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2.5. Cardiovascular Activity | CED | Systolic (SBP) and diastolic (DBP) blood pressure were measured using a Finometer (Finapres Medical Systems, Amsterdam, The Netherlands). A small cuff was placed around the intermediate phalanx of the middle finger, and continuous data were recorded via a Power1401 (CED) connected to a computer programmed in Spike2. An ambulatory monitor (VU-AMS) and 7 Ag/AgCl spot electrodes (Invisatrace, ConMed Corporation; Largo, FL, USA) recorded electrocardiographic and impedance cardiographic signals continuously, in accordance with published guidelines [ | PMC10534483 | |
2.6. Prefrontal Cortical Haemodynamics | Near-infrared spectroscopy (NIRS, NIRO-200NX, Hamamatsu Photonics KK, Shizuoka, Japan) was used to assess prefrontal cortical haemodynamics. The NIRS device measures changes in chromophore concentrations of oxyhaemoglobin (O | PMC10534483 | ||
2.7. Common Carotid Artery Diameter and Blood Flow | Duplex ultrasound was used to assess common carotid artery (CCA) diameter and blood flow. A 15–4 Mhz (15L4 Smart MarK | PMC10534483 | ||
2.8. Mood Questionnaire | Mood was assessed with a short form of the Profile of Mood States (POMS) questionnaire [ | PMC10534483 | ||
2.9. Data Reduction and Statistical Analysis | TMD, finapress | NIRS and cardiovascular measures were averaged per minute of assessment for the Rest and Stress periods. For the NIRS variables, the eight rest values were then averaged to one resting baseline value, and reactivity scores during stress were calculated as Stress minus Rest, for minutes 2, 4, 6, and 8 of stress (corresponding to Stress 1, Stress 2, Stress 3, and Stress 4, respectively). All data were statistically analysed using IBM SPSS software (version 25). Task perceptions and PASAT scores were compared between visits using a one-way repeated measures ANOVA. Cardiovascular variables were analysed using a two-way repeated measures ANOVA with condition (HFM, LFM) and time (Rest, Stress 1, Stress 2, Stress 3, Stress 4) as within-subject factors. NIRS variables at rest and during stress (8 min averaged) were compared using separate one-sample t-tests for both conditions. This was the most appropriate statistical approach given that the resting values were 0, so there is no variability around the mean. We then further analysed the NIRS variables using a two-way repeated measures ANOVA with condition (HFM, LFM) and time (Stress 1, Stress 2, Stress 3, Stress 4) as within-subject factors. CCA diameter and blood flow were analysed using a 2-condition (HFM, LFM) by 5-time (Baseline, Rest, Post-10, Post-30, Post-90) repeated measures ANOVA. TMD was similarly analysed using a 2-condition (HFM, LFM) by 5-time (Baseline, Rest, Stress, Post-30, Post-90) repeated measures ANOVA. Where appropriate, pairwise comparisons using Bonferroni correction were conducted as post-hoc analyses. All values reported in text, tables, and graphs are mean ± standard deviation. Occasional missing data are reflected in the reported ‘n’ values, and include n − 1 due to VU-AMS malfunction, n − 2 due to finapress malfunction, and n − 2 due to NIRS malfunction. All statistical tests were also carried out excluding 7 participants who did not complete both meals; however, as the results were similar to the analyses with the full sample, all participants were included to maximise power. For all analyses, significance was set at | PMC10534483 | |
3. Results | PMC10534483 | |||
3.1. Participant Characteristics | Participants ( | PMC10534483 | ||
3.2. Mental Stress Task Ratings | Two-condition (HFM, LFM) ANOVAs revealed no significant difference in PASAT score between conditions ( | PMC10534483 | ||
3.3. Cardiovascular Responses during Mental Stress | Separate 2-condition (HFM, LFM) × 5-time (Rest, Stress 1, Stress 2, Stress 3, Stress 4) ANOVAs revealed an overall time effect for HR ( | PMC10534483 | ||
3.4. Prefrontal Cortical Haemodynamics during Mental Stress | One sample Separate 2-condition (HFM, LFM) × 4-time (Stress 1, Stress 2, Stress 3, Stress 4) ANOVAs revealed an overall condition effect (One sample A 2 × 4 ANOVA revealed an overall condition effect ( | PMC10534483 | ||
3.5. Common Carotid Arterial Diameter and Blood Flow Following Mental Stress | CCA diameter and blood flow are reported in | PMC10534483 | ||
3.6. Mood Following High and Low-Fat Meal Consumption and Mental Stress | TMD, mood disturbance | Total mood disturbance (TMD) is presented in | PMC10534483 | |
4. Discussion | fatigue, mood disturbance, fat-induced declines, cerebral vasodilation | The current study showed that mental stress induced increases in HR, CO, SBP, and DBP, decreases in HRV and PEP, and increases in PFC tissue oxygenation (as indexed via changes in TOI and OOur observation that mental stress increases PFC tissue perfusion (by virtue of increased TOI and OLittle is known about how fatty acids affect cerebral oxygenation. To our knowledge, this is the first study to show that fat consumption attenuated the increase in PFC tissue oxygenation during stress, indicating that CBF was relatively lower and therefore more oxygen was extracted from the haemoglobin to meet the metabolic demand of the tissue during the task (assuming brain metabolism was similar for the diet conditions). A previous study has also presented a decreased CBF to the hypothalamus following fat consumption at rest [Interestingly, although fat consumption alters cerebral haemodynamics during mental stress, from 10 to 90 min following stress, no differences in resting carotid arterial blood flow between diets were detectable. It should be noted that stress-induced and fat-induced declines in peripheral vascular function have been well established during the period of 30–90 min post stress [Finally, we observed that CCA diameter significantly increased following consumption of both meals and was significantly greater after the high-fat meal compared to the low-fat meal only at 90 min post stress. This is possibly driven by cholecystokinin (CCK), a peptide hormone that increases postprandially to stimulate digestion, and has been shown to induce cerebral vasodilation [Fat consumption had a significant impact on mood in the present study, shown by a greater mood disturbance at rest and immediately following stress in the high-fat condition compared to the low-fat condition. When exploring the individual constructs that are used to calculate total mood disturbance, it was particularly fatigue which was significantly higher following the high-fat meal compared to the low-fat meal, which is in line with previous research [ | PMC10534483 | |
Limitations | One of the potential limitations of the current study was that the meals were not tailored to individual metabolic rate. Yet, previous studies have shown that a similar fat content (50 g) is sufficient to impact vascular function, and the current study was in line with a similar study showing fat consumption impairs endothelial function [ | PMC10534483 | ||
