Sleep microstructure and cognitive trajectories in healthy aging: Insights from a longitudinal cohort study.

Sleep spindles are linked to white matter connectivity differentially in older adults with and without cognitive impairment

Abstract While sleep disturbance increases with age and neurodegeneration, the relationship between sleep micro-architecture and changes in key white matter tracts is unknown. We aimed to determine how sleep spindles and slow oscillations relate to structural connectivity within selected white matter tracts in older adults at risk for dementia. In this cross-sectional study, 67 participants (mean age = 68.1; 47 females) with subjective cognitive decline (n = 21) or mild cognitive impairment (n = 46) underwent neuropsychological assessment, magnetic resonance imaging and polysomnography. White matter connectivity of anterior thalamic radiation and superior longitudinal fasciculus subdivisions II and III was quantified using whole-brain tractography, with left and right tracts combined. Primary sleep micro-architecture outcomes included slow (11–13 Hz) and fast (13–16 Hz) spindle density and slow oscillation (0.25–1 Hz) power. Secondary outcomes included: overall spindle density (11–16 Hz) and amplitude. Linear regressions assessed associations between sleep micro-architecture and structural connectivity, adjusting for age and sex, with cognitive classification as a moderator. Multiple comparisons were controlled for using the Benjamini–Hochberg false discovery rate procedure, with q < 0.1 considered statistically significant. The mild cognitive impairment group exhibited lower frontal and central fast spindle density compared to the subjective cognitive impairment group (P < 0.05), with no other group differences in sleep macro-architecture or slow oscillatory activity. After false discovery rate correction, there were no significant associations between slow spindle density, fast spindle density or slow oscillation power and tract connectivity. An interaction between central fast spindle density and superior longitudinal fasciculus III connectivity was observed prior to false discovery rate correction, explaining 8% of unique variance, but did not remain significant after correction (q > 0.10). Exploratory analyses reveal a significant interaction between superior longitudinal fasciculus II connectivity and cognitive classification on spindle amplitude, with greater connectivity associated with higher spindle amplitude in individuals with mild cognitive impairment (P = 0.001), but not in those with subjective cognitive decline (P > 0.05). Overall, white matter connectivity of the anterior thalamic radiation and superior longitudinal fasciculus was not robustly associated with sleep spindle density or slow oscillatory power in this at-risk cohort. However, superior longitudinal fasciculus II connectivity may differentially relate to spindle amplitude in mild cognitive impairment, potentially reflecting altered thalamocortical network engagement in early neurodegeneration.

Joint trajectories of sleep deviation risk and frailty and their associations with cognitive decline in middle-aged and older adults: a population-based cohort study.

BACKGROUND Few studies have investigated how the joint dynamic evolution of sleep disorders and frailty affects cognitive functions. METHODS This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, ultimately including 7,749 participants. Sleep duration outside the 6-8 h reference range was used to quantify abnormal sleep duration, with greater departures from this range indicating higher sleep-duration deviation. A group-based trajectory model (GBTM) was used to identify joint longitudinal patterns of sleep deviation risk and frailty, resulting in four distinct joint trajectory groups. Subsequently, Multivariate linear mixed-effects models were then used to evaluate longitudinal changes in continuous cognitive function scores across trajectory groups, while Cox proportional hazards regression models were used to estimate the risk of incident mild cognitive impairment (MCI). RESULTS Compared with Group 1 (stable sleep and non-frail), Groups 2 (persistently worsening sleep with pre-frailty), 3 (worsening sleep with progressive pre-frailty), and 4 (persistently worsening sleep with worsening frailty) showed faster cognitive decline (β = -0.017, - 0.022, and - 0.044 SD/year, respectively). Compared with Group 1, Group 4 had the highest risk of incident MCI (HR = 1.48, 95% CI: 1.20-1.82). Elevated risks were also observed in Group 2 (HR = 1.20, 95% CI: 1.04-1.39) and Group 3 (HR = 1.18, 95% CI: 1.02-1.36). Compared with models based on sleep trajectories or frailty trajectories alone, the joint trajectory model yielded a lower AIC and a higher C-index, indicating superior model fit and discriminatory ability for incident MCI. CONCLUSIONS Worsening joint trajectories of sleep deviation risk and frailty were associated with progressively faster cognitive decline and a higher risk of incident MCI. These joint patterns may provide a useful approach for identifying older adults at elevated cognitive risk.

