A two-sample Mendelian randomization study of atherosclerosis and dementia

The causality between atherosclerosis and dementia remains unclear. This study aimed to explore the causal effect of atherosclerosis related indicators on dementia risk based on two-sample Mendelian randomization (MR) using summary statistics of genome-wide association studies (GWASs). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by different sensi-tivity analyses. Suggestive evidence indicated that peripheral arterial disease (PAD) (odds ratio (OR): 0.864, 95% confidence interval (CI): 0.797-0.937), coronary atherosclerosis (CoAS) (OR: 0.927, 95% CI: 0.860-0.998) and atherosclerosis, excluding cerebral, coronary, and PAD (ATHSCLE) (OR: 0.812, 95% CI: 0.725-0.909) were inversely associated with the risk of AD. The sensitivity analysis confirmed a sugges-tive reverse effect of ATHSCLE on the risk of frontotemporal dementia (FTD) (OR, 0.812, 95% CI, 0.725-0.909). Findings provide suggestive evidence that PAD, CoAS, and ATHSCLE might be associated with the risk of AD or FTD, which requires further exploration in larger samples.