Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years

Experimental sleep-wake disruption in rodents and humans causally modulates beta-amyloid (A beta) dynamics (e.g., [1-3]). This leads to the hypothesis that, beyond cross-sectional associations, impaired sleep structure and physiology could represent prospective biomarkers of the speed with which Ab accumulates over time. Here, we test the hypothesis that initial baseline measures of non-rapid eye movement (NREM) sleep slowwave activity (SWA) and sleep quality (efficiency) provide future forecasting sensitivity to the rate of Ab accumulation over subsequent years. A cohort of clinically normal older adults was assessed using objective sleep polysomnography in combination with longitudinal tracking of A beta accumulation with [C-11]PiB positron emission tomography (PET) imaging. Both the proportion of NREM SWA below 1 Hz and the measure of sleep efficiency predicted the speed (slope) of subsequent A beta deposition over time, and these associations remained robust when taking into account additional cofactors of interest (e.g., age, sex, sleep apnea). Moreover, these measures were specific, such that no other macro- and microphysiological architecture metrics of sleep demonstrated such sensitivity. Our data support the proposal that objective sleep markers could be part of a set of biomarkers that statistically forecast the longitudinal trajectory of cortical A beta deposition in the human brain. Sleep may therefore represent a potentially affordable, scalable, repeatable, and non-invasive tool for quantifying of A beta pathological progression, prior to cognitive symptoms of Alzheimer's disease (AD).