Tricco AC, et al. - The comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD) were investigated in this systematic review. The researchers concluded that according to minimal clinically important difference and global ratings, cognitive enhancers had minimal effects on cognition in general. The drugs seemed safe, but this needed to be interpreted carefully because trial participants could have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

• The researchers designed this systematic review and Bayesian network metaanalysis (NMA).
• From inception–March 2016, they searchers MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline.
• Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies were enrolled.
• For this study, 2 reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias.

• The researchers screened 20343 citations.
• They included 142 studies (110 RCTs, 21 non-RCTs, 11 cohort studies).
• Compared to placebo, 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.
• 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 compared to placebo.
• Donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) brought about greater improvement in the behavior.
• Compared to placebo, 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.
• Decreased odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87) was found with the use of galantamine.
• In this study, no agent increased risk of serious adverse events, falls, or bradycardia.
• There were some reports of increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine).