Right caudal hippocampal structural-functional coupling alterations in major depressive disorder: an exploratory pattern linking childhood trauma and executive function alterations at lower depression severity.

The “Not Just Right Experience” (NJRE) has been identified as a core motivator of obsessive–compulsive behavior. Individuals high in obsessive–compulsive tendencies (OCT) have demonstrated deficits in executive functions, including working memory, set shifting, and inhibitory control, yet the role of NJREs in these deficits remains unclear. Across two experiments, we examined whether NJREs contribute to OCT-related executive-function impairments. In Experiment 1, participants completed an NJRE induction or control task, followed by working memory (Backward Digit Span), set-shifting (Digit Symbol Substitution), and inhibitory control (Stroop) tasks, a prospective metacognition test, and the Vancouver Obsessive–Compulsive Inventory. NJREs moderated the link between OCT and working memory and mediated the link between OCT and set shifting. No effects were found for inhibitory control or prospective metacognition. Experiment 2 replicated the mediation result for set shifting. These findings indicate that NJREs are robustly related to set-shifting performance among individuals with higher obsessive–compulsive tendencies, underscoring the potential utility of targeting NJREs in cognitive-behavioural intervention.

Predictors of gains in social functioning after cognitive remediation in schizophrenia: Results from the multicenter ISST (Integrated Social Cognition and Social Skills Therapy) trial.

BackgroundThe Dietary Index for Gut Microbiota (DI-GM) is a novel index reflecting diet quality relative to gut microbiota health.ObjectiveThe study aims to investigate the relationship between DI-GM and cognitive function in older adults.MethodsData were obtained from 2629 participants aged ≥60 years in the National Health and Nutrition Examination Surveys (NHANES) (2011-2014). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), and a global z score. Multivariable linear regression, restricted cubic splines (RCS), and subgroup analysis were performed. Predictive utility of DI-GM was assessed via the receiver operating characteristic (ROC) analysis against a baseline model. Mediation analysis examined relationships among DI-GM, the Dietary Inflammatory Index (DII), and cognitive outcomes.ResultsHigher DI-GM was associated with higher AFT, DSST, and the global z scores (p < 0.001). After full adjustment, participants with DI-GM (≥ 6) showed higher AFT score (β = 1.11, 95% CI 0.46∼1.75), DSST score (β = 4.95, 95% CI 3.05∼6.86) and z score (β = 0.19, 95% CI 0.10∼0.28), compared to those with DI-GM (0-3). No significant direct association was observed with CERAD (β = 0.45, 95% CI -0.29∼1.18, p = 0.233). RCS indicated linear relationships between DI-GM and cognitive function scores. DI-GM had excellent predictive performances based on the ROC. No significant interactions were detected by subgroup analysis. Furthermore, DII partly mediated the relationship between DI-GM and cognitive function.ConclusionsThe DI-GM showed a linear positive correlation with cognitive function in older adults.

Integrating actigraphy with demographic data enhances cognitive performance prediction: a multimodal UK biobank analysis using machine learning.

Air pollution is a risk factor for dementia, but its role in early cognitive dysfunction is not clear. We aimed to investigate the association of air pollution with cognitive function, and the role of cardiovascular risk factors and greenspace in this association. The CAHHM (Canadian Alliance for Healthy Hearts and Minds Cohort Study) is a cohort of Canadian adults recruited between 2014 and 2018, for whom averages of exposures to NO2 and fine particulate matter were estimated for 5 years before recruitment. Outcomes included the Montréal Cognitive Assessment and Digit Symbol Substitution Test for cognitive function, and magnetic resonance imaging-measured covert vascular brain injury. Generalized linear mixed models assessed pollutant associations with outcomes in this cross-sectional analysis. A total of 6878 adults participated in the study, with a mean age of 57.6 years (SD=8.8), and 55.6% were women. Mean (SD; range) 5-year pollutant concentrations preceding enrollment for fine particulate matter were 6.9 μg/m3 (2.0 [1.8-11.2]), and for NO2 were 12.9 parts per billion (5.9 [0.9-33.9]). In adjusted models, a 5 μg/m3 higher fine particulate matter concentration was associated with 0.44 points lower Montréal Cognitive Assessment (95% CI, -0.62 to -0.25) and 1.31 points lower Digit Symbol Substitution Test (95% CI, -2.41 to -0.22) scores. A 5 parts per billion higher NO2 concentration was associated with 0.12 points lower Montréal Cognitive Assessment (95% CI, -0.17 to -0.07) and 0.38 points lower Digit Symbol Substitution Test (95% CI, -0.70 to -0.05) scores. A 5 parts per billion higher NO2 concentration was associated with higher odds of covert vascular brain injury (adjusted odds ratio, 1.08 [95% CI, 1.00-1.17]). Cardiovascular risk factors and greenspace did not change these associations. Fine particulate matter and NO2 were associated with lower cognitive function scores in middle-aged adults living in Canada, independent of cardiovascular risk factors. Our results warrant longitudinal follow-up to study the impact of air pollution on cognitive decline.

