The relationship between cognitive function, Alzheimer's disease and sleep duration: A Mendelian randomisation study

Objective: Sleep duration is associated with cognitive function and dementia. MR evidence to date, points towards a causal relationship in this direction. However, whether cognitive function or dementia may also cause problematic sleep duration remains unclear. Methods: We conducted summary-level Mendelian Randomisation (MR) analyses to estimate the causal association between general cognitive function, 9g9 (177 SNPs), reaction time (44 SNPs), Alzheimer9s disease (AD) (29 SNPs), and self-reported and objective sleep duration. Sensitivity analyses included: MR-Egger, Weighted median estimator and leave-one-out analyses. We used data from recently published cognitive function, AD and sleep duration genome wide association studies. Results: MR results showed that AD was associated with longer, (Beta=0.14, 95% CI=0.04;0.24), whilst 9g9, and reaction time were associated with shorter (Beta=-0.06, 95% CI=-0.11;-0.01 and Beta=-0.15, 95% CI=-0.29;-0.01, respectively), objective sleep duration. No association was observed between our exposures and self-reported sleep duration. Interpretation: These results suggest a causative relationship between AD, 9g9, reaction time and objective sleep duration, where AD is associated with longer sleep duration and 9g9 and reaction time are associated with shorter sleep. This study furthers our understanding of the relationship between brain health and sleep duration and sheds light on the causal nature of these associations.