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

我们的研究表明，APOE4携带者存在脑DHA代谢异常 在阿尔茨海默病(AD)痴呆发作之前。早期和长期大剂量DHA APOE4动物模型中的补充剂保留了认知功能。的亚群分析 几项随机临床试验表明，APOE4携带者可能对omega 3有利 在阿尔茨海默病发作前补充。 在DHA脑递送试验(R01AG054434)中，我们正在研究APOE4对 随机服用2克DHA的160名非痴呆成人对补充DHA的反应 每日服用VS安慰剂2年以上。DHA脑给药研究的目标是确定 载脂蛋白E基因对脑DHA水平的影响(使用脑脊液，主要结果)， 脑体积和功能连接性改变(二次结果)与认知 (探索性结果)补充DHA后，提供了关于机制的新信息 APOE4介导的AD风险。 我们要求追加结清资金，以弥补因以下原因而导致的成本意外增加 新冠肺炎大流行导致更高的参与者辍学率和招聘 2020-2021年期间的延误。

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.