Obstructive sleep apnea syndrome, orexin, and sleep-wake cycle: The link with the neurodegeneration.

Abstract

Obstructive sleep apnea syndrome (OSAS) significantly affects the sleep-wake circadian rhythm through intermittent hypoxia and chronic sleep fragmentation. OSAS patients often experience excessive daytime sleepiness, frequent awakenings, and sleep fragmentation, leading to a disrupted circadian rhythm and altered sleep-wake cycle. These disruptions may exacerbate OSAS symptoms and contribute to neurodegenerative processes, particularly through the modulation of clock gene expression such as CLOCK, BMAL1, and PER. Emerging evidence connects OSAS to cognitive impairment and suggests that these changes may contribute to the development of neurodegenerative disorders such as Alzheimer disease, suggesting that OSAS could be a reversible risk factor for these conditions. Biomarkers, including melatonin and orexin, play crucial roles in understanding these mechanisms. In OSAS patients, melatonin, a marker of circadian rhythmicity, often shows altered secretion patterns that are not fully corrected by continuous positive airway pressure therapy. Orexin, which regulates the sleep-wake cycle, exhibits increased cerebrospinal fluid levels in OSAS patients, possibly due to compensatory mechanisms against sleep impairment and daytime sleepiness. These biomarkers highlight the intricate relationship between circadian rhythm disruptions and neurodegenerative risks in OSAS, emphasizing the need for further research and potential therapeutic strategies to mitigate these effects and improve patient outcomes.