The associations of serum vitamin D status and vitamin D supplements use with all-cause dementia, Alzheimer's disease, and vascular dementia: a UK Biobank based prospective cohort study

Abstract

Background: Prior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations.

Objectives: We aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence.

Methods: With a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank.

Results: Although 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07-1.31) for AD; 1.24 (1.08-1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02-1.19) for AD; 1.15 (1.03-1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively.

Conclusions: Although our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence.

Keywords: Alzheimer’s disease; cohort study; dementia; vascular dementia; vitamin D.

FIGURE 1

Dose-response curves illustrating the relationship between 25-hydroxyvitamin D levels and dementia outcomes in 269,229 UK Biobank participants. Dose-response curves were generated from the imputation data set 1.

FIGURE 2

Forest plots presenting subgroup analyses investigating the associations of vitamin D deficiency with incident all-cause dementia (A), Alzheimer’s disease (B), and vascular dementia (C) in 269,229 UK Biobank participants. HRs with 95% CIs were derived from Cox proportional hazards models. APOE, Apolipoprotein E; BMI, body mass index; CI, confidence interval; HR, hazard ratio.

FIGURE 3

Forest plots illustrating subgroup analyses exploring the associations of vitamin D supplementation with incident all-cause dementia (A), Alzheimer’s disease (B), and vascular dementia (C) in 269,229 UK Biobank participants. HRs with 95% CIs were derived from Cox proportional hazards models. APOE, Apolipoprotein E; BMI, body mass index; CI, confidence interval; HR: hazard ratio.