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

Abstract

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.

Health Risk, Functional Markers and Cognitive Status in Institutionalized Older Adults: A Longitudinal Study

“…These results were consistent with the findings from some previous longitudinal studies, all performed in free-living older people, like in the Rotterdam Study with a follow-up of 2.7 years [19], the Leiden 85-Plus Study (4 years follow-up) [20], or the Chicago Health and Aging Project (6 years follow-up) [21]. However, other studies about this topic show opposite results [22,23]. In a recent study in elderly Austrians [23], not relationship was found between vitamin B12 levels and cognitive decline; nevertheless, authors noted that the average concentrations of serum cobalamin in their sample were within the reference range.…”

“…However, other studies about this topic show opposite results [22,23]. In a recent study in elderly Austrians [23], not relationship was found between vitamin B12 levels and cognitive decline; nevertheless, authors noted that the average concentrations of serum cobalamin in their sample were within the reference range. This aspect is in line with our results, where older adults with normal vitamin B12 levels did not experiment any MMSE score variation; conversely, subjects with abnormal values of vitamin B12 (<148 pmol/L) showed a significative deterioration on MMSE score.…”

Association of Elevated Plasma Total Homocysteine With Dementia With Lewy Bodies: A Case-Control Study

“…In addition, folate and vitamin B12 are important mediators of tHcy levels, indirectly correlated with AD (Selhub et al, 1993). Accordingly, some (Clarke et al, 1998;Ravaglia et al, 2005;Hoffmann et al, 2021), but not all studies (Ma et al, 2017;Rabensteiner et al, 2020) have shown that low levels of folate and vitamin B12 were associated with AD. More recent studies have specifically addressed the association between a significant elevation of tHcy levels and neurodegenerative diseases including Parkinson's disease (PD) and multiple system atrophy (MSA; Zhang et al, 2015;Sleeman et al, 2019).…”

“…B vitamins including vitamin B12 and folate are essential factors involved in nucleotide synthesis, one-carbon metabolism, and DNA-methylation; they are also necessary for the well-being and normal function of the brain and have been linked to cognitive impairment, AD, and dementia, though results have been inconclusive thus far (Clarke et al, 1998;Ravaglia et al, 2005;Gillette Guyonnet et al, 2007;Pusceddu et al, 2017;Rabensteiner et al, 2020;Hoffmann et al, 2021). Homocysteine, the cytotoxic product of the methionine cycle, is a sensitive marker of folate and vitamin B12 status and may have a direct toxic effect on both blood vessels and neurons (Welch and Loscalzo, 1998;Ho et al, 2002;Refsum et al, 2004;Pusceddu et al, 2017).…”

Cognitive Status and Nutritional Markers in a Sample of Institutionalized Elderly People

“…Results on vitamin D and cognitive function suggest that its main circulating form, 25-hydroxyvitamin D (25-OH vitamin D), is closely associated to cognitive function and that may play an important role against cognitive decline ( Kalueff and Tuohimaa, 2007 ; Buell and Dawson-Hughes, 2008 ; Seamans et al, 2010 ; Schlögl and Holick, 2014 ; Toffanello et al, 2014 ; Wilson et al, 2014 ; Jorde et al, 2015 ; Kueider et al, 2016 ; Goodwill et al, 2018 ; Duchaine et al, 2020 ; reviews in Dickens et al, 2011 ; Van der Schaft et al, 2013 ; Goodwill and Szoeke, 2017 ; Chai et al, 2019 ; Sultan et al, 2020 ). Serum folate and serum vitamin B12 levels have also been related to cognitive decline and dementia, although findings are inconclusive ( Elias et al, 2006 ; Kang et al, 2006 ; Michelakos et al, 2013 ; Moore et al, 2014 ; Rabensteiner et al, 2020 ; for a review see Rosenberg, 2008 ; O’Leary et al, 2012 ). One of the less studied vitamins in this context is vitamin A, and its derived factors such as retinoids.…”