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "Higher white matter hyperintensity volume (WMHV) is associated with hippocampal atrophy, cognitive decline, and dementia; however, it is unknown whether continually increasing WMHV is related to hippocampal atrophy. The aim of this study was to determine whether higher WMHV change rate (WMHVR) is related to higher hippocampal atrophy rate (HAR); this relationship is dependent on cardiovascular risk factors (CVRFs), Alzheimer disease (AD) pathology, and genetic risk; and this relationship is mediated by neuroaxonal degradation. Participants from Insight46, a substudy of the 1946 British Birth Cohort, underwent combined [<sup>18</sup>F]florbetapir PET/MRI scans at University College London approximately 2.5 years apart. WMHVR was quantified from T2/fluid-attenuated inversion recovery and HAR from T1 sequences. Life-course blood pressure and CVRF data were measured at 6 and 3 time points, respectively. <i>APOE</i> genotype and neurofilament light chain (NfL) quantification were derived from blood samples. Participants with neurologic conditions were excluded from primary analyses. Linear regression was", "source": "PubMed"}, {"chunk_id": "40829101_1", "pmid": "40829101", "title": "Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging.", "authors": "Brown TM, James SN, Nicholas JM et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "and 3 time points, respectively. <i>APOE</i> genotype and neurofilament light chain (NfL) quantification were derived from blood samples. Participants with neurologic conditions were excluded from primary analyses. Linear regression was used to test the relationships between WMHVR and HAR, adjusting for sex, age, and total intracranial volume (TIV) and CVRF, <i>APOE</i>-\u03b54 status, and \u03b2-amyloid (A\u03b2) in separate models. Semipartial <i>R</i><sup>2</sup> was calculated from these models. In a post hoc analysis, structural equation modeling aimed to determine whether NfL mediated the relationship between WMHVR and HAR. A total of 317 individuals without neurologic conditions (48% female, 100% White British, mean baseline age [SD] = 70.5 [0.6] years) were included. The mean HAR was 0.04 [0.04] mL/y. Each 1 mL/y increase in WMHVR was associated with a 0.014 mL/y (95% CI 0.005-0.022) increase in HAR, adjusted for TIV, age, and sex (<i>p</i> = 0.002). Adjustment for additional variables did not meaningfully attenuate", "source": "PubMed"}, {"chunk_id": "40829101_2", "pmid": "40829101", "title": "Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging.", "authors": "Brown TM, James SN, Nicholas JM et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "WMHVR was associated with a 0.014 mL/y (95% CI 0.005-0.022) increase in HAR, adjusted for TIV, age, and sex (<i>p</i> = 0.002). Adjustment for additional variables did not meaningfully attenuate this association (\u22650.012 mL/y, <i>p</i> \u2264 0.005, all models), and there was no indirect effect through NfL (0.0004 mL/y [95% CI -0.0006 to 0.0012], <i>p</i> < 0.1). Higher WMHVR was associated with HAR between approximately 70 and 73 years, independent of CVRF levels, <i>APOE</i>-\u03b54 status, and A\u03b2 load, and not mediated by markers of neuroaxonal degradation. Although AD-specific pathology is typically considered the main cause of accelerated HAR, we demonstrated that HAR is also linked to deteriorating WM health. These results will need to be replicated in more diverse cohorts with longer follow-up periods to confirm the findings.", "source": "PubMed"}, {"chunk_id": "40829101_3", "pmid": "40829101", "title": "Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging.", "authors": "Brown TM, James SN, Nicholas JM et al.", "year": "2025", "journal": "Neurology", "keywords": "None", "chunk": "with longer follow-up periods to confirm the findings.", "source": "PubMed"}, {"chunk_id": "37812325_0", "pmid": "37812325", "title": "Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.", "authors": "Esquer A, Blanc F, Collongues N", "year": "2023", "journal": "Neurology and therapy", "keywords": "Alzheimer\u2019s Disease, Amyloid, Clinical trials, Donanemab, Immunotherapy, Lecanemab, Monoclonal antibodies, Review, Tau, Treatment", "chunk": "Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most advanced therapeutic approach at present. Three drugs (lecanemab, donanemab and aducanumab) are on track to be marketed in the coming months. In this systematic review, we review all Phase 2 and Phase 3 clinical trials conducted in this indication and the particularities of the molecules tested. The PubMed and ClinicalTrials.gov databases were searched through February 2023 for Phase 2 and 3 clinical trials involving passive anti-amyloid or anti-tau immunotherapies with published results. This review has been compiled in compliance with the PRISMA checklists. Of the 165 studies found and after eliminating duplicates, 40 studies had their results published on PubMed and/or ClinicalTrials.gov. Eight anti-amyloid molecules and four anti-tau molecules were the subject of Phase 2 studies, seven anti-amyloids were the subject of Phase 3 trials,", "source": "PubMed"}, {"chunk_id": "37812325_1", "pmid": "37812325", "title": "Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.", "authors": "Esquer A, Blanc F, Collongues N", "year": "2023", "journal": "Neurology and therapy", "keywords": "Alzheimer\u2019s Disease, Amyloid, Clinical trials, Donanemab, Immunotherapy, Lecanemab, Monoclonal antibodies, Review, Tau, Treatment", "chunk": "their results published on PubMed and/or ClinicalTrials.gov. Eight anti-amyloid molecules and four anti-tau molecules were the subject of Phase 2 studies, seven anti-amyloids were the subject of Phase 3 trials, and two molecules were granted early marketing approval by the US Food and Drug Administration (FDA). The results were compiled in summary tables showing the primary endpoints used, results, age of the study population and specific adverse events for these molecules. Passive immunotherapy in AD is largely dominated by anti-amyloid antibodies, which are more numerous and more advanced in the pipeline. Lecanemab, donanemab and aducanumab are distinguished by their relative efficacy in terms of cognitive and functional evaluation but also by a decrease in amyloid and tau proteins in the brain. These three molecules have in common that they bind to N-terminal ends of amyloid fibrils and plaques. The findings of their studies raise the question of which criteria to", "source": "PubMed"}, {"chunk_id": "37812325_2", "pmid": "37812325", "title": "Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.", "authors": "Esquer A, Blanc F, Collongues N", "year": "2023", "journal": "Neurology and therapy", "keywords": "Alzheimer\u2019s Disease, Amyloid, Clinical trials, Donanemab, Immunotherapy, Lecanemab, Monoclonal antibodies, Review, Tau, Treatment", "chunk": "brain. These three molecules have in common that they bind to N-terminal ends of amyloid fibrils and plaques. The findings of their studies raise the question of which criteria to apply when choosing which patient will receive them when marketed, such as the apoliprotein E gene's fourth allele (APOE4) genetic status of patients. The large number of negative studies may also raise the question of the criteria for defining the disease and the possible interest in redefining it on biological grounds to offer a more personalized medicine to patients suffering from neurodegenerative diseases.", "source": "PubMed"}, {"chunk_id": "41478818_0", "pmid": "41478818", "title": "Tau in Alzheimer's disease: Shaping the future patient journey.", "authors": "Mummery CJ, Li-Hsian CC, Lasagna-Reeves CA et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Biomarkers, Clinical pathways, Tau", "chunk": "Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in the field of tau to envision how an increasing focus on tau could shape the future Alzheimer's disease patient journey. We highlight the potential of tau as both a promising therapeutic target and a valuable biomarker, with the potential to inform treatment decisions and provide insight into disease trajectories. We", "source": "PubMed"}, {"chunk_id": "41478818_1", "pmid": "41478818", "title": "Tau in Alzheimer's disease: Shaping the future patient journey.", "authors": "Mummery CJ, Li-Hsian CC, Lasagna-Reeves CA et al.", "year": "2026", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, Biomarkers, Clinical pathways, Tau", "chunk": "We highlight the potential of tau as both a promising therapeutic target and a valuable biomarker, with the potential to inform treatment decisions and provide insight into disease trajectories. We also consider what a greater focus on tau may bring to an already evolving patient care pathway characterized by an increased influx of patients presenting earlier in the disease continuum, changes in workflow and infrastructural requirements, and increased complexity in treatment decision-making, treatment administration, treatment monitoring, and patient tracking. This review underscores the critical changes that may be required and knowledge gaps to be elucidated to ensure healthcare system preparedness for additional classes of disease-targeted therapy to move toward a next-generation, individualized treatment approach to Alzheimer's disease diagnosis and care.", "source": "PubMed"}, {"chunk_id": "39041391_0", "pmid": "39041391", "title": "Predicting continuous amyloid PET values with CSF tau phosphorylation occupancies.", "authors": "Wisch JK, Gordon BA, Barth\u00e9lemy NR et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "CSF tau occupancy, PET, biomarker concordance, machine learning, novel biomarkers", "chunk": "Cerebrospinal fluid (CSF) tau phosphorylation at multiple sites is associated with cortical amyloid and other pathologic changes in Alzheimer's disease. These relationships can be non-linear. We used an artificial neural network to assess the ability of 10 different CSF tau phosphorylation sites to predict continuous amyloid positron emission tomography (PET) values. CSF tau phosphorylation occupancies at 10 sites (including pT181/T181, pT217/T217, pT231/T231 and pT205/T205) were measured by mass spectrometry in 346 individuals (57 cognitively impaired, 289 cognitively unimpaired). We generated synthetic amyloid PET scans using biomarkers and evaluated their performance. Concentration of CSF pT217/T217 had low predictive error (average error: 13%), but also a low predictive range (ceiling 63 Centiloids). CSF pT231/T231 has