Vitamin D deficiency as a risk factor for dementia and Alzheimer's disease: an updated meta-analysis

Abstract

Background: We aimed to comprehensively explore the associations between serum 25(OH)D deficiency and risk of dementia and Alzheimer's disease(AD).

Methods: We systematically searched Pubmed, the Cochrane Library, Embase and the reference lists of pertinent review articles for relevant articles published from database inception up until January 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with random effects models using the Stata 12.0 statistical software package.

Results: Twelve prospective cohort studies and four cross-sectional studies were included in this meta-analysis. The pooled HRs of dementia and AD, respectively, were 1.32 (95%CI: 1.16, 1.52) and 1.34 (95%CI: 1.13, 1.60) for vitamin D deficiency (< 20 ng/ml). In the subgroup analyses, the pooled HRs of dementia and AD, respectively, were 1.48 (95%CI: 1.19, 1.85) and 1.51 (95%CI: 1.04, 2.18) for moderate vitamin D deficiency (10-20 ng/ml) and 1.20 (95%CI: 0.99, 1.44) and 1.36 (95%CI: 1.01, 1.84) for severe vitamin D deficiency (< 10 ng/ml).

Conclusion: There are significant associations between vitamin D deficiency and both dementia and AD. There are stronger associations between severe vitamin D deficiency (< 10 ng/ml) and both dementia and AD compared to moderate vitamin D deficiency (10-20 ng/ml).

Keywords: Alzheimer’s disease; Dementia; Meta-analysis; Vitamin D deficiency.

Fig. 1

Flowchart of selection of studies for inclusion in the meta-analysis

Fig. 2

HRs of association between dementia and vitamin D deficiency (serum 25(OH)D < 20 ng/ml). The size of each square is proportional to the study’s weight. The estimated pooled HR was 1.32 (95%CI, 1.16 to 1.52) with high statistical significance (P < 0.0001). There was moderate heterogeneity among the studies (I² = 45.1%)

Fig. 3

HRs of association between AD and vitamin D deficiency (serum 25(OH)D < 20 ng/ml). The size of each square is proportional to the study’s weight. The estimated pooled HR was 1.34 (95%CI, 1.13 to 1.60) with high statistical significance (P < 0.0001). There was high heterogeneity among the studies (I² = 53.1%)

Fig. 4

Publication bias for studies examining the associations between vitamin D deficiency (serum 25(OH)D < 20 ng/ml) and dementia and AD. The size of each circle is proportional to the study’s weight. The Begg’s tests for the incidence of dementia (A) and AD (B) were roughly symmetrical (P_(dementia) = 0.061, P_(AD) = 0.076, greater than 0.05)