Meta-analysis investigates sleep disturbances and their connection to Alzheimer's disease risk in diverse cohorts, suggesting significance throughout mid-life.
Sleep is essential for healthy bodily functioning in many aspects, including physiology, psychology and cognition. Due to the reverse causation, it remains inconclusive whether sleep disturbances contribute to Alzheimer’s disease (AD). The purpose of this meta-analysis was to investigate the association between sleep disturbances and AD risk. PubMed, Embase, and Web of Science were searched for longitudinal cohort studies until May 2025. Random-effects models were employed to pool risk ratios (RRs) with 95% confidence intervals (CIs). Of the 2106 records, 31 studies from East Asia (23%), Europe (32%), and North America (45%) were eligible for inclusion, involving 13,109,323 participants. The pooled effect size showed that sleep disturbances were linked to higher risk of AD (RR 1.40, 95% CI 1.29 to 1.51), with the magnitude attenuated but still significant through multivariate adjustment (adj-RR 1.29, 95% CI 1.18 to 1.42). Similar effects persisted even after reducing effects of reverse causation, as implemented by stratified analysis on mid-life cohorts and longer follow-ups (5–15: RR 1.35, 95% CI 1.01 to 1.81; ≥ 15 years: RR 1.26, 95% CI 1.02 to 1.57). Dose–response analysis revealed a U-shaped correlation, with sleep duration < 6 or > 8 h associated with AD risk elevation. Neither baseline age, follow-up length, nor study quality significantly diluted the observed association. This study adds to evidence that sleep disturbances are relevant to incident AD, even in mid-life cohorts and longer follow-ups, supporting sleep disturbances as a mid-life risk factor of AD.
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