Low vitamin B-12 status and risk of cognitive decline in older adults

Abstract

Background: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. Objective: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. Design: Cognitive function was assessed with the Mini-Mental State Examination on ͧ3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. Results: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (Ҁ0.137 to Ҁ0.083), whereas a doubling in tHcy (from 10 to 20 mol/L) or MMA (from 0.25 to 0.50 mol/L) was associated with 50% more rapid cognitive decline (Ҁ0.090 to Ҁ0.169) and (Ҁ0.104 to Ҁ0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. Conclusions: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.Am J Clin Nutr 2007;86:1384 -91.

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

“…It has been hypothesised that unmetabolised folic acid, which is likely to be present in individuals living in areas with mandatory folic acid fortification of food items (8,9) , may mask or exacerbate metabolic and clinical consequences of vitamin B 12 deficiency (10) . The findings from the NHANES study that high folate concentrations were associated with an increased risk of cognitive impairment in individuals with vitamin B 12 deficiency are in line with the results from the Framingham Heart Study including individuals unexposed to folic acid fortification (11) .…”

“…In line with this, cross-sectional analyses within the National Health and Nutrition Examination Survey (NHANES) study revealed that high serum folate status was generally associated with protection against cognitive impairment; however, individuals with low vitamin B 12 status combined with high folate status had an increased risk of cognitive impairment compared with those with a normal status of both vitamins (7) . It has been hypothesised that unmetabolised folic acid, which is likely to be present in individuals living in areas with mandatory folic acid fortification of food items (8,9) , may mask or exacerbate metabolic and clinical consequences of vitamin B 12 deficiency (10) .…”

DTI Correlates of Cognition in Conventional MRI of Normal-Appearing Brain in Patients with Clinical Features of Subacute Combined Degeneration and Biochemically Proven Vitamin B12 Deficiency

“…Some authors have found a strong causal relationship between cognitive decline and vitamin B 12 deficiency, while others have described the relationship as mere coincidence in the geriatric population. 3,5,12 The mechanism for cognition decline is the accumulation of methylmalonic acid secondary to nonactivation of methylmalonyl-CoA mutase, which is myelinotoxic. 35 We also observed a strong correlation of the neuropsychological scores with FA, ADC, and RD changes in some brain regions on DTI.…”

“…A limited number of clinical studies in children demonstrated a correlation between vitamin B 12 deficiency and cognition. 1,2 Studies in elderly subjects suggest that vitamin B 12 deficiency is associated with cognitive decline and may contribute to Alzheimer dementia, 3,4 whereas others have failed to demonstrated an increased risk. 5,6 Subjects with B 12 deficiency may also show changes in the posterolateral column of the spinal cord on MR imaging.…”

Nutritional determinants of cognitive aging and dementia

“…Thus, some of the inconsistent findings across studies of B-vitamin effects on cognitive decline and dementia may be due to the range of nutrient status in the study population. Of ten cohort studies that examined the relations of these B-vitamins and cognitive decline, four reported protective associations with folate (164)(165)(166)(167) and three reported protective associations with vitamin B 12 (165,(168)(169)(170) but many found no association with one or the other Bvitamin (165,(170)(171)(172)(173)(174) . The Chicago Health and Ageing Project study found a deleterious effect of faster decline among persons with food and/or supplement intakes exceeding 400 mg/d (6) .…”