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

项目总结/摘要 越来越多的证据表明，饮食可能在预防散发性迟发性 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， 和英伍德哥伦比亚老龄化项目（WHICAP），一个在曼哈顿的纵向人口队列，已经表明 坚持地中海式饮食或其他健康饮食模式（DP）与以下因素有关： 在非痴呆老年受试者中，LOAD风险降低，大脑和认知指标改善。而 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DP的个别营养或食物成分的影响指向炎症。未控制的慢性 炎症与LOAD风险增加有关，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与 和LOAD通过直接测试炎症（使用大量的 炎症标志物）介导DP与LOAD之间的关系，以及LOAD相关的脑和 WHICAP人群（一个成熟的、多种族的老年人群）的认知变化。作为最佳 有效的抗炎食物的组合将是干预研究的有价值的候选人，我们将 还推导出解释炎症的食物组合，并测试它们与神经成像和 临床结果。具体来说，我们将进行以下研究：1）测量广泛的面板， 使用Multiplex的炎性生物标志物并开发炎性概况（炎性标志物模式， IMP）。检查IMP与饮食之间的关系，以及IMP与LOAD风险之间的关系，或与LOAD相关的关系 大脑和认知测量。2)测试先前确定的有益DP与 LOAD和认知下降由IMP介导。在认知健康的参与者的一个子集中， 接受脑部MRI评估的研究人群，测试先前确定的 有益的DP和大脑措施是由IMP介导的。3）。从经验上得出最佳的炎症- 解释饮食模式（IDP），最大限度地解释测量的炎症标志物的变化。 检查这些IDP与LOAD和LOAD相关的大脑和认知测量的关联。审查 大脑测量是否解释了这些IDP与认知或LOAD的关系。4）。复制和 在具有类似特征的单独队列中验证目标1至目标3中的发现。总体而言，成功 完成拟议的研究将提供重要的信息，炎症是否有助于 饮食和负荷之间的关系。深入了解炎症在饮食中的作用 和LOAD可能有助于优先考虑公共卫生工作，并为饮食提供坚实的基础。 针对认知弹性的建议。

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.