Body Mass Index and Transition to Mild Cognitive Impairment in Cognitively
Intact Apolipoprotein E epsilon-4 Carriers 
   Lead Investigator:    John Woodard
   Institution      :    Wayne State University
   E-Mail           :    john.woodard@wayne.edu
   Proposal ID      :    1231



   Proposal Description:
   In this study, we wish to test the hypothesis that elevated BMI in cognitively healthy APOE4 carriers would be associated with an increased likelihood of developing MCI. Although cognitively healthy APOE4 carriers are already at increased risk for cognitive decline, factors related to an increased likelihood of transition to MCI in this select group of individuals are not well-studied.    Greater BMI has been associated with increased neuroinflammation as well as blood-brain barrier disruption in the hypothalamus, hippocampus, and regions of the cortex. For example, in animal models, greater levels of proinflammatory cytokines in the hippocampus have been associated with memory consolidation deficits.  Moreover, APOE4 carriers are at increased risk for metabolic dysregulation (and its sequelae) and exhibit a proinflammatory profile that promotes AD pathology.  It is possible that the combination of APOE4 and BMI above the normal range prior to conversion to MCI could increase inflammation, thereby creating conditions favorable to faster progression of cognitive decline.    The research done to date that investigates the relationship between BMI and transition to dementia has rarely considered the possible moderating role of the APOE4 allele. The role of BMI in cognitively healthy older adults with the APOE4 allele who subsequently progress to mild cognitive impairment (MCI), the transitional state between healthy aging and dementia, or AD itself, is unknown.