slightly higher error (average error: 19%) but predicted through a greater range (87 Centiloids). Tradeoffs exist in biomarker selection. Some phosphorylation sites offer greater concordance with amyloid PET at lower levels, while others perform better over a", "source": "PubMed"}, {"chunk_id": "39041391_1", "pmid": "39041391", "title": "Predicting continuous amyloid PET values with CSF tau phosphorylation occupancies.", "authors": "Wisch JK, Gordon BA, Barth\u00e9lemy NR et al.", "year": "2024", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "CSF tau occupancy, PET, biomarker concordance, machine learning, novel biomarkers", "chunk": "predicted through a greater range (87 Centiloids). Tradeoffs exist in biomarker selection. Some phosphorylation sites offer greater concordance with amyloid PET at lower levels, while others perform better over a greater range. Novel pTau isoforms can predict cortical amyloid burden. pT217/T217 accurately predicts cortical amyloid burden in low-amyloid individuals. Traditional CSF biomarkers correspond with higher levels of amyloid.", "source": "PubMed"}, {"chunk_id": "39350391_0", "pmid": "39350391", "title": "The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.", "authors": "Walter S, Langford O, Jimenez-Maggiora GA et al.", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, biomarker eligibility, centralized screening, community laboratories, decentralized, plasma biomarkers, preclinical Alzheimer\u2019s disease, recruitment, remote participant engagement, screening, site-agnostic methods", "chunk": "Advances in plasma biomarkers to detect Alzheimer's disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer's Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD. The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual's eligibility for AD preclinical trials. Pilot feasibility study with co-primary outcomes. This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic", "source": "PubMed"}, {"chunk_id": "39350391_1", "pmid": "39350391", "title": "The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.", "authors": "Walter S, Langford O, Jimenez-Maggiora GA et al.", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, biomarker eligibility, centralized screening, community laboratories, decentralized, plasma biomarkers, preclinical Alzheimer\u2019s disease, recruitment, remote participant engagement, screening, site-agnostic methods", "chunk": "pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility. Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months. Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate,", "source": "PubMed"}, {"chunk_id": "39350391_2", "pmid": "39350391", "title": "The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.", "authors": "Walter S, Langford O, Jimenez-Maggiora GA et al.", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, biomarker eligibility, centralized screening, community laboratories, decentralized, plasma biomarkers, preclinical Alzheimer\u2019s disease, recruitment, remote participant engagement, screening, site-agnostic methods", "chunk": "within the prior 6 months. Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [A\u03b242/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study. 300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%-44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71%", "source": "PubMed"}, {"chunk_id": "39350391_3", "pmid": "39350391", "title": "The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.", "authors": "Walter S, Langford O, Jimenez-Maggiora GA et al.", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, biomarker eligibility, centralized screening, community laboratories, decentralized, plasma biomarkers, preclinical Alzheimer\u2019s disease, recruitment, remote participant engagement, screening, site-agnostic methods", "chunk": "40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials. Electronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version", "source": "PubMed"}, {"chunk_id": "39350391_4", "pmid": "39350391", "title": "The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.", "authors": "Walter S, Langford O, Jimenez-Maggiora GA et al.", "year": "2024", "journal": "The journal of prevention of Alzheimer's disease", "keywords": "Alzheimer\u2019s disease, biomarker eligibility, centralized screening, community laboratories, decentralized, plasma biomarkers, preclinical Alzheimer\u2019s disease, recruitment, remote participant engagement, screening, site-agnostic methods", "chunk": "at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.", "source": "PubMed"}, {"chunk_id": "40420448_0", "pmid": "40420448", "title": "[Differential diagnosis of Alzheimer's disease and vascular cognitive disorders].", "authors": "Cherdak MA, Mkhitaryan EA, Tkacheva ON", "year": "2025", "journal": "Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova", "keywords": "Alzheimer\u2019s disease, cerebrovascular diseases, differential diagnosis, mild cognitive impairment, vascular cognitive disorders, vascular dementia", "chunk": "Cognitive disorders (CD) are a common problem in the practice of various medical specialities. Among the most common causes of severe CD (dementia) are Alzheimer's disease (AD) and cerebrovascular diseases. The stage of non-dementia CD precedes dementia. Interventions at the non-dementia stage are believed to be more effective, prolonging the patient's quality of life at a higher functional level with a decrease in the need for nursing care. Currently, there is a pronounced underdiagnosis of CD, especially AD, which reduces the timely availability of specific drug therapy for patients and adversely affects the prognosis of the disease. The article presents basic information on the pathogenesis and methods of clinical and paraclinical diagnosis of AD and CD of vascular origin. The main markers helping to distinguish these diseases and diagnose them at the predementia stage have been identified.", "source": "PubMed"}, {"chunk_id": "40420448_1", "pmid": "40420448", "title": "[Differential diagnosis of Alzheimer's disease and vascular cognitive disorders].", "authors": "Cherdak MA, Mkhitaryan EA, Tkacheva ON", "year": "2025", "journal": "Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova", "keywords": "Alzheimer\u2019s disease, cerebrovascular diseases, differential diagnosis, mild cognitive impairment, vascular cognitive disorders, vascular dementia", "chunk": "main markers helping to distinguish these diseases and diagnose them at the predementia stage have been identified.", "source": "PubMed"}, {"chunk_id": "37783547_0", "pmid": "37783547", "title": "Real-world prediction of preclinical Alzheimer's disease with a deep generative model.", "authors": "Hwang U, Kim SW, Jung D et al.", "year": "2023", "journal": "Artificial intelligence in medicine", "keywords": "Deep generative models, Explainable AI, Preclinical Alzheimer\u2019s disease, Real-world classification", "chunk": "Amyloid positivity is an early indicator of Alzheimer's disease and is necessary to determine the disease. In this study, a deep generative model is utilized to predict the amyloid positivity of cognitively normal individuals using proxy measures, such as structural MRI scans, demographic variables, and cognitive scores, instead of invasive direct measurements. Through its remarkable efficacy in handling imperfect datasets caused by missing data or labels, and imbalanced classes, the model outperforms previous studies and widely used machine learning approaches with an AUROC of 0.8609. Furthermore, this study illuminates the model's adaptability to diverse clinical scenarios, even when feature sets or diagnostic criteria differ from the training data. We identify the brain regions and variables that contribute most to classification, including the lateral occipital lobes, posterior temporal lobe, and APOE \u03f54 allele. Taking advantage of deep generative models, our approach can not only provide inexpensive, non-invasive, and accurate diagnostics for", "source": "PubMed"}, {"chunk_id": "37783547_1", "pmid": "37783547", "title": "Real-world prediction of preclinical Alzheimer's disease with a deep generative model.", "authors": "Hwang U, Kim SW, Jung D et al.", "year": "2023", "journal": "Artificial intelligence in medicine", "keywords": "Deep generative models, Explainable AI, Preclinical Alzheimer\u2019s disease, Real-world classification", "chunk": "including the lateral occipital lobes, posterior temporal lobe, and APOE \u03f54 allele. Taking advantage of deep generative models, our approach can not only provide inexpensive, non-invasive, and accurate diagnostics for preclinical Alzheimer's disease, but also meet real-world requirements for clinical translation of a deep learning model, including transferability and interpretability.", "source": "PubMed"}, {"chunk_id": "41238048_0", "pmid": "41238048", "title": "A modified \u03b1-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis.", "authors": "Coles NP, Elsheikh S, Gouda A et al.", "year": "2026", "journal": "Journal of neuroscience methods", "keywords": "Diagnostics, Lewy body dementia, Machine learning analysis, Raman spectroscopy, \u03b1-synuclein aggregation", "chunk": "Lewy body dementias (LBD), comprising dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are defined by misfolded \u03b1-synuclein aggregation. Seed amplification assays (SAAs), such as RT-QuIC, enable sensitive detection of \u03b1-synuclein aggregates but typically provide binary readouts and require fluorescence labeling. Raman spectroscopy offers a label-free approach to detect subtle biochemical changes, and its diagnostic potential can be enhanced with machine learning. This proof-of-concept study aimed to evaluate whether Raman spectroscopy combined with machine learning can improve SAA-based discrimination of LBD from controls in cerebrospinal fluid (CSF). We analyzed a small number of post-mortem CSF samples from pathologically confirmed DLB (n = 2), PDD (n = 2), and controls (n = 2) using a 7-day SAA. Raman spectra were collected on Days 1, 4, and 7 and analyzed using principal component analysis (PCA) and uniform manifold approximation and projection (UMAP). Following SAA, both PCA and UMAP distinguished combined", "source": "PubMed"}, {"chunk_id": "41238048_1", "pmid": "41238048", "title": "A modified \u03b1-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis.", "authors": "Coles NP, Elsheikh S, Gouda A et al.", "year": "2026", "journal": "Journal of neuroscience methods", "keywords": "Diagnostics, Lewy body