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.

Keywords: B vitamins; FreeSurfer; aging; cognitive performance; gyrification index; interindividual variability; resting state.

Figure 1

Relation of vitamin B1 and cognition. (A) Negative association between vitamin B1 and visual-spatial working memory (Block-Tapping-Test). Residuals derived from extracting age and gender from the scores. (B) Extreme group comparison between B1 and problem solving (Leistungsprüfungssystem-Test 50+, subtest 3). Error bars provide the standard deviation.

Figure 2

Positive relation between vitamin B6 and cortical folding (yellow: p < 0.01; red: p < 0.05) localized in the (A) left hemisphere (lateral-/medial view) (B) right hemisphere (lateral view). (C) Correlation between vitamin B6 blood levels and local gyrification index values, extracted from the most significant vertex cluster, i.e., left inferior parietal lobule (IPL). Residuals, corrected for age and gender. MFG, middle frontal gyrus; IFG, inferior frontal gyrus; INS, insula; HG, Heschl's gyrus; STG, superior temporal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; OP, parietal operculum; SPL, superior parietal lobe; IPS, intraparietal sulcus; dOC, dorsal occipital cortex; LOC, lateral occipital cortex; vOC, ventral occipital cortex; PCC, posterior cingulate cortex; PCUN, precuneus.

Figure 3

Negative association between vitamin B1 and cortical folding (blue: p < 0.05) localized in the (A) left hemisphere (lateral-/frontal-/caudal view) (B) right hemisphere (medial view). (C) Correlation between vitamin B6 blood levels and local gyrification index values, extracted from the most significant vertex cluster, i.e. the right fusiform gyrus (FG). Residuals, corrected for age and gender. FP, frontal pole; OFC, orbitofrontal cortex; SFG, superior frontal gyrus; mSFG, medial superior frontal gyrus; MFG, middle frontal gyrus; fOP, frontal operculum; INS, insula; IPL, inferior parietal lobule; STG, superior temporal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus.

Figure 4

Overview of increased and decreased functional connectivity (FC) in association with vitamin B6 blood levels. Seed regions, derived from cortical folding analysis (peak vertices plus 5 mm sphere; see Figure 2), are depicted in yellow (intense yellow: if FC changes were observed; light yellow: if no FC changes were observed). Regions with of FC changes with one of the seed regions are marked in gray. Dotted arrows indicate decreased FC in association with higher vitamin B6 level, solid arrows show increased FC with higher B6. IFG, inferior frontal gyrus; MFG, middle frontal gyrus; INS, insula; STG, superior temporal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; SMG, supramarginal gyrus; AG, angular gyrus.

Figure 5

Overview of increased and decreased functional connectivity (FC) in association with vitamin B1 blood levels. Seed regions, derived from cortical folding analysis (peak vertices plus 5 mm sphere; see Figure 2), are depicted in blue (intense blue: if FC changes were observed; light blue: if no FC changes were observed). Regions with of FC changes with one of the seed regions are marked in gray. Dotted arrows indicate decreased FC in association with higher vitamin B1 level, solid arrows show increased FC with higher B1. OFC, orbitofrontal cortex; aSFG, anterior superior frontal gyrus; mSFG, medial superior frontal gyrus; pSFG, posterior superior frontal gyrus; fOP, frontal operculum; 44, Broca's region (area 44); MTG, middle temporal gyrus; FG, fusiform gyrus; SMG, supramarginal gyrus; dOC, dorsal occipital cortex; LOC, lateral occipital cortex; Thal, dorsomedian and pulvinar part of the thalamus; Lob IV, lobule IV of the cerebellum.