Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease

Background: Previous studies have suggested that the use of nonsteroidal an tiinflammatory 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 a t base line. The risk of Alzheimer's disease was estimated in relation to t he use of NSAIDs as documented in pharmacy records. We defined four mutuall y exclusive categories of use: nonuse, short-term use (1 month or less of c umulative 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 H(sub 2)-r eceptor antagonists, antihypertensive agents, and hypoglycemic agents. Results: During an average follow-up period of 6.8 years, dementia develope d in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementi a, 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 s hort-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 inte rval, 0.05 to 0.83) in those with long-term use. The risk did not vary acco rding 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 di sease but not against vascular dementia. (N Engl J Med 2001;345:1515-21.) C opyright (C) 2001 Massachusetts Medical Society.