Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study.

Objective: To examine 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 an open trial of parenteral cobalamin therapy.

Settings: Outpatient geriatric assessment centers, inpatient geropsychiatry unit, and tertiary care university hospital.

Participants: Twenty-two subjects with low serum cobalamin (less than 150 pmol/L) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time. Eighteen 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 Mattis Dementia Rating Scale (DRS) was administered both before and at least 6 months after full cobalamin replacement therapy. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori.

Results: After a minimum of 6 months of cobalamin therapy, 11 of 18 patients showed cognitive improvement. There was a striking correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for less than 12 months gained an average of twenty points on the DRS (paired t test P = 0.0076), whereas patients symptomatic greater than 12 months lost an average of three points (paired t test P = .34). Two patients symptomatic for only 3 months normalized their DRS scores, gaining 31 and 28 points, respectively.

Conclusion: There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin.