Efficacy and Safety of Cholinesterase Inhibitors for Mild Cognitive Impairment:A Systematic Review and Meta-Analysis

Shinji Matsunaga, Hiroshige Fujishiro, Hajime Takechi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)513-523
Number of pages11
JournalJournal of Alzheimer's Disease
Volume71
Issue number2
DOIs
Publication statusPublished - 01-01-2019

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Cholinesterase Inhibitors
Meta-Analysis
Safety
Placebos
Randomized Controlled Trials
Rivastigmine
Cognition
Cognitive Dysfunction
Galantamine
Muscle Cramp
Numbers Needed To Treat
Incidence
Sleep Initiation and Maintenance Disorders
Dizziness
Nausea
Vomiting
Headache
Dementia
Weight Loss
Diarrhea

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

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title = "Efficacy and Safety of Cholinesterase Inhibitors for Mild Cognitive Impairment:A Systematic Review and Meta-Analysis",
abstract = "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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Efficacy and Safety of Cholinesterase Inhibitors for Mild Cognitive Impairment:A Systematic Review and Meta-Analysis. / Matsunaga, Shinji; Fujishiro, Hiroshige; Takechi, Hajime.

In: Journal of Alzheimer's Disease, Vol. 71, No. 2, 01.01.2019, p. 513-523.

Research output: Contribution to journalArticle

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