{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:57:50Z","timestamp":1792684670970,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007328","name":"N. Bud Grossman Center for Memory Research and Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidemiologic evidence suggests that nonsteroidal anti\u2010inflammatory drugs (NSAIDs) delay onset of Alzheimer's dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimer's Disease Anti\u2010inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID\u2010assigned groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We continued the double\u2010masked ADAPT protocol for 2 additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF\n                      <jats:italic>tau<\/jats:italic>\n                      to A\u03b2\n                      <jats:sub>1\u201042.<\/jats:sub>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Including 40 new events observed during follow\u2010up of 2071 randomized individuals (92% of participants at treatment cessation), there were 72 AD cases. Overall, NSAID\u2010related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with cognitive impairment\u2013\u2013no dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees who were given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer\u2010type neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2010.12.014","type":"journal-article","created":{"date-parts":[[2011,7,25]],"date-time":"2011-07-25T22:37:38Z","timestamp":1311633458000},"page":"402-411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":298,"title":["Extended results of the Alzheimer's disease anti\u2010inflammatory prevention trial"],"prefix":"10.1002","volume":"7","author":[{"given":"John C.","family":"Breitner","sequence":"first","affiliation":[{"name":"Centre for Studies on Prevention of Alzheimer's Disease Douglas Mental Health University Institute Research Centre Montreal Quebec Canada"},{"name":"Department of Psychiatry McGill University Montreal Quebec Canada"},{"name":"Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D.","family":"Baker","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA"},{"name":"Department of Psychiatry and Behavioral Sciences University of Washington Medical Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Montine","sequence":"additional","affiliation":[{"name":"Division of Neuropathology Department of Pathology University of Washington Medical Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis L.","family":"Meinert","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology and Biostatistics Johns Hopkins Bloomberg School of Public Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine G.","family":"Lyketsos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins Medical Institutions and Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen H.","family":"Ashe","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center Minneapolis VA Medical Center Minneapolis MN USA"},{"name":"Departments of Neurology and Neuroscience N. Bud Grossman Center for Memory Research and Care University of Minnesota School of Medicine Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins Medical Institutions and Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Craft","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA"},{"name":"Department of Psychiatry and Behavioral Sciences University of Washington Medical Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Rush Institute for Healthy Aging Rush University Medical Center Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Green","sequence":"additional","affiliation":[{"name":"Departments of Neurology Genetics and Epidemiology Boston University School of Medicine Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Saleem","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Rochester Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara K.","family":"Martin","sequence":"additional","affiliation":[{"name":"Lancaster Heart &amp; Stroke Foundation Lancaster PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Cleo Roberts Center Banner Sun Health Research Institute Sun City AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre N.","family":"Tariot","sequence":"additional","affiliation":[{"name":"Memory Disorders Center Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7]]},"reference":[{"key":"e_1_2_6_2_2","unstructured":"A National Alzheimer's Strategic Plan: the Report of the Alzheimer's Study Group. 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