Sleep characteristics and risk of stroke and dementia: an observational and Mendelian randomization study

Background and Objectives: Sleep disturbances are implicated as risk factors for both stroke and dementia. However, whether these associations are causal and whether treatment of sleep disorders could reduce stroke and dementia risk remains uncertain. We aimed to evaluate associations and ascertain causal relationships between sleep characteristics and stroke/dementia risk and MRI markers of SVD. Methods: We used datasets from a multicentre population-based study, and summary statistics from genome-wide association studies (GWAS) of sleep characteristics and outcomes. We analysed 502,383 UK Biobank participants with self-reported sleep measurements, including sleep duration, insomnia, chronotype, napping, daytime dozing, and snoring. In observational analyses, the primary outcomes were incident stroke, dementia, and their subtypes, alongside SVD markers. Hazard ratios (HR) and odds ratios (OR) were adjusted for age, sex, and ethnicity, and additional vascular risk factors. In MR analyses, ORs or risk ratios are reported for the association of each genetic score with clinical or MRI endpoints. Results: Among 502,383 participants (mean [SD] age, 56.5 [8.1] years; 54.4% female), there were 7,668 cases of all-cause dementia and 10,334 strokes. In longitudinal analyses, after controlling for cardiovascular risk factors, participants with insomnia, daytime napping and dozing were associated with increased risk of any stroke (HR=1.05, 95% CI=1.01-1.11, p=8.53x10-3; HR=1.09, 95% CI=1.05-1.14, p=3.20x10-5; HR=1.19, 95% CI=1.08-1.32, p=4.89x10-4, respectively). Almost all sleep measures were associated with dementia risk (all p<0.001 except insomnia). Cross-sectional analyses identified associations between napping, snoring, and MRI markers of SVD (all p