The purposes of the proposed research will be to validate the quantitation of urinary methylmalonic acid (MMA) as a screening tool for vitamin B12 (cobalamin) deficiency and to determine the prevalence of B12 deficiency in risk groups of free-living elderly, nursing home elderly, and mental hospital patients. The incidence of B12 deficiency in the free-living cohort will also be determined. All free-living individuals in both the prevalence and incidence studies found B12 deficient along with matched controls will receive neurologic and neuropsychological evaluations before and after six months of B12 therapy to ascertain the extent of deficit suffered and the degree of improvement with therapy. Furthermore, two additional collaborative studies will be accomplished. Urinary MMA will be measured yearly in 100 patients with senile dementia of the Alzheimer type and controls over a three year period. Hospital patients (N=500) being evaluated for B12 deficiency will be tested for MMA levels to examine the possibility of falsely low MMA values. In addition, 300 subjects with normal MMA will receive serum B12 determinations to check for falsely low MMA levels. B12 deficiency in unselected elderly cohorts can perhaps most efficiently be detected through the quantitation of urinary MMA in casual, spot urine samples since MMA requires B12 for conversion to succinic acid. Reliable data have shown that patients with elevated MMA have a B12 deficiency. Quantitation of MMA will be accomplished by a rapid, reliable gas chromatography mass spectrometry method using deuterated MMA as an internal standard. Individuals with elevated MMA will have a serum B12 level to verify the deficiency and a Schilling test, if necessary. Controlled testing of individuals with elevated MMA will establish a criteria for a level of uninary MMA and a confirmation of B12 deficiency. Hence, the urinary MMA test holds promise to be a conclusive, noninvasive, inexpensive screening procedure whereas the serum B12 assay is invasive and inaccurate. New data indicate that thousands of nonanemic elderly suffer dementia from untreated vitamin B12 deficiency. Neurologic disability is common in B12 deficient patients, and since the prevalence of B12 deficiency in the elderly could be as high as 7%, the results of this research could be implemented to significantly reduce the prevalence of undetected vitamin B12 deficiency and its sequelae.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Nutrition Study Section (NTN)
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University of Cincinnati
Schools of Medicine
United States
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