Sleep Functional Connectivity, Hyperexcitability, and Cognition in Alzheimer's Disease.

INTRODUCTION:Sleep disturbances are common in Alzheimer's disease (AD) and may reflect pathologic changes in brain networks. To date, no studies have examined changes in sleep functional connectivity (FC) in AD or their relationship with network hyperexcitability and cognition. METHODS:We assessed electroencephalogram (EEG) sleep FC in 33 healthy controls, 36 individuals with AD without epilepsy, and 14 individuals with AD and epilepsy. RESULTS:AD participants showed increased gamma connectivity in stage 2 sleep (N2), which was associated with longitudinal cognitive decline. Network hyperexcitability in AD was associated with a distinct sleep connectivity signature, characterized by decreased N2 delta connectivity and reversal of several connectivity changes associated with AD. Machine learning algorithms using sleep connectivity features accurately distinguished diagnostic groups and identified "fast cognitive decliners" among study participants who had AD. DISCUSSION:Our findings reveal changes in sleep functional networks associated with cognitive decline in AD and may have implications for disease monitoring and therapeutic development. HIGHLIGHTS:Brain functional connectivity (FC) in Alzheimer's disease is altered during sleep. Sleep FC measures correlate with cognitive decline in AD. Network hyperexcitability in AD has a distinct sleep connectivity signature.