Interactions between plasma concentrations of folate and markers of vitamin B12 status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

A combination of high folate with low vitamin B-12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B-12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B-12 markers (total vitamin B-12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-e4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P=0 center dot 009) between plasma concentrations of folate and vitamin B-12 in relation to cognitive performance. Plasma vitamin B-12 concentrations in the lowest quartile (<274pmol/l) combined with plasma folate concentrations in the highest quartile (>18 center dot 5nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0 center dot 22, 95% CI 0 center dot 05, 0 center dot 92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B-12, was associated with cognitive performance. Among the elderly participants with vitamin B-12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.