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.

项目摘要/摘要 积累的证据表明，饮食可能在预防零星的晚期中起重要作用。 阿尔茨海默氏病的发作形式（负载）。我们以前来自华盛顿高地的工作，汉密尔顿高地， 曼哈顿的纵向人群队列的Inwood哥伦比亚老化项目（WHICAP）已指出 遵守地中海型饮食或其他健康饮食模式（DPS）与 降低了载荷的风险，较老的受试者的大脑和认知措施更好。而 这些DP的有益作用的基本机制是未知的，基于生物学的证据 这些DPS的个人营养素或食物成分的影响指向炎症。不受控制的慢性 炎症已与负载风险增加有关，而长期使用 抗炎治疗 似乎具有神经保护作用。我们旨在阐明饮食之间关系的机制 并通过直接检验注射的假设来加载（使用大量 炎症标记）介导DPS与负载，与负载相关的大脑和 WHICAP人口的认知变化，一个建立了良好的，多种族的，古老的人口。最佳 潜在的抗炎食品的结合将是介入研究的宝贵候选者，我们将 还可以得出炎症来解释食物组合，并测试其与神经影像和神经成像和 临床结果。具体来说，我们将执行以下研究：1）测量广泛的面板 炎症生物标志物使用多重和发展炎症特征（炎症标记模式， 小鬼）。检查Imps和Diet之间的关系，IMPS与负载风险或与负载有关的关系 大脑和认知措施。 2）测试先前确定的有益DPS的关联是否存在 负载和认知下降是由Imps介导的。在认知健康参与者的子集中 接受大脑MRI评估的研究人群，测试先前确定的 有益的DP和大脑测量是由IMPS介导的。 3）。可以得出最佳注入 - 解释饮食模式（IDP），解释了测量的炎症标志物的变化至最大变化。 检查这些IDP与负载和负载相关的大脑和认知措施的关联。检查 大脑测量是否解释了这些IDP和认知或负载的关系。 4）。复制和 验证AIM 1中的发现以在具有相似特征的单独队列中AIM 3。总体而言，成功 拟议研究的完成将提供有关炎症是否有助的重要信息 饮食与负载之间的关联。了解感染在饮食中的作用 负载可能有助于优先考虑公共卫生工作，并为饮食提供牢固的基础 旨在认知弹性的建议。