Sleep and dementia: Assessing established dementia‐related factors using multivariable Mendelian randomization

INTRODUCTION The relationship between sleep, other dementia risk factors, and dementia remains unclear. We aim to explore these associations using a two‐sample Mendelian randomization (MR) approach. METHODS We identified genetic instrumental variables for sleep characteristics from the UK Biobank and obtained summary‐level genetic association data for dementia outcomes, including Alzheimer’s disease (AD), from the FinnGen consortium. We applied inverse‐variance weighted (IVW) MR to examine the associations between sleep characteristics and dementia outcomes. Multivariable MR was subsequently employed to assess the influence of additional dementia‐relevant factors on these relationships. RESULTS Genetic variants for insomnia, among the sleep characteristics, were associated with elevated AD risk (odds ratio [OR] IVW = 3.02, 95% confidence interval [CI]: 1.28–7.10, p = 0.01). Yet this association was largely attenuated after adjusting for education and low‐density lipoprotein (LDL). DISCUSSION These findings indicate that the association between insomnia and AD is complex and indirect, potentially operating through social‐behavioral factors (education) and biological pathways such as LDL cholesterol.