Abstract
Sleep disturbances are increasingly recognized as potential contributors to Alzheimer's disease (AD) progression, but their exact role remains debated. This systematic review aims to synthesize existing evidence on the association between sleep disturbances, particularly disruptions in sleep architecture and obstructive sleep apnea (OSA), and cognitive decline or AD biomarkers, while exploring underlying mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 14 studies were selected from a comprehensive search of PubMed, Excerpta Medica Database (Embase), Psychological Information Database (PsycINFO), and Web of Science. Eligible studies included observational and longitudinal designs assessing sleep disturbances and their links to cognitive outcomes or AD pathology. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). Disruptions in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, such as reduced REM duration and fragmented sleep, were consistently associated with cognitive decline and new-onset dementia. Severe OSA increased AD risk, with hypoxia and sleep fragmentation implicated in neurodegeneration. Both objective (e.g., actigraphy) and subjective sleep measures predicted cognitive impairment, while cerebrospinal fluid (CSF) biomarkers and apolipoprotein E epsilon 4 (APOE ε4) genotype moderated these associations. Mechanistically, sleep disturbances may impair glymphatic clearance and exacerbate amyloid-β accumulation. Sleep disturbances, particularly REM/NREM disruptions and OSA, are robustly linked to AD progression, suggesting their potential as early biomarkers or therapeutic targets. However, causal inferences are limited by observational designs. Future research should prioritize interventional studies to determine whether improving sleep can mitigate AD risk.