Association of vitamin D metabolites with cognitive function and brain atrophy in elderly individuals - the Austrian stroke prevention study

Background: Vitamin D is a well-established regulator of calcium and phosphate metabolism that has neurotrophic and neuroprotective properties. Deficiency of vitamin D has been proposed to promote cognitive dysfunction and brain atrophy. However, existing studies provide inconsistent results. Here we aimed to investigate the association between vitamin D metabolites, cognitive function and brain atrophy in a cohort of well-characterized community-dwelling elderly individuals with normal neurological status and without history of stroke and dementia. Methods: 25(OH)D(3), 25(OH)D(2) and 24,25(OH)(2)D(3) were measured by liquid-chromatography tandem mass-spectrometry in serum samples from 390 community-dwelling elderly individuals. All participants underwent thorough neuropsychiatric tests capturing memory, executive function and visuopractical skills. In 139 of these individuals, MRI of the brain was performed in order to capture neurodegenerative and vascular changes. Results: Total 25(OH)D (ß=0.003, 0.037), 24,25(OH)(2)D(3) (ß=0.0456, p=0.010) and vitamin D metabolite ratio (VMR) (ß=0.0467, p=0.012) were significantly related to memory function. Adjustment for multiple testing weakened these relationships, but trends (p≤0.10) remained. 24,25(OH)(2)D(3) and VMR showed similar trends also for visuopractical skills and global cognitive function. No significant relationships existed between vitamin D metabolites and MRI derived indices of neurodegeneration and vascular changes. Sub-group analyses of individuals with low concentrations of 25(OH)D and 24,25(OH)(2)D(3) showed significantly worse memory function compared to individuals with normal or high concentrations. Conclusions: Vitamin D deficient individuals appear to have a modest reduction of memory function without structural brain atrophy. Future studies should explore if vitamin D supplementation can improve cognitive function.