Longitudinal associations of rest-activity rhythms with executive function, plasma biomarkers, and clinical outcomes in older adults.

Introduction: Daily patterns of activity, rest, and sleep, referred to as rest-activity rhythms (RARs), can be characterized by their day-to-day regularity, within-day fragmentation, and contrast between active and rest periods across the 24-h cycle. Disruptions (e.g., irregular schedules, fragmented activity, or reduced day-night contrast) have been associated with cognitive decline among older adults. Few studies have used repeated actigraphy to distinguish person-level average RARs from visit-specific deviations. Methods: The sample included 169 older adults without MCI or dementia at the first actigraphy visit, based on consensus clinical and neuropsychological review. Seven-day wrist actigraphy required at least three 24-h intervals with <5% missing data each; 122 participants had repeated assessments (362 observations total). RARs were characterized using three non-parametric features: (1) day-night contrast [relative amplitude (RA)], (2) day-to-day regularity [interdaily stability (IS)], and (3) within-day fragmentation [intradaily variability (IV)]. Each metric was decomposed into a person-level average and a visit-specific deviation from that average. Linear mixed-effects models examined associations with executive function and BMI-adjusted plasma markers of Alzheimer's disease-related pathophysiology [pTau181/(Aβ42/Aβ40)], neuroaxonal injury (NfL), and astroglial activation (GFAP); exploratory Cox models evaluated incident MCI; and amyloid PET interaction models were conducted in participants with PET data ( Results: Higher average RA and IS and lower average IV were associated with higher executive function. At the visit level, higher-than-average RA and lower-than-average IV relative to each participant's own average were associated with higher executive function at corresponding assessments. Higher average RA was associated with lower risk of incident MCI. RAR metrics were not significantly associated with GFAP, NfL, or pTau181/(Aβ42/Aβ40) in the plasma biomarker models. Amyloid PET status moderated within-person RAR associations with executive function: higher-than-usual RA and IS and lower-than-usual IV were more strongly associated with better executive function among amyloid PET-positive participants. For the plasma biomarkers, the between-person IS × amyloid PET interaction remained significant after correction only for pTau181/(Aβ42/Aβ40). Discussion: These findings highlight the value of repeated actigraphy for distinguishing average RAR levels from assessment-level departures from each participant's own average RAR profile and suggest that visit-specific RAR variation may be particularly relevant to executive function among amyloid PET-positive older adults.