Brain health disorders (BHDs) remain a concern for people with HIV (PWH) despite antiretroviral therapy access and viral suppression. The contribution of HIV to brain health is often obscured by comorbidities in high-income settings which are less prevalent in sub-Saharan Africa. Neurofilament light chain (NfL), a biomarker of axonal injury, may offer insight into underlying mechanisms. 338 virally-suppressed PWH and 250 people without HIV (PWoH) completed a Research Domain Criteria-informed battery assessing cognitive, sensorimotor, and social processing systems. Demographically-adjusted norms were derived from PWoH. Serostatus differences in impairment (≥ 1SD below the mean) were examined using multivariable logistic regression. Additional models examined associations between NfL (plasma, cerebrospinal fluid [CSF]) and task performance. PWH were similar to PWoH in age (43.9 vs. 43.5yrs), sex (female, 54 vs. 46%), and education (6.1 vs. 5.8yrs). PWH had higher odds of impairment in the cognitive control and attention (Color Trails, Symbol Digit) and sensorimotor (Grooved Pegboard) domains. Plasma NfL was associated with sensorimotor impairment in both groups. Similar trends held in CSF NfL but did not reach statistical significance, likely due to sample size (n = 85). Cognitive and sensorimotor difficulties are common in PWH in Rakai, independent of typical Western confounders. The profile of impairment differs from reports in high-income settings where declarative memory deficits are often observed. NfL was associated with sensorimotor impairment, suggesting that NfL may capture ongoing axonal injury and motor system vulnerability in PWH and PWoH. These findings suggest NfL's potential as a biomarker of sensorimotor impairment in sub-Saharan Africa.

Cardiovascular disease has been consistently associated with cognitive impairment; however, the relationship between Life’s Essential 8 (LE8), a novel composite metric of cardiovascular health (CVH), and cognitive function in older adults remains inadequately characterized. This study aimed to investigate the cross-sectional association between LE8 scores and cognitive function among United States older adults and identify the relative contributions of individual LE8 components. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2011 to 2014 cycles. A total of 2108 participants aged ≥ 60 years with complete cognitive assessment and LE8 data were included. Cognitive function was evaluated using 4 validated neuropsychological tests: Consortium to Establish a Registry for Alzheimer Disease Word Learning and Delayed Recall, animal fluency test, and Digit Symbol Substitution Test. Composite and domain-specific z-scores were computed. Weighted multiple linear regression models were employed to examine LE8-cognition associations, adjusting for demographic and clinical covariates. Weighted quantile sum regression was applied to determine the relative contribution weights of individual LE8 components. In fully adjusted models, each 10-point increment in LE8 score was associated with a 0.09-unit increase in composite cognitive z-score (95% confidence intervals: 0.04–0.14, P < .001). Compared with low CVH (LE8 < 50), high CVH (LE8 ≥ 80) demonstrated significantly higher cognitive z-scores (β = 0.41, 95% confidence intervals: 0.25–0.57, P < .001). Weighted quantile sum regression identified moderate physical activity as the predominant contributor (weight = 0.56) to cognitive performance, followed by blood glucose (0.19) and blood pressure (0.14). Higher LE8 scores are significantly associated with better cognitive function in older adults, with moderate physical activity emerging as the most influential modifiable factor. These findings underscore the potential of integrated CVH optimization as a strategy for cognitive preservation in aging populations.

