Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of prospective cohort studies.
PubMed 38461506 · doi:10.3233/JAD-231381
What was done
Authors searched PubMed, Embase, and Cochrane up to July 2023 for prospective cohort studies evaluating vitamin D levels and incident cognitive impairment, Alzheimer's disease (AD), or all-cause dementia. Pooled relative risks (RR) were estimated using random-effects models, and dose-response associations were modeled using two-stage generalized least squares regression.
What was found
From 9,267 screened records, 23 prospective studies were included in the meta-analyses (9 in dementia dose-response, 4 in AD dose-response). Vitamin D deficiency was associated with an increased risk of dementia (RR = 1.42, 95% CI 1.21–1.65), AD (RR = 1.57, 95% CI 1.15–2.14), and cognitive impairment (RR = 1.34, 95% CI 1.19–1.52). Non-linear relationships were detected for dementia (p_nonlinearity = 0.0000) and AD (p_nonlinearity = 0.0042). A circulating 25-hydroxyvitamin D level of approximately 77.5–100 nmol/L was identified as optimal for dementia risk reduction, while AD risk decreased above 40.1 nmol/L.
Why it matters
This review establishes pooled prospective effect sizes and non-linear threshold estimates for 25-hydroxyvitamin D concentrations, offering specific target ranges for future interventional prevention trials.
Limits
The analysis is restricted to observational cohort studies and cannot establish causality or exclude reverse causation (where preclinical cognitive decline leads to lower outdoor activity or poorer nutrition). The abstract does not report participant sample sizes, specific criteria used to define vitamin D deficiency across heterogeneous cohorts, or adjustment for key confounders like APOE genotype or physical activity.
Cited by
- partial Vitamin D deficiency is a significant risk factor for Alzheimer's disease and accelerates disease progression in people who already have Alzheimer's.