5. Conclusions | This is the first study to explore the relationship between fat consumption and cerebral dynamics during mental stress, providing, for the first time, evidence that fat consumption impairs PFC perfusion during stress. Experiencing stress is tightly associated with consuming high-fat foods [ | PMC10534483 | ||
Author Contributions | Conceptualization, R.B., J.J.C.S.V.v.Z. and C.R.; methodology, R.B., J.J.C.S.V.v.Z. and C.R.; formal analysis, R.B., S.J.E.L., S.R.C.W., J.J.C.S.V.v.Z. and C.R.; investigation, R.B., J.J.C.S.V.v.Z. and C.R.; data curation, R.B., S.J.E.L., S.R.C.W., J.J.C.S.V.v.Z. and C.R.; writing—R.B.; writing—review and editing, S.J.E.L., S.R.C.W., J.J.C.S.V.v.Z. and C.R.; supervision, J.J.C.S.V.v.Z. and C.R.; project administration, J.J.C.S.V.v.Z. and C.R.; funding acquisition, R.B., J.J.C.S.V.v.Z. and C.R. All authors have read and agreed to the published version of the manuscript. | PMC10534483 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of the University of Birmingham (protocol code ERN17_1755D and date of approval: 30 October 2021). | PMC10534483 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10534483 | ||
Data Availability Statement | The data presented in this study are available on request from the corresponding author. | PMC10534483 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10534483 | ||
Methods | nausea, pain | In a single-center, double-blind, parallel-group, randomized controlled trial, a total of 120 patients who were scheduled for elective CS were randomly assigned into two groups. After birth, 1 mg of midazolam was administered to all patients. In addition, 1 mg/kg intranasal ketamine was administered to patients in the intervention group. For patients in control group, normal saline was administered intranasally as a placebo. The severity of pain and nausea in the two groups was evaluated after 15, 30 and 60 minutes, as well as 2, 6 and 12 hours after the initial administration of the medications. | PMC9987284 | |
Results | nausea, pain | The trend of changes in pain intensity was decreasing and these changes were statistically significant (time effect; P<0.001). The pain intensity in the placebo group was higher than the intervention and the observed difference was statistically significant, regardless of the time studied (group effect; P<0.001). In addition, it was shown that regardless of the study group, the trend of changes in nausea severity was decreasing and these changes were statistically significant (time effect; P<0.001). Regardless of the time studied, the severity of nausea in the placebo group was higher than the intervention group (group effect; P<0.001). | PMC9987284 | |
Conclusions | pain | According to the results of this study, it seems that the using of intranasal ketamine (1 mg/kg), can be considered as an effective, well tolerated and safe method in reducing pain intensity as well as the need for postoperative opioid consumption after CS. | PMC9987284 | |
Introduction | acute postoperative pain, postoperative pain, painless, pain | Cesarean section (CS) is one of the most common gynecological surgery, which due to various reasons such as increasing the age of marriage and socioeconomic status of society, its prevalence is increasing.It has been shown that the rates of CS have been increasing globally, as the sustained, unprecedented rise in CS rates is a major public health concern (After all surgeries, including CS, patients inevitably experience pain to varying degrees (The search for the ideal method to manage postoperative pain is ongoing. So far, many studies has been performed for appropriate management of postoperative pain after CS. The multiplicity of studies and modalities indicates the lack of a clear and reliable method in reducing postoperative pain and shows that acute postoperative pain management after CS still remains a problem (Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been widely studied as an analgesic adjuvant for management of postoperative pain. Previous studies evaluate the efficacy of ketamine for managing postoperative pain and analgesic consumption after CS, with conflicting results (Intranasal route of administration offers a variety of attractive options for local and systemic delivery of different medications. Intranasal administration is noninvasive, painless, easily administered, and relatively safe and is associated with a rapid onset of therapeutic effects and higher bioavailability due to avoid the first- pass effect ( | PMC9987284 | |
Results | postoperative pain, vomiting, nausea, pain | COMPLICATION | In this study, 143 women undergoing cesarean section referred to Imam Khomeini Hospital in Sari were evaluated in terms of response to the analgesic effects of intranasal ketamine, in terms of inclusion and exclusion criteria, as well as the satisfaction of participating in the study. 18 people did not meet the inclusion criteria and 5 people did not agree to participate in the study. 120 patients were randomly assigned to the two groups of intranasal ketamine and placebo in a 1: 1 ratio. Finally, all 120 subjects were evaluated in two groups of intervention and placebo (Flow diagram of the studyThe mean age of the patients was 29.28±4.3 years. The basic characteristics of patients were reported in Basic demographic and clinical characteristics of patients in the two groupsPatients' postoperative pain and nausea intensity were assessed using VAS 15, 30 and 60 minutes and 2, 6, and 12 hours after surgery (The mean postoperative pain intensity in the two groupT1: 15 minutes after surgery; T2: 30 minutes after surgery; T3: 60 minutes after surgery; T4: 2 hours after surgery; T5: 6 hours after surgery; T6: 12 hours after surgery.The mean postoperative nausea intensity in the two groupsT1: 15 minutes after surgery; T2: 30 minutes after surgery; T3: 60 minutes after surgery; T4: 2 hours after surgery; T5: 6 hours after surgery; T6: 12 hours after surgeryChanges in pain intensity in the two groups during the follow-up period.Changes in nausea intensity in the two groups during the follow-up periodAs shown in While no person in the intervention group had vomiting, but in the placebo group, 5 people (8.3%) had this complication and the difference in the ratio of vomiting in the two groups was statistically significant ( | PMC9987284 |