Sleep, sedentary behaviors (SB) and physical activity are independently associated with cognitive function in older adults, yet the joint relationship of these 24-hour movement behaviors with cognitive function is less well studied. Additionally, the association between SB and cognitive function may differ depending on whether SB is mentally active or inactive. This study aimed to examine the associations between 24-hour movement behavior compositions and cognitive function in older adults, explore the differential associations of different sedentary behavior (SB) types with cognitive function, and assess the predicted cognitive differences associated with time reallocation among these behaviors. Data were drawn from 2516 US adults aged ≥ 60 years in the 2011-2014 National Health and Nutrition Examination Survey. Sleep, total SB, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) were all assessed via wrist-worn accelerometry. Total SB was disaggregated into TV watching (inactive SB), computer use (active SB), and other SB using individual proportional weights derived from the Global Physical Activity Questionnaire (GPAQ). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (memory), Animal Fluency (language), and Digit Symbol Substitution (executive function) tests. Standardized scores were combined into a global cognition score. Weighted compositional linear regression and isotemporal substitution models were applied. In the 4-component model, greater relative time in MVPA and total SB were positively associated with global cognition (β = 0.191 and β = 0.260, respectively; both P ≤ 0.001), whereas relative sleep and LPA were negatively associated with global cognition. In the 6-component model, disaggregating total SB revealed divergent associations: computer use was positively associated with all cognitive domains (global: β = 0.045, P < 0.001), while TV watching was negatively associated with global cognition (β=-0.050, P = 0.047) and language. Notably, neither "other SB" nor sleep remained significantly associated with cognition in this expanded model. Isotemporal substitution analyses indicated that reallocating time to MVPA or computer use was associated with predicted higher global cognition scores, revealing a pronounced asymmetric trajectory where reducing these behaviors predicted steep cognitive declines. Engaging in MVPA or mentally active SB may help preserve cognitive function in older adults, whereas mentally inactive SB is associated with poorer cognition. Optimizing 24-hour time use by replacing passive sedentary behaviors with MVPA or cognitively engaging activities represents a promising strategy.

Brain network properties in treatment-resistant schizophrenia patients and their healthy siblings.

ABSTRACTTramadol is a widely used analgesic whose bioactivation to O‐desmethyltramadol is primarily mediated by cytochrome P450 2D6 (CYP2D6). Genetic variability and drug–drug interactions affecting CYP2D6 may influence tramadol pharmacokinetics and pharmacological effects. Cyclooxygenase‐2 inhibitors are frequently co‐administered with tramadol in multimodal analgesia, but their potential to affect tramadol disposition and effects remains incompletely characterised. Celecoxib has been reported to act as a weak inhibitor of CYP2D6 in vivo. This randomised, single‐blind, placebo‐controlled crossover study evaluated the effects of 8‐day pretreatment with celecoxib or etoricoxib (200 and 120 mg once daily, respectively), compared with placebo, on the pharmacokinetics and pharmacological effects of a single 100 mg oral dose of tramadol in 12 healthy volunteers. Plasma concentrations of tramadol and O‐desmethyltramadol were measured, and pharmacological effects were assessed using visual analogue scales, psychomotor testing (digit symbol substitution test) and cold pressor pain models. Celecoxib pretreatment did not change tramadol exposure but reduced the formation of O‐desmethyltramadol, decreasing the geometric mean AUC ratio (GMR) of O‐desmethyltramadol to tramadol (AUCm/AUCp) by 24% relative to placebo (90% CI, 0.69–0.84; p < 0.001). Etoricoxib had minimal effects on tramadol exposure or metabolism (GMR 0.92; 90% CI, 0.84–1.02; p = 0.13). In conclusion, celecoxib modestly inhibited the bioactivation of tramadol, but not etoricoxib. Differences in pharmacological effects were negligible.

