Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs

John C.S. Breitner, Kathleen A. Welsh, Michael J. Helms, Perry C. Gaskell, Barbara A. Gau, Allen D. Roses, Margaret A. Pericak-Vance, Ann M. Saunders

Research output: Contribution to journalArticlepeer-review


Factors that modify onset of Alzheimer's disease (AD) may be revealed by comparing environmental exposures in affected and unaffected members of discordant twin pairs or sibships. Among siblings at high risk of AD, sustained use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with delayed onset and reduced risk of AD. After adjustment for use of NSAIDs, there was minimal effect on onset with reported history of any of three common illnesses (arthritis, diabetes, or acid-peptic disease). However, independent of exposure to NSAIDs, onset was unexpectedly delayed in those reporting extended use of histamine H2 blocking drugs. Randomized clinical trials will be needed to affirm the utility of these drugs for prevention, but the present findings may have implications for pathogenesis: because NSAIDs block the calcium-dependent postsynaptic cascade that induces excitotoxic cell death in NMDA-reactive neurons, and because histamine potentiates such events, excitotoxicity may deserve additional investigation in AD.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalNeurobiology of aging
Issue number4
StatePublished - 1995
Externally publishedYes


  • Alzheimer's disease
  • Cyclooxygenase
  • Excitotoxicity
  • Histamine
  • Histamine H2 blocking drugs
  • Inflammation
  • NMDA glutamate receptors
  • Nonsteroidal anti-inflammatory drugs
  • Onset

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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