OBJECTIVE: To find out the prevalence of vitamin B12 deficiency among demented patients and to look at the effects of cobalamin repletion on cognition in elderly, subjects with low serum cobalamin and evidence of cognitive dysfunction. DESIGN: Time series data collected in a single-blinded trial of parenteral cobalamin therapy. SETTINGS: Nursing home facility and Outpatient geriatric assessment center. PARTICIPANTS: Sixty-two subjects with low serum cobalamin (<300 pg/ml) and evidence of cognitive dysfunction were entered consecutively over a two years period of time. Fifty-six subjects completed the study. INTERVENTIONS: Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of six months. OUTPATIENT MEASURE: The Folstein Minimental Status Examination(MMSE), clock drawing tests, and caregiver interviews were administered both before and at 3 months after full cobalamin replacement therapy. Assessment was repeated thereafter every three months. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms. RESULTS: After a minimum of 12 months of cobalamin therapy, 40 of 56 patients revealed cognitive improvement. There was a prominent correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for <12 months gained an average of six points on the MMSE (paired t test P = 0.0065), whereas patients symptomatic >12 months gained an average of four points (paired t test P = 0.25). Six patients symptomatic for only 3 to six months normalized their MMSE scores, gaining 1,2,3, 6, and 9 points, respectively. CONCLUSION: It seems that there may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin.