Apolipoprotein E (APOE) Genotype Effects on Triglycerides and Blood Flow in the Human Brain

Launched by UNIVERSITY OF WASHINGTON · Dec 29, 2020

Keywords

ClinConnect Summary

This clinical trial is exploring how a specific gene related to Alzheimer's disease (called APOE E4) affects triglycerides (a type of fat in the blood) and blood flow in the brain after eating a high-fat diet. Interestingly, while a high-fat diet usually increases the risk of Alzheimer’s, some people with the APOE E4 gene seem to do better after such a diet. Researchers want to understand this better by using brain imaging techniques to see how blood flow and metabolism are affected.

To participate in this study, you need to be 55 years or older, and the researchers are looking for a balanced mix of people with and without the APOE E4 gene, as well as men and women (women must be post-menopausal). You should be able to understand and give your consent, and be comfortable undergoing an MRI scan and consuming dairy products. However, certain health conditions, like diabetes requiring medication or significant heart issues, may prevent you from enrolling. If you join the study, you can expect to undergo some tests, including an MRI, to help researchers learn more about how diet and genetics influence brain health.

Gender

ALL

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.