Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium

Study objectivesPoor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC). MethodsPercent of time spent in stages of sleep (N1, N2, N3, REM sleep), wake after sleep onset and sleep maintenance efficiency were derived from a single night home-based PSG. Dementia was ascertained in each cohort using its cohort-specific criteria. Each cohort performed Cox proportional hazard regressions for each sleep exposure and incident dementia, adjusting for age, sex, body mass index, anti-depressant use, sedative use, and APOE e4 status. Results were then pooled in random effects meta-analyses. ResultsThe pooled sample comprised 4,657 participants (30% women) aged [≥]60 years (mean age was 74 years at sleep assessment). There were 998 (21.4%) dementia cases (median follow-up time of 5 to 19 years). Pooled effects of the five cohorts showed no association between sleep architecture and incident dementia. When meta-analyses were restricted to the three cohorts which had dementia case ascertainment based on DSM-IV/V criteria (n=2,374), higher N3% was marginally associated with an increased risk of dementia (HR: 1.06; 95%CI: 1.00-1.12, per percent increase N3, p=0.050). ConclusionsThere were no consistent associations between sleep macro-architecture measured and the risk of incident dementia. Implementing more nuanced sleep metrics remains an important next step for uncovering more about sleep-dementia associations. STATEMENT OF SIGNIFICANCEPoor sleep may represent a potential lifestyle risk factor for dementia. Sleep is thought to be important for the clearance of toxic Alzheimers disease proteins, but whether sleep is associated with dementia risk remains unclear. In the largest study of its kind, utilizing overnight polysomnographic assessment of sleep and data from 5 large U.S cohort studies, we examined the association between sleep macro-architecture and dementia risk. Meta-analysis revealed no clear associations between sleep measures and dementia risk, though there was a suggestion that a higher proportion of N3 sleep may be associated with greater dementia risk. Further exploration of sleep patterns across time, latent sleep traits across metrics, and sleep micro-architecture remain as important next steps for understanding sleep-dementia associations.