Triglyceride Effects on Blood Flow in the Human Brain

Overview: High fat feeding (HFF) is a risk factor for AD, but this risk factor is modulated by APOE genotype. Acute meal studies including lipid tolerance tests are increasingly being used to understand mechanisms by which diet affects disease processes. Investigators have consistently shown that E4 carriers respond differently to HFF in acute meal challenges; this study will further explore this phenomenon in older adults by assessing cerebral blood flow (CBF), given its tight coupling to brain metabolism. Here investigators propose to use arterial spin labeling (ASL) MRI as this non-invasive imaging technique can detect small changes in global and regional CBF, and acute ∆CBF in response to nutrients have been demonstrated in humans. With this project investigators will determine the most optimal time point for detecting post-lipid ∆CBF, as well as determine which regions of the brain respond to HFF. To our knowledge, this study would be the first to assess ∆CBF using ASL; these pilot data will then assist with future grant applications in this area.

Specific aims: 1. To determine which time point (1, 2, or 3 hours) produces the most robust ∆CBF after ingestion of a lipid drink in 30 older adults. 2. To determine which regions of the brain respond to HFF.

Methods: Participants: All study procedures will be submitted to the UW Institutional Review Board for approval. Investigators maintain a database of ~40-50 participants from the Meal and Memory study who have already agreed to be contacted for future studies; investigators will recruit 30 participants. Inclusion criteria are as follows: age 55 and older, able to read and understand English, able to give informed consent, and able to undergo MRI and ingest dairy products. All interested participants will undergo telephone screening to ensure they meet inclusion criteria. If they meet criteria, they will be mailed a reminder letter which will instruct them to fast the night before. They will also receive a copy of the consent form to look over, and a medical history form to fill out, including an MRI safety checklist which asks them about prior surgeries and whether they have any metal in their body.

Study visit: Participants will fast the night prior (12 hours prior to the visit time); medications and water are ok. They will arrive at the South Lake Union facility between 8 and 10 am. They will undergo informed consent in a quiet room from the study team (either the PI or the study coordinator) and given plenty of opportunities to ask questions. If they choose not to enroll in the study, they will be discharged from the unit and parking or transportation will be reimbursed. As a part of the consent process, investigators will ask participants to give optional written permission on the consent form to release their APOE genotype from the Meal and Memory Study, or other Alzheimer's research study they may have participated in. Investigators will not disclose this genotype to anyone outside the study team including the participant.

If the participant enrolls in the study and signs a consent form and a research HIPAA form, then the protocol will begin. Vitals will be assessed by the study team, including blood pressure, heart rate, and height/weight and BMI calculation. Participant will be escorted to the MRI machine by the study team, who will also bring down the lipid drink in a cooler. An MRI technician experienced with research MRI procedures will conduct the MRI portion. First a 15 minute ASL protocol will be run, then the participant will be given the heavy cream (100 mls, or just under half a cup, which contains 370 calories, 40.4 grams of total fat, 23.6 grams of saturated fat). Investigators will encourage the participant to drink the product over 5 minutes. Participants will then undergo 3 more 15-minute scans at 1, 2, and 3 hours post drink. It is possible that some of the acquisition times can be slightly longer than 15 minutes. After the last MRI image acquisition, lunch will be offered (up to $15 at a nearby restaurant), participants will receive a gift card, and parking or transportation will be reimbursed, and be discharged.