Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study

Abstract

BackgroundNutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive.ObjectiveThe aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations.MethodsMen and women aged 45–69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006–2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n = 4166) and follow-up (n = 2739) cognitive domain-specific z-scores were estimated using multiple linear regression.ResultsAfter adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p < 0.01) and immediate recall (p < 0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (β = 0.12; 95% CI = 0.02, 0.21).ConclusionsFolate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline.

One-Carbon Metabolism Biomarkers and Cognitive Decline in the Very Old: The Newcastle 85+ Study

“…Results of folate and global cognition and/or specific cognitive domains in prospective cohort studies are frequently in disagreement. This study confirmed findings from studies that showed that folate, as measured by serum folate or RBC folate, was associated with global cognition or specific cognitive domains, 11 , 12 , 13 , 14 , 35 , 36 , 37 whereas others did not find these relationships. 16 , 17 , 38 However, apart from Leiden 85-Plus, these studies focused on younger populations.…”

Cognitive decline: A vitamin B perspective

“…Recently, it was reported that a nutraceutical formulation, consisting of folate and vitamin B12 amongst others, significantly improved cognitive performance and behavioral and psychological symptoms of dementia in 24 patients with AD [40]. Similarly, in the HAPIEE (health, alcohol and psychosocial factors in Eastern Europe) study comprising 4,166 participants, folate and vitamin B12 were positively associated with performance (verbal fluency, immediate recall) [41]. In addition, in 7,030 postmenopausal women without memory cognitive impairment or probable dementia, monitored for over 5 years, those with folate intake below the recommended daily allowance were associated with increased risk of mild cognitive impairment and probable dementia [42].…”

Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing

“…Studies involving populations with lower baseline folate status in general support the role of folate in cognitive dysfunction [160,161,162] and cognitive decline [163,164], whereas those in countries with food fortification policies and thus overall higher mean concentrations of folate, are generally less supportive for a role in cognitive dysfunction [165,166], cognitive decline [167,168,169] or dementia [170]. Similarly, a number of large cohort studies have associated low vitamin B12 status (using more sensitive biomarkers of status including MMA and HoloTC) with cognitive dysfunction [160,166,171] and cognitive decline [162,172,173] in older people. However, the evidence for B12 is less convincing, and one meta-analysis has shown no association of vitamin B12 with cognitive decline or dementia ( n = 14,325) [174].…”