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.

Keywords: Cox proportional hazards model; apolipoprotein E ε4 status; clinical cognitive diagnosis; dementia; modifiable risk factors; sex; survival analysis; vitamin D deficiency; vitamin D supplementation.

FIGURE 1

Flowchart illustrating the step‐by‐step process of the participant inclusion/exclusion criteria. MCI, mild cognitive impairment; NACC, National Alzheimer's Coordinating Center; NC, normal cognition.

FIGURE 2

(A) KM curve of dementia‐free survival over 10 years, stratified by exposure to vitamin D. (B) Adjusted HR for dementia across vitamin D exposure groups. The reference groups were the non‐exposed group (N = 7,751) for vitamin D exposure, male (N = 5,487) for sex, White (N = 10,105) for race, NC (N = 8,076) for cognitive diagnosis, non‐depressed group (N = 11,117) for depression status, and non‐carriers (N = 7,924) for APOE ε4 status. Error bars represent the 95% CI. The star notation indicates statistical significance. APOE, apolipoprotein E; CI, confidence interval; HR, hazard ratio; KM, Kaplan–Meier; MCI, mild cognitive impairment; NC, normal cognition.