Effects of Polyunsaturated Fatty Acid Serum Levels on Vascular Dementia: A Two-Sample Mendelian Randomization Study

<b><i>Introduction:</i></b> Several observational studies have indicated that polyunsaturated fatty acid serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies. <b><i>Methods:</i></b> The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR‐Egger regression, weighted median, penalized weighted median, and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses. <b><i>Results:</i></b> No causality was found for PUFAs (odds ratio, 1.14; 95% confidence interval, 0.91–1.42; <i>p</i> = 0.25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity. <b><i>Conclusion:</i></b> In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD.