Vitamin D and brain health: an observational and Mendelian randomization study

Background: 

Higher vitamin D status has been suggested to have beneficial effects on the brain.

Objective: 

To investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features and the risk of dementia and stroke.

Design: 

We used prospective data from the UK Biobank (37-73 years at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N=33,523) and the risk of dementia and stroke (N=427,690; 3,414 and 5,339 incident cases respectively).

Observational analyses were adjusted for age, sex, ethnicity, month, center, socioeconomic, lifestyle, sun behavior and illness-related factors. Non-linear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N=23,901) and dementia and stroke (N=294,514; 2,399 and 3,760 cases, respectively).

Results: 

Associations between 25(OH)D and total, grey matter, white matter and hippocampal volumes were non-linear, with lower volumes both for low and high concentrations (adjusted Pnon-linear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume (per 10nmol/L 25(OH)D, adjusted β: -6.1, 95%CI -11.5, -7.0).

Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25nmol/L (vs. 50-75.9 nmol/L, adjusted HR: 1.79, 95%CI 1.57, 2.04, and HR: 1.40, 95%CI 1.26, 1.56, respectively).

Non-linear MR analyses confirmed the threshold effect of 25(OH)D on dementia, with the risk predicted to be 54% (95%CI 1.21, 1.96) higher for participants at 25nmol/l compared to 50nmol/l.25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses.

Potential impact fraction suggests 17% (95%CI 7.22, 30.58) of dementia could be prevented by increasing 25(OH)D to 50nml/L.

Conclusions: 

Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia but not on stroke risk.