Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists - The Cache County Study

Objective: To test the hypothesis that nonsteroidal anti-inflammatory drugs (NSAIDs) and histamine H2 receptor antagonists (H2RAs) are associated with a decreased risk of AD in late life. Background: Sustained use of non-aspi rin NSAIDs has been repeatedly associated with a reduced occurrence of AD. Similar effects with aspirin have been weaker. One prior study showed a str ong association between use of H2RAs and reduced AD prevalence. Methods: In a population study of AD in Cache County, UT, we used a sequenced plan of sampling and case ascertainment to identify 201 cases of AD and 4425 partic ipants with no indication of cognitive impairment. Independently, an interv iew and medicine chest inventory assessed use of several medicines includin g aspirin, non-aspirin NSAIDs, H2RAs, and three classes of "control" drugs not thought to be associated with AD. Follow-up questioning probed possible indications for use of these drugs. Results: Compared with cognitively int act individuals, the AD cases had significantly less reported current use o f NSAIDs, aspirin, and H2RAs. Stronger associations appeared when subjects reported use of both NSAIDs and aspirin (no H2RAs), two different NSAIDs (n o H2RAs), or two different H2RAs (with neither aspirin nor NSAIDs). There w as little or no such association with use of the control medicines, Adjustm ent for usage indication did not influence these findings, and there was no appreciable variation with number of APOE epsilon 4 alleles. Conclusions: As predicted, use of NSAIDs and aspirin were specifically associated with r educed occurrence of AD. Notably, a previous observation of an inverse asso ciation of AD and use of H2RAs was also affirmed. Definitive evidence for a preventive action of these agents will require randomized prevention trial s.