BMJ  2003;327:128 (19 July), doi:10.1136/bmj.327.7407.128

Paper

Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies

¹ Department of Clinical Epidemiology, Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1, ² Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Department of Health Policy, Management and Evaluation, University of Toronto, Canada M6A 2E1, ³ Department of Neurology, University of Washington, Seattle, Washington 98195, USA

Objectives To quantify the risk of Alzheimer's disease in users of all non-steroidal anti-inflammatory drugs (NSAIDs) and users of aspirin and to determine any influence of duration of use.

Design Systematic review and meta-analysis of observational studies published between 1966 and October 2002 that examined the role of NSAID use in preventing Alzheimer's disease. Studies identified through Medline, Embase, International Pharmaceutical Abstracts, and the Cochrane Library.

Results Nine studies looked at all NSAIDs in adults aged > 55 years. Six were cohort studies (total of 13 211 participants), and three were case-control studies (1443 participants). The pooled relative risk of Alzheimer's disease among users of NSAIDs was 0.72 (95% confidence interval 0.56 to 0.94). The risk was 0.95 (0.70 to 1.29) among short term users (< 1 month) and 0.83 (0.65 to 1.06) and 0.27 (0.13 to 0.58) among intermediate term (mostly < 24 months) and long term (mostly > 24 months) users, respectively. The pooled relative risk in the eight studies of aspirin users was 0.87 (0.70 to 1.07).

Conclusions NSAIDs offer some protection against the development of Alzheimer's disease. The appropriate dosage and duration of drug use and the ratios of risk to benefit are still unclear.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

Effect of NSAIDs on risk of Alzheimer's disease: Confounding factors were not discussed

Michael Robertson
BMJ 2003 327: 751. [Extract] [Full Text]

Effect of NSAIDs on risk of Alzheimer's disease: Conclusions on NSAIDs and Alzheimer's disease were overstated

David Price
BMJ 2003 327: 752. [Extract] [Full Text]

Alzheimer's disease may be prevented with NSAIDs
BMJ 2003 327: 0. [Full Text]

This article has been cited by other articles:

