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Review Paper

Nonsteroidal Anti-Inflammatory Drugs for the Prevention of Alzheimer’s Disease: A Systematic Review

Szekely C.A.a · Thorne J.E.a,b · Zandi P.P.a · Ek M.a · Messias E.a · Breitner J.C.S.c · Goodman S.N.a,b

Author affiliations

aJohns Hopkins Bloomberg School of Public Health, bJohns Hopkins School of Medicine, Baltimore, Md., and cVA Puget Sound Health Care System and University of Washington School of Medicine, Seattle, Wash., USA

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Neuroepidemiology 2004;23:159–169

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Article / Publication Details

First-Page Preview
Abstract of Review Paper

Published online: July 02, 2004
Issue release date: July – August

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 2

ISSN: 0251-5350 (Print)
eISSN: 1423-0208 (Online)

For additional information: https://www.karger.com/NED

Abstract

Objective: Alzheimer’s disease, the most prevalent dementia, is a prominent source of chronic illness in the elderly. Laboratory evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the onset of Alzheimer’s disease. Since the early 1990s, numerous observational epidemiological studies have also investigated this possibility. The purpose of this meta-analysis is to summarize and evaluate available evidence regarding exposure to nonaspirin NSAIDs and risk of Alzheimer’s disease using meta-analyses of published studies. Methods: A systematic search was conducted using Medline, Biological Abstracts, and the Cochrane Library for publications from 1960 onwards. All cross-sectional, retrospective, or prospective observational studies of Alzheimer’s disease in relation to NSAID exposure were included in the analysis. At least 2 of 4 independent reviewers characterized each study by source of data and design, including method of classifying exposure and outcome, and evaluated the studies for eligibility. Discrepancies were resolved by consensus of all 4 reviewers. Results: Of 38 publications, 11 met the qualitative criteria for inclusion in the meta-analysis. For the 3 case-control and 4 cross-sectional studies, the combined risk estimate for development of Alzheimer’s disease was 0.51 (95% CI = 0.40–0.66) for NSAID exposure. In the prospective studies, the estimate was 0.74 (95% CI = 0.62–0.89) for the 4 studies reporting lifetime NSAID exposure and it was 0.42 (95% CI = 0.26–0.66) for the 3 studies reporting a duration of use of 2 or more years. Conclusions: Based on analysis of prospective and nonprospective studies, NSAID exposure was associated with decreased risk of Alzheimer’s disease. An issue that requires further exploration in future trials or observational studies is the temporal relationship between NSAID exposure and protection against Alzheimer’s disease.

