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

我们的研究表明，APOE 4携带者的大脑DHA代谢异常， 早于阿尔茨海默病（AD）痴呆的发作。早期和长期高剂量DHA 在APOE 4动物模型中补充APOE 4可保留认知功能。的亚组分析 几项随机临床试验表明，APOE 4携带者可能受益于欧米茄3， 在AD发作之前补充。 在DHA脑递送试验（R 01 AG 054434）中，我们正在研究APOE 4对 160名非痴呆成年人随机接受2克DHA补充剂的反应 每天一次，与安慰剂相比，持续2年以上。DHA脑递送研究的目标是确定 APOE基因型对脑DHA水平的影响（使用脑脊液，主要结果）， 脑容量和功能连接变化（次要结局）和认知 （探索性结果）补充DHA后，提供有关机制的新信息 APOE 4介导的AD风险。 我们正在申请补充关闭资金，以支付由于以下原因而导致的意外成本增加 2019冠状病毒病大流行导致参与者辍学率和招募人数增加 2020-2021年期间延迟。

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.