Discussion | drowsiness, nystagmus, pain, dizziness, traumatic limb injuries, dry mouth, adverse drug reactions, Frey | NYSTAGMUS, DRY MOUTH, ADVERSE DRUG REACTIONS, COMPLICATIONS, FREY | Postoperative analgesia after CS is challenging since we need not only to consider maternal comfort, but the anesthetic technique should also have no adverse drug reactions on the newborn. The results of the present study showed that intranasal administration of ketamine significantly reduced the pain intensity of patients after CS and the amount of morphine consumption in the postoperative period. Very limited studies have investigated the effect of intranasal ketamine for reducing the pain intensity after surgery, especially CS. Most studies that have been performed to evaluate the analgesic effect of intranasal ketamine have been performed in the emergency department. In a study by El-Halwagy et al., intranasal administration of ketamine at a dose of 0.5 mg/kg, compared with intramuscular pethidine, significantly reduced the pain intensity of patients after CS (In another study, it was shown that intranasal ketamine (1.5 mg/kg) and intranasal fentanyl were associated with a significant reduction in pain intensity after tonsillectomy in children. There was no statistically significant difference between the two groups in the postoperative period, although the incidence of sedative effects was higher in the intranasal ketamine group than in the other group (Another study in patients undergoing spinal surgery showed that intranasal administration of S-ketamine (6 mg) as well as intranasal midazolam, compared with morphine administration using a PCA pump, was significantly associated with lower postoperative pain intensity. In general, there was no statistically significant difference in the incidence of complications in the three groups, although the incidence of nystagmus in the S-ketamine group and dry mouth in patients receiving morphine were slightly higher than the other groups (In their study, Frey et al. showed that intranasal ketamine use significantly reduced the severity of pain in children with traumatic limb injuries referred to the emergency department compared to intranasal fentanyl (In a study conducted by Quinn et al. which aimed to determine and compare the effect of intramuscular ketamine and fentanyl on moderate and severe pain in children referred to the emergency department, the results showed that in terms of pain intensity in two groups, there was no statistically significant difference 20 minutes after drug administration. However, the incidence of side effects in the ketamine group was significantly higher than the fentanyl group (Intranasal ketamine has been shown to have 45% bioavailability, which is higher than other methods of prescribing this drug. The clinical effects of ketamine can probably be explained by the absorption of the drug through the nasal mucosa, which allows it to act on the brain without first-pass metabolism. In a study evaluating the efficacy and pharmacokinetics of ketamine, it was shown that within 2 minutes after intranasal administration, ketamine was measurable in the blood at concentrations much higher than its less active metabolite, norectamine (In previous studies, drowsiness and dizziness have been mentioned as common side effects, which are usually mild or moderate, as well as temporary and transient and disappeared within 7–10 minutes ( | PMC9987284 |
Objectives | To compare blood flow (BF) changes of teeth subjected to orthodontic forces during curve of Spee (COS) leveling using different archwires (AW). | PMC10264509 | ||
Material and methods | Thirty subjects with COS > 5 mm were randomly assigned (1:1:1) into three groups based on the AW used: group 1: 0.017 × 0.025-inch stainless-steel (SS)AW, group 2: 0.019 × 0.025-inch SSAW, and group 3: 0.021 × 0.025-inch β-titanium (TMA)AW. In the 3 groups, a 5 mm-depth reverse COS was placed in the AWs. A laser Doppler flowmeter was used to measure BF at different time intervals (T0–T4). | PMC10264509 | ||
Results | teeth was reduced 20 min after force application. | In the 3 AWs group, BF of all measured teeth was reduced 20 min after force application. Afterwards, the BF values started to increase until the baseline values were almost restored within 1 week. Differences in BF changes between the extrusion and intrusion subgroups were observed within groups 1 and 3 during the first 20 min of force application ( | PMC10264509 | |
Conclusions | incisors, Tooth | During CoS leveling, similar BF changes were recorded using the 3 different AWs. Tooth type and the amount of COS depth change were associated with BF changes within the first 20 min of force application. Greater BF reduction was found in premolars compared to incisors during the first 20 min of AW placement. | PMC10264509 | |
Clinical relevance | It is important to select a type of applied forces that minimally affect the BF. Intrusive forces appeared to have lower negative effects on the BF of teeth during COS leveling. | PMC10264509 | ||
Trial registration | ClinicalTrial.gov (# NCT04549948). | PMC10264509 | ||
Keywords | Open Access funding provided by the Qatar National Library. | PMC10264509 | ||
Introduction
| luxation injuries, incisors, caries, restorations, periodontium, TMA, tooth, orthodontic, trauma | PULP NECROSIS | The curve of Spee (COS) refers to the upward progression of the teeth curvature from the incisors through the premolars and molars. A deep COS is usually associated with an increased anterior overbite. During orthodontic treatment, COS is leveled by bringing the incisal edges of the anterior teeth and the buccal cusps of the posterior teeth into a horizontal plane level [The COS correction is usually achieved by posterior teeth extrusion and lower incisor intrusion [The application of orthodontic forces to teeth has been reported to induce molecular changes in the cells of the periodontal ligament, alveolar bone, and the pulp–dentine complex [The application of a contentious force to the teeth not only results in an inflammatory reaction within the periodontium but also has a significant effect on pulpal neural responsiveness, possibly for the entire duration of the orthodontic treatment [Most alterations in the BF that result from orthodontic treatment are reversible unless the pulp has been previously irritated by caries, restorations, or trauma [Intrusion applied to the teeth during orthodontic treatment is thought to have the greatest impact on the apical region. Therefore, a significant reduction in the BF during the application of a continuous intrusive force is expected. This is substantiated by results from trauma studies where intrusion injuries cause the highest percentage of pulp necrosis particularly in teeth with closed apices, compared to other luxation injuries [On the other hand, Sabuncuoglu and Ersahan [In the current orthodontic practice, 0.17 × 0.025-inch stainless steel (SS), 0.019 × 0.025-inch (SS), and 0.021 × 0.025-inch β-titanium (TMA) AWs are used for COS leveling during orthodontic treatment [To investigate BF changes of incisors subjected to orthodontic intrusive force during COS leveling using 0.017 × 0.025-inch stainless steel (SS) AW, 0.019 × 0.025-inch SS AW, and 0.021 × 0.025-inch β-titanium Titanium (TMA) AW at different time points (20 min, 48 h, 1 week, 1 month)To investigate BF changes of molars and premolars subjected to orthodontic extrusive force during COS leveling using 0.017 × 0.025-inch SS AW, 0.019 × 0.025-inch SS AW, and 0.021 × 0.025-inch TMA AW at the above 4 time pointsTo compare BF changes based on tooth type and type of force (intrusive and extrusive forces) within the same AW size groupTo compare BF changes between teeth in the three different AW size groups as per tooth type and type of forceTo investigate the association between BF changes, type of force, AW type, tooth type, and the amount of change in COS | PMC10264509 |