The aim of this study is to investigate the association between tooth loss and cognitive decline and to explore the potential role of salivary microbial genera in this relationship in a nationally representative population. Data from 1,413 adults aged ≥ 60 years in NHANES 2011-2012 were analyzed. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning Tests, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Salivary microbiome profiles were obtained from a subsample of 661 participants using 16S rRNA sequencing. Complex survey regression, PERMANOVA, and multivariable microbial association analyses were applied. Mediation analyses were conducted as exploratory analyses to evaluate potential microbial pathways linking tooth loss with cognitive outcomes. Moderate tooth loss was associated with higher odds of low global cognition (OR=2.91, 95%CI: 2.01-4.23), low AFT (OR=1.57, 95%CI: 1.03-2.39), and low DSST (OR=2.15, 95%CI: 1.47-3.16) after adjustment. Sixteen genera were associated with at least one cognitive metric, including Prevotellaceae_NA, Phocaeicola, and Lactobacillus. In exploratory mediation analyses, three organic acid-producing genera (Lactobacillus, Lachnospiraceae_NA, and Leptotrichiaceae_NA) were identified as potential contributors to the association between tooth loss and cognition. Tooth loss was associated with cognitive decline in older adults, and both conditions were accompanied by differences in salivary microbial composition. Exploratory mediation analyses suggested that certain organic acid-producing taxa may contribute to the observed association. Tooth loss is common in older adults and has been linked to problems with memory and thinking, but the reasons for this connection are not fully understood. In this study, we used data from a large national health survey of adults aged 60 years and older to examine tooth loss, results from several cognitive tests, and the types of bacteria found in saliva. We found that older adults with more missing teeth were more likely to perform poorly on tests measuring memory, attention, and processing speed. We also observed that some types of oral bacteria were related to both tooth loss and cognitive performance. In exploratory analyses, several groups of bacteria that produce organic acids were linked to the relationship between tooth loss and cognitive outcomes. These findings suggest that differences in the oral microbial community may be one of several biological pathways connecting oral health and cognitive function. Understanding how oral health, diet, and oral bacteria interact may help researchers better understand factors related to cognitive aging and to identify potential targets for future research and prevention strategies.

Development and validation of revised battery for ECT-related cognitive deficits (B4ECT ReCoDe).

Excessive daytime sleepiness (EDS) substantially impairs health-related quality of life and cognitive function in obstructive sleep apnea (OSA) patients. However, the underlying neuropathological mechanisms remain poorly understood. To investigate the associations between EDS, cognitive deficits, and brain alterations in OSA patients. Prospective. One hundred two OSA patients (16 female, median age (IQR) 33.00 [28.00-41.00]) and 86 healthy controls (HCs) (16 female, median age (IQR) 33.00 [25.00-50.25]) were prospectively recruited. 3 T, 3D spoiled gradient-echo, diffusion-weighted spin-echo, blood oxygen level-dependent gradient-echo planar. The Epworth Sleepiness Scale, multiparameter MRI, and a series of neuropsychological tests (the number connection tests A and B, digit symbol test, line tracing test, serial dotting test, and Stroop Color/Word test) were performed to evaluate EDS, brain alterations, and cognitive performances. Mann-Whitney U test, independent samples t-test, chi-square test, Spearman's correlation, and mediation analyses were used. Significance level: p < 0.05. OSA patients exhibited statistically poorer cognitive performance (effect size = 0.23-0.37), lower diffusion tensor imaging along the perivascular space (DTI-ALPS) index (effect size = 0.25), and abnormal network topology (effect size = -0.80 to 0.57) compared with HCs. EDS significantly correlated with poorer cognitive performance (r = -0.173 to 0.258), lower DTI-ALPS index (r = -0.199), and abnormal network topology (r = -0.364 to 0.279) in all participants. Furthermore, aberrant degree centrality and nodal efficiency in the bilateral middle frontal gyrus (MFG) and left inferior parietal lobule (IPL) may mediate the relationship between EDS and cognitive deficits (indirect effect = -0.13 to 0.36). These results demonstrate that cognition, DTI-ALPS index, and network topology were all compromised in OSA. Furthermore, abnormal network topology in the bilateral MFG and left IPL may mediate the relationship between EDS and cognitive deficits. Level 2. Stage 2.

