Lower slow wave sleep and rapid eye movement sleep are associated with brain atrophy of Alzheimer's disease-vulnerable regions

Abstract

Study objectives: Sleep deficiency is associated with Alzheimer's disease (AD) pathogenesis. We examined the association of sleep architecture with anatomical features observed in AD: (1) atrophy of hippocampus, entorhinal, inferior parietal, parahippocampal, precuneus, and cuneus regions ("AD-vulnerable regions") and (2) cerebral microbleeds (CMBs).

Methods: In 270 participants of the Atherosclerosis Risk in the Communities Study, we examined the association of baseline sleep architecture with anatomical features identified on brain magnetic resonance imaging 13-17 years later. Sleep architecture was quantified as the proportion of slow wave sleep (SWS), proportion of rapid eye movement (REM) sleep, and arousals index using polysomnography. Outcomes included (1) volumetric measurements of each AD-vulnerable region and (2) the presence of any CMBs and that of lobar CMBs, which are more specifically associated with AD. We analyzed the association of each sleep predictor with each magnetic resonance imaging outcome, adjusting for covariates.

Results: Median age was 61, 53% were female, 100% were White, and 47% had 16+ years of education. Median times in SWS and REM were 17.4% and 21.5%, respectively. Having less SWS was associated with smaller volumes of the inferior parietal region (β = -44.18 mm³ [95% confidence interval = -76.62, -11.74] per -1 percentage point of SWS) and cuneus (β = -11.98 [= -20.92, -3.04] mm³ per -1 percentage point). Having less REM was associated with smaller volumes of the inferior parietal region (β = -75.54 [-129.36, -21.72] mm³ per 1 percentage point of REM) and precuneus (β = -31.92 [-63.78, -0.06] mm³ per 1 percentage point). After Bonferroni adjustments, lower SWS and REM were associated with significantly smaller inferior parietal region volumes. Arousal index was not associated with the volumes of AD-vulnerable regions. None of the sleep architecture variables were associated with CMBs or lobar CMBs.

Conclusions: Sleep deficiency is associated with the atrophy of the inferior parietal region, which is observed in early AD. Sleep architecture may be a modifiable risk factor for AD.

Citation: Cho G, Mecca AP, Buxton OM, Liu X, Miner B. Lower slow wave sleep and rapid eye movement sleep are associated with brain atrophy of Alzheimer's disease-vulnerable regions. J Clin Sleep Med. 2025;21(7):1165-1173.

Keywords: Alzheimer’s disease; brain atrophy; cerebral microbleeds; inferior parietal region; sleep architecture.