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Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network meta-analysis

Andrea C Tricco1, Sondra vanderVaart1, Charlene Soobiah1, Erin Lillie1, Laure Perrier1, Maggie H Chen1, Brenda Hemmelgarn2, Sumit R Majumdar34 and Sharon E Straus14*

Author Affiliations

1 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 209 Victoria Street, East Building, Toronto, ON, M5B 1T8, Canada

2 Division of Nephrology, Department of Medicine, University of Calgary, Calgary, AB, Canada

3 Division of General Internal Medicine, Department of Medicine, University of Alberta, Calgary, AB, Canada

4 Department of Geriatric Medicine, University of Toronto, Toronto, ON, Canada

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Systematic Reviews 2012, 1:31  doi:10.1186/2046-4053-1-31

Published: 28 June 2012



Approximately 35 million people world-wide have Alzheimer’s disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine) and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) have been approved for the treatment of Alzheimer’s disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer’s disease through a systematic review.


Studies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer’s patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials), quasi-experimental studies (controlled before-after, interrupted time series), and observational studies (cohort, case–control studies) will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination.

We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline) from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites). Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect comparisons) meta-analysis will be conducted.


Our systematic review will inform the decision of healthcare providers, policy-makers, Alzheimer’s patients and family members about the use of cognitive enhancers, by improving their understanding of the costs, benefits and harms that are associated with these agents.

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