Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status

Maryam Ghahremani; Eric E Smith; Hung-Yu Chen; Byron Creese; Zahra Goodarzi; Zahinoor Ismail

doi:10.1002/dad2.12404

Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status

Alzheimers Dement (Amst). 2023 Mar 1;15(1):e12404. doi: 10.1002/dad2.12404. eCollection 2023 Jan-Mar.

Authors

Maryam Ghahremani^{1

2}, Eric E Smith^{2

3

4}, Hung-Yu Chen^{1

2}, Byron Creese⁵, Zahra Goodarzi^{2

3

6}, Zahinoor Ismail^{1

2

3

4

5

6}

Affiliations

¹ Department of Psychiatry Cumming School of Medicine University of Calgary Calgary Alberta Canada.
² Hotchkiss Brain Institute Cumming School of Medicine University of Calgary Calgary Alberta Canada.
³ Department of Community Health Sciences University of Calgary Calgary Alberta Canada.
⁴ Department of Clinical Neurosciences Cumming School of Medicine University of Calgary Calgary Alberta Canada.
⁵ College of Medicine and Health University of Exeter Medical School University of Exeter Exeter UK.
⁶ O'Brien Institute of Public Health University of Calgary Calgary Alberta Canada.

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.