• Andrea C Tricco, Charlene Soobiah, Erin Lillie, Laure Perrier, Maggie H Chen, Brenda Hemmelgarn, Sumit R Majumdar, and Sharon E Straus.
• Li Ka Shing Knowledge Institute, St, Michael's Hospital, 209 Victoria Street, East Building, Toronto, ON, M5B 1T8, Canada.
• Syst Rev. 2012 May 30; 1: 25.

BackgroundElderly individuals who have memory problems without significant limitations in activities of daily living are often diagnosed as having mild cognitive impairment (MCI). Some of these individuals progress to dementia. Several cognitive enhancers (for example donepezil, galantamine, rivastigmine, memantine) have been approved for use in people with Alzheimer's dementia but their use in patients with MCI is unclear. We aimed to determine the comparative effectiveness, safety, and cost of cognitive enhancers for MCI through a systematic review and network (that is, indirect comparisons) meta-analysis.Design/MethodsWe will include studies that examine the use of cognitive enhancers compared to placebo, supportive care, or other cognitive enhancers among patients diagnosed with MCI. Outcomes of interest include cognition and function (primary outcomes), as well as behavior, quality of life, safety, and cost (secondary outcomes). We will include all 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 Studies will be included regardless of publication status (that is, we will include unpublished studies), year, or language of dissemination.To identify potentially relevant material, we will search the following electronic databases from inception onwards: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and Ageline. The electronic database search will be supplemented by scanning the reference lists of included studies, searching Google and organization websites for unpublished or difficult to locate material literature, and contacting experts.Two reviewers will independently screen the studies for inclusion using the eligibility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 epidemiology studies. Meta-analysis and network meta-analysis are planned, if the studies are deemed statistically, methodologically, and clinically homogenous.DiscussionOur systematic review will provide important information regarding the benefits, costs, and harms of cognitive enhancers for patients with MCI. This information can be used to assist healthcare providers, policy-makers, MCI patients and their family regarding the use of these agents. PROSPERO REGISTRY NUMBER: CRD42012002234.

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