Vascular Contributions to Dementia and Genetic Risk Factors for Alzheimer?s
Disease 


   Note: An Official Proposal has not been Submitted to NACC.


   Lead Investigator:    Joey Contreras
   Institution      :    U Southern California
   E-Mail           :    joeycont@usc.edu
   Proposal ID      :    954



   Proposal Description:
   Examine the temporal relationship between BBB permeability (DCE-MRI), CBF (ASL-MRI) and WML. Hypothesis: An increase in BBB permeability in APOE4 or PSEN1 mutation carriers relative to non-carriers precedes and predicts reductions in CBF, increased WML volume, and these vascular markers predict preclinical AD progression and cognitive decline. Understanding the temporal sequence of brain changes associated with AD and the prediction of cognitive change. Few studies have investigated the temporal relationship between changes in brain structure and function, and no studies to our knowledge have examined change over time in both markers of connectivity in those at risk for AD, or in relation to cognition. In a cross-sectional study of cognitively normal APOE4 carriers, white matter integrity was lower in APOE4 carriers with only a marginal difference in medial temporal lobe functional connectivity when compared to non-carriers. In a separate study of MCI vs. NCI, disruptions in both structural and functional connectivity of the posterior cingulate gyrus-to-hippocampus was reported. In cognitively normal adults, scores on verbal memory list learning were positively correlated with right hippocampus activity, supporting a positive relationship between brain activity and successful memory processing. Understanding the relationship between neuronal changes (indexed by connectivity changes) associated with AD pathophysiological process is critical for identifying sensitive biomarkers in clinical trials and for selecting sensitive outcome measures that are clinically meaningful.    I wanted to use subjects neuroimaging data  obtained using our PPG funds and process them using HCP (human connectome project) minimal preprocessing pipelines. I searched our own IADC database to identify subjects that were scanned using HCP acquisition sequences and now wish to use their diagnostic data to identify early signs of aging and dementia (specifically related to AD) using neuroimaging