The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs

Abstract

Introduction: At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD. Methods: Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library and Web of Science from inception to May 10, 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0. Results: Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD -1.57; 95% CI -2.64 to -0.51), Clinician’s Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD -0.28; 95% CI -0.41 to -0.15), the Neuropsychiatric Inventory (NPI) (both SMD -1.67; 95% CI -2.88 to -0.47 for 10-tiem total score and SMD -1.83; 95% CI -3.25 to -0.42 for 12-tiem total score), and the AD Cooperative Study–Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI 1.29 to 3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death. Conclusions: Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.