e12709 Background: The majority (70-80%) of invasive breast cancers (BC) express estrogen receptors, making endocrine therapy a cornerstone of most BC treatments. However, this therapy can induce menopause or hypoestrogenism in premenopausal women, and is associated with numerous negative symptoms (e.g., sleep problems). Many BC survivors also report cognitive dysfunction both during and after treatment, which is also associated with poor sleep quality, underscoring the need to examine cognitive function and sleep quality in relation to menopausal status. This study examines differences in cognitive function and sleep disturbance among BC survivors by menopausal status (1: pre/peri-menopausal, 2: naturally post-menopausal, and 3: cancer- or treatment-induced post-menopausal). Methods: This secondary, cross-sectional analysis included baseline data from 180 BC survivors from two cohorts (n = 128 stages 0-III; n = 52 stage IV). Sociodemographic information, clinical characteristics, and PROMIS Sleep Disturbance 4a assessments were collected via REDcap surveys. Administration of remote cognitive test batteries (via BrainCheck) included the Trail Making Test – Parts A and B (TMT-A, TMT-B), Digit Symbol Substitution Test (DSST), Stroop Color-Word Test, and the Immediate and Delayed Memory Tests. Analysis of covariance was conducted to assess the effect of menopausal status on the standardized cognitive test scores and sleep disturbance (t scores), covarying for years of education and age. Post hoc comparisons with Bonferroni corrections and effect sizes were also calculated. Results: Significant main effects of menopausal status were found for sleep disturbance (p = 0.012; ω² = 0.049) and TMT-A scores (p = 0.045; ω² = 0.036). Post hoc comparisons indicated that pre/peri-menopausal survivors had significantly lower sleep disturbance than naturally post-menopausal survivors (p = 0.009, Cohen’s d = 0.84). Naturally post-menopausal survivors performed worse than cancer-induced post-menopausal survivors on the TMT-A (p = 0.043, Cohen’s d = 0.51). Since Homogeneity of Variance was violated for Delayed Memory scores, nonparametric models (Kruskal-Wallis) and post hoc tests (Dunn’s) were conducted. A significant main effect for menopausal status was found (p = 0.02; rank ε² = 0.045), with pre/peri-menopausal survivors having significantly higher scores than naturally post-menopausal survivors (p = 0.022) and cancer-induced post-menopausal survivors (p = 0.022). Conclusions: After controlling for age, BC survivors who have gone through natural menopause before treatment may be more vulnerable to sleep disruption, slower processing speed, and worsened memory performance compared to pre/peri-menopausal BC survivors. Further, BC survivors who have gone through cancer- or treatment-induced menopause may be more vulnerable to worsened memory performance compared to pre/peri-menopausal BC survivors.

To compare the therapeutic effect of intermittent theta burst stimulation (iTBS) and repetitive transcranial magnetic stimulation (rTMS) on cognitive function in patients with post-stroke cognitive impairment (PSCI) and investigate underlying neuroelectrophysiological mechanisms using microstate analysis. In this randomized, double-blind, sham-controlled trial, 45 patients with PSCI were assigned 2:2:1 to iTBS, rTMS, and sham groups, with stimulation targeting the left dorsolateral prefrontal cortex. All participants also received therapist-delivered cognitive training in addition to stimulation. Outcomes were evaluated before (T0) and 10 days after (T1). The primary outcome measure was Montreal Cognitive Assessment (MoCA) score. Secondary outcomes were auditory verbal learning test, Wechsler Adult Intelligence Scale-Ⅲ digit symbol coding test and digit span test scores as well as microstate indices. ΔMoCA(T1-T0) scores were significantly improved in both the iTBS (median [interquartile range]: 2.00 [1.00, 4.00]) and rTMS groups (2.00 [1.00, 3.00]) compared with sham group (P < .05). There was no significant difference in ΔMoCA between the 2 active protocols. Significant within-group improvements in memory and working memory were observed in the iTBS group (P < .05). Both iTBS and rTMS group showed significantly increased microstate C parameters between T0 and T1 (P < .05). Furthermore, the transition probabilities in the iTBS group showed more diversity between microstates, while the other groups showed no significant transformation. iTBS and 5-Hz rTMS were effective in improving overall cognitive ability in PSCI, and iTBS may represent a practical, time-efficient alternative to 5-Hz rTMS. EEG microstate suggested distinct modulation patterns, serving as a useful exploratory tool.Clinical Trial Registry Name:Effect of different transcranial magnetic stimulation protocols on cognitive function in patients with post-stroke cognitive impairment. https://www.chictr.org.cn/Clinical Trial Registration Number:ChiCTR2200064233.

Safety-critical odor identification failure and cognitive performance in older U.S. adults: a cross-sectional NHANES analysis.

Heavy metal exposure has been associated with various diseases. The purpose of this study was to determine the single and mutually adjusted associations between blood heavy metals and cognitive function in older adults. This observational study utilizes data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 and involved 1460 participants aged ≥ 60 years. The concentrations of blood lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Immediate Recall Test (IRT), delayed recall test (DRT), animal fluency test (AFT), and digit symbol substitution test (DSST). Mutually adjusted linear regression models, restricted cubic spline (RCS) analyses, and subgroup analyses were performed to evaluate individual and mutually adjusted associations between blood metal concentrations and cognitive function. Multiple linear regression analysis revealed an inverse association between Cd concentrations and cognitive scores (β=-2.698, 95% CI: -4.842, -0.554). Blood Se levels were positive associations with cognitive scores (β = 0.049, 95% CI: 0.022, 0.076) and all four cognitive domains. The RCS showed that the dose-response association between Cd and cognitive scores appeared to be linear (P-nonlinear = 0.566), while Se exhibited a left-skewed inverted U-shaped curve with cognitive scores (P-nonlinear = 0.013). A high concentration of Cd is strongly associated with cognitive decline. However, the protective effect of Se on cognitive function plateaus after reaching a certain concentration. These findings may have significance for the development of interventions aimed at alleviating cognitive impairment.

