title: Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs as Alzheimer's disease therapies: an updated umbrella review of systematic reviews and meta-analyses.
abstract: Alzheimer's Disease (AD) is a major neurological disorder marked by an amyloid-beta plaque and neurofibrillary tau-tangle depositions in the brain. Cognitive dysfunction is the key manifestation of AD. In this study, we conducted an umbrella review of meta-analyses on the risk factors and therapeutics targeting cognitive impairment and AD.
  
  
  
  We searched PubMed from January 2000-August, 2016, and screened systematic reviews and meta-analyses of studies that examined the effects of cholinesterase inhibitors in AD patients. We also included studies on non-steroidal anti-inflammatory drugs and AD. The studies comprised meta-analyses of randomized controlled trials and prospective cohorts, with 95% confidence interval. We considered the heterogeneity between different studies, denoted by I2.
  
  
  
  We scanned a total of 750 novel meta-analyses on the topics, "risk factors for AD" and "cholinesterase inhibitors and NSAIDs" that target the disease. The search yielded three relevant studies on risk factors, and seven and three studies for ChEIs and NSAIDs respectively. A thorough examination of the studies reinforced the therapeutic role of ChEIs in AD. A combination of the glutamatergic inhibitor, memantine, with ChEIs also proved effective in ameliorating AD progression and occurrence. Contradicting the observational studies, therapeutic role of NSAIDs in AD seemed uncertain. Nonetheless, the studies showed variability in the severity of dementia and number of patient trials. Hence, we claim the need for detailed meta-analyses and superior-quality cohort studies on a larger patient population of AD.
  
  
  
  Overall, our umbrella systematic review offers a unique and immensely helpful resource for researchers and clinicians in the field of AD, and identifies vital research gaps as well.
authors.affiliation: Department of Neurology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China. beijing_nz@yahoo.com.
authors.forename: C-H
authors.initials: CH
authors.lastname: Wang
authors.forename: L-S
authors.initials: LS
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine; D015201:Meta-Analysis as Topic; D011446:Prospective Studies; D000078202:Systematic Reviews as Topic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002800:Cholinesterase Inhibitors; D008559:Memantine