Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

Noll Campbell¹, Amir Ayub², Malaz A Boustani², Chris Fox³, Martin Farlow⁴, Ian Maidment³, Robert Howard⁵

¹Wishard Health Services, Indianapolis, Indiana; ²Indiana University Center for Aging Research, Regenstrief Institute, Inc., Indianapolis, Indiana; ³University of Kent, Kent, United Kingdom; ⁴Indiana University School of Medicine, Indianapolis, Indiana; ⁵King’s College, London, United Kingdom

Objective: To determine the efficacy of cholinesterase inhibitors (ChEIs) in improving the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease (AD).

Data sources: We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies.

Data extraction: We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF) guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis.

Results: We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confidence interval [CI]; −0.18, −0.01) and a weighted mean difference (WMD) of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46). In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66); and in studies with severe AD patients, the WMD was −0.06 (95% CI; −2.12, +0.57).

Conclusion: Cholinesterase inhibitors lead to a statistical significant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.

Keywords: Alzheimer’s disease, dementia, cholinesterase inhibitors, behavioral and psychological symptoms