Associations Between Biomarkers of Alzheimer's Disease and Sleep in Cognitively Unimpaired Older Adults

Objective Sleep disturbances have been implicated as a risk factor for developing Alzheimer's disease (AD), but evidence linking plasma AD biomarkers to sleep in cognitively unimpaired individuals remains limited. The present study examined associations between evening, morning, and overnight changes in plasma AD biomarkers and measures of sleep macro‐ and microstructure and subjective sleep quality in older adults. Methods Forty cognitively unimpaired adults aged 55 to 75 years (20 females) without sleep or mental disorders underwent overnight polysomnography. Plasma AD biomarkers p‐tau181, p‐tau217, t‐tau, Aβ42, Aβ40, and Aβ42/40 were assessed in the evening and in the morning and related to sleep macro‐ and microstructure (sleep spindles, EEG spectral power), and subjective sleep measures by using correlational analyzes. Results Higher evening t‐tau and p‐tau181 were associated with reduced N3 sleep, whereas higher morning t‐tau and greater overnight increases in t‐tau were related to longer nocturnal wakefulness. Amyloid‐β measures showed the most consistent associations with sleep microstructure. Higher Aβ42 and Aβ40 concentrations were associated with shorter duration and lower density of sleep spindles, particularly at frontal sites. Higher evening and morning amyloid‐β concentrations were also associated with lower alpha, beta, and spindle‐frequency EEG power, mainly during non‐rapid eye movement sleep. Tau associations with EEG spectral power were less consistent. Interpretation In cognitively unimpaired older adults, plasma AD biomarkers were associated with PSG sleep features, especially amyloid‐β markers with sleep microstructure. These exploratory, correlational findings suggest that sleep spindles and spectral power may reflect early AD‐related biological processes but require replication in larger cohorts.