dementia, Machine learning analysis, Raman spectroscopy, \u03b1-synuclein aggregation", "chunk": "were collected on Days 1, 4, and 7 and analyzed using principal component analysis (PCA) and uniform manifold approximation and projection (UMAP). Following SAA, both PCA and UMAP distinguished combined LBD samples from controls within 24 h (Day 1), reflecting biochemical changes consistent with \u03b1-synuclein fibrillation. Spectral shifts indicated decreased \u03b1-helical content with increased \u03b2-sheet structures. No consistent separation between DLB and PDD was observed. This preliminary study demonstrates that combining Raman spectroscopy with machine learning can enable rapid, label-free detection of disease-specific changes. Despite the very limited sample size, these findings highlight the potential of this novel workflow and strongly warrant its validation in larger cohorts.", "source": "PubMed"}, {"chunk_id": "37718812_0", "pmid": "37718812", "title": "Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.", "authors": "Davidson S, Allenback G, Decourt B et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, National Alzheimer\u2019s Coordinating Center, Uniform Data Set, cognitive progression, neuropsychological test battery, type 2 diabetes mellitus", "chunk": "Although insulin dysregulation and resistance likely participate in Alzheimer's disease (AD) etiologies, little is known about the correlation between type 2 diabetes mellitus (T2DM) and the progression of cognitive decline in patients with AD. To determine whether AD patients with T2DM experience more rapid cognitive decline than those without T2DM. All cognitive performance data and the presence or absence of T2DM comorbidity in patients with AD were derived from the US National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). A search of the UDS identified 3,055 participants with AD who had more than one epoch completed. The data set culled clinically diagnosed AD dementia patients who were assessed for diabetes type identified during at least 1 visit. These patients were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological", "source": "PubMed"}, {"chunk_id": "37718812_1", "pmid": "37718812", "title": "Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.", "authors": "Davidson S, Allenback G, Decourt B et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, National Alzheimer\u2019s Coordinating Center, Uniform Data Set, cognitive progression, neuropsychological test battery, type 2 diabetes mellitus", "chunk": "were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological test battery scores and a Clinician Dementia Rating using a general linear model. Comparisons of the mean scores for 16 selected tests from the neuropsychological test battery showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and nondiabetic groups. The results revealed no differences in cognitive decline metrics over the course of 5 visits in either study group. These data indicate that the presence of T2DM does not increase the rate of cognitive decline in AD. This finding contradicts expected disease burden and will need to be explored further.", "source": "PubMed"}, {"chunk_id": "37718812_2", "pmid": "37718812", "title": "Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.", "authors": "Davidson S, Allenback G, Decourt B et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer\u2019s disease, National Alzheimer\u2019s Coordinating Center, Uniform Data Set, cognitive progression, neuropsychological test battery, type 2 diabetes mellitus", "chunk": "need to be explored further.", "source": "PubMed"}, {"chunk_id": "39692213_0", "pmid": "39692213", "title": "White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status.", "authors": "Kern KC, Vohra M, Thirion ML et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "dementia, diffusion tensor imaging, magnetic resonance imaging, placental growth factor, vascular cognitive impairment, white matter hyperintensities", "chunk": "Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment. MarkVCID consortium participants \u226555 years old with plasma PlGF and brain MRI were included. We tested cross-sectionally whether FW mediated the associations between PlGF and WMH, or PlGF and cognition, measured using the Clinical Dementia Rating (CDR) scale and an executive function (EF) composite (Uniform Data Set version 3 [UDS3]-EF). For 370 participants (mean age 72), a higher PlGF was associated with higher FW, higher WMH, and higher CDR, but not UDS3-EF. Higher FW was associated with higher WMH, higher CDR, and lower UDS3-EF. FW explained 26% of the association between PlGF and CDR and 73% of the association between PlGF and WMH. Elevated PlGF may contribute to WMH and cognitive", "source": "PubMed"}, {"chunk_id": "39692213_1", "pmid": "39692213", "title": "White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status.", "authors": "Kern KC, Vohra M, Thirion ML et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "dementia, diffusion tensor imaging, magnetic resonance imaging, placental growth factor, vascular cognitive impairment, white matter hyperintensities", "chunk": "and lower UDS3-EF. FW explained 26% of the association between PlGF and CDR and 73% of the association between PlGF and WMH. Elevated PlGF may contribute to WMH and cognitive impairment through white matter FW accumulation. NCT06284213 HIGHLIGHTS: PlGF is a promising blood-based biomarker for vascular cognitive impairment. In MarkVCID, higher PlGF was associated with accumulated white matter FW on MRI. FW mediated the association between higher PlGF and MRI-visible white matter injury. FW mediated the association between PlGF and worse CDR scale. PlGF may contribute to cognitive dysfunction via accumulated interstitial fluid.", "source": "PubMed"}, {"chunk_id": "41488126_0", "pmid": "41488126", "title": "Characterizing Amyloid Pathogenic Spread in Alzheimer's Disease Through A Network Diffusion Model.", "authors": "Xu FH, Duong-Tran D, Huang H et al.", "year": "2025", "journal": "ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine", "keywords": "Alzheimer\u2019s disease, amyloid PET imaging, disease progression, structural brain network", "chunk": "Early amyloid-<i>\u03b2</i> deposition is a hallmark of Alzheimer's disease (AD), though the exact nature of amyloid pathogenesis is not fully characterized. In this study, we designed a network diffusion model to simulate the spread of amyloid pathology through white matter brain networks of diagnostic subpopulations of healthy control (HC), mild cognitive impairment (MCI), and AD. Our network diffusion model was able to successfully model the spread of amyloid, recapturing regional distributions of amyloid observed in <sup>18</sup>F-florbetapir positron emission tomography (r=0.44-0.46, P<0.01). When tuning the optimal parameters, we found that the optimal diffusion time (<i>t</i>) provided a notion of temporal progression, where the HC group had the lowest time (<i>t</i> = 107.22 \u00b1 16.67), followed by MCI (<i>t</i> = 122.78 \u00b1 19.63), and lastly AD (<i>t</i> =136.20 \u00b1 24.47). The optimal starting seeds were the brainstem in all three diagnostic groups, followed by the lateral orbitofrontal lobes for HC and MCI", "source": "PubMed"}, {"chunk_id": "41488126_1", "pmid": "41488126", "title": "Characterizing Amyloid Pathogenic Spread in Alzheimer's Disease Through A Network Diffusion Model.", "authors": "Xu FH, Duong-Tran D, Huang H et al.", "year": "2025", "journal": "ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine", "keywords": "Alzheimer\u2019s disease, amyloid PET imaging, disease progression, structural brain network", "chunk": "19.63), and lastly AD (<i>t</i> =136.20 \u00b1 24.47). The optimal starting seeds were the brainstem in all three diagnostic groups, followed by the lateral orbitofrontal lobes for HC and MCI and the lingual gyri in AD. Our findings corroborate evidence from amyloid staging studies where amyloid starts in the primary neocortex and associative cortex. The significance of the white matter structural network in the diffusion process provides evidence for the trans-synaptic spread hypothesis of amyloid in AD. In conclusion, our study provides novel insights into the pathogenesis of amyloid in AD and its subsequent propagation throughout the brain.", "source": "PubMed"}, {"chunk_id": "35855631_0", "pmid": "35855631", "title": "Alzheimer's disease: a scoping review of biomarker research and development for effective disease diagnosis.", "authors": "Faldu KG, Shah JS", "year": "2022", "journal": "Expert review of molecular diagnostics", "keywords": "Alzheimer\u2019s disease, artificial intelligence (AI), biomarkers, machine learning (ML), metabolomics, miRNA, neuronal injury, proteomics, tau, \u03b2-amyloid", "chunk": "Alzheimer's disease (AD) is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population. Characterized by extracellular accumulation of amyloid-beta (A\u03b2), intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition. Amyloid/tau/neurodegeneration (ATN) classification is utilized for research purposes and involves amyloid, tau, and neuronal injury staging through MRI, PET scanning, and CSF protein concentration estimations. CSF sampling is invasive, and MRI and PET scanning requires sophisticated radiological facilities which limit its widespread diagnostic use. ATN classification lacks effectiveness in preclinical AD. This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments. It is an accepted observation that AD-related pathological changes occur", "source": "PubMed"}, {"chunk_id": "35855631_1", "pmid": "35855631", "title": "Alzheimer's disease: a scoping review of biomarker research and development for effective disease diagnosis.", "authors": "Faldu KG, Shah JS", "year": "2022", "journal": "Expert review of molecular diagnostics", "keywords": "Alzheimer\u2019s disease, artificial intelligence (AI), biomarkers, machine learning (ML), metabolomics, miRNA, neuronal injury, proteomics, tau, \u03b2-amyloid", "chunk": "samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments. It is an accepted observation that AD-related pathological changes occur over a long period of time before the first symptoms are observed providing ample opportunity for detection of biological alterations in various biological samples that can aid in early diagnosis and modify treatment outcomes.", "source": "PubMed"}, {"chunk_id": "31152974_0", "pmid": "31152974", "title": "Optimization of solid-phase extraction (SPE) in the