Research Paper Volume 13, Issue 7 pp 9455—9467

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

Sieglinde Zelzer1, , Edith Hofer2,3, , Andreas Meinitzer1, , Eva Fritz-Petrin1, , Sebastian Simstich1, , Walter Goessler4, , Reinhold Schmidt2, , Markus Herrmann1, ,

  • 1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
  • 2 Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria
  • 3 Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria
  • 4 Institute of Chemistry, University of Graz, Austria

Received: February 9, 2021       Accepted: March 27, 2021       Published: April 7, 2021
How to Cite

Copyright: © 2021 Zelzer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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)D3, 25(OH)D2 and 24,25(OH)2D3 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)2D3 (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)2D3 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)2D3 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.


AD: Alzheimer`s disease; ASPS: Austrian Stroke Prevention Study; ASPS-Fam: Austrian Stroke Prevention Family Study; MRI: Magnetic Resonance Imaging; LC-MS/MS: liquid-chromatography tandem mass-spectrometry; 25(OH)D: 25-hydroxyvitamin D; 1,25(OH)2D: 1,25-dihydroxy vitamin D; 25(OH)D3: 25-hydroxyvitamin D3; 25(OH)D2: 25-hydroxyvitamin D2; 24,25(OH)2D3: 24,25-dihydroxyvitamin D3; VDR: vitamin D receptor; VMR: vitamin D metabolite ratio; NGF: nerve growth factor; GDNF: glial-derived nerve growth factor; NTF3: neurotrophin 3; PTAD: 4-phenyl-1,2,4-triazoline-3,5-dione; m/z: mass to charge ratio; RT: retention time; STD: standard deviation; IQR: interquartile range; β: regression coefficient; SE: standard error of the regression coefficient; and p: p-values.