A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults

Abstract

Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults (N > 600; age: 55–85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels.

Vitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis

“…Risk ratio or hazard ratio data are rounded to 2 decimal places. B6 on cognitive function in older adults with normal vitamin B6 blood levels [55].…”

“…Additionally, both vitamin B6 and folate are involved in the synthesis of several key neurotransmitters, and folate deficiency has been related to oxidative stress and DNA damage in neurons [68,69]. However, one study showed that a positive association with cortical folding was detectable in a population taking supplemental B vitamins, but cognitive function did not improve [55]. The uncertain mechanism by which B vitamins affect cognition may potentially explain the lack of association between the concentrations or intake of vitamin B12, folate, or vitamin B6 and cognition in the current meta-analysis.…”

A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels

“…A doubling of serum levels during the washout period was observed exclusively with thiamine. If this effect is already apparent in healthy people, then it is even more valuable, e.g., in older people [24] whose poor vitamin B 1 metabolism leads to processing deficits and further to a lack of vitamin B 1 in the brain [25]. Sufficient supply is also required among others, for children [26], celiac disease patients [27], or alcoholics [28].…”

Prevalence of thiamine deficiency in older hospitalized patients

“…A recent cross-sectional study of older adults (aged 55–85 years) demonstrated that despite the normal to high thiamine blood levels of all study participants, insufficient metabolization of thiamine could result in an effective thiamine metabolite deficiency in the target tissue (ie, brain). 30 …”