preparation of [<sup>18</sup>F]D3FSP: A new PET imaging agent for mapping A\u03b2 plaques.", "authors": "Yao X, Zha Z, Zhao R et al.", "year": "2019", "journal": "Nuclear medicine and biology", "keywords": "Alzheimer's disease, Brain imaging, Deuterium, Radiosynthesis, Solid-phase extraction", "chunk": "Alzheimer's disease is a common neurodegenerative disease that is characterized by the presence of A\u03b2 plaques in the brain. The FDA has approved the use of Amyvid (florbetapir f18, AV-45) as a PET imaging agent for detecting A\u03b2 plaques in the living human brain. In an attempt to reduce N-demethylation in vivo by taking advantage of more stable C-D bonds, an analog of AV-45, [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7), was synthesized to improve image contrast for detecting and monitoring the A\u03b2 plaques. A convenient and improved preparation of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) is needed for widespread clinical application. We report herein the optimization of the radiosynthesis and solid-phase extraction (SPE) procedure. Radiosyntheses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) under different fluorination conditions were evaluated, and the intermediate, containing an N-Boc protecting group, was deprotected using different acids. One of the major objectives was to simplify the final purification step via SPE to avoid the commonly employed HPLC purification", "source": "PubMed"}, {"chunk_id": "31152974_1", "pmid": "31152974", "title": "Optimization of solid-phase extraction (SPE) in the preparation of [<sup>18</sup>F]D3FSP: A new PET imaging agent for mapping A\u03b2 plaques.", "authors": "Yao X, Zha Z, Zhao R et al.", "year": "2019", "journal": "Nuclear medicine and biology", "keywords": "Alzheimer's disease, Brain imaging, Deuterium, Radiosynthesis, Solid-phase extraction", "chunk": "an N-Boc protecting group, was deprotected using different acids. One of the major objectives was to simplify the final purification step via SPE to avoid the commonly employed HPLC purification and maximize the radiochemical yields of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) while simultaneously removing several chemical impurities (pseudocarriers). Washing various solid-phase cartridges with different combinations of ethanol/water and acetonitrile/water was explored to optimize the purification step. To evaluate the potential interference in A\u03b2 plaques imaging from the presence of pseudocarriers, each chemical was identified and quantified by LC/MS and HPLC. An in vitro binding assay was employed to evaluate the binding affinities of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) and the pseudocarriers to A\u03b2 plaques using postmortem AD brain tissue. Using the optimized radiosynthesis method and SPE purification, the final dose of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) was obtained in 50 min with a very low content of pseudocarriers (21.7 \u00b1 5.5 \u03bcg). The radiochemical yield was 44.4 \u00b1 5.7%", "source": "PubMed"}, {"chunk_id": "31152974_2", "pmid": "31152974", "title": "Optimization of solid-phase extraction (SPE) in the preparation of [<sup>18</sup>F]D3FSP: A new PET imaging agent for mapping A\u03b2 plaques.", "authors": "Yao X, Zha Z, Zhao R et al.", "year": "2019", "journal": "Nuclear medicine and biology", "keywords": "Alzheimer's disease, Brain imaging, Deuterium, Radiosynthesis, Solid-phase extraction", "chunk": "purification, the final dose of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) was obtained in 50 min with a very low content of pseudocarriers (21.7 \u00b1 5.5 \u03bcg). The radiochemical yield was 44.4 \u00b1 5.7% (decay corrected), and the radiochemical purity was >95%. SPE-purified doses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) displayed excellent binding affinity and specificity for A\u03b2 plaques as measured in an in vitro binding assay using AD brain homogenates, and the OH-pseudocarrier, 8 (K<sub>i</sub> = 19.5 \u00b1 0.5 nM), and the Cl-pseudocarrier, 10 (K<sub>i</sub> = 18.6 \u00b1 3.9 nM), showed lower binding affinities for A\u03b2 plaques than those of AV-45 (K<sub>i</sub> = 8.6 \u00b1 0.5 nM) and D3FSP, 7 (K<sub>i</sub> = 9.8 \u00b1 0.5 nM). An optimized radiosynthesis and fast SPE purification method suitable for the preparation of clinical doses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) was accomplished. The results of quality control tests and binding studies suggested that the SPE-purified doses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) are appropriate for", "source": "PubMed"}, {"chunk_id": "31152974_3", "pmid": "31152974", "title": "Optimization of solid-phase extraction (SPE) in the preparation of [<sup>18</sup>F]D3FSP: A new PET imaging agent for mapping A\u03b2 plaques.", "authors": "Yao X, Zha Z, Zhao R et al.", "year": "2019", "journal": "Nuclear medicine and biology", "keywords": "Alzheimer's disease, Brain imaging, Deuterium, Radiosynthesis, Solid-phase extraction", "chunk": "the preparation of clinical doses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) was accomplished. The results of quality control tests and binding studies suggested that the SPE-purified doses of [<sup>18</sup>F]D3FSP ([<sup>18</sup>F]7) are appropriate for imaging A\u03b2 plaques in the human brain.", "source": "PubMed"}, {"chunk_id": "41691976_0", "pmid": "41691976", "title": "Association between the triglyceride-glucose frailty index and Parkinson's disease in middle-aged and older adults: a comparative cross-national analysis of NHANES and CHARLS.", "authors": "Ou C, Chen B, Yu H et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "CHARLS, Frailty index, NHANES, Parkinson's disease, Triglyceride-glucose index", "chunk": "Parkinson's disease (PD) is a growing global health burden. Metabolic dysfunction and frailty have been implicated in PD risk, but integrated biomarkers remain limited. The triglyceride-glucose frailty index (TyGFI), combining metabolic and frailty measures, may provide a novel indicator for PD risk. We used nationally representative data from NHANES (2011-2018) and CHARLS (2011-2020), including adults aged \u226545 years (NHANES: n = 5544; CHARLS: n = 7666). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PD by TyGFI (continuous and quartiles), adjusting for demographic, metabolic, and lifestyle factors. Restricted cubic spline (RCS) and subgroup analyses assessed dose-response and effect modification. Higher TyGFI was significantly associated with increased PD risk in both populations. In fully adjusted models, each unit increase in TyGFI corresponded to 88% higher PD odds in NHANES (OR = 1.88, 95% CI: 1.49-2.38) and 114% higher odds in CHARLS (OR = 2.14, 95% CI: 1.43-3.16).", "source": "PubMed"}, {"chunk_id": "41691976_1", "pmid": "41691976", "title": "Association between the triglyceride-glucose frailty index and Parkinson's disease in middle-aged and older adults: a comparative cross-national analysis of NHANES and CHARLS.", "authors": "Ou C, Chen B, Yu H et al.", "year": "2026", "journal": "Parkinsonism & related disorders", "keywords": "CHARLS, Frailty index, NHANES, Parkinson's disease, Triglyceride-glucose index", "chunk": "unit increase in TyGFI corresponded to 88% higher PD odds in NHANES (OR = 1.88, 95% CI: 1.49-2.38) and 114% higher odds in CHARLS (OR = 2.14, 95% CI: 1.43-3.16). Participants in the highest TyGFI quartile had 7.91-fold and 3.62-fold increased PD risk in NHANES and CHARLS, respectively (p-trend<0.01). RCS analyses suggested a linear positive association, and no significant interactions were observed across subgroups. TyGFI is a simple, practical biomarker strongly linked to PD risk in U.S. and Chinese older adults. Integrating metabolic and frailty assessment may aid early PD risk stratification and prevention.", "source": "PubMed"}, {"chunk_id": "41009668_0", "pmid": "41009668", "title": "Exploring Molecular and Clinical Dimensions of Glaucoma as a Neurodegenerative Disease.", "authors": "Dur\u00e1n-Cristiano SC, Duque-Chica GL, Torres-Osorio V et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "cognitive function, glaucoma, neurodegeneration, transcriptomic", "chunk": "Glaucoma is traditionally defined as an ocular disease characterized by progressive retinal ganglion cell degeneration, in some cases with elevated intraocular pressure (IOP), and optic nerve damage. However, growing evidence indicates that glaucoma shares critical features with neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. This study aimed to explore the systemic nature of primary open-angle glaucoma (POAG) by integrating visual function, cognitive performance, and transcriptomic profiling. We conducted a multidimensional assessment of POAG patients and age-matched controls, accounting for demographic factors. Structural parameters included retinal nerve fiber layer (RNFL) thickness, measured using optical coherence tomography (OCT), and visual field indices mean deviation (MD) and pattern standard deviation (PSD). Cognitive function was evaluated across multiple domains, encompassing visual memory, executive function, processing speed, and verbal fluency. Additionally, transcriptomic analysis was performed from conjunctival samples to identify differentially expressed genes (DEGs) and enriched pathways. POAG patients exhibited significant RNFL thinning, which correlated", "source": "PubMed"}, {"chunk_id": "41009668_1", "pmid": "41009668", "title": "Exploring Molecular and Clinical Dimensions of Glaucoma as a Neurodegenerative Disease.", "authors": "Dur\u00e1n-Cristiano SC, Duque-Chica GL, Torres-Osorio V et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "cognitive function, glaucoma, neurodegeneration, transcriptomic", "chunk": "processing speed, and verbal fluency. Additionally, transcriptomic analysis was performed from conjunctival samples to identify differentially expressed genes (DEGs) and enriched pathways. POAG patients exhibited significant RNFL thinning, which correlated with both visual field loss and cognitive impairments, particularly in terms of visual memory and executive function. Transcriptomic profiling revealed a distinct gene expression signature in POAG, including upregulation of <i>TTBK1</i> and <i>CCN2</i> (<i>CTGF</i>), genes associated with tau phosphorylation and extracellular matrix remodeling. Functional enrichment analysis indicated the involvement of neurodegenerative pathways, such as glutamate signaling, calcium signaling, and cell adhesion. Our findings support the reclassification