Histamine-2 receptor antagonist use and incident dementia in an older cohort

Shelly L. Gray, Rod Walker, Sascha Dublin, Sebastien Haneuse, Paul K. Crane, John C.S. Breitner, James Bowen, Wayne McCormick, Eric B. Larson

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Objective: To examine whether histamine-2 receptor antagonist medications (H2RAs) are associated with a lower incidence of all-cause dementia or Alzheimer's disease (AD), as some studies have suggested. Design: Prospective population-based cohort Setting: Group Health, an integrated health maintenance organization, Seattle, Washington. Participants: Two thousand nine hundred twenty-three participants aged 65 and older without dementia at baseline, with initial recruitment between 1994 and 1996. Measurements: Follow-up occurred every 2 years to identify incident dementia and AD using standard criteria. Exposure to H2RAs was determined based on automated pharmacy data. Three aspects of exposure (time-varying) were examined based on standard daily dose (SDD): cumulative use, intensity of use (highest SDD in any prior 2-year window), and cumulative use stratified according to recency (1-3 years vs >3 years before). Results: Over a mean follow-up of 6.7 years, 585 subjects developed dementia (453 developed AD). Total cumulative exposure was not associated with dementia (P=.35; omnibus test) or AD (P=.23). The adjusted hazard ratios for the highest exposure category (>1,080 SDDs) compared with light or no use were 1.28 (95% confidence interval (CI)=0.95-1.72) for dementia and 1.41 (95% CI=1.00-1.97) for AD. Intensity of use was not associated with dementia (P=.39) or AD (P=.63). Examining exposure according to recent and distant cumulative use also showed no association with dementia (P=.11) or AD (P=.30). Conclusion: No association was found between H2RA use and risk of all-cause dementia or AD using more-detailed and -extensive information about past H2RA use than any prior study.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of the American Geriatrics Society
Issue number2
StatePublished - Feb 2011
Externally publishedYes


  • Alzheimer's disease
  • cohort study
  • dementia
  • histamine-2 receptor antagonist
  • pharmacoepidemiology

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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