Contribution of APOE E4 and Vascular Risk Factors to Cerebrovascular Disease,
Neurodegeneration, Cognitive Decline and Dementia 
   Lead Investigator:    Emily Rosenich
   Institution      :    Monash University
   E-Mail           :    kgauthreaux@gmail.com
   Proposal ID      :    1594



   Proposal Description:
   The overarching goal of the proposed research is to clarify the contribution of genetic (APOE E4) and cardiovascular risk factors on cerebrovascular disease, neurodegeneration, cognitive decline and progression to vascular and/or Alzheimer?s disease dementia. It is expected that middle-aged APOE E4 carriers with high vascular risk will demonstrate greater cognitive decline in midlife relative to E4 carriers with low vascular risk, and that older E4 carriers with high vascular risk will demonstrate higher rates of cognitive decline and progression to dementia relative to E4 carriers with low vascular risk. It is anticipated that middle and older-aged E4 carriers with high vascular risk will demonstrate higher rates of cerebrovascular disease and neurodegeneration relative to E4 carriers with low vascular risk. Clarifying how genetic and vascular risk factors interact to drive cerebrovascular disease, neurodegeneration and cognitive decline in middle and older-age would help elucidate disease mechanisms and may provide important benefits/information regarding early intervention (prevention) and diagnosis and the development of novel disease-modifying therapies.    The objective of the proposed research is to explore two distinct aims and to test a series of corresponding hypotheses.    Aim 1: Investigate the contribution of apolipoprotein E (APOE) E4 and vascular risk factors on cognitive decline and progression to vascular and/or Alzheimer?s dementia in middle-aged and older adults.    Hypothesis 1a: Middle-aged E4 carriers with high vascular risk will demonstrate greater cognitive decline in midlife relative to E4 carriers with low vascular risk.    Hypothesis 1b: Older E4 carriers with high vascular risk will demonstrate higher rates of cognitive decline and progression to dementia relative to E4 carriers with low vascular risk.    Aim 2: Investigate the contribution of APOE E4 and vascular risk factors on cerebrovascular disease and neurodegeneration in middle-