Self-reported sleep and Alzheimer disease CSF biomarkers: A wake-up call

Alzheimer disease (AD) is the most prevalent cause of dementia, and numerous studies have described sleep disturbances and circadian abnormalities in persons with symptomatic AD.¹ A rapidly accumulating body of research suggests that disturbed sleep is not only a consequence of pathologic brain changes of AD, but may also contribute to AD pathophysiologic mechanisms, even in the preclinical stages of AD.² Sleep disturbances are associated with amyloid deposition, the first known stage of preclinical AD. Poorer sleep quality, as measured by wrist actigraphy, and more frequent napping were tied to CSF evidence of amyloid deposition,³ and self-report of poorer sleep quality and shorter sleep duration were associated with greater amyloid burden, measured by amyloid PET imaging.^4,5 The hypothesized underlying mechanism is sleep-related decreases in soluble β-Amyloid (Aβ) levels: sleep disturbance acutely increases soluble Aβ in humans and mice,⁶ and chronically increases deposition of Aβ into plaques in mouse models.⁷ Insufficient sleep is therefore a plausible promoter of amyloid deposition.