Carrying the APOE ɛ4 allele is the strongest genetic risk factor for developing Alzheimer's disease. The goal of this project is to identify whether carrying the APOE ɛ4 allele is associated with reduced delivery of DHA to the brain. This information will help us identify the target population that could benefit from DHA supplementation to prevent cognitive decline.

The Brain DHA Delivery Trial will examine the effect of APOE genotype on the changes of cerebrospinal fluid (CSF) DHA to Arachidonic acid (AA) ratio in 184 cognitively healthy older individuals in response to DHA supplementation. Randomized clinical trials have yielded mixed results on the effect DHA supplementation on cognitive outcomes. This study asks the critical question of whether DHA gets into the brain in sufficient amounts after supplementation, and whether APOE genotype affects brain penetrance.

This trial will also test the effect of DHA supplementation on changes in brain structural and functional connectivity assessed by MRI, and changes in cognition after two years of supplementation in all 368 participants.

Inclusion Criteria:

• Age: ≥ 55 and ≤ 80
• At least one dementia risk factor (obesity, education years, hypertension, hyperlipidemia)
• Mini-Mental State Examination (MMSE) ≥ 25
• Logical Memory II delayed recall score ≥ 6 and ≤ 18 .

Exclusion Criteria:

• Diagnosis of dementia as assessed by the investigator
• Use of omega-3 preparations in the last 3 months
• > 200 mg/day of DHA consumption using a validated questionnaire
• Use of donepezil, rivastigmine, galantamine and/or memantine
• Alcohol or drug abuse
• A concomitant serious disease such as active cancer treatment or HIV.
• Participation in a clinical trial in the last 30 days
• Use of anticoagulants such as Plavix or Coumadin or the newer generation blood thinners.

available by request to study principal investigator and after approval by study committee.

within 1 year after study publication