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Holmes RH, JAMA (1955)
Pathogenesis of coronary disease in American soldiers killed in Korea., 158
Green RC, Neurology (2007)
Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial., 68
In reply Results regarding the a priori primary hypothesis of ADAPT, that administration of the tested NSAIDs would reduce the incidence of clinically diagnosed AD, were reported in a previous article.1 We regret any possible lack of clarity on this point. In our later article, we addressed the major secondary aim of the trial by comparing the treatment groups with respect to their longitudinal cognitive function scores. We agree that the early termination of ADAPT “limits the conclusions that can be drawn” and that we cannot say definitively from the results of the trial whether NSAIDs can prevent dementia or decline in cognitive function. However, we do not agree that the ability to test hypotheses regarding differences in cognitive function across treatment groups depends on showing “significant reductions in cognitive scores in the control group.” Validly examining such potential differences across treatment groups does not logically depend on the direction of change in one group but instead depends on measuring cognitive function equally well in all of the groups. It is well established that changes over time in a healthy population are small and that test scores might actually initially improve, for reasons such as practice effects and increasing comfort with testing. In fact, the lack of decline in the control group is a demonstration of precisely why a control group is necessary to make inferences about the effects of treatment. We think that defining primary prevention as therapy started “prior to the occurrence of the first pathological process, not just prior to the onset of clinical symptoms,” is somewhat artificial and limiting. For example, does the finding of coronary atherosclerosis in a high proportion of young Korean War combat casualties2 preclude efforts toward the primary prevention of coronary heart disease in middle age? Bregman et al state that we should not conclude “that NSAIDs, if taken during adulthood and for an extended period, cannot prevent or delay the onset of dementia.” We did not. Correspondence: Dr Martin, Lancaster Heart and Stroke Foundation, 354 N Prince St, Ste 200, Lancaster, PA 17603 (bmartin@lancasterheart.org). Financial Disclosure: None reported. References 1. Lyketsos CGBreitner JCGreen RC et al. ADAPT Research Group, Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007;68 (21) 1800- 1808PubMedGoogle ScholarCrossref 2. Enos WF JrBeyer JCHolmes RH Pathogenesis of coronary disease in American soldiers killed in Korea. JAMA 1955;158 (11) 912- 914PubMedGoogle ScholarCrossref
Archives of Neurology – American Medical Association
Published: Apr 1, 2009
Keywords: dementia,anti-inflammatory agents, non-steroidal
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