title: Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.
abstract: 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 > or = 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.
authors.affiliation: Geriatric Research Education and Clinical Center, Department of Veterans Affairs Medical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA. jcsb@u.washington.edu
authors.forename: J C S
authors.initials: JC
authors.lastname: Breitner
authors.forename: S J P A
authors.initials: SJ
authors.lastname: Haneuse
authors.forename: R
authors.initials: R
authors.lastname: Walker
authors.forename: S
authors.initials: S
authors.lastname: Dublin
authors.forename: P K
authors.initials: PK
authors.lastname: Crane
authors.forename: S L
authors.initials: SL
authors.lastname: Gray
authors.forename: E B
authors.initials: EB
authors.lastname: Larson
mesh_terms: D017677:Age Distribution; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000453:epidemiology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015984:Causality; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013995:Time
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal