Project validating the use of the CDR Sum of Boxes as a single primary efficacy
  
   Lead Investigator:    Mark Jaros
   Institution      :    Elan Corporation
   E-Mail           :    mark.jaros@elan.com
   Proposal ID      :    93



   Proposal Description:
   Cognitive and functional outcome measures in use for clinical trials in AD  clinical change in clinical trials with reasonable numbers of study subjects  and manageable study durations when applied in early stages of the disease.  This problem is further confounded by regulatory considerations that require  clinical trials do separately demonstrate statistically significant outcomes on BOTH a cognitive and a functional outcome measures. The ability to utilize a single primary outcome measure in early AD clinical trials could greatly  enhance our ability to advance meaningful therapies in this critical stage of  the disease.     Tractenberg et al suggested that the CDR-SB can be broken down into separate  Cognitive and Functional subsums, which correlate with external tests that  probe the 2 respective domains. We have replicated these findings in both the  ADNI and REAL.Fr datasets. However, these populations, which were recruited for natural history studies, might not be representative of a population from which clinical trial subjects might be drawn. Therefore, in order to expand our validation exercise to support regulatory use of the CDR as a clinical trial outcome measure in early AD trials, we would like to test our hypotheses in yet a 3rd database, and one which might be more representative of practice populations at large.     Furthermore, despite the relatively large size of these data sets (N =  200-400), these databases are relatively small for conducting factor analyses. We believe that our factor analytical assessments of the CDR-SB could be improved and validated by replicating our findings in  the much larger NACC data set.   Finally, the NACC contains 2 proposed new CDR items, tracking behavior and  language functions. We would like to explore the changes in these items with  progression of AD from the MCI stage to Dementia.