Harmonizing cognitive domains (memory, executive functioning, language,
visuospatial functioning) across different Alzheimer's disease studies 
   Lead Investigator:    Shubhabrata Mukherjee
   Institution      :    University of Washington
   E-Mail           :    smukherj@uw.edu
   Proposal ID      :    1357



   Proposal Description:
   Genetics of Resilience project: Among older adults with normal cognition there appears to be substantial variation in the amount of neuropathology that is present at autopsy. For example, in the Religious Orders Study and Rush Memory and Aging Project, approximately 30 of cognitive normal older adults have substantial Alzheimer's disease (AD) neuropathology. However, limited empirical attention has focused on elucidating factors underlying "asymptomatic" AD. This study will evaluate markers of resilience across multiple large studies of AD. Specifically, we will define resilience using multiple approaches including, but not limited to, assessing better-than-expected cognitive performance given an individual's level of AD biomarkers. We will perform genomic and proteomic analyses to highlight pathways of resilience in individuals with normal cognition, mild cognitive impairment, or AD. The outcome of this work will be a list of potential markers of resilience that seem to postpone the onset of clinical symptoms and possibly identify potential targets for clinical intervention.   Here we are requesting the ability to create and evaluate a resilience phenotype using data from the National Alzheimer's Coordinating Center (NACC). We will then leverage co-calibrated composite measures of memory and cognition that will be harmonized across additional publicly available datasets. We will use Confirmatory Factor Analysis (CFA)