Sleep homeostasis impairment across obstructive sleep apnea severity: findings from a population-based cohort study

Obstructive sleep apnea (OSA) is a sleep disorder that causes recurrent airway obstruction and sleep fragmentation and increases cardiometabolic, cognitive, and mortality risk. Although slow-wave activity (SWA) and sleep homeostasis (SH) are central to restorative sleep and synaptic regulation, the extent to which SH is disrupted across OSA severity remains unclear.

In this population-based cohort study, we analyzed 945 polysomnography (PSG) studies from adults with mild, moderate, severe OSA, or no OSA. Sleep parameters including apnea-hypopnea index (AHI) and slow wave activity (SWA 0.5-4 Hz) from electroencephalography (EEG) in non-rapid eye movement (NREM) sleep were extracted. SH was assessed with overnight decay of SWA, slopes of slow waves, and change in SWA with wake after sleep onset (WASO). Liner regression models were used to identify independent predictors of SH measures.

SWA decay across successive NREM episodes was attenuated in severe OSA group. Higher AHI (p < 0·001) and greater WASO (p < 0·001) were associated with a flatter decay of SWA. For a given level of SWA decay, males exhibited higher AHI than females (p < 0·0001). Slope of slow waves decreased from the first to last hour of NREM sleep in all groups (p < 0.01) except severe OSA. Multivariable models revealed that diabetes, use of antidepressant, anti-anxiety, antihypertensive, and sedative medications and high caffeine intake independently predicted impaired SH, whereas greater N3 sleep percentage was associated with preserved SWA decline.

These data demonstrate SH is disrupted in OSA but additionally modulated by metabolic and pharmacologic factors. Targeting SH may represent a strategy to mitigate neurocognitive and physiological consequences of OSA. Obstructive sleep apnea (OSA) is associated with adverse health outcomes including hypertension, cardiovascular complications, cognitive decline as well as mortality. Impaired sleep homeostasis in OSA may represent a mechanistic link between sleep-disordered breathing and adverse health outcomes as slow wave activity is critical for synaptic downscaling, memory consolidation, and metabolic regulation. OSA is known to impair sleep homeostasis though it is unknown if OSA severity matters. Our data suggested that severe OSA impaired sleep homeostasis but clinical factors should be considered as they can impact sleep homeostasis as well. Future research should evaluate whether therapeutic interventions for OSA can reverse all these impairments and whether treatments should also be directed towards correcting sleep homeostasis impairment as well.