RecruitingPhase 2NCT07392723

ALA-enriched Nutrition for Prevention of Cognitive Decline in APOE4 Older Adults

Alpha Linolenic Acid-enriched Nutrition for Prevention of Cognitive Decline in APOE4 Older Adults With Mild Cognitive Impairment: Targeting Cerebrovascular and Blood-brain Barrier Health

Sponsor

Michal Schnaider Beeri, Ph.D.

Enrollment

20 participants

Start Date

Jan 12, 2025

Study Type

INTERVENTIONAL

Conditions

Cognitive Dysfunction Alzheimer Disease Fatty Acids, Omega-3 Blood-Brain Barrier Apolipoprotein E, Deficiency or Defect of Brain Aging

Summary

This randomized, double-blind, placebo-controlled pilot trial will evaluate the effects of alpha-linolenic acid (ALA) supplementation on cognitive function, blood-brain barrier integrity, and brain vascular health in older adults with mild cognitive impairment and APOE4 genotype. By targeting the endogenous synthesis of docosahexaenoic acid (DHA) through ALA supplementation, the investigators aim to overcome the limitations of direct DHA supplementation, particularly in APOE4 carriers who exhibit low brain DHA levels and impaired blood-brain barrier function. This innovative approach offers a safe, cost-effective, and easily implementable therapeutic strategy for older adults at high risk for Alzheimer's dementia, especially APOE4 carriers, addressing a critical need given the limited cognitive benefits and significant adverse events of current amyloid-clearing drugs in this population.

Eligibility

Min Age: 60 Years

Inclusion Criteria6

Age 60 years or older
Have amnestic Mild Cognitive Impairment (MCI) - memory problems that do not interfere with daily life.
Carry at least one APOE4 gene allele (determined by a blood test).
Be fluent in English or Spanish.
Have a study partner (family member or friend) who can provide information about daily function.
Have the ability to give informed consent and comply with study visits and procedures.

Exclusion Criteria9

A diagnosis of dementia or any other brain disease that significantly affects thinking or memory (e.g., Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, traumatic brain injury).
History of stroke or other major neurological condition.
Short life expectancy due to end-stage disease or other serious medical condition.
Active cancer treatment that could interfere with study participation.
Allergy or sensitivity to flaxseed oil or corn oil.
Current use of flaxseed, flax oil, or fish oil supplements more than once per week.
MRI contraindications, such as pacemakers, metallic implants, or severe claustrophobia.
Current or past history of prostate cancer, regardless of remission status, OR a prostate-specific antigen (PSA) level \> 20 ng/mL at screening.
Use of experimental Alzheimer's treatments (e.g., amyloid monoclonal antibodies) unless on a stable regimen as confirmed by the treating physician.

Interventions

DRUGAlpha-Linolenic Acid (2.6 g/day)

Participants in this group will take flaxseed oil that contains 2.6 grams of alpha-linolenic acid (ALA) each day for six months. The oil will be provided in 5 mL prefilled oral syringes prepared by the Rutgers Clinical Research Pharmacy. Participants will take one syringe daily in the morning with food. They may mix the oil with cold foods such as yogurt or applesauce but should not heat it. The ALA supplement is intended to improve cognitive and brain health by enhancing the body's natural production of DHA that supports blood-brain barrier integrity and brain function.

DIETARY_SUPPLEMENTPlacebo Control Group

Participants in this group will take corn oil that does not contain ALA. The oil will be provided in the same 5 mL prefilled oral syringes as the active supplement and will look, taste, and smell similar to the ALA oil. Participants will take one syringe daily in the morning with food for six months. The placebo is used to compare effects against the ALA supplement and to maintain blinding for both participants and study staff.