of glaucoma as a neurodegenerative disease with both ocular and cognitive manifestations. Furthermore, biomarkers such as <i>TTBK1</i> and <i>CCN2</i> may serve as potential targets for early detection and neuroprotective therapy.", "source": "PubMed"}, {"chunk_id": "41009668_2", "pmid": "41009668", "title": "Exploring Molecular and Clinical Dimensions of Glaucoma as a Neurodegenerative Disease.", "authors": "Dur\u00e1n-Cristiano SC, Duque-Chica GL, Torres-Osorio V et al.", "year": "2025", "journal": "International journal of molecular sciences", "keywords": "cognitive function, glaucoma, neurodegeneration, transcriptomic", "chunk": "for early detection and neuroprotective therapy.", "source": "PubMed"}, {"chunk_id": "40972226_0", "pmid": "40972226", "title": "Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study.", "authors": "Sol O, Mermoud J, Hallikainen M et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Active immunotherapy, Alzheimer's disease, Immunogenicity, Paired helical filament, Tau, Vaccine, phosphoTau", "chunk": "Active immunotherapies targeting C-terminal phosphorylated Tau species have the potential to efficiently reduce Tau spreading. ACI-35.030, a SupraAntigen\u00ae-based liposome, and JACI-35.054, a CRM197 carrier-protein conjugate, share the same immunogenic pTau sequence and were assessed to determine the best formulation for preferential activation of B cells specific to pathological Tau forms. Individuals with early AD were enrolled in this randomised, double-blind, placebo-controlled study (NCT04445831). Participants were randomly assigned to 2 cohorts (ACI-35.030 at 300, 900, 1800 \u03bcg or placebo; and JACI-35.054 at 15, 60 \u03bcg or placebo) and received 4 intramuscular injections over 48 weeks, followed up to week 74. Participants receiving at least one dose of study drug were included in the intention-to-treat analysis. The primary objectives were safety, tolerability and immunogenicity. Among the 57 randomised participants, 41 were assigned to the ACI-35.030 cohort and 16 to the JACI-35.054 cohort. The most frequent adverse events observed consistently in both active", "source": "PubMed"}, {"chunk_id": "40972226_1", "pmid": "40972226", "title": "Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study.", "authors": "Sol O, Mermoud J, Hallikainen M et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Active immunotherapy, Alzheimer's disease, Immunogenicity, Paired helical filament, Tau, Vaccine, phosphoTau", "chunk": "and immunogenicity. Among the 57 randomised participants, 41 were assigned to the ACI-35.030 cohort and 16 to the JACI-35.054 cohort. The most frequent adverse events observed consistently in both active groups were injection site reactions (16.7%-100%) and headaches (16.7%-50%). No relevant MRI findings and no adverse events leading to study discontinuation were reported. ACI-35.030 required only one injection to induce anti-pTau IgG titres in all participants and consistently boosted levels with subsequent immunisations. JACI-35.054 raised a strong but more heterogenous anti-pTau IgG response and required multiple administrations to reach consistent titres in all participants. ACI-35.030 induced a robust polyclonal antibody response binding enriched PHF from AD brain tissue while concurrently sparing the response to non-phosphorylated Tau. A post-hoc statistical analysis revealed statistically significant differences between some randomised actively treated groups and the pooled placebo group on plasma pTau217 and brain-derived Tau changes from baseline. ACI-35.030 and JACI-35.054 were well tolerated.", "source": "PubMed"}, {"chunk_id": "40972226_2", "pmid": "40972226", "title": "Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study.", "authors": "Sol O, Mermoud J, Hallikainen M et al.", "year": "2025", "journal": "EBioMedicine", "keywords": "Active immunotherapy, Alzheimer's disease, Immunogenicity, Paired helical filament, Tau, Vaccine, phosphoTau", "chunk": "revealed statistically significant differences between some randomised actively treated groups and the pooled placebo group on plasma pTau217 and brain-derived Tau changes from baseline. ACI-35.030 and JACI-35.054 were well tolerated. ACI-35.030 induced a more rapid and sustained antibody response selective to p-Tau species with evidence of altering AD-related plasma biomarkers and was selected for testing in the ongoing Phase 2b trial. AC Immune SA and Johnson & Johnson Innovative Medicine.", "source": "PubMed"}, {"chunk_id": "34899265_0", "pmid": "34899265", "title": "Diagnostic Utility of Integrated<sup>11</sup>C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study.", "authors": "Chang Y, Liu J, Wang L et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid, cerebral amyloid angiopathy, cerebral microbleed, positron emission tomography/magnetic resonance imaging", "chunk": "<b>Objective:</b> We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer's disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated <sup>11</sup>C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value. <b>Methods:</b> Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an <sup>11</sup>C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated. <b>Results:</b> Lobar CMBs were detected in all the CAA", "source": "PubMed"}, {"chunk_id": "34899265_1", "pmid": "34899265", "title": "Diagnostic Utility of Integrated<sup>11</sup>C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study.", "authors": "Chang Y, Liu J, Wang L et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid, cerebral amyloid angiopathy, cerebral microbleed, positron emission tomography/magnetic resonance imaging", "chunk": "regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated. <b>Results:</b> Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 \u00b1 0.10 vs. 1.42 \u00b1 0.16 and 1.17 \u00b1 0.08; <i>p</i> < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 \u00b1 0.06 vs. 1.21 \u00b1 0.06; <i>p</i> < 0.0001) and significantly lower than in AD patients (1.66 \u00b1 0.06 vs. 1.86 \u00b1 0.17; <i>p</i> < 0.0001). In contrast, the occipital/global PIB", "source": "PubMed"}, {"chunk_id": "34899265_2", "pmid": "34899265", "title": "Diagnostic Utility of Integrated<sup>11</sup>C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study.", "authors": "Chang Y, Liu J, Wang L et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid, cerebral amyloid angiopathy, cerebral microbleed, positron emission tomography/magnetic resonance imaging", "chunk": "0.06 vs. 1.21 \u00b1 0.06; <i>p</i> < 0.0001) and significantly lower than in AD patients (1.66 \u00b1 0.06 vs. 1.86 \u00b1 0.17; <i>p</i> < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 \u00b1 0.02) relative to AD patients (1.05 \u00b1 0.02 vs. 0.99 \u00b1 0.04; <i>p</i> < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR. <b>Conclusion:</b> Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.", "source": "PubMed"}, {"chunk_id": "34899265_3", "pmid": "34899265", "title": "Diagnostic Utility of Integrated<sup>11</sup>C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study.", "authors": "Chang Y, Liu J, Wang L et al.", "year": "2021", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, amyloid, cerebral amyloid angiopathy, cerebral microbleed, positron emission tomography/magnetic resonance imaging", "chunk": "potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.", "source": "PubMed"}, {"chunk_id": "33610084_0", "pmid": "33610084", "title": "An anatomical knowledge-based MRI deep learning pipeline for white matter hyperintensity quantification associated with cognitive impairment.", "authors": "Liang L, Zhou P, Lu W et al.", "year": "2021", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "Anatomical knowledge, Cognitive impairment, Deep learning, Segmentation, White matter hyperintensities", "chunk": "Recent studies have confirmed that white matter hyperintensities (WMHs) accumulated in strategic brain regions can predict cognitive impairments associated with Alzheimer's disease (AD). The knowledge of white matter anatomy facilitates lesion-symptom mapping associated with cognition, and provides important spatial information for lesion segmentation algorithms. However, deep learning-based methods in the white matter hyperintensity (WMH) segmentation realm do not take full advantage of anatomical knowledge in decision-making and lesion localization processes. In this paper, we proposed an anatomical knowledge-based MRI deep learning pipeline (<sup>A</sup>U-Net), handcrafted anatomical-based spatial features developed from brain atlas were integrated with a well-designed U-Net configuration to simultaneously segment and locate WMHs. Manually annotated data from WMH segmentation challenge were used for the evaluation. We then applied this pipeline to investigate the association between WMH burden and cognition within another publicly available database. The results showed that <sup>A</sup>U-Net significantly improved segmentation performance compared with methods that did not", "source": "PubMed"}, {"chunk_id": "33610084_1", "pmid": "33610084", "title": "An anatomical knowledge-based MRI deep learning pipeline for white matter hyperintensity quantification associated with cognitive impairment.", "authors": "Liang L, Zhou P, Lu W et al.", "year": "2021", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "Anatomical knowledge, Cognitive impairment, Deep learning, Segmentation, White matter hyperintensities", "chunk": "pipeline to investigate the association between WMH burden and cognition within another publicly available database. The results showed that <sup>A</sup>U-Net significantly improved segmentation performance compared with methods that did not incorporate anatomical knowledge (p < 0.05), and achieved a 14-17% increase based on area under the curve (AUC) in the cohort with mild WMH burden. Different configurations for incorporating anatomical knowledge were evaluated, the proposed stage-wise <sup>A</sup>U-Net-two-step method achieved the best performance (Dice: 0.86, modified Hausdorff distance: 3.06 mm), which was comparable with the state-of-the-art method (Dice: 0.87, modified Hausdorff distance: 3.62 mm). We observed different WMH accumulation patterns associated with normal aging and cognitive impairments. Furthermore, the characteristics of individual WMH lesions located in strategic regions (frontal and parietal subcortical white matter, as well as corpus callosum) were significantly correlated with cognition after adjusting for total lesion