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

Abstract

Objective: To determine the effi cacy 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 effi cacy 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-defi ned 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 suffi cient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a benefi cial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confi dence 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 signifi cant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.

The Efficacy of Licensed-Indication Use of Donepezil and Memantine Monotherapies for Treating Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: Systematic Review and Meta-Analysis

“…Outcome measures at the 24-week time point were used in the analysis where available. The inclusion criteria allowed for the inclusion of outcomes measured between 3 months and 1 year from baseline (as per the meta-analysis by Campbell et al [ 14 ] in 2008).…”

“…There is meta-analysis evidence that ChEIs as a class have a statistically significant benefit compared with placebo in treating symptoms of BPSD in patients with AD [ 14 ]. In particular, donepezil (licensed for the symptomatic treatment of mild to moderately severe AD), which contributed the majority of studies to this analysis (6 of 10 studies), was found to have a statistically significant benefit compared with placebo when analysed separately [ 14 ].…”

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial

“…Currently, a meta-analysis showed that cholinesterase inhibitors had beneficial effects on reducing BPSD with a weighted mean difference of − 1.38 neuropsychiatry inventory point (95% CI − 2.30, − 0.46) with mild to severe AD compared with placebo [35], but most of studies was conducted in AD patients. In this large-scale VaD trial, TZ and donepezil showed modest therapeutic effects for BPSD, with a mean change of − 3.03 for TZ, − 2.21 for donepezil.…”

Management of visual hallucinations in dementia and Parkinson’s disease

“…A meta-analysis (Campbell et al, 2008) of nine RCTs of AchEi including donepezil, galantamine, and rivastigmine found a significant improvement on neuropsychiatric symptoms with a mean reduction in NPI of −0.1 (standard) and −1.38 (weighted) means.…”