REM Sleep is Associated with Cognition and Biomarkers Longitudinally in Older Adults Across the Alzheimer Disease Continuum

Sleep disturbances represent a potentially modifiable risk factor for Alzheimer disease (AD). The extent to which changes in rapid eye movement (REM) sleep are related to the accumulation of AD pathology and brain tissue loss is not well understood. In the current study, ninety-four individuals 74 clinically unimpaired [CU] and 20 clinically impaired [CI]) underwent polysomnography (PSG), cognitive assessments, and neuroimaging. Cross-sectional and longitudinal models examined the associations between PSG outcomes of interest (percentage of sleep period spent in REM [%REM] and REM latency) and pre-clinical Alzheimers cognitive composite-5 (PACC5) scores, entorhinal tau-positron emission tomography (PET; 18F-flortaucipir), cerebral amyloid-PET (11C-Pittsburgh Compound B; PiB), AD signature cortical thickness, and hippocampal volume, after adjusting for covariates. Across CU and CI individuals, less time spent in REM sleep and prolonged REM latency were associated with poorer cognition after adjusting for age, sex, and years of education. Additionally, these factors were associated with a greater AD pathologic burden after adjusting for age and sex. Longitudinal data, spanning up to 16 years, demonstrated that the rate of change in cognition and AD biomarkers in the time preceding PSG assessment was also strongly associated with REM characteristics. Our findings highlight the potentially bidirectional relationship between the accumulation of AD pathology and the disruption of REM sleep. Future studies are needed to better understand the longitudinal relationship between sleep characteristics, AD progression, and cognitive decline, and to assess the potential of sleep-focused interventions to alter the course of AD clinical, cognitive, and pathological progression. One Sentence SummaryCognitive and biomarker data are associated with REM sleep characteristics in unimpaired and impaired individuals cross-sectionally and over time.