Folic acid (FA) is a crucial component of the nervous system's functions at all ages and is involved in a number of metabolic activities. We hypothesized that prenatal FA supplementation may profoundly affect women's postnatal cognitive function, which has not been tested before. This study was based on a cohort study (GDM follow-up study, GFS), which is a sub-cohort study derived from Ma'anshan Birth Cohort Study (MABC). A total of 182 women who had prenatal FA supplementation information and completed postnatal cognitive function tests were included in this study. FA supplementation data were prospectively collected in the 1st /2nd /3rd trimester of pregnancy by questionnaires. Cognitive functions were assessed with Stroop Color-Word Test (SCWT), Digit Symbol Substitution Test (DSST) and Montreal Cognitive Assessment (MoCA) in-person interviews conducted by qualified investigators at postpartum follow-up (the mean duration of postpartum follow-up of 7.9 (± 0.4) years). The associations between prenatal FA supplementation at different periods, cumulative FA supplementation, and early postnatal cognitive performance were investigated using linear regression models. After adjusting for confounding factors, FA supplementation during the 1st trimester of pregnancy (β = 9.15, 95%CI: 2.67 ~ 15.62, p = 0.006) and entire pregnancy (β = 8.88, 95%CI: 1.61 ~ 16.15, p = 0.017) were significantly associated with higher DSST scores. Supplementation of FA one month prior pregnancy was significantly associated with shorter Stroop Test A time (β= -0.67, 95%CI: -1.30~-0.05, p = 0.035), Stroop Test A time/Correct number (β= -0.03, 95%CI: -0.05 ~ 0.00, p = 0.036), and Stroop Test B time (β= -0.87, 95%CI: -1.73~-0.01, p = 0.047). Supplementation of FA during the 3rd trimester of pregnancy was significantly linked to shorter Stroop Test B time/Correct number (β= -0.06, 95%CI: -0.12 ~ 0.00, p = 0.048). FA supplementation during the entire pregnancy was associated with shorter Stroop Test B time (β= -1.95, 95%CI: -3.53~-0.37, p = 0.016), Stroop Test B time/Correct number (β= -0.09, 95%CI: -0.15~-0.02, p = 0.014). Furthermore, cognitive function scores increases progressively with longer periods of prenatal FA supplementation. Our study is the first study suggested that FA supplementation from one month prior pregnancy to delivery could significantly improve maternal postpartum cognitive performance, and that the longer FA were taken, the greater benefit was likely to be.

Vornorexant is a novel dual orexin receptor antagonist for insomnia treatment with the shortest half-life in its class. This study aimed to compare the next-morning residual effects of vornorexant and zopiclone following bedtime administration in healthy older adults. In this randomized, double-blind, placebo- and active-controlled, four-way crossover study, 16 healthy participants aged ≥65 years received single bedtime doses of vornorexant (5 and 10 mg), placebo, or zopiclone (positive control) administered during hospitalization. Pharmacodynamic endpoints were assessed 8 h after administration. The primary endpoint, area of body sway with eyes open (calculated using the root mean square of the center of pressure), was significantly smaller in the vornorexant 5 mg and 10 mg groups compared to zopiclone (p=0.001 and 0.003, respectively), but not significantly different from placebo (p=0.289 and 0.547, respectively). Similarly, significant impairments in word recall and psychomotor vigilance task performance were observed in the zopiclone group compared to the vornorexant groups, while no such effects were seen between the vornorexant and placebo groups. No significant difference was observed in the digit symbol substitution test between groups. Somnolence was observed in one, three, and two cases treated with vornorexant 5 mg, vornorexant 10 mg, and zopiclone, respectively. Our findings indicated that vornorexant 5 mg and 10 mg did not exhibit next-morning residual effects at 8 h from bedtime administration. ClinicalTrial.gov ( https://clinicaltrials.gov/ ): NCT05819710, registered on April 6, 2023. jRCT ( https://jrct.mhlw.go.jp/ ): jRCT2071230009, registered on April 17, 2023.