Multimodal investigation of the early associations between sleep‐wake regulation, cognition and Alzheimer’s disease neuropathology and risk

Abstract

AbstractBackgroundAlterations in sleep‐wake regulation are hallmarks of the ageing process and emerge as risk factors for Alzheimer’s disease (AD). While the fine‐tuned coalescence of sleep microstructure elements may influence age‐related cognitive trajectories, its association with AD‐related processes is not fully known. Likewise, whether markers of sleep‐wake regulation assessed during wakefulness are associated with the risk of developing AD is not established.MethodHere, we sought associations between key elements of the electrophysiology of sleep microstructure and of sleep‐wake regulation and hallmarks of AD neuropathology (early Aβ/Tau/neuroinflammation brain burden) or the polygenetic risk in 360 young adults (18‐31y) and 100 late‐midlife healthy individuals (50‐70y). We further investigated relationships with cognitive performance.ResultWe first found that spontaneous arousal during sleep are heterogenous and differently associated with Aβ and cognition. We further found the young‐like co‐occurrence of sleep spindles and slow‐depolarisation slow waves was associated to lower early burden of Aβ and was predictive of memory decline at 2‐year follow‐up. We also find that the dynamics of the daily change in cortical excitability and EEG markers of sleepiness are respectively not associated with early Ab burden and associated with the polygenic risk of developing AD. Cortical excitability dynamics is, however, association with cognitive performance.ConclusionThese findings unravel early links between sleep‐wake regulation, AD‐related processes or genetic risks and their association with cognitive performance. Spontaneous arousals and the altered coupling of sleep microstructure elements that are key to its mnesic functions may contributes to poorer brain and cognitive trajectories in ageing. In addition, associations between markers of sleep‐wake regulation and AD can be detected during quiet wakefulness.Support: ULiège, Wallonia‐Brussels Federation, Fonds de la Recherche Scientifique (FNRS Belgium), Fondation Recherche Alzheimer (SOA‐FRA Belgium), Fondation Léon Fredericq, EU FEDER programme