Null hypothesis | TMA | There is no significant difference in BF changes between intrusive and extrusive forces during COS leveling regardless of the AW used: 0.017 × 0.025-inch SS AW, 0.019 × 0.025-inch SS AW, and 0.021 × 0.025-inch TMA AW. | PMC10264509 | |
Material and methods | PMC10264509 | |||
Study design | incisors, orthodontic, trauma | ENDODONTICALLY TREATED TEETH, ROOT RESORPTION, BLIND | This study was a randomized clinical trial with a 1:1:1 allocation ratio. The methods were not changed after trial initiation. The study was approved by the Institutional Review Board at the Jordan University of Science and Technology (approval number 78/117/2018). This trial was registered with ClinicalTrial.gov with identifier number NCT04549948.The sample size was calculated using the G*power 3.1.9 program. Univariate analysis revealed significant variability between subjects (The participants for this study were recruited from patients attending postgraduate orthodontic clinics. All subjects who agreed to participate in the study signed a consent form for participation after clarifying the purpose of the intervention. Subjects were selected based on the inclusion criteria: age ≥ 16 years and ≤ 25 years, normally inclined or retroclined lower incisors, presence of deep bite, depth of COS ≥ 5 mm, non-extraction treatment plan, averaged or reduced lower vertical height, good oral hygiene, and healthy periodontium, and all permanent teeth are present except for the third molars.Exclusion criteria were history of previous orthodontic treatment, teeth with root resorption, endodontically treated teeth, history of previous trauma, restoration on measured teeth, presence of a medical condition or being under medication that could affect the treatment, and smoking.After recruiting patients who met the inclusion criteria and just before the insertion of the leveling AWs, the intervention was randomly allocated using the permuted random block size of 3 with a 1:1:1 allocation ratio by one research assistant (S.D.). The allocation sequence was concealed from the researcher (Y.N.) by sequentially numbered, opaque, sealed, and stapled envelopes before the intervention. Patients were then asked to pick a sealed envelope to assign the method of intervention. The methods were not changed after trial initiation. The patient was blinded to the intervention used, but it was not possible to blind the clinician during treatment. However, the measurements of the BF were performed by one research assistant (H.D.) who was blinded to the type of intervention used. | PMC10264509 |
Outcomes | PMC10264509 | |||
Primary outcome: blood flow (BF) (Fig. | MP | BF measurement using LDF (courtesy of Alhaija et al. 2021) [Measurements of the BF were taken by the use of LDF (Moor lab, Moor instruments, UK) with a wavelength of 780 nm and a dental probe MP 13 (Moor instruments, UK; 2 fibers, 0.25 mm diameter, centers 0.5 mm spaced a part). The flowmeter was calibrated according to the manufacturer’s instructions. Room temperature was maintained from 20 to 25 °C. Volunteers were provided with 15 min’ rest before each session.Before starting the measurements, a silicone splint was fabricated to stabilize the dental probe during the measurements. The retentive areas of the brackets were covered with a layer of utility wax. Holes were made below the imprints of the brackets in the mold with a stainless-steel drill of 1.5 mm diameter to allow the probe to pass through the mold to touch the teeth to allow measurement of teeth on the same position at different times. The silicone splints were fabricated to extend over the attached gingiva. The retentive areas of the brackets and the labial gingiva were covered with utility wax. In addition, 4 cotton rolls were applied in the gingival sulcus to keep the lower lip and cheeks away. This helped in isolating the teeth during measurements to minimize contamination of the blood flow signals from adjacent tissues [BF was recorded at 5 points:Before placement of interventional AWs in both groups. These values were considered the basal blood flow (T0).Twenty minutes after placement of the interventional AW (T1).Forty-eight hours after placement of the interventional AW (T2).One week after placement of the interventional AW (T3).One month after placement of the interventional AW (T4). | PMC10264509 | |
Secondary outcome: depth of COS | incisors | The depth of COS was measured manually just before the placement of interventional AW and at the end of the intervention (1 month) using a digital caliper as the perpendicular distance between the deepest cusp tip and a flat plane that was laid on top of the mandibular dental cast, touching the incisal edges of the central incisors and the distal cusp tips of the second molars. It was measured on the right and left sides of the mandibular arch, and the average value was included in the analysis. All dental casts were trimmed and mounted equally on a dental surveyor to ensure accurate results. | PMC10264509 | |
Method error | Measurement error using Dahlberg formula and Houston’s coefficient of reliability was calculated. Dahlberg error was 0.6 PU for BF and 0.1 mm for COS, and the coefficients of reliability were above 88% indicating substantial agreement. | PMC10264509 | ||
Statistical analysis | tooth | REGRESSION | Data analysis was carried out using SPSS (28.0, SPSS Inc., NY, USA). Descriptive statistics for BF and COS depth at different time intervals were calculated. The Shapiro–Wilk test was applied to assess the normality of numeric data, and the result indicated that data were not normally distributed. The Wilcoxon signed-rank test was applied to detect differences between the right and left sides. The non-parametric Friedman test with a pairwise comparison of related samples and Bonferroni correction for multiple tests was applied to examine within-group differences in BF at the different time points. Kruskal–Wallis H test was used to detect differences between groups (AW groups and type of force subgroups). Linear regression analysis was applied to determine any association between BF changes within the first 20 min and the first 48 h of force application and AW size, type of force, tooth type, and the COS depth change. The | PMC10264509 |
