Effects of APOE genotype on brain blood flow and triglycerides

APOE Genotype Effects on Triglycerides and Blood Flow in the Human Brain

This study is testing how a specific gene related to Alzheimer's affects blood flow in the brain and fat levels in older adults after drinking a high-fat beverage.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT04692441 on ClinicalTrials.gov

What this trial studies

This study aims to enroll 90 older adults to investigate how the APOE E4 genotype influences changes in global cerebral blood flow in response to a high-fat drink. Participants will undergo a series of assessments, including an oral triglyceride tolerance test and MRI scans using arterial spin labeling to measure cerebral blood flow. The study will compare responses between E4 carriers and non-carriers, providing insights into the relationship between lipid metabolism and Alzheimer's disease risk. The research will also include cognitive assessments and multiple blood draws to gather relevant health data.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 55 or older, with equal representation of APOE E4 carriers and non-carriers.

Not a fit: Patients with diabetes requiring medication or significant hypertension may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of how genetic factors influence brain health and potentially lead to targeted interventions for Alzheimer's disease.

How similar studies have performed: While studies have explored the relationship between APOE genotype and Alzheimer's disease, this specific approach using high-fat feeding and cerebral blood flow measurement is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Aged 55 or older at the date of the screening visit
2. Equal representation of APOE E4 carriers and non-carriers
3. Strive for equal numbers of men and women; women need to be post-menopausal for at least 1 year or medical equivalent (hysterectomy)
4. Able to read and understand English
5. Able to cognitively and physically give informed consent 6.Able to undergo an MRI and ingest dairy products

Exclusion Criteria:

1. Diabetes requiring medication: Known type 1 or type 2 diabetes requiring oral diabetic medications or insulin. Diet-controlled diabetes, 'pre-diabetes,' remote use of diabetic agents, or a history of gestational diabetes is ok to enroll.
2. Hypertension requiring medication: Participants taking medication for hypertension will be excluded, unless they can safely stop the medication for 2 weeks, per their primary care provider, before the study visit (The MRI visit).
3. Significant lipid abnormalities: Diagnosis of hyperlipidemia requiring statin, bile acid resins, fibrate medications, and/or high dose niacin will be excluded. If participants are willing to stop their medications 4 weeks before the screening visit (as long as they are not on medication for secondary prevention of heart attack or stroke), this is ok. If participants are taking over-the-counter medications known to affect lipid metabolism including omega-3 fatty acids, niacin, or red yeast rice, they can enroll if they agree to stop the medication 4 weeks before the screening visit. Also excluded are significant cholesterol abnormalities as defined by the 2018 American College of Cardiology/American Heart Association (ACC/AHA) lipid guidelines including a fasting LDL cholesterol ≥190 mg/dL or fasting triglycerides \> 500 mg/dL. Total cholesterol levels and HDL levels outside of the typical range are ok.
4. Dementia and cognitive impairment: Known diagnosis of dementia, use of dementia medications, or identification of dementia during the baseline visit, will be excluded. Also excluded are other significant neurologic diseases which affect cognition, such as recent stroke, recent severe head injury, or advanced Parkinson's disease. Mild cognitive impairment with no functional deficits is ok.
5. Psychiatric disorders: Participants who report active untreated major depression, psychosis, or mania, or who present with those symptoms at the baseline visit, or who act belligerent or unprofessional toward the clinical staff, will be excluded. Psychiatric conditions which are stable and treated with medication or therapy are ok. Similarly, individuals who meet criteria for active alcohol or drug abuse disorder will also be excluded as many of these substances could affect the study outcome.
6. Other significant medical illnesses: Illnesses which would cause a hardship on the participant to attend study visits and undergo a glucose tolerance test and an MRI. This includes unstable angina, moderate or severe chronic obstructive pulmonary disease (COPD), class III-IV Congestive heart failure (CHF), active liver or kidney disease causing cognitive symptoms, active cancer undergoing systemic chemotherapy or radiation, as well as other illnesses which in the study physician's view would put the participant at risk and also may place an undue burden on the participant.
7. Major digestive disorders: Disorders which would affect fat tolerance and absorption will be excluded including inflammatory bowel disease, gastric bypass or banding, or small intestine resection. Also excluded are allergies or major intolerance to milk or dairy products.
8. Contraindications to MRI: Metal in body that is not compatible with an MRI, other conditions that preclude an MRI (such as not being able to lie still or lie flat for an extended time) are excluded.

Where this trial is running

Seattle, Washington

• University of Washington Medical Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Angela J Hanson, MD — University of Washington
• Study coordinator: Angela J Hanson, MD

Conditions Alzheimer Disease; Dementia; APOE genotype; lipid metabolism