Triglyceride Effects on Blood Flow in the Human Brain

The 'Western diet' characterized by high fat feeding (HFF) is a risk factor for Alzheimer's disease (AD); however, little is known about mechanisms. Paradoxically, individuals who carry the AD risk gene APOE E4 cognitively improve after HFF and show different metabolic responses to fat intake. These responses include a more pronounced drop in systolic blood pressure and a decrease in cerebrospinal fluid glucose and lactate levels. This proposal will further examine the brain metabolic response to HFF using non-invasive imaging. Cerebral blood flow (CBF) as assessed by functional MRI is increasingly utilized to investigate brain function, given that CBF is tightly coupled to brain metabolism. Acute changes in CBF have been described in response to carbohydrate ingestion in regions important for learning and memory; however, no one has yet assessed CBF response to lipid. Here investigators propose to characterize CBF changes to a high fat drink in older adults. This study will include a time course assessment as well as analyses of global and regional change in CBF. These data would serve as feasibility pilot data for an R01 application which would include cognitive and peripheral metabolic data. These types of studies will provide a clearer picture of acute brain metabolic response to HFF in older adults, including the effects of APOE.