Genetic Insights into the Risk of Metabolic Syndrome and Its Components on Dementia: A Mendelian Randomization

Background: The role of metabolic syndrome (MetS) on dementia is disputed. Objective: We conducted a Mendelian randomization to clarify whether the genetically predicted MetS and its components are casually associated with the risk of different dementia types. Methods: The genetic predictors of MetS and its five components (waist circumference, hypertension, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol [HDL-C]) come from comprehensive public genome-wide association studies (GWAS). Different dementia types are collected from the GWAS in the European population. Inverse variance weighting is utilized as the main method, complemented by several sensitivity approaches to verify the robustness of the results. Results: Genetically predicted MetS and its five components are not causally associated with the increasing risk of dementia (all p > 0.05). In addition, no significant association between MetS and its components and Alzheimer's disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, and dementia due to Parkinson's disease (all p > 0.05), except the association between HDL-C and dementia with Lewy bodies. HDL-C may play a protective role in dementia with Lewy bodies (OR: 0.81, 95% CI: 0.72-0.92, p = 0.0010). Conclusions: From the perspective of genetic variants, our study provides novel evidence that MetS and its components are not associated with different dementia types.