Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis. Issue 1 (29th September 2017)

• Record Type: Journal Article
• Authors: Tricco, Andrea C.; Ashoor, Huda M.; Soobiah, Charlene; Rios, Patricia; Veroniki, Areti Angeliki; Hamid, Jemila S.; Ivory, John D.; Khan, Paul A.; Yazdi, Fatemeh; Ghassemi, Marco; Blondal, Erik; Ho, Joanne M.; Ng, Carmen H.; Hemmelgarn, Brenda; Majumdar, Sumit R.; Perrier, Laure; Straus, Sharon E.
• Is Part Of: Journal of the American Geriatrics Society. Volume 66:Issue 1(2018)
• Page Start: 170
• Page End: 178
• Publication Date: 2017-09-29
• Subjects: cholinesterase inhibitors -- Alzheimer's disease -- systematic review -- network meta‐analysis -- knowledge synthesis; Geriatrics -- Periodicals; 618.97
• DOI: 10.1111/jgs.15069
• Languages: English
• ISSNs: 0002-8614

Abstract

Abstract : Background/Objectives: To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). Design: Systematic review and Bayesian network metaanalysis (NMA). Setting: MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception–March 2016). Participants: Individuals with AD in randomized controlled trials (RCTs), quasi‐RCTs, and nonrandomized studies. Intervention: Any combination of donepezil, rivastigmine, galantamine, or memantine. Measurements: Two reviewers independently screened titles, abstracts, and full‐texts; abstracted data; and appraised risk of bias. Results: Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCTs, 21 non‐RCTs, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine (MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil (MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine (MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine (MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine (MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). Conclusion: An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.