The role of mixed B vitamin intakes on cognitive performance: Modeling, genes and miRNAs involved

To assess the relationships between mixed B vitamin intakes (B1, B2, B3, B6, B9, B12) and cognitive performance, as well as their molecular mechanisms.

The associations of mixed B vitamin intakes with cognitive function were assessed using multivariate regression models, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). GeneMANIA, Comparative Toxicogenomics Database, MIENTURNET, miRNAsong were employed as the main data-mining methods.

Overall effects of the B vitamin intake mixture were significantly associated with global cognition in the WQS, qgcomp, and BKMR models. A mixture of B vitamins (B1, B2, B3, B9) interacted with the five genes (IL1B, BCL2, CASP3, BAX, PTGS2) and was associated with better cognitive function, especially CASP3 and BAX. Physical interactions (77.6%) were observed to be the most important interactions in gene networks. The IL-18 signaling pathway, apoptosis, and Alzheimer's disease were annotated as the key molecular mechanisms involved in mixed B vitamins' improving cognitive function. NFKB1, ATF3, and NR3C1 were the key significant transcription factors associated with cognitive function targeted by a mixture of B vitamins. The strong interaction and expression of hsa-miR-34a-5p, hsa-miR-128-3p, hsa-miR-181a-5p, and hsa-miR-204-5p are involved in mixed B vitamins' better cognitive performance. We also created and evaluated miRNA sponge sequences for these miRNAs, which might be used to alleviate cognitive decline. The cutoff thresholds for B vitamin intake levels that are associated with cognition performance were reported.

Given the increased incidence of dementia across the world, increasing daily mixed B vitamin intake via regular meals may contribute to minimizing dementia risk. Further studies are warranted to identify these links in well-characterized cohorts of diverse populations, either independently or together.