Vitamin D Supplementation and Incident Dementia: Effects of Sex, APOE, and Baseline Cognitive Status

Abstract Introduction Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia‐free persons from the National Alzheimer's Coordinating Center. Methods Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D−. Kaplan–Meier curves compared dementia‐free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E (APOE) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. Results Across all formulations, vitamin D exposure was associated with significantly longer dementia‐free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55–0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. Discussion Vitamin D may be a potential agent for dementia prevention. Highlights In a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset. Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure. Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment. Vitamin D effects were significantly greater in apolipoprotein E ε4 non‐carriers versus carriers. Vitamin D has potential for dementia prevention, especially in the high‐risk strata.