The Role of 25-OH Vitamin D in Alzheimer's Disease through Mendelian Randomization and MRI

Abstract INTRODUCTION The mechanism underlying the relationship between Alzheimer's disease (AD) and minerals (serum calcium, copper, iron, magnesium, zinc), vitamins (25-OH vitamin D, vitamin A1 [retinol], B9 [folic acid], B12, C) is unclear. METHODS In a two-step Mendelian randomization analysis, the association between positive nutritional elements and 3935 MRI phenotypes was examined, and the mediation proportion was calculated. Horizontal pleiotropy and heterogeneity of Mendelian randomisation were assessed using MR-Egger, Cochran's Q test, MR-PRESSO. RESULTS 25-OH vitamin D (p = 0.0019, OR = 0.6179, 95% CI = 0.4562—0.8368, IVW) is negatively associated with AD among 10 nutrients. The mediation proportion of the effect of vitamin D on AD mediated by IDP_dMRI_TBSS_L3_Superior_fronto-occipital_fasciculus_L was approximately 7.08%. DISCUSSION Our results support 25-OH vitamin D as a causal protective factor for Alzheimer disease. It was found that the Superior_fronto-occipital_fasciculus_L may play a minimal mediating role.