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From the Department of Epidemiology (Dr. Stewart), Johns Hopkins School of Public Health; Department of Neurology (Dr. Kawas and M. Corrada), Johns Hopkins School of Medicine; and Gerontology Research Center/National Institute on Aging (Drs. Kawas and Metter), Baltimore, MD.
Supported in part by a grant from the National Institute on Aging (NIA) (R01AG08325).
Received May 15, 1996. Accepted in final form August 30, 1996.
Address correspondence and reprint requests to Dr. Walter F. Stewart, Department of Epidemiology, School of Hygiene and Public Health, 615 N. Wolfe Street, Baltimore, MD 21205.
Article abstract-In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29) for those with less than 2 years of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.
NEUROLOGY 1997;48: 626-632
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G. P. Lim, F. Yang, T. Chu, P. Chen, W. Beech, B. Teter, T. Tran, O. Ubeda, K. H. Ashe, S. A. Frautschy, et al. Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease J. Neurosci., August 1, 2000; 20(15): 5709 - 5714. [Abstract] [Full Text] [PDF]
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J. C. Anthony, J. C. S. Breitner, P. P. Zandi, M. R. Meyer, I. Jurasova, M. C. Norton, and S. V. Stone Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: The Cache County Study Neurology, June 13, 2000; 54(11): 2066 - 2071. [Abstract] [Full Text] [PDF]
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C. Kawas, S. Gray, R. Brookmeyer, J. Fozard, and A. Zonderman Age-specific incidence rates of Alzheimer's disease: The Baltimore Longitudinal Study of Aging Neurology, June 13, 2000; 54(11): 2072 - 2077. [Abstract] [Full Text] [PDF]
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P. L. McGeer and E. G. McGeer Autotoxicity and Alzheimer Disease Arch Neurol, June 1, 2000; 57(6): 789 - 790. [Abstract] [Full Text] [PDF]
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G. M. Halliday, C. E. Shepherd, H. McCann, W. G. J. Reid, D. A. Grayson, G. A. Broe, and J. J. Kril Effect of Anti-inflammatory Medications on Neuropathological Findings in Alzheimer Disease Arch Neurol, June 1, 2000; 57(6): 831 - 836. [Abstract] [Full Text] [PDF]
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 P. E. Lipsky, P. Brooks, L. J. Crofford, R. DuBois, D. Graham, L. S. Simon, L. B. A. van de Putte, and S. B. Abramson Unresolved Issues in the Role of Cyclooxygenase-2 in Normal Physiologic Processes and Disease Arch Intern Med, April 10, 2000; 160(7): 913 - 920. [Abstract] [Full Text] [PDF]
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N. C. Fox, S. Cousens, R. Scahill, R. J. Harvey, and M. N. Rossor Using Serial Registered Brain Magnetic Resonance Imaging to Measure Disease Progression in Alzheimer Disease: Power Calculations and Estimates of Sample Size to Detect Treatment Effects Arch Neurol, March 1, 2000; 57(3): 339 - 344. [Abstract] [Full Text] [PDF]
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P. S. Aisen, K. L. Davis, J. D. Berg, K. Schafer, K. Campbell, R. G. Thomas, M. F. Weiner, M. R. Farlow, M. Sano, M. Grundman, et al. A randomized controlled trial of prednisone in Alzheimer's disease Neurology, February 8, 2000; 54(3): 588 - 588. [Abstract] [Full Text] [PDF]
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F. Nourhashemi, S. Gillette-Guyonnet, S. Andrieu, A. Ghisolfi, P. J. Ousset, H. Grandjean, A. Grand, J. Pous, B. Vellas, and J.-L. Albarede Alzheimer disease: protective factors1 Am. J. Clinical Nutrition, February 1, 2000; 71(2): 643s - 649s. [Abstract] [Full Text] [PDF]
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C. K. Combs, D. E. Johnson, J. C. Karlo, S. B. Cannady, and G. E. Landreth Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of beta -Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARgamma Agonists J. Neurosci., January 15, 2000; 20(2): 558 - 567. [Abstract] [Full Text] [PDF]
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R. Mayeux and M. Sano Treatment of Alzheimer's Disease N. Engl. J. Med., November 25, 1999; 341(22): 1670 - 1679. [Full Text] [PDF]
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T. V. Petrova, K. T. Akama, and L. J. Van Eldik Selective Modulation of BV-2 Microglial Activation by Prostaglandin E2. DIFFERENTIAL EFFECTS ON ENDOTOXIN-STIMULATED CYTOKINE INDUCTION J. Biol. Chem., October 1, 1999; 274(40): 28823 - 28827. [Abstract] [Full Text] [PDF]
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S. Scharf, A. Mander, A. Ugoni, F. Vajda, and N. Christophidis A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease Neurology, July 1, 1999; 53(1): 197 - 197. [Abstract] [Full Text] [PDF]
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M. Stalder, A. Phinney, A. Probst, B. Sommer, M. Staufenbiel, and M. Jucker Association of Microglia with Amyloid Plaques in Brains of APP23 Transgenic Mice Am. J. Pathol., June 1, 1999; 154(6): 1673 - 1684. [Abstract] [Full Text] [PDF]
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K. Yasojima, C. Schwab, E. G. McGeer, and P. L. McGeer Up-Regulated Production and Activation of the Complement System in Alzheimer's Disease Brain Am. J. Pathol., March 1, 1999; 154(3): 927 - 936. [Abstract] [Full Text] [PDF]
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C. K. Combs, D. E. Johnson, S. B. Cannady, T. M. Lehman, and G. E. Landreth Identification of Microglial Signal Transduction Pathways Mediating a Neurotoxic Response to Amyloidogenic Fragments of beta -Amyloid and Prion Proteins J. Neurosci., February 1, 1999; 19(3): 928 - 939. [Abstract] [Full Text] [PDF]
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D. Praticò, V. M.-Y.Lee, J. Q. Trojanowski, J. Rokach, and G. A. Fitzgerald Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo FASEB J, December 1, 1998; 12(15): 1777 - 1783. [Abstract] [Full Text]
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M. H. Pillinger, C. Capodici, P. Rosenthal, N. Kheterpal, S. Hanft, M. R. Philips, and G. Weissmann Modes of action of aspirin-like drugs: Salicylates inhibit Erk activation and integrin-dependent neutrophil adhesion PNAS, November 24, 1998; 95(24): 14540 - 14545. [Abstract] [Full Text] [PDF]
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M. Nakayama, K. Uchimura, R. L. Zhu, T. Nagayama, M. E. Rose, R. A. Stetler, P. C. Isakson, J. Chen, and S. H. Graham Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia PNAS, September 1, 1998; 95(18): 10954 - 10959. [Abstract] [Full Text] [PDF]
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R. N. Dubois, S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon, L. B. A. van de putte, and P. E. Lipsky Cyclooxygenase in biology and disease FASEB J, September 1, 1998; 12(12): 1063 - 1073. [Abstract] [Full Text]
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G. M. Murphy Jr., L. Yang, and B. Cordell Macrophage Colony-stimulating Factor Augments beta -Amyloid-induced Interleukin-1, Interleukin-6, and Nitric Oxide Production by Microglial Cells J. Biol. Chem., August 14, 1998; 273(33): 20967 - 20971. [Abstract] [Full Text] [PDF]
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