© 2004 S. Karger AG, Basel


References

  1. Selkoe DJ: Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann NY Acad Sci 2000;924:17–25.
  2. Brookmeyer R, Gray S: Methods for projecting the incidence and prevalence of chronic diseases in aging populations: application to Alzheimer’s disease. Stat Med 2000;19:1481–1493.
  3. Breitner JC, Zandi PP: Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med 2001;345:1567–1568.
  4. Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R: Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996;348:429–432.
  5. Henderson VW: The epidemiology of estrogen replacement therapy and Alzheimer’s disease. Neurology 1997;48(5 suppl 7):S27–S35.
  6. Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, Bacal C, Lingle DD, Metter E: A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging. Neurology 1997;48:1517–1521.
  7. Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC: Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County Study. JAMA 2002;288:2123–2129.
  8. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF: Intake of flavonoids and risk of dementia. Eur J Epidemiol 2000;16:357–363.
  9. Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB: Wine consumption and dementia in the elderly: A prospective community study in the Bordeaux area. Rev Neurol (Paris) 1997;153:185–192.
  10. Anthony JC, Breitner JC, Zandi PP, Meyer MR, Jurasova I, Norton MC, Stone SV: Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: The Cache County study. Neurology 2000;54:2066–2071.
  11. Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, Pericak-Vance MA, Saunders AM: Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 1995;16:523–530.
  12. McGeer PL, Schulzer M, McGeer EG: Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: A review of 17 epidemiologic studies. Neurology 1996;47:425–432.
  13. McGeer PL, McGeer E, Rogers J, Sibley J: Anti-inflammatory drugs and Alzheimer disease. Lancet 1990;335:1037.
  14. Myllykangas-Luosujarvi R, Isomaki H: Alzheimer’s disease and rheumatoid arthritis. Br J Rheumatol 1994;33:501–502.
  15. Jenkinson ML, Bliss MR, Brain AT, Scott DL: Rheumatoid arthritis and senile dementia of the Alzheimer’s type. Br J Rheumatol 1989;28:86–88.
  16. Broe GA, Henderson AS, Creasey H, McCusker E, Korten AE, Jorm AF, Longley W, Anthony JC: A case-control study of Alzheimer’s disease in Australia. Neurology 1990;40:1698–1707.
  17. McGeer PL, Harada N, Kimura H, McGeer EG: Prevalence of dementia amongst elderly Japanese with leprosy: Apparent effect of chronic drug therapy. Dementia 1992;3:146–149.
    External Resources
  18. Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N: A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology 1999;53:197–201.
  19. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ: Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: A randomized controlled trial. JAMA 2003;289:2819–2826.
  20. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P: Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993;43:1609–1611.
  21. Zandi PP, Breitner JC: Do NSAIDs prevent Alzheimer’s disease? And, if so, why? The epidemiological evidence. Neurobiol Aging 2001;22:811–817.
  22. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T: Inflammation and Alzheimer’s disease. Neurobiol Aging 2000;21:383–421.
  23. Giulian D: Microglia and the immune pathology of Alzheimer disease. Am J Hum Genet 1999;65:13–18.
  24. Casper D, Yaparpalvi U, Rempel N, Werner P: Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Neurosci Lett 2000;289:201–204.
  25. Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, Currie J, Ames D, Weidemann A, Fischer P: The amyloid precursor protein of Alzheimer’s disease is released by human platelets. J Biol Chem 1990;265:15977–15983.
  26. Etminan M, Gill S, Samii A: Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: Systematic review and meta-analysis of observational studies. BMJ 2003;327:128–132.
  27. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, DSM-III-R, ed 3, revised. Washington, American Psychiatric Association, 1987.
  28. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
  29. Stata Statistical Software: Release 7.0. College Station. Texas, Stata Corporation, 2000.
  30. Paganini-Hill A, Clark LJ, Henderson VW, Birge SJ: Clock drawing: Analysis in a retirement community. J Am Geriatr Soc 2001;49:941–947.
  31. Beard CM, Kokman E, Kurland LT: Rheumatoid arthritis and susceptibility to Alzheimer’s disease. Lancet 1991;337:1426.
  32. Breteler MM, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Mortimer JA, et al: Medical history and the risk of Alzheimer’s disease: A collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2):36–42.
  33. Li G, Shen YC, Li YT, Chen CH, Zhau YW, Silverman JM: A case-control study of Alzheimer’s disease in China. Neurology 1992;42:1481–1488.
  34. Graves AB, White E, Koepsell TD, Reifler BV, van Belle G, Larson EB, Raskind M: A case-control study of Alzheimer’s disease. Ann Neurol 1990;28:766–774.
  35. French LR, Schuman LM, Mortimer JA, Hutton JT, Boatman RA, Christians B: A case-control study of dementia of the Alzheimer type. Am J Epidemiol 1985;121:414–421.
  36. Heyman A, Wilkinson WE, Stafford JA, Helms MJ, Sigmon AH, Weinberg T: Alzheimer’s disease: A study of epidemiological aspects. Ann Neurol 1984;15:335–341.
