SummaryBackgroundAlterations in resting-state neural activity have been reported in people with sleep disruptions and in patients with Alzheimer's disease, but the direct impact of sleep quality on Alzheimer's disease-related neurophysiological aberrations is unclear.MethodsWe collected cross-sectional resting-state magnetoencephalography and extensive neuropsychological and clinical data from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal older control participants. Sleep efficiency was quantified using the Pittsburgh Sleep Quality Index.FindingsNeural activity in the delta frequency range was differentially affected by poor sleep in patients on the Alzheimer's disease spectrum. Such neural changes were related to processing speed abilities and regional amyloid accumulation, and these associations were mediated and moderated, respectively, by sleep quality.InterpretationTogether, our results point to a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the Alzheimer's disease spectrum, with implications for basic research and clinical intervention.Funding10.13039/100000002National Institutes of Health, USA.