Low status of vitamin B12, B6, and riboflavin, as well as elevated homocysteine, were each associated with increased odds of cognitive dysfunction in older adults, according to a study of 4,553 participants aged 60 and older. Those carrying the ApoE e4 genotype—a known genetic risk factor for Alzheimer’s disease—had significantly higher odds of cognitive dysfunction when combined with low B12 or high homocysteine levels.
Participants were assessed using the Repeatable Battery for Assessment of Neuropsychological Status, with a score below 80 indicating cognitive dysfunction. Of the cohort, 1,170 (35%) of non-ApoE e4 carriers and 506 (42%) of e4 carriers had cognitive dysfunction.
After adjustment for covariates, individuals with the lowest holotranscobalamin (holoTC) levels had 30% higher odds of cognitive dysfunction compared with those in the highest quartile. For vitamin B6 (measured as plasma pyridoxal 5′-phosphate), the third and fourth quartiles were each associated with increased odds: 35% and 37% higher, respectively.
Poor riboflavin status, indicated by high erythrocyte glutathione reductase activation coefficient (EGRac), was strongly associated with cognitive dysfunction. The highest quartile of EGRac had 73% higher odds compared with those in the lowest quartile.
Elevated plasma homocysteine also showed a strong association, with the highest quartile conferring a 50% increase in odds versus the lowest quartile.
A gene–nutrient interaction was observed between ApoE e4 and B12 status. Carriers of ApoE e4 with low holoTC had 40% higher odds of cognitive dysfunction. ApoE e4 carriers with high homocysteine had a 51% increase in odds compared with those with lower homocysteine levels.
ApoE e4 carriers also had lower adjusted mean RBANS scores (81.9 vs 85.7 among non-carriers) and lower scores across all subdomains including memory, visuospatial, attention, and language.
Each additional year of education was associated with a 21% lower risk of cognitive dysfunction. Participants in the most socioeconomically deprived quintile had a 51% increased risk compared with those in the least deprived quintile.
The study used holotranscobalamin rather than total serum B12 due to its greater sensitivity as a functional biomarker. Neither total vitamin B12 nor folate levels were significantly associated with cognitive dysfunction.
“Our findings underscore the importance of considering both nutritional and genetic factors when assessing the risk of cognitive dysfunction in ageing populations,” said Shane Gordon, BSc, of the Nutrition Innovation Centre for Food & Health at Ulster University, Coleraine, Northern Ireland, and colleagues.
Although causality cannot be inferred due to the cross-sectional design, the findings support the role of B-vitamin status in cognitive health—particularly among genetically at-risk populations. Randomized trials are needed to determine whether improving B-vitamin status can reduce the risk of cognitive decline.
The authors reported no conflicts of interest.
Source: BMC Medicine