title: Association Between Non-Steroidal Anti-Inflammatory Drug Use and Cognitive Decline: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used medications in the elderly. They have been widely studied as possible preventive agents against cognitive decline because of the properties of anti-inflammatories, which sustain cerebral blood flow and mitigate the neurotoxicity of microglial cells. However, the results remain controversial.
  
  
  
  Our objective was to assess the effects of NSAID use on the risk of cognitive decline. We reviewed and quantitatively synthesized the evidence from prospective cohort studies via a meta-analysis.
  
  
  
  We identified pertinent studies by searching the PubMed, EMBASE, and China National Knowledge Infrastructure databases through to December 2015 and by reviewing the reference lists of retrieved articles. We used fixed- or random-effects models to pool relative risks (RRs) with 95 % confidence intervals (CIs) and performed sensitivity analyses to evaluate the robustness of the results. Small-study effect was evaluated using Egger's test and funnel plots.
  
  
  
  Of the 2171 articles identified through searching the databases, ten articles including 11 prospective cohort studies were eligible. Overall, NSAID use was associated with a 13 % decreased risk of cognitive decline (pooled RR 0.87; 95 % CI 0.81-0.94). In subgroup analysis, the pooled RRs were 0.89 (95 % CI 0.81-0.98) for follow-up time ≥5 years, 0.85 (95 % CI 0.75-0.96) for follow-up time <5 years, and 0.85 (95 % CI 0.78-0.93) for studies conducted in North America, respectively. Sensitivity analyses found results to be robust. No evidence of significant small-study effect was identified.
  
  
  
  This meta-analysis of prospective cohort studies indicates that NSAID use may be associated with a decreased risk of cognitive decline. Larger, high-quality randomized controlled trials are needed to verify the effects of NSAID use on the risk of cognitive decline.
authors.affiliation: Department of Epidemiology and Health Statistics, The Medical College of Qingdao University, 38 Dengzhou Road, Qingdao, 266021, Shandong, People's Republic of China.
authors.forename: WeiJing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: YanPing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Health Statistics, The Medical College of Qingdao University, 38 Dengzhou Road, Qingdao, 266021, Shandong, People's Republic of China. zhangdf1961@126.com.
authors.forename: DongFeng
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal