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Vitamin B12, cognition, and brain MRI measures

A cross-sectional examination

C.C. Tangney, PhD,
N.T. Aggarwal, MD,
H. Li, MS,
R.S. Wilson, PhD,
C. DeCarli, MD,
D.A. Evans, MD and
M.C. Morris, ScD

+ Author Affiliations

From the Department of Clinical Nutrition (C.C.T.), Section of Nutrition & Nutritional Epidemiology, Department of Internal Medicine (C.C.T., H.L., M.C.M.), Rush Institute for Healthy Aging, Chicago; Departments of Internal Medicine (N.T.A., R.S.W., D.A.E.), Preventive Medicine (D.A.E., M.C.M.), and Neurological Sciences (N.T.A., R.S.W.), Rush Alzheimer's Disease Center (N.T.A., R.S.W., D.A.E.), Rush University Medical Center, Chicago, IL; and Department of Neurology and Center for Neuroscience (C.D.), University of California-Davis, Sacramento, CA.

Address correspondence and reprint requests to Dr. Christine C. Tangney, Department of Clinical Nutrition 425 TOB, Rush University Medical Center, 1700 West Van Buren St., Chicago, IL 60612 ctangney@rush.edu


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.