  37. Jones RW: Inflammation and Alzheimer’s disease. Lancet 2001;358:436–437.
  38. Delanty N, Vaughan C: Risk of Alzheimer’s disease and duration of NSAID use. Neurology 1998;51:652.
  39. Halliday GM, Shepherd CE, McCann H, Reid WG, Grayson DA, Broe GA, Kril JJ: Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease. Arch Neurol 2000;57:831–836.
  40. Haruda FD: Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease. Neurology 1995;45:2116.
  41. Mortimer JA: New findings consistent with Alzheimer’s-NSAIDs link. Neurobiol Aging 1998;19:615–616.
  42. Van Muiswinkel FL, Eikelenboom P: Do nonsteroidal anti-inflammatory drugs have a protective effect against dementia? Drugs Aging 1996;9:1–7.
  43. Kokmen E, Beard CM, O’Brien PC, Kurland LT: Epidemiology of dementia in Rochester, Minnesota. Mayo Clin Proc 1996;71:275–282.
  44. in ‘t Veld BA, Launer LJ, Hoes AW, Ott A, Hofman A, Breteler MM, Stricker BH: NSAIDs and incident Alzheimer’s disease. The Rotterdam Study. Neurobiol Aging 1998;19:607–611.
    External Resources
  45. in ‘t Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH: Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 2001;345:1515–1521.
  46. Wolfson C, Perrault A, Moride Y, Esdaile JM, Abenhaim L, Momoli F: A case-control analysis of nonsteroidal anti-inflammatory drugs and Alzheimer’s disease: Are they protective? Neuroepidemiology 2002;21:81–86.
  47. The Canadian Study of Health and Aging: Risk factors for Alzheimer’s disease in Canada. Neurology 1994;44:2073–2080.
  48. Rich JB, Rasmusson DX, Folstein MF, Carson KA, Kawas C, Brandt J: Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease. Neurology 1995;45:51–55.
  49. Henderson AS, Jorm AF, Christensen H, Jacomb PA, Korten AE: Aspirin, anti-inflammatory drugs and risk of dementia. Int J Geriatr Psychiatry 1997;12:926–930.
  50. Mackenzie IR, Munoz DG: Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 1998;50:986–990.
  51. Mackenzie IR, Munoz DG: Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease. Arch Neurol 2001;58:517–519.
  52. Harris Y, Gorelick PB, Freels S, Billingsley M, Brown N, Robinson D: Neuroepidemiology of vascular and Alzheimer’s dementia among African-American women. J Natl Med Assoc 1995;87:741–745.
  53. Lucca U, Tettamanti M, Forloni G, Spagnoli A: Nonsteroidal antiinflammatory drug use in Alzheimer’s disease. Biol Psychiatry 1994;36: 854–856.
  54. Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MM, Hofman A: Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study. Neurology 1995;45:1441–1445.
  55. Broe GA, Grayson DA, Creasey HM, Waite LM, Casey BJ, Bennett HP, Brooks WS, Halliday GM: Anti-inflammatory drugs protect against Alzheimer disease at low doses. Arch Neurol 2000;57:1586–1591.
  56. Stewart WF, Kawas C, Corrada M, Metter EJ: Risk of Alzheimer’s disease and duration of NSAID use. Neurology 1997;48:626–632.
  57. Breitner JC, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ, Anthony JC: Inverse association of anti-inflammatory treatments and Alzheimer’s disease: Initial results of a co-twin control study. Neurology 1994;44:227–232.
  58. Beard CM, Waring SC, O’Brien PC, Kurland LT, Kokmen E: Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: A case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc 1998;73:951–955.
  59. Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC: Reduced incidence of AD with NSAID but not H2 receptor antagonists: The Cache County Study. Neurology 2002;59:880–886.
  60. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I: Risk factors for Alzheimer’s disease: A prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 2002;156:445–453.
  61. Landi F, Cesari M, Onder G, Russo A, Torre S, Bernabei R: Non-steroidal anti-inflammatory drug (NSAID) use and Alzheimer disease in community-dwelling elderly patients. Am J Geriatr Psychiatry 2003;11:179–185.
  62. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, ed 4, revised. Washington, American Psychiatric Association, 1994.
  63. Breitner JC: Exposure classification: the bugbear of dementia epidemiology. Neurobiol Aging 1998;19:613–614.
  64. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO: Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 1989;262:2551–2556.
  65. Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, D’Agostino RB, White LR: Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992;42:115–119.
  66. Henderson AS, Easteal S, Jorm AF, Mackinnon AJ, Korten AE, Christensen H, Croft L, Jacomb PA: Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet 1995;346:1387–1390.
  67. 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.
  68. Ioannidis JP: Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. JAMA 1998;279:281–286.
  69. Breitner JC: New epidemiologic strategies in Alzheimer’s disease may provide clues to prevention and cause. Neurobiol Aging. 1994;15(suppl 2):S175–S177.
    External Resources
  70. Martin BK, Meinert CL, Breitner JC: Double placebo design in a prevention trial for Alzheimer’s disease. Control Clin Trials 2002;23:93–99.

Article / Publication Details

First-Page Preview
Abstract of Review Paper

Published online: July 02, 2004
Issue release date: July – August

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 2

ISSN: 0251-5350 (Print)
eISSN: 1423-0208 (Online)

For additional information: https://www.karger.com/NED


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