Complement activation mainly mediates the association of heart rate variability and cognitive impairment in adults with obstructive sleep apnea without dementia.

STUDY OBJECTIVES: The relationship between autonomic nervous system (ANS) dysfunction measured by heart rate variability (HRV) and cognitive impairment in obstructive sleep apnea (OSA) patients is complex and still not well understood. We aimed to analyze the role of complement activation, Alzheimer's disease (AD) biomarkers and white matter hyperintensity (WMH) in modulating the association of HRV with cognitive performance.

METHODS: There were 199 subjects without dementia, including 42 healthy controls, 80 OSA patients with mild cognitive impairment (MCI) and 77 OSA patients without cognitive impairment. All participants completed polysomnography (PSG), cognition, WMH volume and 5-min HRV analysis were recorded during wakefulness and sleep periods. Neuron-derived exosome (NDE) and astrocyte-derived exosome (ADE) proteins were measured by ELISA kits.

RESULTS: The OSA with MCI group were associated with lower mean of standard deviations of R-R intervals for 5-minute intervals (SDANN index) during wakefulness, standard deviation of the R-R interval (SDNN) during sleep stage and percentage of adjacent R-R intervals differing by more than 50 ms (PNN50) in each stage compared with OSA without MCI. The influence of HRV on cognition was partially mediated by complement activation (C5b-9 mediated a maximum of 51.21%), AD biomarkers and WMH.

CONCLUSIONS: Lower SDANN index and PNN50 during wakefulness and SDNN and PNN50 during sleep periods were found in OSA patients with MCI, suggesting potential vulnerability to autonomic and parasympathetic dysfunction. Complement activation, AD biomarkers and WMH might partially mediate and interact the influence of HRV on cognitive impairment in OSA patients.