Results | incisors | Thirty subjects (20 females and 10 males) received the planned intervention. Complete records for all subjects were available during the analysis stage. The age averaged 21.60 (3.62) years, 23.50 (4.66) years, and 20.20 (2.51) years in groups 1, 2, and 3, respectively. Before the intervention, the lower incisors’ inclination was 94.8 (3.7), 92.5 (4.0), and 93.4 (3.6) degrees, and the maxillary/mandibular plane angle was 24.1 (4.3), 24.6 (4.8), and 23.9 (2.9) degrees in groups 1, 2, and 3, respectively (CONSORT flow chart showing patients’ flow during the trialTeeth on both sides were assessed. The Wilcoxon signed-rank test revealed no significant differences in BF changes between the right and left sides within each group. Therefore, the right and left sides were averaged, and the mean BF values were used in the final analysis. The results are presented according to tooth type and type of applied force. The incisors were analyzed in the intrusion group (total of 60 teeth/20 teeth in each AW group), while the extrusion group was subdivided into 2 subgroups: premolars only (total of 60 teeth/20 teeth in each AW group) and first molars only as the second subgroup (total of 30 teeth/10 teeth in each AW group). | PMC10264509 | |
Primary outcome | PMC10264509 | |||
Secondary outcome | PMC10264509 | |||
Reduction of COS | Within the 1-month trial, COS was reduced in all groups. The baseline depth of the COS before the intervention averaged 5.30±0.46 mm, 5.60 ± 0.92 mm, and 5.40±0.49 mm in groups 1, 2, and 3, respectively. After 1 month, COS was on average 4.40±0.49 mm, 4.70±0.91, and 4.70±0.46 in groups 1, 2, and 3, respectively ( | PMC10264509 | ||
Discussion | TMA, luxation injuries, orthodontic, tooth | REGRESSION | Although BF changes during extrusion and intrusion orthodontic forces have been previously reported [In the current orthodontic practice, 0.017 × 0.025-inch SS, 0.019 × 0.025-inch SS, and 0.21 × 0.025 TMA AWs are used for COS leveling during orthodontic treatment. The reported stiffness values for 0.019 × 0.025-inch SS AW are higher than 0.021 × 0.025-inch-TMA AW which means the amount of the delivered force when using 0.19 × 0.025-inch SS is higher [In the current study, only subjects with good oral hygiene and healthy periodontium were included. The oral health status during the study was maintained by giving the patients oral hygiene instructions both verbally and using social media [It has been demonstrated that tooth morphology affects the distribution, the amount of orthodontic force, and the developed strain within the PDL [Different types of tooth movement were reported during leveling the COS in subjects with different vertical proportions. Rozzi et al. [Within the first 20 min of force application, BF showed more reduction in the extrusion subgroup as compared to the intrusion subgroup. Although intrusion is associated with more crushing of cells and vessels in the apical tissues than luxation injuries, and more detrimental effect on the vasculature of the pulp [In the current study, significant BF recovery occurred within 48 h of force application (intrusion and extrusion) in group 1, while it continued to increase in the premolar extrusion subgroups in 0.019 × 0.25-inch SS and 0.21 × 0.025-inch TMA AWs and in the intrusion subgroup in the TMA AW group. The continued BF increase after 1 week of extrusive force application in groups 2 and 3 could be explained by the higher force applied to the teeth using the larger dimension AWs in groups 2 and 3. Also, the less AW/bracket play in group 3 may have produced more frictional forces.These results agree with previous studies [These results were also inconsistent with studies that used NiTi AWs; McDonald and Pitt Ford [When comparing BF changes between the 3 AWs, only the canines showed significant differences. The canines showed more BF changes (more BF reduction during the first 20 min and more recovery during the first 48 h) when the SS AWs were used. This may be due to higher forces applied to the canines when using the stiffer SS AWs. Also, the position of the canines in the middle of the lower arch connecting the intrusion and extrusion parts of the reverse COS AWS may have subjected the canines to more complex types of orthodontic forces.When the type of force was compared between the 3 AWs, premolars subgroup showed more BF return toward their baseline value in group 2 (0.019 × 0.025-inch SS AW) as compared to group 3 (TMA AW) within the first 48 h of force application. As the premolars are in the deepest point of the accentuated COS, they are subjected to more extrusive forces when COS is placed in the AW. This indicates that the premolars in SS group may have been subjected to more insults due to higher forces that necessitated an increase in BF changes to help in recovery.In the current study, 1 month after force application, BF increased beyond its original value. This was contrary to the previous studies [Regression analysis revealed an association between BF changes with the type of tooth and the amount of COS depth changes. The change of the COS reflects the outcome of orthodontic force application. Therefore, it is expected to detect changes in the pulp as a result of this force. Based on the above results, it seems prudent to evaluate the amount of change in COS required and to select the type of AW that may produce the least amount of force to avoid detrimental pulpal effects during extrusion.Limitations of the current study include the following: BF measurements were carried out during active orthodontic treatment, and teeth were not in a fixed position, the extrusive and intrusive forces were applied to teeth with different morphology, and the presence of the orthodontic appliance limits the measurement area and hinders the placement of a black rubber dam sheet during BF measurements to reduce signals from the gingival blood vessels [ | PMC10264509 |
Conclusions | incisors |
During CoS leveling, BF was reduced after 20 min and then started to increase at 48 h. It returned to its baseline values 1 week after AW insertion in all AW size groups and type of force subgroups.Similar BF changes were recorded in all teeth using different AWs sizes and materials.In groups 1 and 3, more BF reduction were found in the extruded premolars compared to that of the intruded incisors during the first 20 min of AW placement.After 1 week of reverse CoS AW placement, BF continued to increase in the extruded premolars in groups 2 and 3 and in the intruded incisors in group 3.In the premolars “extrusion subgroup,” BF showed more increase toward baseline values within the first 48 h of force application in the SS AW groups (groups 1 and 2).Tooth type and the amount of COS depth change were associated with BF changes within the first 20 min of force application. | PMC10264509 | |
Author contribution | Conceptualization: Elham S. Abu Alhaija. Methodology: Elham S. Abu Alhaija, Nessrin Taha, Hasan Daher, Saba Daher, Yousef H. Nasrawi. Data acquisition: All authors. Formal analysis and investigation: Raidan Ba-Hattab. Interpretation: Raidan Ba-Hattab. Writing—original draft preparation: Elham S. Abu Alhaija, Nessrin Taha, Raidan Ba-Hattab. Writing—review and editing: All authors. Funding acquisition: Elham S. Abu Alhaija. Correspondence: Raidan Ba-Hattab. | PMC10264509 | ||
Funding | Open Access funding provided by the Qatar National Library. The study was supported by the Deanship of Research at the Jordan University of Science and Technology, research grant number (436/2018). | PMC10264509 | ||