• Coley, N., Andrieu, S., Gardette, V., Gillette-Guyonnet, S., Sanz, C., Vellas, B., Grand, A. (2008). Dementia Prevention: Methodological Explanations for Inconsistent Results. Epidemiol Rev 0: mxn010v1-mxn010 [Abstract] [Full text]  
• Szekely, C. A., Breitner, J.C.S., Fitzpatrick, A. L., Rea, T. D., Psaty, B. M., Kuller, L. H., Zandi, P. P. (2008). NSAID use and dementia risk in the Cardiovascular Health Study*: Role of APOE and NSAID type. Neurology 70: 17-24 [Abstract] [Full text]  
• Fan, R., Xu, F., Previti, M. L., Davis, J., Grande, A. M., Robinson, J. K., Van Nostrand, W. E. (2007). Minocycline Reduces Microglial Activation and Improves Behavioral Deficits in a Transgenic Model of Cerebral Microvascular Amyloid. J. Neurosci. 27: 3057-3063 [Abstract] [Full text]  
• Ellul, J, Archer, N, Foy, C M L, Poppe, M, Boothby, H, Nicholas, H, Brown, R G, Lovestone, S (2007). The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration. J. Neurol. Neurosurg. Psychiatry 78: 233-239 [Abstract] [Full text]  
• Rentzos, M., Zoga, M., Paraskevas, G. P., Kapaki, E., Rombos, A., Nikolaou, C., Tsoutsou, A., Vassilopoulos, D. (2006). IL-15 Is Elevated in Cerebrospinal Fluid of Patients With Alzheimer's Disease and Frontotemporal Dementia.. J Geriatr Psychiatry Neurol 19: 114-117 [Abstract]  
• Townsend, K. P., Pratico, D. (2005). Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 19: 1592-1601 [Abstract] [Full text]  
• Mor, F., Izak, M., Cohen, I. R. (2005). Identification of Aldolase as a Target Antigen in Alzheimer's Disease. J. Immunol. 175: 3439-3445 [Abstract] [Full text]  
• Lane, R. M., Farlow, M. R. (2005). Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease. J. Lipid Res. 46: 949-968 [Abstract] [Full text]  
• Gorelick, P. B. (2005). William M. Feinberg Lecture: Cognitive Vitality and the Role of Stroke and Cardiovascular Disease Risk Factors. Stroke 36: 875-879 [Abstract] [Full text]  
• Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., Cole, G. M. (2005). Curcumin Inhibits Formation of Amyloid {beta} Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. J. Biol. Chem. 280: 5892-5901 [Abstract] [Full text]  
• de Craen, A. J. M., Gussekloo, J., Vrijsen, B., Westendorp, R. G. J. (2005). Meta-Analysis of Nonsteroidal Antiinflammatory Drug Use and Risk of Dementia. Am J Epidemiol 161: 114-120 [Abstract] [Full text]  
• Cordle, A., Landreth, G. (2005). 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate {beta}-Amyloid-Induced Microglial Inflammatory Responses. J. Neurosci. 25: 299-307 [Abstract] [Full text]  
• Morgan, G. (2005). What next for low dose aspirin?. J. Epidemiol. Community Health 59: 3-4 [Full text]  
• Rentzos, M., Michalopoulou, M., Nikolaou, C., Cambouri, C., Rombos, A., Dimitrakopoulos, A., Kapaki, E., Vassilopoulos, D. (2004). Serum Levels of Soluble Intercellular Adhesion Molecule-1 and Soluble Endothelial Leukocyte Adhesion Molecule-1 in Alzheimer's Disease. J Geriatr Psychiatry Neurol 17: 225-231 [Abstract]  
• Gorelick, P. B. (2004). Risk Factors for Vascular Dementia and Alzheimer Disease. Stroke 35: 2620-2622 [Abstract] [Full text]  
• Wallace, J. L., Muscara, M. N., de Nucci, G., Zamuner, S., Cirino, G., del Soldato, P., Ongini, E. (2004). Gastric Tolerability and Prolonged Prostaglandin Inhibition in the Brain with a Nitric Oxide-Releasing Flurbiprofen Derivative, NCX-2216 [3-[4-(2-Fluoro-{alpha}-methyl-[1,1'-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester]. J. Pharmacol. Exp. Ther. 309: 626-633 [Abstract] [Full text]  
• Abell, J E, Hootman, J M, Helmick, C G (2004). Prevalence and impact of arthritis among nursing home residents. Ann Rheum Dis 63: 591-594 [Abstract] [Full text]  
• Stradling, J. (2004). Con: Sleep Apnea Does Not Cause Cardiovascular Disease. Am. J. Respir. Crit. Care Med. 169: 148-149 [Full text]  
• (2003). From the library. Br. J. Ophthalmol. 87: 1532-1532 [Full text]  
• Jacoby, R. (2003). Rofecoxib or naproxen do not slow progression of mild to moderate Alzheimer's disease. Evid. Based Ment. Health 6: 110-110 [Full text]  
• (2003). Update on NSAIDs and Alzheimer's Disease. JWatch Psychiatry 2003: 9-9 [Full text]  
• (2003). Update on NSAIDs and Alzheimer's Disease. JWatch Gastroenterology 2003: 11-11 [Full text]  
• Price, D. (2003). Effect of NSAIDs on risk of Alzheimer's disease: Conclusions on NSAIDs and Alzheimer's disease were overstated. BMJ 327: 752-752 [Full text]  
• Robertson, M. (2003). Effect of NSAIDs on risk of Alzheimer's disease: Confounding factors were not discussed. BMJ 327: 751-751 [Full text]  
• (2003). Update on NSAIDs and Alzheimer's Disease. Journal Watch Dermatology 2003: 11-11 [Full text]  
• (2003). Update on NSAIDs and Alzheimer's Disease. JWatch General 2003: 2-2 [Full text]  
• Martyn, C. (2003). Anti-inflammatory drugs and Alzheimer's disease. BMJ 327: 353-354 [Full text]  

Rapid Responses:

Read all Rapid Responses

Confounding

Michael Robertson
bmj.com, 18 Jul 2003 [Full text]

Aspirin and Alzheimer’s disease

Gareth P Morgan
bmj.com, 21 Jul 2003 [Full text]

Reducing the risk of Alzheimer's disease: NSAIDs, fish oils, and diet

William B. Grant
bmj.com, 31 Jul 2003 [Full text]

Conclusions on NSAIDs and Alzheimer’s Disease Overstated

David W. Price
bmj.com, 4 Aug 2003 [Full text]

NSAIDs in Alzheimer's disease: Where is the clinical evidence?

Naji Tabet
bmj.com, 5 Aug 2003 [Full text]

NSAIDs and Alzheimer's: Quality before quantity

Nandi L Siegfried, et al.
bmj.com, 15 Aug 2003 [Full text]