Abstract

Ageing is characterized by a progressive decline of sleep quality. Sleep difficulties are increasingly recognized as a risk factor for Alzheimer’s disease (AD), and have been associated with cognitive decline. However, the brain substrates underlying this association remain unclear. In this review, our objective was to provide a comprehensive overview of the relationships between sleep changes and brain structural, functional and molecular integrity, including amyloid and tau pathologies in cognitively unimpaired older adults. We especially discuss the topography and causality of these associations, as well as the potential underlying mechanisms. Taken together, current findings converge to a link between several sleep parameters, amyloid and tau levels in the CSF, and neurodegeneration in diffuse frontal, temporal and parietal areas. However, the existing literature remains heterogeneous, and the specific sleep changes associated with early AD pathological changes, in terms of topography and neuroimaging modality, is not clearly established yet. Notably, if slow wave sleep disruption seems to be related to frontal amyloid deposition, the brain correlates of sleep-disordered breathing and REM sleep disruption remain unclear. Moreover, sleep parameters associated with tau- and FDG-PET imaging are largely unexplored. Lastly, whether sleep disruption is a cause or a consequence of brain alterations remains an open question.

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