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Published online before print April 22, 2009, doi:10.1212/WNL.0b013e3181a18691)
Accepted January 26, 2009 Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohortJ. C.S. Breitner MD, MPH*,
From the Geriatric Research Education and Clinical Center (J.C.S.B.), Department of Veterans Affairs Medical Center, Seattle; University of Washington School of Medicine (J.C.S.B., P.K.C.), Seattle; Center for Health Studies (S.J.P.A.H., R.W., S.D., E.B.L.), Group Health Cooperative, Seattle; Department of Epidemiology (S.D.), University of Washington School of Public Health and Community Medicine, Seattle; and University of Washington School of Pharmacy (S.L.G.), Seattle. * To whom correspondence should be addressed. E-mail: jcsb{at}u.washington.edu.
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). Methods: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged Results: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24–2.24) and 1.57 (95% confidence interval, 1.10–2.23). Addition of self-reported exposure data did not alter these results. Conclusions: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation.
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65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500+ SDD), with some analyses also adding consecutive biennial self-reports of NSAID use.
