APOE ε4 and amyloid status moderate the associations between sleep, physical activity, and tau‐PET burden in cognitively unimpaired older adults

Abstract INTRODUCTION Disturbed sleep and physical inactivity are associated with increased risk for dementia. However, associations with Alzheimer's disease (AD) pathology, and whether these associations differ depending on underlying disease risk, remain unclear. METHODS We examined associations of actigraphy‐derived total volume of physical activity (TVPA), total sleep time (TST), and wake after sleep onset (WASO) with tau burden measured by positron emission tomography (PET) in Braak I–II subregions among 120 cognitively unimpaired older adults. Moderation by APOE ε4 carrier status and amyloid positivity, based on amyloid PET, was examined to evaluate risk‐dependent associations. RESULTS Greater WASO was associated with higher tau burden among APOE ε4 carriers and amyloid beta (Aβ)‐positive individuals. TVPA was associated with higher tau burden among Aβ‐positive individuals and lower tau burden among Aβ‐negative individuals. DISCUSSION Associations of sleep and physical activity with early tau pathology differ by genetic risk and Aβ status, highlighting the importance of risk stratification.