volumes. Our findings suggest that <sup>A</sup>U-Net is a reliable method to segment", "source": "PubMed"}, {"chunk_id": "33610084_2", "pmid": "33610084", "title": "An anatomical knowledge-based MRI deep learning pipeline for white matter hyperintensity quantification associated with cognitive impairment.", "authors": "Liang L, Zhou P, Lu W et al.", "year": "2021", "journal": "Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society", "keywords": "Anatomical knowledge, Cognitive impairment, Deep learning, Segmentation, White matter hyperintensities", "chunk": "subcortical white matter, as well as corpus callosum) were significantly correlated with cognition after adjusting for total lesion volumes. Our findings suggest that <sup>A</sup>U-Net is a reliable method to segment and quantify brain WMHs in elderly cohorts, and is valuable in individual cognition evaluation.", "source": "PubMed"}, {"chunk_id": "41337161_0", "pmid": "41337161", "title": "Sampling Rate Guidelines for Eye-Tracking in Neurological Disorders: A Task-Specific Multimetric Analysis.", "authors": "Wang Y, Butala AA, Thebaud T et al.", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "Variations in eye-tracking sampling rates across devices pose challenges for research characterizing Neurodegenerative Disorders (ND) where precise measurement of eye movements is essential for detection of disease-specific features. This study proposes three metrics-TOST Test Equivalence (TTE), Mean Absolute Error Percentage (MAE%), and Kullback-Leibler Divergence (KLD)-to systematically evaluate how downsampling impacts data quality and feature integrity. Applied to three common tasks (prosaccade, text reading, picture description), results revealed task-specific sampling rate requirements: \u2a7e400Hz preserved saccadic dynamics in prosaccade, while cognitively complex reading and picture description tasks demanded \u2a7e600Hz to maintain fidelity. Downsampling degraded key features that are salient to differentiating neurological disorders. \u2a7e200Hz is required to maintain the discriminative power of key saccade and fixation features. We propose task- and feature-specific recommendations for sampling selection to balance analytical rigor with practical constraints. These findings provide actionable guidelines for standardizing eye-tracking protocols in behavioral research, enhancing reproducibility and robust cross-study comparisons and", "source": "PubMed"}, {"chunk_id": "41337161_1", "pmid": "41337161", "title": "Sampling Rate Guidelines for Eye-Tracking in Neurological Disorders: A Task-Specific Multimetric Analysis.", "authors": "Wang Y, Butala AA, Thebaud T et al.", "year": "2025", "journal": "Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference", "keywords": "None", "chunk": "recommendations for sampling selection to balance analytical rigor with practical constraints. These findings provide actionable guidelines for standardizing eye-tracking protocols in behavioral research, enhancing reproducibility and robust cross-study comparisons and biomarker validation.Clinical relevanceThis study provides guidelines for selecting eye-tracking sampling rates to ensure reliable detection of disease-specific eye movement features in Alzheimer's, Parkinson's, and related disorders.", "source": "PubMed"}, {"chunk_id": "36744339_0", "pmid": "36744339", "title": "Impaired Early Insulin Response to Glucose Load Predicts Episodic Memory Decline: A 10-Year Population-Based Cohort Follow-Up of 45-74-Year-Old Men and Women.", "authors": "Toppala S, Ekblad LL, Viitanen M et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Cognitive decline, early insulin response, episodic memory, insulin resistance, insulin secretion, oral glucose tolerance test", "chunk": "Diabetes increases the risk for cognitive decline, but the mechanisms behind this association remain unknown. Impaired early insulin secretion in elderly men and insulin resistance, both of which are pathophysiological features of type 2 diabetes, have previously been linked to Alzheimer's disease. To examine if the early insulin response to oral glucose load predicts cognitive performance after 10 years in men and women aged 45-74 years. This study was based on a subpopulation of the Health 2000 Survey, a Finnish nationwide, population-based health examination study, and its follow-up, the Health 2011 Study. In total, 961 45-74-year-old individuals (mean age at baseline 55.6 years, 55.8% women) were examined. An oral glucose tolerance test was performed in 2001-2002, and early insulin response was defined as the ratio of the 30-min increment in insulin concentration to that of glucose concentration. Cognitive function was evaluated at baseline and follow-up with categorical verbal fluency, word-list", "source": "PubMed"}, {"chunk_id": "36744339_1", "pmid": "36744339", "title": "Impaired Early Insulin Response to Glucose Load Predicts Episodic Memory Decline: A 10-Year Population-Based Cohort Follow-Up of 45-74-Year-Old Men and Women.", "authors": "Toppala S, Ekblad LL, Viitanen M et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Cognitive decline, early insulin response, episodic memory, insulin resistance, insulin secretion, oral glucose tolerance test", "chunk": "was defined as the ratio of the 30-min increment in insulin concentration to that of glucose concentration. Cognitive function was evaluated at baseline and follow-up with categorical verbal fluency, word-list learning, and word-list delayed recall. Statistical analyses were performed using multivariable linear models adjusted for age, sex, education, APOE&z.epsi;4 genotype, vascular risk factors including diabetes, and depressive symptoms. A lower early insulin response to glucose load predicted lower performance (\u03b2: 0.21, p = 0.03) and greater decline (\u03b2: 0.19, p = 0.03) in the word-list delayed recall test. Baseline early insulin response did not predict verbal fluency or word-list learning (all p-values\u22650.13). Our results suggest that decreased early insulin secretion predicts episodic memory decline in middle-aged to elderly men and women.", "source": "PubMed"}, {"chunk_id": "36744339_2", "pmid": "36744339", "title": "Impaired Early Insulin Response to Glucose Load Predicts Episodic Memory Decline: A 10-Year Population-Based Cohort Follow-Up of 45-74-Year-Old Men and Women.", "authors": "Toppala S, Ekblad LL, Viitanen M et al.", "year": "2023", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Cognitive decline, early insulin response, episodic memory, insulin resistance, insulin secretion, oral glucose tolerance test", "chunk": "women.", "source": "PubMed"}, {"chunk_id": "41266692_0", "pmid": "41266692", "title": "A mechanistic insight of neuro-inflammation signaling pathways and implication in neurodegenerative disorders.", "authors": "Shafi A, Akmal M, Sethi A et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "JAK/STAT pathway, MAPK pathway, Microglia activation, NF-\u03baB signaling, NLRP3 inflammasome, Neurodegenerative diseases, Neuroinflammation, Pro-inflammatory cytokines", "chunk": "Neuroinflammation is a multifaceted and carefully regulated process within the central nervous system (CNS) that serves a dual function in both protecting neurons and contributing to neurodegenerative processes. This process is mainly driven by activated microglia, astrocytes, and immune cells that infiltrate in response to neuronal damage, infections, or toxic exposures. This review emphasizes the key molecular pathways involved in neuroinflammatory reactions, such as the JAK/STAT, NF-\u03baB, NLRP3 inflammasome, and MAPK signaling pathways. Each of these pathways plays a role in the generation and release of pro-inflammatory substances that maintain and increase inflammation in the CNS. Furthermore, the review examines the significance of crucial pro-inflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-\u03b1) as well as the chemokines CCL2 and CXCL10, which coordinate the recruitment of immune cells and contribute to neuronal injury. Gaining an understanding of the interactions among these signaling pathways and mediators sheds light on", "source": "PubMed"}, {"chunk_id": "41266692_1", "pmid": "41266692", "title": "A mechanistic insight of neuro-inflammation signaling pathways and implication in neurodegenerative disorders.", "authors": "Shafi A, Akmal M, Sethi A et al.", "year": "2026", "journal": "Inflammopharmacology", "keywords": "JAK/STAT pathway, MAPK pathway, Microglia activation, NF-\u03baB signaling, NLRP3 inflammasome, Neurodegenerative diseases, Neuroinflammation, Pro-inflammatory cytokines", "chunk": "CCL2 and CXCL10, which coordinate the recruitment of immune cells and contribute to neuronal injury. Gaining an understanding of the interactions among these signaling pathways and mediators sheds light on the molecular mechanisms connected to various neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Targeting these inflammatory signaling networks may provide valuable therapeutic approaches to manage neuroinflammation and avert its long-lasting neurotoxic effects.", "source": "PubMed"}, {"chunk_id": "40261388_0", "pmid": "40261388", "title": "Alpha-1-acid glycoprotein as a potential serum biomarker for cerebral amyloid angiopathy.", "authors": "Nishigaki A, Ishikawa H, Nishiguchi Y et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarkers, cerebral amyloid angiopathy, cerebral small vessel diseases, hemopexin, microbleeds, \u03b11-acid glycoproteins", "chunk": "BackgroundCerebral amyloid angiopathy (CAA) is a form of cerebral small vessel disease (SVD) associated with Alzheimer's disease, intracerebral hemorrhage, and cognitive decline. Despite its clinical significance, no reliable serum biomarker exists for early diagnosis or monitoring of disease progression.ObjectiveThis study hypothesizes that \u03b11-acid glycoprotein (\u03b11-AGP) and other serum biomarkers can aid CAA diagnosis and assessment using gel-based mass spectrometry. A comparative analysis was performed to investigate associations between serum biomarkers and radiological scores.MethodsSerum proteins from individuals with probable or possible CAA (n = 10), classified using the modified Boston criteria, and age-matched controls (n = 10) were analyzed via two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS). Candidate proteins were validated using enzyme-linked immunosorbent assay (ELISA). Outcome measures included biomarker diagnostic accuracy, assessed by receiver operating characteristic (ROC) curve analysis, and correlations