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This Article Full Text Full Text (PDF) CME: Take the course for this article: Volume 72, Number 22, June 2, 2009 Data Supplement Japanese Translation All Versions of this Article: WNL.0b013e3181a18691v1 72/22/1899    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Breitner, J.C.S. Articles by Larson, E. B. PubMed PubMed Citation Articles by Breitner, J.C.S. Articles by Larson, E. B. Related Collections Alzheimer's disease Cohort studies Incidence studies Risk factors in epidemiology Related Article

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort

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.

Address correspondence and reprint requests to Dr. Breitner, GRECC (S-182), VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108 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 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.

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.

ACT = Adult Changes in Thought; AD = Alzheimer dementia; ADL = activities of daily living; aHR = adjusted hazard ratio; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; GH = Group Health; HR = hazard ratio; NSAID = nonsteroidal anti-inflammatory drug; OR = odds ratio; SDD = standard daily dose.

Received October 20, 2008. Accepted in final form January 26, 2009.

Supplemental data at www.neurology.org

Editorial, page 1884

e-Pub ahead of print on April 22, 2009, at www.neurology.org.

*These authors contributed equally.

Supported by the US Department of Veterans Affairs and NIH Grants U01-AG-06781, R01-AG-24010, U01-AG-15477, and K23-AG-28954 (Paul Beeson award to S.D., supported in part by the American Federation for Aging Research, the Hartford Foundation, the Atlantic Philanthropies, and the Starr Foundation).

Disclosure: The authors report no disclosures.

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