Interactions between plasma concentrations of folate and markers of vitamin B₁₂status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

Abstract

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-14 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P¼0·009) between plasma concentrations of folate and vitamin B 12 in relation to cognitive performance. Plasma vitamin B 12 concentrations in the lowest quartile (, 274 pmol/l) combined with plasma folate concentrations in the highest quartile (.18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). 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.Key words: Vitamin B 12 : Folate: Cognition: Elderly Folate and vitamin B 12 status have been directly associated with cognitive performance in cross-sectional and prospective studies (1 -4) . Some earlier case reports have observed accelerated neurological deterioration in patients with pernicious anaemia and severe vitamin B 12 deficiency after treatment with folic acid (5,6) . These observations in combination with the known metabolic interrelation of folate and vitamin B 12 suggest that the effects of one of these B-vitamins on cognitive * Corresponding author: E. L. Doets, fax þ 31 317 483342, email doets@pallashrc.com

Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA)

“…The findings of the present study are consistent with other studies using European population data; those of Clarke et al (11) and Doets et al (13) showing no association of low vitamin B 12 /high folate status with an increased risk to cognitive function. In addition, the Sacramento Area Latino Study on Aging in America (12) did not demonstrate a negative association with cognitive function (n 1535) using a vitamin B 12 deficiency cut-off of <148 pmol/l and high folate of >45•3 nmol/l, although biochemical anomalies were observed.…”

“…conducted in diverse populations have not replicated such adverse associations (11)(12)(13) . There is considerable heterogeneity among the published studies, including differences in vitamin status cut-offs, biochemical methodologies and the instruments used to assess cognitive function (14) .…”

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

“…In 425 Iranian young adults (mean age 32.5 years), those with folate intake above the recommendation had significantly lower scores when assessing depressive affect, somatic complaints and interpersonal difficulties [159]. In a cohort of more than 2200 healthy Norwegian individuals aged 71-75 years, high plasma folate levels were associated with improved cognitive performance [160]. Such associations have been confirmed in two recent meta-analyses.…”

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

“…Furthermore, Moore et al (58) showed participants with high red cell folate and low serum B 12 were three times more likely to have impaired cognitive performance. In contrast, however, analysis from the Hordaland Health study failed to confirm this association in their analysis (59) .…”