Elsevier

Neurobiology of Aging

Volume 16, Issue 4, July–August 1995, Pages 523-530
Neurobiology of Aging

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

https://doi.org/10.1016/0197-4580(95)00049-KGet rights and content

Abstract

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.

References (42)

  • J.C.S. Breitner et al.

    The use of twin cohorts for research in Alzheimer's disease

    Neurology

    (1993)
  • J.C.S. Breitner et al.

    Inverse association of anti-inflammatory treatments and Alzheimer's disease: Initial results of a co-twin control study

    Neurology

    (1994)
  • J.C.S. Breitner et al.

    Age-dependent expression of familial risk in Alzheimer's disease

    Am. J. Epidemiol.

    (1988)
  • J.C.S. Breitner et al.

    Case-control studies of environmental influences in diseases with genetic determinants, with an application to Alzheimer's disease

    Am. J. Epidemiol.

    (1991)
  • M.M.B. Breteler et al.

    Epidemiology of Alzheimer's disease

    Epidemiol. Rev.

    (1992)
  • E.H. Corder et al.

    Apolipoprotein E type 2 allele decreases the risk of late onset Alzheimer disease

    Nature Genet.

    (1994)
  • E.H. Corder et al.

    Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families

    Science

    (1993)
  • D.R. Cox

    Regression models and tables (with discussion)

    J. R. Stat. Soc. Series B

    (1972)
  • P. Eikelenboom et al.

    Complement activation in amyloid plaques in Alzheimer's dementia

    Virchows Arch. [B]

    (1989)
  • A. Goate et al.

    Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

    Nature

    (1991)
  • W.S.T. Griffin et al.

    Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease

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      Therefore, a therapeutic intervention targeting neuroinflammation, particularly in early disease processes (McGeer et al., 1996; Stewart et al., 1997; Vlad et al., 2008), seems to potentially restrain AD's further progression. NSAID use is associated with a lower risk of developing AD in a range of ethnodemographic populations (Breitner et al., 1995; Côté et al., 2012; Fischer et al., 2008; Landi et al., 2003; Stewart et al., 1997; Szekely et al., 2008; Veld et al., 2001; Vlad et al., 2008) besides various preclinical studies (Lim et al., 2000; Weggen et al., 2001; Yan et al., 2003). Importantly, a greatly reduced risk of AD was noticed in rheumatoid arthritis patients on long-term NSAIDs (Mcgeer et al., 1990).

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