The role of inflammation in the association between diet and Alzheimer's disease

项目摘要/摘要 越来越多的证据表明，饮食可能在预防散发性迟发性心脏病中发挥重要作用。 阿尔茨海默病的发病形式(LOAD)。我们之前在华盛顿高地，汉密尔顿高地， 曼哈顿的纵向人口队列因伍德哥伦比亚老龄化项目(WHICAP)表示， 坚持地中海式饮食或其他健康饮食模式(DPS)与 非痴呆症老年受试者的负荷风险降低，大脑和认知测量更好。而当 这些DP的有益作用的潜在机制尚不清楚，基于生物学的证据 这些DPS的个别营养或食物成分的影响指向炎症。失控的慢性 炎症与负荷风险的增加有关，而长期使用 抗炎治疗 似乎有神经保护作用。我们的目标是阐明饮食和饮食之间关系的机制 并通过直接测试炎症(使用大量的 炎症标志物)介导DPS与负荷的关系，负荷相关的脑和 WHICAP人口的认知变化，这是一个成熟的、多种族的老年人口。作为一个最佳选择 强效抗炎食品的组合将是干预性研究的有价值的候选，我们将 还可以得出炎症--解释食物组合，并测试它们与神经成像和 临床结果。具体地说，我们将进行以下研究：1)测量广泛的小组 使用复合体的炎性生物标记物并开发炎性分布(炎性标记物模式， 小鬼)。检查IMPS和饮食之间的关系，以及IMPS和负荷风险或负荷相关之间的关系 大脑和认知测量。2)测试以前确定的有益的存款保障计划是否与 负荷和认知能力下降是由小儿麻痹症调节的。在认知健康的受试者中， 研究接受脑MRI评估的人群，测试以前发现的 有益的DPS和脑措施是由IMPS介导的。3)。经验性地得出最佳炎症- 最大限度地解释饮食模式(IDP)，解释测量的炎症标志物的变化。 检查这些国内流离失所者与负荷和负荷相关的大脑和认知测量的关联。考查 大脑测量是否解释了这些国内流离失所者与认知或负荷的关系。4)。复制和 在具有相似特征的单独队列中验证目标1至目标3中的结果。总体而言，成功 拟议研究的完成将提供关于炎症是否有助于 饮食和负荷之间的联系。深入了解炎症在饮食中的作用 和负荷可能有助于确定公共卫生工作的优先顺序，并为饮食提供坚实的基础 旨在提高认知韧性的建议。

Project Summary/Abstract Accumulating evidence suggests that diet may play an important role in the prevention of sporadic late- onset form of Alzheimer’s disease (LOAD). Our previous work from the Washington Heights, Hamilton Heights, and Inwood Columbia Aging Project (WHICAP), a longitudinal population cohort in Manhattan, has indicated that adherence to either a Mediterranean-type diet or to other healthy dietary patterns (DPs) was related to decreased risk for LOAD and better brain and cognitive measures in non-demented elderly subjects. While the underlying mechanisms for the beneficial role of these DPs are unknown, evidence based on the biological effects of individual nutrient or food components of these DPs point to inflammation. Uncontrolled chronic inflammation has been linked to increased risk of LOAD, while long-term use of anti-inflammatory treatment seems to have neuroprotective effects. We aim to elucidate the mechanism for the relationship between diet and LOAD by directly testing the hypothesis that inflammation (measured using a large number of inflammatory markers) mediates the relationship between DPs with LOAD, and LOAD-related brain and cognitive changes in WHICAP population, a well-established, multiethnic, elderly population. As an optimum combination of potent anti-inflammatory foods will be valuable candidates for interventional studies, we will also derive inflammation-explaining food combinations and test their association with both neuroimaging and clinical outcomes. Specifically, we will perform the following studies: 1) Measure an extensive panel of inflammatory biomarkers using Multiplex and develop inflammatory profiles (inflammatory marker patterns, IMP). Examine the relationship between IMPs and diet, and between IMPs and LOAD risk, or LOAD-related brain and cognitive measures. 2) Test whether the association of previous identified beneficial DPs with risk of LOAD and cognitive decline is mediated by IMPs. In a subset of the cognitively healthy participants of the study population who received brain MRI assessments, test whether previous identified association between beneficial DPs and brain measures is mediated by IMPs. 3). Empirically derive optimum inflammation- explaining dietary patterns (IDPs) that explain measured inflammatory markers’ variations to the maximum. Examine the association of these IDPs with LOAD and LOAD-related brain and cognitive measures. Examine whether brain measures explain the relationship of these IDPs and cognition or LOAD. 4). Replicate and validate the findings in Aim 1 to Aim 3 in a separate cohort that has similar characteristics. Overall, successful completion of the proposed studies will provide important information on whether inflammation contributes to the association between diet and LOAD. Obtaining insight into the role of inflammation in the context of diet and LOAD may assist to prioritize public health efforts and provide a firm foundation for dietary recommendations aiming for cognitive resilience.