Intrepad

Neurology

Neurology, 2007

2011

Alzheimers & Dementia, 2011

Alzheimer's & Dementia, 2013

ObjectivesThe Alzheimer's Disease Anti‐inflammatory Prevention Trial Follow‐up Study (ADAPT‐FS) was designed to evaluate the efficacy of naproxen and celecoxib for the primary prevention of Alzheimer's disease (AD) several years after cessation of treatment in ADAPT.MethodsADAPT was a randomized, double‐masked, multicenter clinical trial of naproxen or celecoxib vs placebo (1:1:1.5 assignment ratio) at six U.S.‐based clinics. The trial enrolled 2528 people between 2001 and 2004. Treatments were discontinued in December 2004 and participants were monitored regularly until 2007. In 2010 and 2011, ADAPT‐FS screened 1537 participants by telephone and, if indicated, examined them in person using standardized clinical assessments. The primary outcome was time to diagnosis of AD. Death index searches were performed for participants not located.ResultsEighty‐nine additional AD events were identified (24 celecoxib, 25 naproxen, and 40 placebo) yielding a total of 161 events (48 [6.6%...

Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) and Follow-up Study (ADAPT-FS) examined effects of naproxen and celecoxib on cognition in the elderly. We report here results describing trajectories of cognitive evaluation test scores. A total of 2356 participants completed baseline and at least one follow-up cognitive evaluation between 2001 and 2004. Study treatments were discontinued in 2004, but participants were followed until 2007. A total of 1537 participants were reevaluated in 2010 to 2011. Outcomes include seven cognitive evaluations administered yearly in person in ADAPT and three of these evaluations that were administered by telephone near the end of ADAPT and again in ADAPT-FS. There were no important differences over time by treatment group on any ADAPT cognitive measure, a global composite, or the three cognitive measures reassessed in ADAPT-FS by telephone. Treatment for 1 to 3 years with naproxen or celecoxib did not protect against cognitive ...

BMC Medicine, 2012

Since the first description of the case of Auguste Deter, presented in Tübingen in 1906 by Alois Alzheimer, there has been an exponential increase in our knowledge of the neuropathological, cellular, and molecular foundation of Alzheimer's disease (AD). The concept of AD pathogenesis has evolved from a static, binary view discriminating cognitive normality from dementia, towards a dynamic view that considers AD pathology as a long-lasting morbid process that takes place progressively over years, or even decades, before the first symptoms become apparent, and thus operating in a continuum between the two aforementioned extreme states. Several biomarkers have been proposed to predict AD-related cognitive decline, initially in cases with mild cognitive impairment, and more recently in cognitively intact individuals. These early markers define at-risk individuals thought to be in the preclinical phase of AD. However, the clinical relevance of this preclinical phase remains controver...

The Journal of Prevention of Alzheimer's Disease, 2016

We describe events spanning over 20 years that have shaped our approach to identification of interventions that may delay symptoms in Alzheimer’s disease (AD). These events motivated the development of a new Centre for Studies on Prevention of AD that includes an observational cohort of cognitively normal high-risk persons and INTREPAD, a nested two-year randomized placebo-controlled trial of the non-steroidal anti-inflammatory drug naproxen sodium. INTREPAD enrolled 217 persons and will follow 160 in a modified intent-to-treat analysis of persons who remained on-protocol through at least one follow-up evaluation. The trial employs dual endpoints: 1) a composite global cognitive score generated by a battery of 12 psychometric tests organized into five subscales; and 2) a summary Alzheimer’s Progression Score derived from latent variable modeling of multiple biomarker data from several modalities. The dual endpoints will be analyzed by consideration of their joint probability under t...

International Journal of Geriatric Psychiatry, 2002

Alzheimer's & Dementia, 2011