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

炎症在饮食与阿尔茨海默病之间的关系中的作用

• 批准号: 10059157
• 负责人: Yian Gu
• 金额: $ 76.39万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059157
• 关键词: Address; Adherence; Adult; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Anti-Inflammatory Agents; Biological; Biological Markers; Biological Response Modifiers; Blood Vessels; Brain; Cardiovascular system; Characteristics; Chronic; Clinical; Cognition; Cognitive; Communities; Consumption; Data; Demographic Factors; Development; Diagnosis; Diagnostic; Diet; Dietary Assessment; Dietary Component; Dietary Factors; Dietary Practices; Disease; Elderly; Ethnic Origin; Evaluation; Food; Foundations; Genetic; Health; Immune; Impaired cognition; Individual; Inflammation; Inflammation Process; Inflammatory; Intervention Studies; Late Onset Alzheimer Disease; Link; Logic; Magnetic Resonance Imaging; Measures; Mediating; Medical History; Neurons; Neuropsychological Tests; Nutrient; Outcome; Participant; Pathway interactions; Pattern; Peripheral; Play; Population; Prevention; Process; Public Health; Race; Recommendation; Research; Resources; Risk; Role; Sampling; Sampling Studies; Serum; Signal Transduction; Socioeconomic Status; Structure; Testing; Variant; Washington; Work; aging population; base; clinical Diagnosis; cognitive change; cohort; comorbidity; dietary; evidence base; good diet; healthy aging; inflammatory marker; inflammatory modulation; insight; multi-ethnic; multimodality; multiplex assay; neuroimaging; non-demented; novel; pre-clinical; preservation; prevent; protective effect; resilience; study population; systemic inflammatory response

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.

项目概要/摘要 越来越多的证据表明，饮食可能在预防散发性晚期疾病方面发挥重要作用。 阿尔茨海默氏病（LOAD）的发病形式。我们之前的作品来自华盛顿高地、汉密尔顿高地， 曼哈顿纵向人口队列 Inwood Columbia 老龄化项目 (WHICAP) 表明 坚持地中海式饮食或其他健康饮食模式（DP）与 非痴呆老年受试者的 LOAD 风险降低，大脑和认知能力得到改善。虽然 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 中的单个营养素或食物成分的影响表明炎症。不受控制的慢性 炎症与 LOAD 风险增加有关，而长期使用 抗炎治疗 似乎具有神经保护作用。我们的目标是阐明饮食与饮食之间关系的机制。 和负载通过直接测试炎症的假设（使用大量测量 炎症标记物）介导 DP 与 LOAD 以及 LOAD 相关的大脑和 WHICAP 人群（一个成熟的多种族老年人口）的认知变化。作为一个最优 强效抗炎食物的组合将成为介入研究的有价值的候选者，我们将 还推导出解释炎症的食物组合，并测试它们与神经影像学和 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 分析炎症生物标志物并开发炎症特征（炎症标志物模式、 IMP）。检查 IMP 与饮食之间的关系，以及 IMP 与 LOAD 风险或 LOAD 相关的关系 大脑和认知测量。 2) 测试先前确定的有益 DP 是否与风险相关 负荷和认知能力下降是由 IMP 介导的。在认知健康的参与者的子集中 研究接受脑部 MRI 评估的人群，测试之前确定的之间是否存在关联 有益的 DP 和大脑测量是由 IMP 介导的。 3）。根据经验得出最佳炎症- 解释饮食模式（IDP），最大限度地解释测量的炎症标记物的变化。 检查这些 IDP 与 LOAD 以及与 LOAD 相关的大脑和认知测量的关联。检查 大脑测量是否可以解释这些 IDP 与认知或负载的关系。 4).复制并 在具有相似特征的单独队列中验证目标 1 至目标 3 中的发现。总体来说，成功 完成拟议的研究将提供关于炎症是否有助于 饮食与负荷之间的关联。深入了解炎症在饮食中的作用 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。