Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study

Am J Clin Nutr. 2020 Nov 12;113(1):179-186. doi: 10.1093/ajcn/nqaa293. Online ahead of print.


Background: There is evidence that low plasma vitamin B-12 and folate individually, as well as an imbalance of high folic acid and low vitamin B-12 status, may be associated with lower cognitive function.

Objectives: We examined dietary and plasma folate and vitamin B-12 status, and their interaction, in relation to cognitive function in a cohort of older Puerto Rican adults.

Methods: The design is cross-sectional, with 1408 participants from the Boston Puerto Rican Health Study (mean ± SD age: 57.1 ± 7.9 y). Cognitive function was assessed with a comprehensive test battery and a global composite score was derived. Plasma folate, vitamin B-12, and methylmalonic acid (MMA) were assessed in fasting blood samples.

Results: After adjusting for covariates, high plasma folate and high plasma vitamin B-12 were each positively associated with global cognitive score (β: 0.063; 95% CI: -0.0008, 0.127; P = 0.053 and β: 0.062; 95% CI: 0.009, 0.12; P = 0.023, respectively, for logged values, and β: 0.002; 95% CI: 0.00005, 0.004; P-trend = 0.044 and β: 0.00018; 95% CI: 0.00001, 0.0003; P-trend = 0.036, respectively, across tertiles). Nine percent of participants had vitamin B-12 deficiency (plasma vitamin B-12 < 148 pmol/L or MMA > 271 nmol/L), but none were folate deficient (plasma folate < 4.53 nmol/L). Deficient compared with higher vitamin B-12 was significantly associated with lower cognitive score (β: -0.119; 95% CI: -0.208, -0.029; P = 0.009). We could not examine the interaction for vitamin B-12 deficiency and high plasma folate, because there were too few individuals (<1% of the cohort) in this category to draw conclusions.

Conclusions: Low plasma vitamin B-12 and low plasma folate were each associated with worse cognitive function in this population. Vitamin B-12 deficiency was prevalent and clearly associated with poorer cognitive function. More attention should be given to identification and treatment of vitamin B-12 deficiency in this population. Additional, larger studies are needed to examine the effect of vitamin B-12 deficiency in the presence of high exposure to folic acid.

Keywords: Puerto Rican adults; cognition; diet; folate; folic acid; vitamin B-12.