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

Objectives: 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.