Associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure: evidence from 466,224 UK Biobank participants

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] =1.34, 95% confidence interval [CI] =1.06 to 1.69, p=0.015) and VD (HR=1.61, 95% CI=1.21 to 2.13, p=0.001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (β= -95.25 mm3, 95% CI= -165.31 to -25.19 mm3, p=0.014) and amygdala (β= -51.85 mm3, 95% CI= -88.02 to -15.68 mm3, p=0.012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p>0.05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.