Coupled sleep rhythm disruption predicts cognitive decline in Alzheimer’s disease

The effect of sleep on memory consolidation depends on the precise interaction of slow oscillations (SOs), theta bursts, and spindles. Disruption in coupling of these sleep rhythms has been reported for individuals with Alzheimer's disease (AD). However, it is unknown how the sleep rhythms evolve during AD progression and whether disrupted sleep rhythms facilitate cognitive decline in AD. Here, we analyze data of 93 individuals from sleep electroencephalography (EEG), MRI, cerebrospinal fluid (CSF) AD biomarkers, and two-year cognitive assessments among three populations: AD dementia (n = 33), mild cognitive impairment (MCI) due to AD (n = 38), and cognitively normal (CN, n = 22). Our study identifies the evolving pattern of coupled sleep rhythm disruption with advancing cognitive stages in AD. Specifically, the frequency of SO-theta burst coupling and SO-spindle coupling decreases from CN to MCI; SO-theta burst coupling and SO-spindle coupling further misalign from MCI to AD dementia. The APOE ε4 allele and elevated amyloid and tau burden are associated with coupled sleep rhythm disruption. Hippocampal and medial prefrontal cortex atrophy are respectively linked to disruption of SO-theta burst coupling and SO-spindle coupling. Notably, coupled sleep rhythm disruption predicts accelerated cognitive decline over a two-year follow-up period. Our study presents that integrating sleep EEG with CSF and MRI biomarkers enhances the predictive ability for AD progression, which unravels the potential of sleep rhythms as monitoring and interventional targets for AD.