Sleep architecture and self-reported sleep quality are associated with Alzheimer’s disease biomarkers in older adults without dementia

BACKGROUND: Sleep disruption is common in older adults and is a significant risk factor for developing Alzheimer's disease (AD). This study examines the association between self-reported sleep quality, actigraphy- and electroencephalogram (EEG)-measured sleep parameters, and plasma amyloid-tau-neurodegeneration (ATN) biomarkers in older adults without dementia. METHODS: We analyzed baseline data from a randomized controlled trial of 103 sedentary community-dwelling older adults with insomnia symptoms but without dementia. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy, provided blood samples for plasma biomarker assays (amyloid-beta [Aβ] 42, Aβ40, Aβ42/40 ratio, total tau, and neurofilament light [NfL]), and a subsample (n = 56) underwent a 2-night ambulatory EEG. Multiple regression models tested associations between sleep measures and plasma ATN biomarkers. RESULTS: Participants averaged 70.0 ± 6.0 years old, and 80.6% were female. Adjusted analyses showed greater rapid eye movement (REM) sleep percentage was associated with lower Aβ40 (β = -0.018; 95% confidence interval [CI] = -0.027, -0.010) and higher Aβ42/40 ratio (β = 0.016; 95% CI = 0.007, 0.025). Higher PSQI scores were nominally associated with higher Aβ42 (β = 0.017, 95% CI = 0.004, 0.031) and NfL (β = 0.034, 95% CI = 0.007, 0.062), but these associations did not sustain false discovery rate correction. CONCLUSIONS: Greater REM sleep was associated with a more favorable plasma amyloid profile, whereas associations between subjective sleep quality and plasma biomarkers were nominal and require confirmation in larger studies. These findings suggest that REM sleep architecture measured using ambulatory EEG may be particularly sensitive to amyloid-related changes prior to dementia. Clinical Trial Registration Number: NCT03959202.