Sleep apnea in REM sleep as an amplifier of vascular contributions to Alzheimer's disease.

Obstructive sleep apnea (OSA), a common though underdiagnosed disorder in older adults, represents a potential upstream vascular stressor linked to increased Alzheimer's disease (AD) risk. In this Perspective article, we propose a stage-informed framework in which rapid eye movement (REM) sleep-related respiratory events amplify vascular contributions to AD. This framework is unified across four linked lines of evidence suggesting that (1) REM sleep physiology magnifies the hypoxic and hemodynamic burden of OSA, (2) the cardiometabolic consequences of sleep apnea are heightened in REM sleep, (3) REM-related hypoxemia is associated with markers of cerebrovascular pathology, and (4) vascular effects associated with REM-related hypoxemia are associated with medial temporal lobe vulnerability and memory dysfunction: core features of AD. Although direct evidence linking REM-specific OSA to AD biomarkers is lacking, we highlight REM sleep as a potentially critical window through which sleep-disordered breathing may amplify vascular contributions to AD.