Molecular Drivers of Cognitive Decline and Neuroprotection in Obstructive Sleep Apnea: A Narrative Review

Obstructive sleep apnea is a common sleep disorder characterized by chronic intermittent hypoxia (CIH), sleep fragmentation, and upper-airway collapse. Beyond respiratory issues, OSA significantly impacts the central nervous system, increasing the risk for mild cognitive impairment and dementia. This review synthesizes the dual nature of CIH-induced molecular cascades, describing pathways driving neurodegeneration, such as SUMOylation dysregulation, toll-like receptor signaling, and inflammasome overactivation (largely characterized in experimental and animal CIH models), and those activating endogenous neuroprotective adaptations. Physiological defense mechanisms, such as the upregulation of erythropoietin, shifts toward anaerobic glycolysis, and the activation of neurotrophic factors, may act to mitigate neuronal injury. Rather than acting as independent processes, these molecular responses form a dynamic balance between neuronal injury and endogenous neuroprotection. Here, we introduce the concept of 'neuroprotective reserve' as a novel, hypothesis-generating framework to describe this intrinsic buffering capacity against hypoxic stress. Understanding and clinically validating these pathways is critical for developing early diagnostic biomarkers and targeted adjunctive interventions that complement standard therapy to prevent irreversible neurocognitive decline.