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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITIONAL MODULATION OF GAIT AND COGNITION IN AGING

Location: Human Nutrition Research Center on Aging

Title: Status of vitamin B-12 and B-6 but not of folate, homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults

Authors
item Moorthy, Denish -
item Inga, Peter -
item Scott, Tammy -
item Parnell, Laurence
item Lai, Chao Qiang
item Crott, Jimmy -
item Ordovas, Jose -
item Selhub, Jacob -
item Griffith, John -
item Rosenberg, Irwin -
item Tucker, Katherine -
item Troen, Aron -

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2012
Publication Date: June 27, 2012
Citation: Moorthy, D., Inga, P., Scott, T.M., Parnell, L.D., Lai, C., Crott, J.W., Ordovas, J.M., Selhub, J., Griffith, J., Rosenberg, I.H., Tucker, K.L., Troen, A.M. 2012. Status of vitamin B-12 and B-6 but not of folate, homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults. Journal of Nutrition. 142(8):1554-1560.

Interpretive Summary: The frequency of the C677T variant of the human methylene tetrahydrofolate reductase (MTHFR) gene differs across ethnic groups, which have differing prevalence of age-related impairments in cognition, meaning mental processes of perception, memory, judgment, and reasoning. We used a battery of neuropsychological tests to examine the relationship between the MTHFR C677T variant with cognition and depression and whether that variant modifies the effect of folic acid (a dietary component) and homocysteine (a biomarker of cardiovascular disease) on the C677T relationships with cognition and depression. This study analyzed data from two ethnically diverse groups of community living adults - the Boston Puerto Rican Health Study (BPRHS, N=938) and the Nutrition, Aging, and Memory in Elders study (NAME, N=1017). Individuals underwent body and laboratory measurements, dietary and health assessment using validated questionnaires between the years 2003-2007. Cognitive outcomes included measures of global cognition (Mini-Mental Status Exam, MMSE), depression (Center for Epidemiological Studies Depression Scale, CESD), and three factor scores for the domains of attention, executive function and memory that were derived from a detailed set of neuropsychological tests. Low blood levels of vitamin B12 showed a relationship to poorer MMSE scores and higher depression scores, while low vitamin B6 levels showed a relationship to lower MMSW scores and worse attention and executive function. In contrast, the status at the C677T variant, folate and homocysteine were not associated with cognition or depression, regardless of the type of analysis performed. In conclusion, this study does not support the hypothesis that persons carrying two copies of the less common T variant of C677T at the MTHFR gene show impaired cognition or depression, in a population with adequate dietary folate and a high prevalence of cognitive impairment and depression.

Technical Abstract: The C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene differs in frequency in different ethnic groups which have differing prevalence of age-related cognitive impairments. We used a battery of neuropsychological tests to examine association of the MTHFR C677T polymorphism with cognition and depression and whether genotype modifies the effect of folate and homocysteine on these outcomes. Methods This study analyzed pooled cross-sectional data from two ethnically diverse cohorts of community living adults - the Boston Puerto Rican Health Study (BPRHS, N=938) and the Nutrition, Aging, and Memory in Elders study (NAME, N=1017). Individuals in both cohorts underwent anthropometric and laboratory measurements, dietary and health assessment using validated questionnaires between the years 2003-2007. Cognitive outcomes included measures of global cognition (Mini-Mental Status Exam, MMSE), depression (Center for Epidemiological Studies Depression Scale, CESD), and three factor scores for the domains of attention, executive function and memory that were derived from a detailed set of neuropsychological tests. Results: Low plasma vitamin B12 levels were associated with poorer MMSE scores and higher depression scores, and low vitamin B6 levels were associated with lower MMSE and worse attention and executive function in the multivariate analysis. In contrast, MTHFR genotype, folate and homocysteine were not associated with cognition or depression in both ethnicity-pooled and stratified analysis. Conclusions: The current study does not support the hypothesis that MTHFR C677T TT genotype is associated with impaired cognition or depression, in a population with adequate folate status and a high prevalence of cognitive impairment and depression.

Last Modified: 10/1/2014
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