The delivery of essential fatty acids to the Brain in Alzheimer's disease

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Our studies suggest that APOE4 carriers have abnormalities in brain DHA metabolism that precede the onset of Alzheimer’s disease (AD) dementia. Early and long-term high dose DHA supplementation in APOE4 animal models preserves cognitive functions. Subgroup analyses of several randomized clinical trials suggest that APOE4 carriers may benefit for omega 3 supplementation prior to the onset of AD. In the DHA Brain Delivery Trial (R01AG054434) we are studying the effect of APOE4 on the response to DHA supplementation in 160 non-demented adults randomized to 2 grams of DHA daily vs placebo for over 2 years. The goal of DHA brain delivery study is to determine the effect of APOE genotype on brain DHA levels (using cerebrospinal fluid, primary outcome), on brain volumetric and functional connectivity change (secondary outcomes) and cognition (exploratory outcomes) after DHA supplementation, providing novel information on mechanisms for APOE4 mediated AD risk. We are requesting supplemental close out funds to cover unanticipated increase in costs due to the COVID-19 pandemic that resulted in greater participant drop-out rates and recruitment delays during 2020-2021.