Data Availability | The data that support the findings of this study are available from the corresponding author upon reasonable request. | PMC10264509 | ||
Declarations | PMC10264509 | |||
Ethics approval | The study was approved by the institutional ethics and research committee at the Jordan University of Science and Technology, and it is registered with clinicaltrials.gov registration number NCT04549948. | PMC10264509 | ||
Informed consent | A written informed consent was obtained from all participants before the treatment. | PMC10264509 | ||
Conflict of interest | The authors declare no competing interests. | PMC10264509 | ||
References | PMC10264509 | |||
Subject terms | psychiatric | REGRESSION | Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future. | PMC10267115 |
Introduction | psychiatric, substance dependence | REGRESSION, CORTEX | Psychedelics like psilocybin and lysergic acid diethylamide (LSD) have emerged as promising new treatment candidates for a variety of psychiatric conditions including substance dependence [Functional connectivity (FC) [Firstly, FC is an undirected measure of connectivity, because computation of the correlation coefficient is commutative. Secondly, it ignores two important organisational principles of the cortex: (1) the asymmetry of connections [In this exploratory analysis, we estimated whole-brain EC using regression dynamic causal modelling (rDCM; [To assess this, we also compared FC and EC in terms of their ability to distinguish LSD from placebo at the individual level. In future studies, these computationally-informed biomarkers could potentially be leveraged to predict the subjective effects of psychedelics. | PMC10267115 |
Materials and methods | PMC10267115 | |||
Participants | Data from two randomised, placebo-controlled, double-blind, cross-over trials were aggregated comprising 20 healthy participants (10 male, 10 female; age 32 ± 11 [mean ± SD]; range 25 − 60 years; body weight, 68.8 ± 7.7 kg; trial A: NCT02308969 [ | PMC10267115 | ||
Experimental procedure | Participants were administered 100 μg LSD orally in capsules (trial A) or vials (trial (B) and identical mannitol and ethanol-filled placebo capsules/vials in a cross-over design across two separate experimental sessions with a time between sessions of at least 7 days (17 ± 35.3 days [median ± SD], range: 7−182 days). Each session included an assessment of brain activity during rest using fMRI, which was acquired 140.5 ± 10.9 min [median ± SD] (range: 121−200 min) after administration of LSD or placebo. (see Supplement for data acquisition parameters and preprocessing procedure). Participants were instructed to close their eyes and remain awake during the scan. Subjective effects were assessed with the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale [ | PMC10267115 | ||
Data analysis | PMC10267115 | |||
Functional connectivity | We computed FC using Pearson correlations between the BOLD signal time series of each pair of the 132 distinct brain regions derived from the Harvard-Oxford atlas, yielding 8648 unique correlation coefficients. Please, see Table | PMC10267115 | ||
Effective connectivity | EC for fully connected whole-brain networks was estimated from the raw time series of all 132 regions of interest (ROIs) using rDCM [ | PMC10267115 | ||
Results | PMC10267115 | |||
The effect of LSD on functional connectivity | Mass-univariate tests suggested that about 23% (1993/8646) unique correlation coefficients significantly differed across LSD and placebo conditions ( | PMC10267115 | ||
Partial least squares correlation analysis | PLSC analysis of FC showed a significant condition effect on the first LV (LSD condition score: 4.442 [3.785, 5.076], placebo: −4.442[−5.076, −3.785], | PMC10267115 | ||
Machine learning analysis | The random forest trained on FC as features (FC model) discriminated between LSD and placebo with a BAC of 86% ( | PMC10267115 | ||
The effect of LSD on effective connectivity | Mass-univariate tests suggested that about 13% (2184/17424) effective connections coefficients significantly differed across conditions ( | PMC10267115 | ||
Connectogram views of thalamic effective connectivity (EC). | Across-participant t-statistic values of the difference between LSD and placebo conditions in outgoing ( | PMC10267115 | ||
Partial least squares correlation analysis | PLSC analysis of EC showed a statistically significant condition effect on the first LV (LSD condition score: 0.060 [0.067, 0.052], placebo: −0.060 [−0.053, −0.067], | PMC10267115 | ||
Machine learning analysis | The random forest trained on EC as features (EC model) performed with a BAC of 91.1% ( | PMC10267115 | ||
Comparing functional vs effective connectivity changes under LSD | PMC10267115 | |||
The effect of LSD on inhibitory self-connections | As pointed out in the Introduction, an advantage of using EC over FC is that rDCM allows estimation of inhibitory self-connections (see Supplement). These all-negative values can be interpreted as ‘decay-rate’ coefficients (in view of the DCM state equation) since they capture the tendency of different regions to return to baseline, rather than increasing activity indefinitely. Also note that these values reflect local as opposed to global (inter-regional) dynamics.Mass-univariate tests suggested that about 30% (39/132) inhibitory self-connections significantly differed across conditions ( | PMC10267115 | ||
Asymmetry in directed connectivity | Recall that while FC provides a measure of the correlation between the activities of each pair of brain regions, EC provides an estimate of directed effects between pairs of regions, which may be asymmetrical. We tested for the presence of asymmetry (by mass-univariate comparison) in each condition (LSD and placebo), and tested whether asymmetry was affected by LSD (drug-by-asymmetry interaction). The number of forward-backward pairs of endogenous connectivity coefficients that were significantly different ( | PMC10267115 | ||
Comparing functional and effective connectivity classifiers | Lastly, we compared the performances of classifiers trained on either FC or EC to test whether modelling additional physiological details (i.e., self-inhibition and asymmetry) translated into a better classification performance of drug condition. While BACs differed numerically between the FC and EC classification models (86% vs 91% BAC), a McNemar’s test comparing the models’ performances suggested that these differences were not significantly different ( | PMC10267115 | ||
