An intervention that delayed onset of Alzheimer's disease (AD) by several years would yield huge public health benefits. Several studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may produce such a delay. NSAIDs may also attenuate progressive age-related cognitive decline (ARCD) when this conditions represents a prodrome of AD. Both prevention strategies can be evaluated definitively only in randomized trials. Such trials can also examine attendant risks of long- term NSAID use in the moderate doses that appear to afford protection against AD and ARCD. Improved safety may be available with selective cyclooxygenase-2 (COX-2) inhibitors, but it is not clear that COX-2 inhibition offers the protective effect apparent with conventional NSAIDs. We therefore propose a parallel trial of the common NSAID ibuprofen and the selective COX-2 inhibitor celecoxib vs. placebo for prevention of AD and for attenuation of ARCD. The trial will involve four sites and enroll 2625 dementia-free subjects aged 72-88 with a history of Alzheimer-like dementia for a first degree relative. Therefore, a conspicuous decline in periodic cognitive screening test results will identify subjects with suspected incident dementia. We will evaluate these subjects clinically using structured, standardized methods of assessment and diagnosis. The proposed sample presumes 7 years of observation, with realistic estimates of attrition through mortality and other causes, and of treatment """"""""drop-outs"""""""" and """"""""drop-ins."""""""" It should provide 80% power (2-tailed a=0.05) to detect a 30% reduction in incidence among the treated groups. In this application we proposed the first 42-54 months of treatment with an interim analysis of efficacy after the last-enrolled subject has completed 30 months. At that point, the study will have 80% power to detect a 50% reduction in AD incidence with either agent, in which case the trial can be stopped. The trial should also be stropped if there is no apparent benefit of treatment, or if safety issues mandate. Otherwise, the intermit estimate of treatment effects will dictate the shape of a competing renewal application an additional 0.25 to 4 years of observation and a final analysis. As a secondary outcome, we will examine the trajectory of cognitive scores to assess ARCD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AG015477-05S3
Application #
7188320
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Ryan, Laurie M
Project Start
2000-03-01
Project End
2009-07-31
Budget Start
2006-03-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2006
Total Cost
$5,397,013
Indirect Cost
Name
University of Washington
Department
Psychiatry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Abdullah, Laila; Evans, James E; Emmerich, Tanja et al. (2017) APOE ?4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease. Aging (Albany NY) 9:964-985
ADAPT-FS Research Group (2015) Follow-up evaluation of cognitive function in the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial and its Follow-up Study. Alzheimers Dement 11:216-25.e1
Drye, Lea T; Casper, Anne S; Sternberg, Alice L et al. (2014) The transitioning from trials to extended follow-up studies. Clin Trials 11:635-47
Leoutsakos, Jeannie-Marie S; Bartlett, Alexandra L; Forrester, Sarah N et al. (2014) Simulating effects of biomarker enrichment on Alzheimer's disease prevention trials: conceptual framework and example. Alzheimers Dement 10:152-61
Reckess, Gila Z; Brandt, Jason; Luis, Cheryl A et al. (2013) Screening by telephone in the Alzheimer's disease anti-inflammatory prevention trial. J Alzheimers Dis 36:433-43
Alzheimer's Disease Anti-inflammatory Prevention Trial Research Group (2013) Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). Alzheimers Dement 9:714-23
Stern, Robert A; Daneshvar, Daniel H; Baugh, Christine M et al. (2013) Clinical presentation of chronic traumatic encephalopathy. Neurology 81:1122-9
Rosenberg, P B; Mielke, M M; Han, D et al. (2012) The association of psychotropic medication use with the cognitive, functional, and neuropsychiatric trajectory of Alzheimer's disease. Int J Geriatr Psychiatry 27:1248-57
Fields, Cynthia; Drye, Lea; Vaidya, Vijay et al. (2012) Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial. Am J Geriatr Psychiatry 20:505-13
Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S et al. (2012) Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial. Int J Geriatr Psychiatry 27:364-74

Showing the most recent 10 out of 27 publications