Research Paper Volume 12, Issue 15 pp 15478—15491

The impact of folate and vitamin B12 status on cognitive function and brain atrophy in healthy elderly and demented Austrians, a retrospective cohort study

Jasmin Rabensteiner1, , Edith Hofer2,3, , Günter Fauler1, , Eva Fritz-Petrin1, , Thomas Benke4, , Peter Dal-Bianco5, , Gerhard Ransmayr6, , Reinhold Schmidt2, , Markus Herrmann1, ,

  • 1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, 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 Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  • 5 Department of Neurology, Medical University of Vienna, Vienna, Austria
  • 6 Department of Neurology 2, Med Campus III, Faculty of Medicine, Johannes Kepler University, Kepler University Hospital, Linz, Austria

Received: April 16, 2020       Accepted: July 6, 2020       Published: July 24, 2020
How to Cite

Copyright © 2020 Rabensteiner 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: Dementia, and in particular Alzheimer’s disease (AD), is a debilitating progressive disease with high prevalence in our society. Vitamin B12 and folate deficiency are potential modifiable risk factors. However, previous studies reported inconsistent results.

Results: The average concentrations of all biochemical markers were within the respective reference ranges. Cross-sectional and longitudinal analyses did not reveal significant associations between biochemical markers and cognitive function, global or regional brain volume, cortical thickness or cortical surface area, neither in controls nor in AD patients.

Conclusions: Variations of direct and indirect markers of B12 and folate status are not associated with cognitive dysfunction and brain atrophy.

Methods: This retrospective study explored the association between biochemical markers of B12 and folate status, cognitive function and MRI-based brain atrophy in cognitive normal elderly (controls) and AD patients. Folate, total and active vitamin B12 and MMA were measured in blood samples from 378 controls and 217 AD patients. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in 155 controls and 217 AD patients. In a subset of participants cognitive testing (n=234) and MRI (n=182) was repeated after an average median between 1.25 and 6.25 years.


AD: Alzheimer’s disease; ASPS: Austrian Stroke Prevention Study; ASPS-Fam: Austrian Stroke Prevention Family Study; BHMT: betain-homocysteine-methyltransferase; CERAD: Consortium to Establish a Registry for Alzheimer’s disease; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; ECLIA: electrochemiluminescence immunoassays; eGFR: estimated glomerular filtration rate; GFR: glomerular filtration rate; HPLC: high performance liquid chromatography; IQR: interquartile range; MMA: methyl-malonic acid; MRI: Magnetic Resonance Imaging; MS: mass spectrometry; OHAP: Oxford Healthy Aging Project; PRODEM: Prospective Dementia Registria Austria; STD: standard deviation.