Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination

Abstract

Objective: To investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally. Methods:In 121 community-dwelling participants of the Chicago Health and Aging Project, serum markers of vitamin B12 status were related to summary measures of neuropsychological tests of 5 cognitive domains and brain MRI measures obtained on average 4.6 years later among 121 older adults. Results:Concentrations of all vitamin B12-related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume. Conclusions:Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms. Neurology White matter hyperintensity volume (WMHV), cerebral infarcts, and total brain volume (TBV) have been related to performance in multiple cognitive domains 1-4 but few reports exist in which both cognitive performance and structural brain abnormalities are examined in the context of vitamin B12 status. 5,6 To date, no study has investigated these relations with vitamin B12 status among nonwhites or in populations with folic acid fortification policies such as in the United States.In our ongoing study of the risk factors for cognitive disorders in a biracial community, the Chicago Health and Aging Project (CHAP), we reported that brain MRI measures were associated with cognitive performance, especially perceptual speed in both blacks and whites. Moreover, we found that serum vitamin B12 and methylmalonic acid (MMA) concentrations were associated with 6-year cognitive decline.7 However, neither performance in specific cognitive domains nor brain MRI measures were examined in relation to vitamin B12-related markers in these reports. Thus, our primary objective in this study was to examine the relations of circulating levels of