Development of Composite Cognitive Endpoints for Presymptomatic AD Trials 

 
   Lead Investigator:    Napatkamon Ayutyanont
   Institution      :    Arizona ADC
   E-Mail           :    Napatkamon.Ayutyanont@bannerhealth.com
   Proposal ID      :    234


   Publications:


1  Ayutyanont N, Langbaum JBS, Hendrix SB, Fleisher AS, Caselli R,  Monsell SE , Chen K,  Kukull WA , Bennett D, Tariot PN, Reiman EM
   Validation of the Alzheimer's Prevention Initiative Composite Cognitive Test Score
   Abstract  Alzheimers Dement,9:P320,2013,

   PUBLISHED





   Proposal Description:
   There is an urgent need to evaluate promising treatments to reduce the risk of Alzheimer???s disease (AD) symptoms or prevent those symptoms completely. Unfortunately, it currently takes too many cognitively healthy volunteers and too many years to evaluate promising presymptomatic AD treatments using clinical endpoints. The Alzheimer???s Prevention Initiative (API) was established to evaluate investigational amyloid-modifying treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD. To help accelerate the evaluation of presymptomatic AD treatments, we have begun to use longitudinal data sets that have followed individuals from cognitive normality to the clinical onset of AD (i.e., to mild cognitive impairment or probable AD dementia) to empirically identify the combination of neuropsychological test scores that track presymptomatic AD decline with greatest statistical power and then apply these endpoints to at-risk populations to estimate sample sizes that the API and others are now planning [12]. In this grant application, we propose to a) determine the extent to which a test score weighting strategy improves the statistical power of our empirically generated composite endpoint to track preclinical AD and evaluate presymptomatic AD treatments in our currently used longitudinal late-onset and early-onset AD data sets, b) establish the extent to which the composite cognitive endpoint is associated with comparable power to track preclinical AD in other available data sets c) provide sample size estimates for several planned presymptomatic AD trials, d) set the stage for their use as primary endpoints in at least two presymptomatic AD trials that are likely to begin in 2013, and e) provide a foundation for a grant application to further develop, test, and use the composite cognitive endpoint in the preclinical study and treatment of AD.