Clinical Question: Are cholinesterase inhibitors useful in the treatment of Alzheimer's disease?

Setting: Various (meta-analysis)

Study Design: Meta-analysis of randomized controlled trials

Synopsis: Cholinesterase inhibitors are widely touted as being useful in the treatment of Alzheimer's disease. The authors of this study performed a thorough search of the English and non-English literature, including MEDLINE, PsychINFO, the Cochrane Registry, and collected references from bibliographies of reviews and other articles of interest. A total of 29 randomized, double-blind, placebo-controlled trials of outpatients diagnosed with mild to moderate Alzheimer's disease were included.

Two investigators independently extracted study data. Outcomes were measured with the Neuropsychiatric Inventory (NPI) (0 to 120 points possible) and the Alzheimer's Disease Assessment Scale (ADAS; 0 to 50 points possible). Functional outcomes were measured with instruments evaluating activities of daily living. Compared with patients receiving placebo, those treated with cholinesterase inhibitors improved 1.72 points on the NPI and 0.03 points on the ADAS. Improvements on scales that evaluated activites of daily living also were very minimal (0.1 or less standard deviation from baseline). There was no difference in efficacy among the various medications.

Bottom Line: Cholinesterase inhibitors are unlikely to be of much clinical benefit in the treatment of Alzheimer's disease. More patient-oriented research of long-term outcomes, such as quality of life, caregiver burden, and institutionalization, is needed. (Level of Evidence: 1a-)