The Effect of CPAP Intervention on Sleep Architecture and Cognition in Alzheimer’s Disease Patients with Obstructive Sleep Apnea

Background Obstructive sleep apnea (OSA) is highly prevalent in the early stages of Alzheimer’s disease (AD), and its hallmark, sleep fragmentation, may accelerate cognitive decline. Continuous positive airway pressure (CPAP) improves OSA-related hypoxia during slow-wave sleep, but its cognitive benefits in AD remain unclear. Methods We performed a 12-month sub-analysis of a prospective, longitudinal pilot study that enrolled 21 adults (median age = 77 yr; 71% women) with MCI with AD confirmed biomarkers and polysomnography-diagnosed OSA. All participants underwent baseline overnight PSG and neuropsychological testing (CDR, MMSE, RBANS) that were repeated after 12 months. Twelve participants were CPAP-compliant (moderate/severe OSA) and nine were non-users (mild OSA/intolerance). Cognitive change scores (D = 12 months – baseline) were compared with generalized linear models adjusted for baseline cognition and apnea-hypopnea index; associations between baseline sleep parameters and cognitive trajectories were examined. And the association of sleep variables with the use of CPAP was also evaluated. Results Compared with non-users, CPAP users showed significantly slower global decline (D MMSE: p = 1.60e-02) and improvements in overall cognition (D RBANS Total: p = 2.80e-02), and RBANS sub-domains (Δ RBANS FC: p = 1.06e-02; Δ RBANS SF: p = 4.53e-02). Longer baseline NREM stage 3 and REM sleep, greater total sleep time and sleep efficiency, and right-side sleeping were each linked to better cognitive outcomes, whereas extended NREM stage 2, wakefulness, and supine sleeping were associated with poorer trajectories. Conclusions Twelve months of CPAP use was associated with attenuated cognitive decline and domain-specific gains in AD-related MCI with OSA. Sleep architecture and body position during sleep predicted cognitive outcomes, underscoring the therapeutic relevance of optimizing breathing and sleep quality. Larger, longer-term trials are warranted to confirm CPAP’s disease-modifying potential and to clarify the mechanistic role of sleep in AD progression.