TY - JOUR
T1 - Efficacy and Safety of Cholinesterase Inhibitors for Mild Cognitive Impairment:A Systematic Review and Meta-Analysis
AU - Matsunaga, Shinji
AU - Fujishiro, Hiroshige
AU - Takechi, Hajime
PY - 2019
Y1 - 2019
N2 - Background: The clinical benefit of cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) remains inconclusive. Objective: We performed a systematic review and meta-analysis of the efficacy/safety of ChEIs on subjects with MCI. Methods: We included randomized controlled trials (RCTs) of ChEIs in subjects with MCI, using cognitive function scores as a primary outcome measure. Results: Fourteen RCTs (six using donepezil, four using galantamine, and four using rivastigmine) with 5,278 subjects were included. We found no significant difference in cognitive function scores between the ChEIs and placebo groups [standardized mean difference (SMD)=-0.06, p=0.38, I2=76% ]. However, in the secondary outcomes, ChEIs were associated with a lower incidence of progression to dementia compared with placebo (risk ratio=0.76, the number needed to treat=20). For safety outcomes, ChEIs were associated with a lower prevalence of fall than placebo. On the other hand, compared with placebo, ChEIs were associated with a higher incidence of discontinuation due to all causes, discontinuation due to adverse events, at least one adverse event, abnormal dreams, diarrhea, dizziness, headache, insomnia, loose stools, muscle cramps, nausea, vomiting, and weight loss. Conclusions: Although ChEIs have a slight efficacy in the treatment of MCI, there are many safety issues. Therefore, ChEIs are difficult to recommend for MCI. However, the efficacy and safety of ChEIs on MCI with a biomarker-based diagnosis is unclear. Further RCTs are needed to confirm the efficacy and safety of ChEIs when used for individual neuropathological classifications of MCI.
AB - Background: The clinical benefit of cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) remains inconclusive. Objective: We performed a systematic review and meta-analysis of the efficacy/safety of ChEIs on subjects with MCI. Methods: We included randomized controlled trials (RCTs) of ChEIs in subjects with MCI, using cognitive function scores as a primary outcome measure. Results: Fourteen RCTs (six using donepezil, four using galantamine, and four using rivastigmine) with 5,278 subjects were included. We found no significant difference in cognitive function scores between the ChEIs and placebo groups [standardized mean difference (SMD)=-0.06, p=0.38, I2=76% ]. However, in the secondary outcomes, ChEIs were associated with a lower incidence of progression to dementia compared with placebo (risk ratio=0.76, the number needed to treat=20). For safety outcomes, ChEIs were associated with a lower prevalence of fall than placebo. On the other hand, compared with placebo, ChEIs were associated with a higher incidence of discontinuation due to all causes, discontinuation due to adverse events, at least one adverse event, abnormal dreams, diarrhea, dizziness, headache, insomnia, loose stools, muscle cramps, nausea, vomiting, and weight loss. Conclusions: Although ChEIs have a slight efficacy in the treatment of MCI, there are many safety issues. Therefore, ChEIs are difficult to recommend for MCI. However, the efficacy and safety of ChEIs on MCI with a biomarker-based diagnosis is unclear. Further RCTs are needed to confirm the efficacy and safety of ChEIs when used for individual neuropathological classifications of MCI.
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U2 - 10.3233/JAD-190546
DO - 10.3233/JAD-190546
M3 - Article
C2 - 31424411
AN - SCOPUS:85072149218
VL - 71
SP - 513
EP - 523
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -