LAUSR

Recent work has characterized polysomnographic (PSG) changes in Alzheimer’s Dementia (AD) that correlate with disease severity and precede clinical diagnosis, although these findings are limited by relatively small sample sizes and a lack of studies examining sleep microarchitecture. In this study we examined sleep macro- and microarchitectural features in large cohorts of patients with AD and mild cognitive impairment (MCI). Using a database of over 15,000 clinical PSGs with associated clinical metadata, 125 and 173 subjects were identified with mild AD and MCI, respectively. 260 age and sex matched subjects without neurological disease were identified as healthy controls (HC). Sleep staging results were based on AASM criteria, and micro-architectural features were assessed using an algorithm (Wake EEG Similarity Index, WESI) trained to predict state using spectral data from a unique healthy adult cohort. Sleep fragmentation was apparent in both the MCI and AD cohorts (relative to healthy controls), with AD subjects demonstrating substantially more severe PSG disturbances. Healthy controls demonstrated 400 minutes of total sleep time, in contrast to 374 minutes for MCI subjects and 362 minutes for AD subjects. Healthy subjects demonstrated 33 minutes of wake after sleep onset (WASO), compared to 60 and 67 minutes for MCI and AD subjects, respectively. As has been previously reported in smaller cohorts, wakeful bouts and N1 durations were substantially prolonged for AD and (to a lesser extent) MCI subjects, while N2, N3, and REM durations were reduced (with a pronounced reduction in AD N3 percentage). Sleep microarchitectural features assessed using WESI demonstrated that AD and MCI subjects had markedly higher relative wakefulness in all sleep stages except for N3, which showed the same sleep depth as HC. We confirm increased sleep fragmentation and loss of deeper sleep stages that correlate to disease severity. Spectral features of all sleep stages except N3 appear more wakeful in AD and MCI subjects, suggesting microarousals or impaired sleep maintenance contribute to sleep pathology. While N3 duration was markedly reduced, depth of sleep as measured by the WESI algorithm was comparable between populations. PSG findings offer promise as early diagnostic and therapeutic targets.