Dementing disorders in the elderly exact a high cost in both human suffering and health care dollars and are the leading cause of the loss of employability and independent living in the older population. It has been known for many years that vitamin B12 (cobalamin) deficiency can cause dementia and other neurobehavioral symptoms which are indistinguishable from Alzheimer's disease. Prospective studies which employ specific methods of diagnosis investigating the role of cobalamin deficiency in dementia are needed. This proposal plans to determine the prevalence of cobalamin deficiency in the following groups of patients: 1) Unselected elderly patients; 2) patients presenting to memory and movement disorders clinics; 3) patients admitted to state mental hospitals; and 4) residents of nursing homes. Sensitive and specific gas chromatography/mass spectrometry assays for serum methylmalonic acid and homocysteine, two metabolites related to the two human cobalamin-dependent enzymes, will be used to confirm tissue deficiency in patients with low serum cobalamin levels. A group of elderly patients and a group of demented patients who are found to have low serum cobalamin levels will be recruited for two prospective studies which evaluate the pattern of hematologic, neurologic, radiographic, electroencephalographic and neuropsychological abnormalities present at baseline and after 8 weeks, 6 months and 1 year of parental cobalamin therapy. The patients in these studies with low serum cobalamin levels and elevated methylmalonic acid and/or homocysteine levels will be compared to the patients with low serum cobalamin levels and normal metabolites and to a group of control patients matched for age and sex without dementia or cobalamin deficiency. The prevalence of elevated cerebrospinal fluid methylmalonic acid levels will be evaluated in patients with low serum cobalamin levels also. This project is designed to determine the prevalence of biochemically significant cobalamin deficiency in elderly populations and patients with neurologic or psychiatric abnormalities. In addition, in two subsets of patients, the pattern of neurobehavioral abnormalities will be defined using sensitive, multifaceted methodology, and the nature and extent of response to cobalamin therapy will be determined.
