Association of vitamin D with risk of dementia : a dose-response meta-analysis of observational studies

Abstract

Background: The relationship between serum vitamin D levels and dementia risk remains unclear. This meta-analysis aims to evaluate the association and dose-response relationship between vitamin D levels and dementia risk.

Methods: A systematic literature search was conducted in Cochrane Library, PubMed, and Embase up to October 2024. A total of 22 studies comprising 53,122 participants were included. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. A dose-response meta-analysis explored linear and non-linear relationships.

Results: Participants in the lowest vitamin D category had a 49% higher risk of dementia compared to those in the highest category (RR = 1.49, 95% CI: 1.32-1.67; I ² = 37.8%, p = 0.039). The dose-response analysis indicated a linear association, with each 10 nmol/L increase in vitamin D associated with a 1.2% lower dementia risk (RR = 0.988, 95% CI: 0.982-0.994; p = 0.007). Although statistically significant, the magnitude of this effect suggests limited clinical relevance at the individual level, though potential public health impact may be greater in populations with widespread deficiency. No evidence of non-linearity was observed (p for non-linearity = 0.61).

Conclusions: This meta-analysis of observational studies suggests an inverse association between serum vitamin D levels and dementia risk, with a small but consistent dose-response effect. While these findings are robust across subgroups, causality cannot be inferred from observational data. Randomized controlled trials are needed to confirm whether vitamin D supplementation can reduce dementia risk.

Keywords: cognitive impairment; dementia; dose-response; meta-analysis; vitamin D.

Graphical abstract illustrating the association between serum vitamin D levels and dementia risk. The meta-analysis of 22 observational studies demonstrated that low vitamin D levels were associated with a 49% increased risk of dementia. Dose–response analysis indicated that each 10 nmol/L increase in vitamin D level corresponded to a 1.2% reduction in dementia risk.

Figure 1

PRISMA flowchart of study selection.

Figure 2

Forest plots for the lowest vs. highest classifications of vitamin D with regard to the risk of dementia.

Figure 3

Dose-response relationship between serum vitamin D and dementia risk. Spline model (solid line) and linear model (dashed line). Shaded area: 95% confidence intervals. Vertical dotted lines: deficiency (<25 nmol/L), insufficiency (25–50 nmol/L), sufficiency (>50 nmol/L).