between \u03b11-AGP levels and CAA-SVD scores.ResultsFour proteins-hemopexin, complement C3, complement C9, and", "source": "PubMed"}, {"chunk_id": "40261388_1", "pmid": "40261388", "title": "Alpha-1-acid glycoprotein as a potential serum biomarker for cerebral amyloid angiopathy.", "authors": "Nishigaki A, Ishikawa H, Nishiguchi Y et al.", "year": "2025", "journal": "Journal of Alzheimer's disease : JAD", "keywords": "Alzheimer's disease, biomarkers, cerebral amyloid angiopathy, cerebral small vessel diseases, hemopexin, microbleeds, \u03b11-acid glycoproteins", "chunk": "assay (ELISA). Outcome measures included biomarker diagnostic accuracy, assessed by receiver operating characteristic (ROC) curve analysis, and correlations between \u03b11-AGP levels and CAA-SVD scores.ResultsFour proteins-hemopexin, complement C3, complement C9, and \u03b11-AGP-were significantly elevated, while apolipoprotein A-1 was reduced in the CAA group. ELISA confirmed higher \u03b11-AGP levels in individuals with CAA (p < 0.0001). ROC analysis demonstrated that \u03b11-AGP could indicate the presence of CAA with a sensitivity and specificity of 1.00 (95%CI: 1.000, 1.000). Additionally, \u03b11-AGP levels correlated with the CAA-SVD score (R\u00b2 = 0.783).Conclusions\u03b11-AGP may serve as a novel serum biomarker for CAA. Larger cohorts and external validation are required to substantiate these findings and determine their clinical relevance.", "source": "PubMed"}, {"chunk_id": "39690275_0", "pmid": "39690275", "title": "Subcortical tau deposition and plasma glial fibrillary acidic protein as predictors of cognitive decline in mild cognitive impairment and Alzheimer's disease.", "authors": "Chang Y, Liu J, Xu X et al.", "year": "2025", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cognitive decline, Glial fibrillary acidic protein, Mild cognitive impairment, Positron emission tomography, Subcortical tau", "chunk": "This study aimed to investigate the correlation between subcortical tau-positron emission tomography (Tau-PET) and plasma glial fibrillary acidic protein (GFAP) levels and cognitive function in participants with cognitively unimpaired (CU), mild cognitive impairment (MCI) and Alzheimer's disease (AD) conditions. 105 participants with amyloid (A\u03b2) PET and Tau-PET scans were enrolled. Region of interest (ROI) level and voxel-wise comparisons were performed between those three groups. Correlations between standardized uptake value ratio (SUVR) and cognitive performance were analyzed. The diagnostic performance of Tau-PET, A\u03b2-PET, and plasma GFAP, both individually and combined, was evaluated by calculating the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. Plasma GFAP levels in the AD and MCI groups were higher than those in the CU group. The AD and MCI groups showed higher Tau-PET load at the amygdala, accumbens, putamen, pallidum, hippocampus, para-hippocampus and olfactory tubercle than the CU group (p < 0.05). In", "source": "PubMed"}, {"chunk_id": "39690275_1", "pmid": "39690275", "title": "Subcortical tau deposition and plasma glial fibrillary acidic protein as predictors of cognitive decline in mild cognitive impairment and Alzheimer's disease.", "authors": "Chang Y, Liu J, Xu X et al.", "year": "2025", "journal": "European journal of nuclear medicine and molecular imaging", "keywords": "Alzheimer\u2019s disease, Biomarkers, Cognitive decline, Glial fibrillary acidic protein, Mild cognitive impairment, Positron emission tomography, Subcortical tau", "chunk": "CU group. The AD and MCI groups showed higher Tau-PET load at the amygdala, accumbens, putamen, pallidum, hippocampus, para-hippocampus and olfactory tubercle than the CU group (p < 0.05). In the MCI group, the mean tau SUVR in the combined subcortical ROI negatively correlated with cognitive scores (r = -0.38, p = 0.02). The combination of Tau-PET, A\u03b2-PET and plasma GFAP provided optimal diagnostic accuracy for classifying AD from MCI, with an AUC of 0.82, a sensitivity of 0.69 and a specificity of 0.81. Subcortical tau deposition and increased plasma GFAP levels are associated with cognitive impairment in MCI patients.", "source": "PubMed"}, {"chunk_id": "41085221_0", "pmid": "41085221", "title": "Impact of kidney function on biomarkers of neurodegeneration, white matter hyperintensities, and cognition in older adults.", "authors": "Dhana A, DeCarli CS, Dhana K et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "MRI, biomarkers of neurodegeneration, cognition, dementia, epidemiology, kidney function, white matter hyperintensities", "chunk": "We evaluated the association between kidney function, neurodegenerative biomarkers (i.e., neurofilament light chain [NfL], total tau [t-tau], and glial fibrillary acidic protein [GFAP]), white matter hyperintensities, and global cognition. The study consisted of 1207 participants living on the south side of Chicago, Illinois, enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. Kidney function was assessed using the estimated glomerular filtration rate (eGFRcr), calculated according to the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) based on age, sex, and serum creatinine levels. In a multivariable-adjusted model, lower levels of eGFRcr were associated with higher levels of biomarkers of neurodegeneration. Specifically, for a 1-SD decrease of eGFRcr, there was a 22% increase in NfL levels in serum. eGFRcr levels were not associated with white matter hyperintensities or global cognition. Kidney function may be considered when interpreting NfL, GFAP, and t-tau levels for risk stratification in research and clinical", "source": "PubMed"}, {"chunk_id": "41085221_1", "pmid": "41085221", "title": "Impact of kidney function on biomarkers of neurodegeneration, white matter hyperintensities, and cognition in older adults.", "authors": "Dhana A, DeCarli CS, Dhana K et al.", "year": "2025", "journal": "Alzheimer's & dementia : the journal of the Alzheimer's Association", "keywords": "MRI, biomarkers of neurodegeneration, cognition, dementia, epidemiology, kidney function, white matter hyperintensities", "chunk": "levels were not associated with white matter hyperintensities or global cognition. Kidney function may be considered when interpreting NfL, GFAP, and t-tau levels for risk stratification in research and clinical applications. Kidney function is associated with higher neurfilament light chain (NfL), total tau (t-tau), and glial fibrillary acidic protein (GFAP) serum concentrations, while there was no association with white matter hyperintensities or global cognition. Individuals with severely impaired kidney function had 146.7% higher serum concentrations of NfL when compared to people with normal kidney function. This study suggests assessing kidney function in older adults when interpreting NfL, GFAP, and t-tau levels in the serum for risk stratification.", "source": "PubMed"}, {"chunk_id": "39849121_0", "pmid": "39849121", "title": "Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.", "authors": "Bamford AR, Parkin GM, Corey-Bloom J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Biomarker, Neurodegeneration, Neurodegenerative, Neurofilament, Saliva, Tau", "chunk": "Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays. In addition, salivary levels of NfL, t-tau, and GFAP were quantified from a larger cohort (n = 95). We found both positive and negative correlations in the levels of these biomarkers among different biofluids. Most notably, in contrast to the significant positive correlations observed between CSF and plasma levels for NfL and GFAP, we detected significant negative correlations between the CSF and saliva levels of", "source": "PubMed"}, {"chunk_id": "39849121_1", "pmid": "39849121", "title": "Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.", "authors": "Bamford AR, Parkin GM, Corey-Bloom J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Biomarker, Neurodegeneration, Neurodegenerative, Neurofilament, Saliva, Tau", "chunk": "notably, in contrast to the significant positive correlations observed between CSF and plasma levels for NfL and GFAP, we detected significant negative correlations between the CSF and saliva levels of NfL and GFAP. With regard to clinical measures, both plasma and CSF levels of NfL were significantly positively correlated with Total Motor Score and chorea, whereas saliva levels of NfL showed significant correlations in the opposite direction. Additional correlations between salivary biomarkers with clinical data, adjusting for age, sex and CAG repeat length, confirmed that salivary NfL was significantly negatively associated with chorea scores in manifest HD, but not premanifest (PM), individuals. In contrast, salivary t-tau was positively associated with measures of cognition in PM participants. These findings suggest that salivary levels of NfL and t-tau proteins may exemplify non-invasive biomarkers for disease symptoms at different stages of illness. Further, these findings highlight the notion that different forms of disease", "source": "PubMed"}, {"chunk_id": "39849121_2", "pmid": "39849121", "title": "Comparisons of neurodegenerative disease biomarkers across different biological fluids from patients with Huntington's disease.", "authors": "Bamford AR, Parkin GM, Corey-Bloom J et al.", "year": "2025", "journal": "Journal of neurology", "keywords": "Biomarker, Neurodegeneration, Neurodegenerative, Neurofilament, Saliva, Tau", "chunk": "salivary levels of NfL and t-tau proteins may exemplify non-invasive biomarkers for disease symptoms at different stages of illness. Further, these findings highlight the notion that different forms of disease proteins exist in different biological fluids.", "source": "PubMed"}, {"chunk_id": "26003667_0", "pmid": "26003667", "title": "High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents.", "authors": "Petrov D, Pedr\u00f3s I, Artiach G et al.", "year": "2015", "journal": "Biochimica et biophysica acta", "keywords": "APPSwe/PS1dE9, Alzheimer disease, Hippocampus, Insulin receptor, Mitochondria, TAU", "chunk": "Global obesity is a pandemic status, estimated to affect over 2 billion people, that has resulted in an enormous strain on healthcare systems worldwide. The situation is compounded by the fact that apart from the direct costs associated with overweight pathology, obesity presents itself with a number of comorbidities, including an increased risk for the development of neurodegenerative disorders. Alzheimer disease (AD), the main cause of senile dementia, is no exception. Spectacular