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Association Between Non-Steroidal Anti-Inflammatory Drug Use and Cognitive Decline: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

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Abstract

Background

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.

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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References

  1. Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21:383–421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Patrono C, Roth GJ. Aspirin in ischemic cerebrovascular disease. How strong is the case for a different dosing regimen? Stroke. 1996;27:756–60.

    Article  CAS  PubMed  Google Scholar 

  3. Rozzini R, Ferrucci L, Losonczy K, Havlik RJ, Guralnik JM. Protective effect of chronic NSAID use on cognitive decline in older persons. J Am Geriatr Soc. 1996;44:1025–9.

    Article  CAS  PubMed  Google Scholar 

  4. Sturmer T, Glynn RJ, Field TS, Taylor JO, Hennekens CH. Aspirin use and cognitive function in the elderly. Am J Epidemiol. 1996;143:683–91.

    Article  CAS  PubMed  Google Scholar 

  5. Hanlon JT, Schmader KE, Landerman LR, Horner RD, Fillenbaum GG, Pieper CF, Wall WE, Koronkowski MJ, Cohen HJ. Relation of prescription nonsteroidal antiinflammatory drug use to cognitive function among community-dwelling elderly. Ann Epidemiol. 1997;7:87–94.

    Article  CAS  PubMed  Google Scholar 

  6. Peacock JM, Folsom AR, Knopman DS, Mosley TH, Goff DC, Szklo M, Investig ARCS. Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults. Neuroepidemiology. 1999;18:134–43.

    Article  CAS  PubMed  Google Scholar 

  7. Jonker C, Comijs HC, Smit JH. Does aspirin or other NSAIDs reduce the risk of cognitive decline in elderly persons? Results from a population-based study. Neurobiol Aging. 2003;24:583–8.

    Article  CAS  PubMed  Google Scholar 

  8. Kang JH, Grodstein F. Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women. Neurology. 2003;60:1591–7.

    Article  PubMed  Google Scholar 

  9. Cote S, Carmichael PH, Verreault R, Lindsay J, Lefebvre J, Laurin D. Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer’s disease. Alzheimers Dement. 2012;8:219–26.

    Article  CAS  PubMed  Google Scholar 

  10. Wichmann MA, Cruickshanks KJ, Carlsson CM, Chappell R, Fischer ME, Klein BE, Klein R, Schubert CR. NSAID use and incident cognitive impairment in a population-based cohort. Alzheimer Dis Assoc Disord. 2016;30(2):105–12. doi:10.1097/WAD.0000000000000098

    Article  CAS  PubMed  Google Scholar 

  11. Fourrier A, Letenneur L, Begaud B, Dartigues JF. Nonsteroidal antiinflammatory drug use and cognitive function in the elderly: inconclusive results from a population-based cohort study. J Clin Epidemiol. 1996;49:1201.

    Article  CAS  PubMed  Google Scholar 

  12. Ancelin ML, Carriere I, Helmer C, Rouaud O, Pasquier F, Berr C, Chaudieu I, Ritchie K. Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia. Neurobiol Aging. 2012;33:2082–90.

    Article  CAS  PubMed  Google Scholar 

  13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336–41.

    Article  PubMed  Google Scholar 

  14. Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.

    Article  PubMed  Google Scholar 

  15. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zandi PP, Breitner JC. Do NSAIDs prevent Alzheimer’s disease? And, if so, why? The epidemiological evidence. Neurobiol Aging. 2001;22:811–7.

    Article  CAS  PubMed  Google Scholar 

  19. Klegeris A, McGeer PL. Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease. Curr Alzheimer Res. 2005;2:355–65.

    Article  CAS  PubMed  Google Scholar 

  20. Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001;414:212–6.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, The Medical College of Qingdao University, 38 Dengzhou Road, Qingdao, 266021, Shandong, People’s Republic of China

    WeiJing Wang & DongFeng Zhang

  2. Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China

    YanPing Sun

Authors
  1. WeiJing Wang
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  2. YanPing Sun
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  3. DongFeng Zhang
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Correspondence to DongFeng Zhang.

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Source of funding

This work was supported by the National Natural Science Foundation of China (No. 31371024).

Conflict of interest

WeiJing Wang, YanPing Sun, and DongFeng Zhang declare that they have no conflicts of interest relevant to the content of this article.

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Wang, W., Sun, Y. & Zhang, D. Association Between Non-Steroidal Anti-Inflammatory Drug Use and Cognitive Decline: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Drugs Aging 33, 501–509 (2016). https://doi.org/10.1007/s40266-016-0379-9

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  • DOI: https://doi.org/10.1007/s40266-016-0379-9

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