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bioRxiv · 10.1101/2025.01.12.632386

Lower slow wave sleep and rapid eye-movement sleep are associated with brain atrophy of AD-vulnerable regions

Abstract

Study objectivesSleep deficiency is associated with Alzheimers 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. MethodsIn 271 participants of the Atherosclerosis Risk in the Communities Study, we examined the association of baseline sleep architecture with anatomical features identified on brain MRI 13[~]17 years later. Sleep architecture was quantified as the proportion of slow wave sleep (SWS), proportion of rapid eye-movement sleep (REM), and arousals index using polysomnography. Outcomes included (1) volumetric measurements of each AD-vulnerable region and (2) the presence of any cerebral microbleeds (CMBs) and that of lobar CMBs, which are more specifically associated with AD. We analyzed the association of each sleep predictor with each MRI outcome, adjusting for covariates. ResultsHaving less SWS was associated with smaller inferior parietal region ({beta}=-44.19 mm3 [95%CI=-76.63,-11.76]) and cuneus ({beta}=-11.99 mm3 [-20.93,-3.04]) after covariate adjustment. Having less REM was associated with smaller inferior parietal region ({beta}=-75.52 mm3 [-129.34, -21.70]) and precuneus ({beta}=-31.93 mm3 [-63.79,-0.07]). After FDR adjustments, lower SWS and REM, respectively, were associated with smaller inferior parietal region. 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. ConclusionsSleep 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. Brief summarya. Current Knowledge/Study Rationale: two sentences summarizing why the study was doneWhile impaired sleep architecture has been associated with Alzheimers disease [AD] diagnosis and cognitive decline. To better understand the impact of sleep on AD pathogenesis, this study examined the association of sleep architecture with anatomical features observed in AD, including the atrophy of AD-vulnerable regions and CMBs. b. Study Impact: two sentences summarizing how the study impacts the fieldOur study shows that lower slow wave sleep and rapid eye movement sleep may be precipitating factors of inferior parietal region atrophy, which is associated with AD risk. Importantly, the current studys findings can help characterize underlying mechanisms of how sleep deficiency, a prevalent disturbance among middle-aged and older adults, may facilitate AD pathogenesis and cognitive impairment.

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Cho, G., MEcca, A. P., Buxton, O. M., Liu, X., Miner, B.. 2025-01-14. Lower slow wave sleep and rapid eye-movement sleep are associated with brain atrophy of AD-vulnerable regions. https://doi.org/10.1101/2025.01.12.632386

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