The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review

J Alzheimers Dis. 2022;85(3):1195-1204. doi: 10.3233/JAD-215423.


Background: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse.

Objective: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients.

Methods: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles.

Results: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Aβ agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD.

Conclusion: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.

Keywords: Acetylcholinesterase inhibitors; Alzheimer’s disease; anti-Aβ agents; systematic review; umbrella review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Activities of Daily Living / psychology*
  • Alzheimer Disease / drug therapy*
  • Amino Acids / therapeutic use
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition / drug effects
  • Donepezil / therapeutic use
  • Galantamine / therapeutic use
  • Ginkgo biloba
  • Humans
  • Nootropic Agents / therapeutic use*
  • Patient Safety*
  • Plant Extracts / therapeutic use
  • Rivastigmine / therapeutic use


  • Amino Acids
  • Cholinesterase Inhibitors
  • Nootropic Agents
  • Plant Extracts
  • Galantamine
  • Ginkgo biloba extract
  • cerebrolysin
  • Donepezil
  • Rivastigmine