Discussion | The goal of this study was to investigate the effects of LSD on whole-brain EC and gauge its potential as a biomarker to decode or predict subjective effects in the future. To this end, we studied LSD-induced effects on whole-brain EC through multivariate, and machine-learning analyses and compared EC to FC. Multivariate PLSC analyses revealed stronger EC between parietal, temporal and inferior frontal regions under LSD, but weaker EC between regions in occipital cortices. When comparing FC to EC, we found notable changes in self-inhibition in around 30% of the brain regions under LSD, indicating that LSD may perturb the excitation/inhibition (E/I) balance of the brain. Moreover, our results suggest that—while EC was asymmetric (10–14% of connections)—asymmetry was largely unaffected by LSD (1.4% of connections). Lastly, our behavioural PLS and machine learning analyses showed that both FC and EC constitute promising biomarkers for future individual-level predictions of subjective effects. These analyses revealed that changes in FC and EC between several regions including angular gyrus and inferior frontal gyrus as well as connections between occipital and cerebellar regions correlated with global subjective effects of LSD and classifiers trained on either FC or EC could discriminate between LSD and placebo with high accuracy of 86% and 91%, respectively. | PMC10267115 | ||
Face validity of whole-brain effective connectivity | To assess the face validity of EC measures, we compared thalamic connections and found that the effects (sign and significance) were consistent across FC and EC, although a recent study argued that this does not necessarily need to be the case [Comparing all connections, we found that FC and EC measures were broadly in agreement with one another as both indicated generally stronger connectivity under LSD, with some notably weaker connectivity between bilateral occipital areas, though this effect was more pronounced in the EC measure. Feature importance also suggested that the EC classification relied more heavily on the bilateral occipital connections than the FC classification, wherein connections involving more varied areas were represented among the highlighted ‘important` features (Figure | PMC10267115 | ||
Comparison with other studies investigating directed connectivity | Unlike another study that investigated directed connectivity using Granger causality based on magnetoencephalography (MEG) recordings [Moreover, [ | PMC10267115 | ||
Implications for the thalamic gating hypothesis and brain entropy accounts | BRAIN | Our results are in line with the thalamic gating hypothesis, which postulates that psychedelics may temporally reduce thalamic gating leading to excessive information flow from thalamus to cortical regions [Brain entropy accounts of psychedelics propose that altered states of consciousness observed following administration of psychedelics result from increased entropy in the brain [It is interesting to note that connections between occipital regions appear to dominate EC under placebo (Fig. | PMC10267115 | |
Does LSD perturb the excitation/inhibition (E/I) balance? | CORTEX | Recent studies have begun to investigate the impact of psychedelics on glutamate-mediated excitation of the cortex. At least two different pathways for glutamatergic effects have been proposed: (1) Agonism at 5-HTOur results along with preclinical studies [ | PMC10267115 | |
Limitations | A few limitations of this study merit attention. Despite a washout period of at least two weeks, we cannot fully exclude carry-over effects due to potential long-term effects of psychedelics [Moreover, LSD is known to affect heart rate, blood pressure and body temperature [Due to the salient subjective effects of LSD, blinding is inherently difficult. Thus, knowledge about the condition could have impacted neural effects and future studies should include active control conditions. Although do note that one of the studies included an active control [Finally, while classification performances in this study were promising, they should be taken as preliminary until replicated in an external sample. | PMC10267115 | ||
Future directions | visual hallucinations, psychosis | CORTEX | Our results suggest that local gain is changed under LSD implicating disturbances of the E/I balance as a neural mechanism underlying LSD effects. Because rDCM summarises region-specific E/I balance by a single parameter per region, we cannot determine whether excitation, inhibition, or both are impacted. Future studies should employ more detailed models that allow to pinpoint these changes and compare them empirically to other conditions in which the E/I balance is affected, for example psychosis [Furthermore, our results suggest that visual regions may be impacted quite differently both in terms of between-region connectivity as well as in terms of local gain compared to the rest of the cortex warranting further investigation. The physiological basis of these changes and the relationship with subjective effects—visual hallucinations in particular—should be examined in future studies. A comparison of eyes-open vs eyes-closed resting states would be valuable to determine whether the EC changes observed here are a reflection of eyes-open-like behaviour of the visual system.Finally, we found that both whole-brain FC and EC were equally capable of discriminating between LSD and placebo with high accuracy suggesting that both are promising candidates for more challenging prediction targets. More research is needed to assess whether machine learning models trained on either FC and EC estimates are able to predict subjective effects of LSD at an individual level or from baseline EC measured before LSD intake. | PMC10267115 |
Conclusions | To the best of our knowledge, this is the first study to examine the impact of LSD on whole-brain EC. We found that compared to placebo, LSD impacted local gain and was associated with primarily stronger FC and EC with the notable exception of connections involving occipital and subcortical regions. Moreover, EC correlated with global subjective effects and discriminated experimental conditions with high accuracy (91.11%) highlighting that EC preserved classification accuracy while providing additional mechanistic information pointing towards LSD-induced disturbances of the E/I balance. This result suggests that EC is a promising candidate biomarker to decode or predict subjective effects of LSD in the future. | PMC10267115 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41386-023-01574-8. | PMC10267115 | ||
Author contributions | FM | FM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed substantially to this work as outlined below: Concept and design: SB, DJH, MEL, FM. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: PB, DJH. Critical revision of the manuscript for important intellectual content: All authors. Obtained funding for the original studies: SB, MEL. Administrative, technical, or material support: SB, AOD, MEL, FM, VR, ZW. Supervision: SB, AOD, MEL, FM, VR. | PMC10267115 | |
Funding | We are grateful for support from the Swiss National Science Foundation (trial A: SNF project grant, 320030_1449493 to MEL, trial B: SNF project grant, 320030_170249 to SB and MEL, Doc.Mobility, P1BSP3_200054 to DJH, Ambizione, PZ00P3_167952 to AOD) and the Krembil Foundation (to AOD). | PMC10267115 | ||
