Lea T. Grinberg

INTRODUCTION Sleep–wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non‐amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. METHODS Overnight electroencephalography monitoring was performed on 48 subjects, including 15 amnestic, 19 atypical AD, and 14 controls. AD was defined based on neuropathological or biomarker confirmation. We compared sleep architecture by visual scoring and spectral power analysis in each group. RESULTS Overall, AD cases showed increased sleep fragmentation and N1 sleep compared to controls. Compared to atypical AD groups, typical AD showed worse N3 sleep dysfunction and relatively preserved rapid eye movement (REM) sleep. DISCUSSION Results suggest differing effects of amnestic and atypical AD variants on slow wave versus REM sleep, respectively, corroborating the hypothesis of differential selective vulnerability patterns of the subcortical nuclei within variants. Optimal symptomatic treatment for sleep dysfunction in clinical phenotypes may differ. Highlights Alzheimer's disease (AD) variants show distinct patterns of sleep impairment. Amnestic/typical AD has worse N3 slow wave sleep (SWS) impairment compared to atypical AD. Atypical AD shows more rapid eye movement deficits than typical AD. Selective vulnerability patterns in subcortical areas may underlie sleep differences. Relatively preserved SWS may explain better memory scores in atypical versus typical AD.