Longitudinal Trajectories of Cognitive Control and Theory of Mind in Amnestic and Non-Amnestic Mild Cognitive Impairment: Prospective Associations of Objective Sleep Duration

Background/Objectives: Sleep disturbances are increasingly implicated in age-related cognitive decline and may contribute to heterogeneity in cognitive and social–cognitive functioning in Mild Cognitive Impairment (MCI). Nevertheless, it remains unclear whether longitudinal actigraphy-derived sleep parameters predict social cognition, including theory of mind (ToM), across amnestic (aMCI) and non-amnestic (naMCI) MCI subtypes. This study examined longitudinal trajectories of cognitive control and ToM in individuals with aMCI and naMCI and healthy older adults, and investigated whether actigraphy-derived sleep indices prospectively predict subsequent cognitive control and higher-order social cognition across these groups. Methods: A total of 179 participants (46 healthy controls, 75 aMCI, 58 naMCI) were assessed across three waves over approximately 16–20 months. Actigraphy-derived sleep indices were obtained using wrist actigraphy. Cognitive control was assessed with Delis–Kaplan Executive Function System subtests, whereas ToM was evaluated through tasks involving non-literal language comprehension, metaphor and proverb interpretation, higher-order mentalizing, and emotion recognition. Longitudinal trajectories were examined using mixed-design ANOVAs, and prospective sleep effects were tested using longitudinal path models. Results: Both cognitive control and ToM declined over time in the MCI groups, whereas healthy controls showed relative stability. Subtype differences in cognitive control emerged primarily in higher-order planning and rule-monitoring processes, with naMCI showing greater impairment. ToM revealed a clearer and more consistent gradient (healthy controls > aMCI > naMCI), particularly in higher-order inferential tasks. Among the actigraphy-derived sleep indices, only TST prospectively predicted later ToM performance, whereas prospective associations with cognitive control were limited and inconsistent. Conclusions: Reduced sleep duration was prospectively associated with poorer subsequent performance in higher-order social cognition, independently of the executive-control measures examined. These findings highlight phenotypic heterogeneity across MCI subtypes and suggest that objectively measured sleep duration may serve as a clinically relevant longitudinal marker of social–cognitive vulnerability. Future studies are needed to determine whether interventions targeting sleep duration are associated with improved social–cognitive outcomes.

Circadian syndrome, subjective cognitive decline, and plasma biomarkers: Sex-specific patterns and non-linear biomarkers associations.

CircS is associated with SCD severity, while exploratory analyses suggest possible nonlinear associations between CircS score and selected plasma biomarkers and male participants showed a stronger association with SCD-domain scores.

Cross-sectional and Longitudinal Relationships Between Multi-Dimensional Sleep Composites and Cognition in Multi-Ethnic Study of Atherosclerosis (MESA).

How Life-Course Trajectories of Physical Activity Track With Cognitive Decline.

BACKGROUND Physical activity (PA) may help to delay or possibly prevent cognitive decline and dementia. However, few studies have adopted a life-course approach to prospectively examine repeated measures of PA in relation to cognitive decline. METHODS Framingham Heart Study Offspring and Omni 1 participants without prevalent dementia who had ≥3 self-reported PA measures and ≥2 cognitive domain factor score measures were included (n = 2229). Memory, executive function, and language factor scores were previously derived using bifactor confirmatory factor analysis models. Group-based multitrajectory models characterized PA patterns over the adult life-course (ages 17-96 y). Linear mixed-effects models estimated annual changes in cognitive domain factor scores across PA trajectory groups over the same time period. RESULTS We identified 4 PA trajectories: (1) stabilizers: decline from early adulthood through midlife and then stable after age 50 (n = 176), (2) decliners: constant decline over adulthood (n = 526), (3) reversers: increase from early adulthood through midlife and then decline after age 70 (n = 1145), and (4) plummeters: slow decline from early adulthood through midlife and then sharp decline after age 75 (n = 382; reference). Compared with the reference group, stabilizers had 0.012 SD/year (95% CI, 0.004-0.02) slower memory decline, 0.012 SD/year (95% CI, 0.005-0.02) slower executive function decline, and 0.015 SD/year (95% CI, 0.007-0.02) slower language decline. Decliners had slower cognitive decline across all domains, and reversers had slower language decline. CONCLUSIONS Our findings suggest that sustaining PA in mid-to-late life and preventing later life declines may help mitigate cognitive decline with aging.