Competing interests | ML is a consultant for Mind Medicine, Inc. The other authors report no financial interests or potential conflicts of interest. Knowhow and data associated with this work and owned by the University Hospital Basel were licensed by Mind Medicine, Inc. Mind Medicine, Inc., had no role in financing, planning, or conducting the present study or the present publication. While Mindmed, Inc., has a collaboration with the University Hospital including a licence for using clinical data exclusively for medication development and regulatory purposes, none of the present data or other fMRI data has been shared with Mindmed, Inc. | PMC10267115 | ||
References | PMC10267115 | |||
Keywords: | sleep disturbances | REGRESSION | Equal contributionThe list of the Medit-Ageing Research Group’s members is provided at the end of this article.Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition. | PMC10564409 |
INTRODUCTION | cognitive decline, SWS, AD dementia, dementia | OBSTRUCTIVE SLEEP APNEA | Sleep disturbances are a frequent complaint in older adults, affecting more than a half of older individuals [A number of studies have investigated the impact of sleep changes on cognitive performance and dementia risk, providing inconsistent findings. Different methodological approaches have been used, ranging from large epidemiological studies using self-reports of sleep quality, to more specific experimental designs using polysomnography. Various aspects of sleep including poor self-reported sleep quality, short sleep duration and sleep fragmentation have been quite consistently associated with an increased risk of cognitive decline and AD dementia (see [SWS is markedly affected by the aging process. SWS-related parameters, including reduced Slow Wave Activity (SWA; corresponding to the spectral power of slow waves), have been associated with poorer executive functioning [Above methodological differences in terms of age range, sample sizes and the type of sleep measures used (subjective vs objective), the heterogeneity of previous results could be explained by different capacities of older individuals to tolerate the effects of sleep disruption. Indeed, older adults appear to better tolerate the effects of sleep deprivation than their younger counterparts [The potential impact of CR in the context of sleep disturbances has hardly been explored. In a study conducted in patients with obstructive sleep apnea, in which CR was assessed using IQ, Alchanatis et al. [Given that SWS is markedly reduced in aging [ | PMC10564409 |
RESULTS | PMC10564409 | |||
Associations between demographics, sleep, cognition and CR proxies | In 135 cognitively unimpaired older adults from the Age-Well cohort aged 65 and above (mean age = 69.4 ± 3.8; 83 women), a polysomnography was acquired and allowed to obtain the proportion of SWS relative to total sleep time. A neuropsychological battery allowed to compute an episodic memory and an executive function composite score (see Methods for details). Finally, the number of years of schooling (education), the Cognitive Activities Questionnaire (CAQ) [ | PMC10564409 | ||
Participants’ characteristics ( | Abbreviations: NA: not applicable; REM: rapid-eye movement; SD: standard deviation; SWS: slow wave sleep; TST: total sleep time. | PMC10564409 | ||
Interaction between CR proxies and SWS on cognition | REGRESSION | To evaluate the moderating effect of CR on the link between SWS and cognition, separated multiple linear regression were used to assess the interaction between each CR proxies (total and period-specific scores) and SWS on each cognitive composite score, controlling for age and sex ( | PMC10564409 | |
Interactions between cognitive reserve proxies and slow wave sleep on cognition adjusted for age, sex and AHI. | Results in bold were considered significant at | PMC10564409 | ||
DISCUSSION AND CONCLUSION | sleep disturbances, AD, dementia | PATHOLOGY | In this study, we assessed the association between SWS and cognition in a cohort of cognitively unimpaired older adults and examined whether CR, assessed using different proxies reflecting mental activities over the life-course, could modulate these links. Our results show that the association between SWS and executive function and episodic memory performance differs according to CR, and this result seems more robust when considering the practice of cognitive/mental activities during mid-life.Our analyses showed a positive, yet not robust, association between the proportion of SWS and episodic memory, while no association was found with executive performance. These findings support the major role of this sleep stage in memory processes [Interestingly, we found that the moderating effects of CR were observed only in women. Considering that several studies have shown greater cognitive resilience against AD pathology or age-related changes in women than in men [Our study has several strengths. Analyses were conducted in a large sample of older participants who underwent a detailed cognitive assessment and polysomnography, the gold-standard for an objective sleep assessment. We also combined a classically used CR proxy (education) and more fine-grained proxies reflecting the exposure to stimulating activities over the life-course. The cognitive assessment included several tasks allowing us to investigate both executive functioning and episodic memory, particularly relevant as they are known to be sensitive to aging and dementia. Finally, most of the findings remained significant after applying FDR correction. Nonetheless, we could only partially replicate our findings when controlling for or splitting individuals according to their AHI. It could be due to a reduced sample size or collinearity in the model controlling for AHI (i.e., AHI and SWS are correlated, r = −0.3, We showed, for the first time in a large sample of older adults, that individuals with a higher CR were able to maintain good executive and episodic memory performance even in case of low amounts of SWS measured objectively by polysomnography. In contrast, older adults with a low CR were more vulnerable to SWS reduction and showed poor cognitive performance. These results suggest that CR may protect against the negative effect of sleep changes in older-age on cognitive performance, and that mid-life could be a potential period of interest which remains to be further investigated in prospective studies. These findings are important to understand the factors promoting successful aging and suggest that the deleterious impact of sleep disturbances could be counteracted by an enriched lifestyle. This will help to design non-pharmacological interventions to promote successful aging and counter age-related sleep changes. | PMC10564409 |
MATERIALS AND METHODS | PMC10564409 | |||
Participants | We included 135 cognitively unimpaired older adults from the baseline visit of the Age-Well randomized controlled trial (see [ | PMC10564409 | ||
Sleep | Participants underwent a polysomnography (PSG) at home using an ambulatory device (Siesta | PMC10564409 |
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