title: Comparative safety and effectiveness of cognitive enhancers for Alzheimer's dementia: protocol for a systematic review and individual patient data network meta-analysis.
abstract: BACKGROUND
  Alzheimer's dementia (AD) is the most common cause of dementia, and several organisations, such as the National Institute for Health and Care Excellence, suggest that management of patients with AD should be tailored to their needs. To date, little research has been conducted on the treatment effect in different subgroups of patients with AD. The aim of this study is to examine the comparative effectiveness and safety of cognitive enhancers for different patient characteristics.
  
  
  METHODS
  We will update our previous literature search from January 2015 forward, using the same terms and electronic databases (eg, MEDLINE) from our previous review. We will additionally search grey literature and scan the reference lists of the included studies. Randomised clinical trials of any duration conducted at any time comparing cognitive enhancers alone or in any combination against other cognitive enhancers, or placebo in adults with AD will be eligible. The outcomes of interest are cognition according to the Mini-Mental State Examination, and overall serious adverse events. For each outcome and treatment comparison, we will perform a Bayesian hierarchical random-effects meta-analysis combining the individual patient data (IPD) from each eligible study. If the identified treatment comparisons form a connected network diagram, we will perform an IPD network meta-analysis (NMA) to estimate subgroup effects for patients with different characteristics, such as AD severity and sex. We will combine aggregated data from studies that we will not be able to obtain IPD, with the IPD provided by the original authors, in a single model. We will use the PRISMA-IPD and PRISMA-NMA statements to report our findings.
  
  
  BACKGROUND
  The findings of this study will be of interest to stakeholders, including decision makers, guideline developers, clinicians, methodologists and patients, and they will help to improve guidelines for the management of patients with AD.
  
  
  BACKGROUND
  CRD42015023507.
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Areti Angeliki
authors.initials: AA
authors.lastname: Veroniki
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Geriatric Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Straus
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Huda M
authors.initials: HM
authors.lastname: Ashoor
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jemila S
authors.initials: JS
authors.lastname: Hamid
authors.affiliation: Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.affiliation: Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jayna
authors.initials: J
authors.lastname: Holroyd-Leduc
authors.affiliation: Department of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Majumdar
authors.affiliation: Ontario Public Drug Programs, Ministry of Health and Long-Term Care, Toronto, Ontario, Canada.
authors.forename: Glenn
authors.initials: G
authors.lastname: McAuley
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome; D055815:Young Adult; D015201:Meta-Analysis as Topic
chemical_list: D018697:Nootropic Agents
keywords: Alzheimer Disease; Nootropic Agents; individual participant data; multiple treatments meta-analysis; network meta-analysis