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Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer’s Disease

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Volume 345:1515-1521 November 22, 2001 Number 21

Bas A. in ‘t Veld, M.D., Ph.D., Annemieke Ruitenberg, M.D., Ph.D., Albert Hofman, M.D., Ph.D., Lenore J. Launer, Ph.D., Cornelia M. van Duijn, Ph.D., Theo Stijnen, Ph.D., Monique M.B. Breteler, M.D., Ph.D., and Bruno H.C. Stricker, M.B., Ph.D.

ABSTRACT

Background Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer’s disease. The results, however, have been inconsistent.

Methods We studied the association between the use of NSAIDs and Alzheimer’s disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line. The risk of Alzheimer’s disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use).

Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine H2-receptor antagonists, antihypertensive agents, and hypoglycemic agents.

Results During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer’s disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer’s disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia.

Conclusions The long-term use of NSAIDs may protect against Alzheimer’s disease but not against vascular dementia.

Source Information

From the Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands (B.A.V., A.R., A.H., C.M.D., T.S., M.M.B.B., B.H.C.S.); the Epidemiology, Demography, and Biometry Program, National Institute on Aging, National Institutes of Health, Bethesda, Md. (L.J.L.); and the Inspectorate for Health Care, The Hague, the Netherlands (B.A.V., B.H.C.S.).

Address reprint requests to Dr. Stricker at the Department of Epidemiology and Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands.

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