failure of the pharmaceutical industry to come up with effective AD treatment strategies is forcing the broader scientific community to rethink the underlying molecular mechanisms leading to cognitive decline. To this end, the emphasis is once again placed on the experimental animal models of the disease. In the current study, we have focused on the effects of a high-fat diet (HFD) on hippocampal-dependent memory in C57/Bl6 Wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice, a well-established mouse model of familial", "source": "PubMed"}, {"chunk_id": "26003667_1", "pmid": "26003667", "title": "High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents.", "authors": "Petrov D, Pedr\u00f3s I, Artiach G et al.", "year": "2015", "journal": "Biochimica et biophysica acta", "keywords": "APPSwe/PS1dE9, Alzheimer disease, Hippocampus, Insulin receptor, Mitochondria, TAU", "chunk": "current study, we have focused on the effects of a high-fat diet (HFD) on hippocampal-dependent memory in C57/Bl6 Wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice, a well-established mouse model of familial AD. Our results indicate that the continuous HFD administration starting at the time of weaning is sufficient to produce \u03b2-amyloid-independent, hippocampal-dependent memory deficits measured by a 2-object novel-object recognition test (NOR) in mice as early as 6months of age. Furthermore, the resulting metabolic syndrome appears to have direct effects on brain insulin regulation and mitochondrial function. We have observed pathological changes related to both the proximal and distal insulin signaling pathway in the brains of HFD-fed WT and APP/PS1 mice. These changes are accompanied by a significantly reduced OXPHOS metabolism, suggesting that mitochondria play an important role in hippocampus-dependent memory formation and retention in both the HFD-treated and AD-like rodents at a relatively young age.", "source": "PubMed"}, {"chunk_id": "26003667_2", "pmid": "26003667", "title": "High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents.", "authors": "Petrov D, Pedr\u00f3s I, Artiach G et al.", "year": "2015", "journal": "Biochimica et biophysica acta", "keywords": "APPSwe/PS1dE9, Alzheimer disease, Hippocampus, Insulin receptor, Mitochondria, TAU", "chunk": "suggesting that mitochondria play an important role in hippocampus-dependent memory formation and retention in both the HFD-treated and AD-like rodents at a relatively young age.", "source": "PubMed"}, {"chunk_id": "32093643_0", "pmid": "32093643", "title": "GenEpi: gene-based epistasis discovery using machine learning.", "authors": "Chang YC, Wu JT, Hong MY et al.", "year": "2020", "journal": "BMC bioinformatics", "keywords": "Epistasis, GWAS, Machine learning", "chunk": "Genome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD). In this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to", "source": "PubMed"}, {"chunk_id": "32093643_1", "pmid": "32093643", "title": "GenEpi: gene-based epistasis discovery using machine learning.", "authors": "Chang YC, Wu JT, Hong MY et al.", "year": "2020", "journal": "BMC bioinformatics", "keywords": "Epistasis, GWAS, Machine learning", "chunk": "stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power. The results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future.", "source": "PubMed"}, {"chunk_id": "41064116_0", "pmid": "41064116", "title": "Quantitative analysis of serum metabolites in a rat model of Alzheimer's disease.", "authors": "Smolentsev AA, Telegina DV, Kolosova NG et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, OXYS rats, aging, metabolomic profile, serum", "chunk": "OXYS rats are a unique animal model of sporadic Alzheimer's disease (AD) that demonstrates all the key signs of AD in humans. Studying metabolic processes in OXYS rats in comparison with control Wistar rats can contribute to understanding the mechanisms of AD development, as well as to establishing metabolomic biomarkers of AD. The main goals of the work are to establish differences in the metabolomic profiles of OXYS and Wistar rat serum at different stages of AD-like pathology (presymptomatic, early and late). NMR-based metabolomics was applied for metabolomic profiling of blood serum of OXYS and Wistar rats at the age of 20 days (presymptomatic period), 4 months (first manifestation of signs of AD) and 16 months (active development of signs). We determined the concentrations of 55 metabolites present in rat serum. We found that age-related changes in both rat strains reflect animal maturation (20 days to 4 months) and aging", "source": "PubMed"}, {"chunk_id": "41064116_1", "pmid": "41064116", "title": "Quantitative analysis of serum metabolites in a rat model of Alzheimer's disease.", "authors": "Smolentsev AA, Telegina DV, Kolosova NG et al.", "year": "2025", "journal": "Frontiers in aging neuroscience", "keywords": "Alzheimer\u2019s disease, OXYS rats, aging, metabolomic profile, serum", "chunk": "We determined the concentrations of 55 metabolites present in rat serum. We found that age-related changes in both rat strains reflect animal maturation (20 days to 4 months) and aging (4 months to 16 months), and correspond mainly to amino acid metabolism, purine metabolism, and energy pathways. Potential AD blood biomarkers include lysine, BCAAs, alanine, ornithine, creatine, glutamine and pyruvate. The most significant differences between OXYS and Wistar blood metabolomes were found for 20-day-old animals, which corresponds to the preclinical period of AD development in humans. Metabolomic changes observed in the brain and blood are different and often opposite in sign. Blood serum is potentially promising fluid for AD diagnosis.", "source": "PubMed"}, {"chunk_id": "41644028_0", "pmid": "41644028", "title": "Identifying Subclinical Transthyretin Cardiac Amyloidosis in V142I TTR Carriers: Design, Rationale, and Methods of the VISTA (Variant Imaging of Subclinical Transthyretin Amyloidosis) Study.", "authors": "Jefferson A, Kozlitina J, Zaha VG et al.", "year": "2026", "journal": "The American journal of cardiology", "keywords": "amyloidosis, screening, transthyretin", "chunk": "Approximately 1.5 million of the 44 million individuals of African descent in the United States are carriers of the p.V142I variant in transthyretin (TTR). This is the most common cause of variant amyloid cardiomyopathy (ATTR-CM) worldwide which leads to heart failure (HF) and premature death. Despite promising new treatments, ATTR-CM is often diagnosed at an advanced stage and conventional diagnostic tools lack specificity to detect early disease. Thus, the overall objectives of the Variant Imaging of Subclinical Transthyretin Amyloidosis (VISTA) study are to determine imaging and biomarker evidence of subclinical ATTR-CM that indicates amyloid progression in p.V142I TTR carriers. In a multisite nested case-control study, contrast-enhanced cardiac resonance imaging (CMRI) and amyloid-specific blood biomarker measurements will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of p.V142I TTR carriers without HF with age-, sex-, and race-matched non-carrier controls. A sub-sample of participants will undergo novel exercise", "source": "PubMed"}, {"chunk_id": "41644028_1", "pmid": "41644028", "title": "Identifying Subclinical Transthyretin Cardiac Amyloidosis in V142I TTR Carriers: Design, Rationale, and Methods of the VISTA (Variant Imaging of Subclinical Transthyretin Amyloidosis) Study.", "authors": "Jefferson A, Kozlitina J, Zaha VG et al.", "year": "2026", "journal": "The American journal of cardiology", "keywords": "amyloidosis, screening, transthyretin", "chunk": "metrics associated with cardiac amyloid infiltration between a cohort of p.V142I TTR carriers without HF with age-, sex-, and race-matched non-carrier controls. A sub-sample of participants will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Completion of VISTA will establish evidence of subclinical variant ATTR-CM in p.V142I TTR carriers, will change how we think about ATTR-CM, and will justify future research in screening and treatment strategies for disease prevention.", "source": "PubMed"}, {"chunk_id": "23687103_0", "pmid": "23687103", "title": "Low cerebral blood flow is associated with lower memory function in metabolic syndrome.", "authors": "Birdsill AC, Carlsson CM, Willette AA et al.", "year": "2013", "journal": "Obesity (Silver Spring, Md.)", "keywords": "None", "chunk": "Metabolic syndrome (MetS)--a cluster of cardiovascular risk factors--is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed. Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface,", "source": "PubMed"}, {"chunk_id": "23687103_1", "pmid": "23687103", "title": "Low cerebral blood flow is associated with lower memory function in metabolic syndrome.", "authors": "Birdsill AC, Carlsson CM, Willette AA et al.", "year": "2013", "journal": "Obesity (Silver Spring, Md.)", "keywords": "None", "chunk": "Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF. The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population.", "source": "PubMed"}, {"chunk_id": "39202326_0", "pmid": "39202326", "title": "Cognitive Impairment in Cerebral Small Vessel Disease Is Associated with Corpus Callosum Microstructure Changes Based on Diffusion MRI.", "authors": "Dobrynina LA, Kremneva EI, Shamtieva KV et al.", "year": "2024", "journal": "Diagnostics (Basel, Switzerland)", "keywords": "cognitive impairment, corpus callosum, diffusion models, small vessel disease, tract profiles", "chunk": "The cerebral small vessel disease (cSVD) is one of the main causes of vascular and mixed cognitive impairment (CI), and it is associated, in particular, with brain ageing. An understanding of structural tissue changes in an intact cerebral white matter in cSVD might allow one to develop the sensitive biomarkers for early diagnosis and monitoring of disease progression. to evaluate microstructural changes in the corpus callosum (CC) using diffusion MRI (D-MRI) approaches in cSVD patients with different severity of CI and reveal the most sensitive correlations of diffusion metrics with CI. the study included 166 cSVD patients (51.8% women; 60.4 \u00b1 7.6 years) and 44 healthy volunteers (65.9% women; 59.6 \u00b1 6.8 years). All subjects underwent D-MRI (3T) with signal (diffusion tensor and kurtosis) and biophysical (neurite orientation dispersion and density imaging, NODDI, white matter tract integrity, WMTI, multicompartment spherical mean technique, MC-SMT) modeling in three CC segments as well", "source": "PubMed"}]