Role of Systemic Inflammation in Cognitive Decline: Rheumatoid Arthritis as a Prototype

全身炎症在认知能力下降中的作用：以类风湿关节炎为原型

• 批准号: 10642807
• 负责人: Elena Myasoedova
• 金额: $ 74.44万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642807
• 关键词: Address; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Antirheumatic Agents; Apolipoprotein E; Autoimmune; Autoimmunity; Biological Products; Brain; Brain Pathology; Cardiovascular Diseases; Characteristics; Chronic; Clinic; Clinical; Cognition; Cognitive; Data; Data Set; Dementia; Deterioration; Development; Disease; Disease model; Education; Epidemiology; Evolution; Exposure to; Funding; Future; General Population; Impaired cognition; Individual; Inflammation; Inflammatory; Infrastructure; Knowledge; Late Onset Alzheimer Disease; Longitudinal Studies; Measures; Medical Record Linkage; Mental Depression; Modeling; Nerve Degeneration; Neuropsychology; Obesity; Participant; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Phenotype; Play; Prevention; Prevention strategy; Proteins; Research; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Risk Factors; Risk Reduction; Role; Series; Serology; Smoking; Socioeconomic Status; System; Time; age related; cardiovascular disorder risk; cardiovascular risk factor; cerebrovascular pathology; cognitive change; cognitive function; cohort; comorbidity; data resource; dementia risk; demographics; genetic risk factor; immunomodulatory therapies; inflammatory marker; insight; lifetime risk; magnetic resonance imaging biomarker; modifiable risk; neuroimaging marker; novel; population based; prognostication; protective effect; prototype; radiological imaging; research study; response; secondary analysis; sex; systemic inflammatory response; therapeutic target

PROJECT SUMMARY/ABSTRACT Age-related increase in the burden of systemic inflammation is a key player and potential treatment target in Alzheimer’s disease (AD) and other age-related dementias. Rheumatoid arthritis (RA) is an autoimmune hyper- inflammatory disease and an excellent model for understanding the role of chronic inflammation and autoimmunity in cognitive decline and the modulating effects of anti-rheumatic therapies. Longitudinal studies on the magnitude of the risk and timing of dementia in chronic inflammatory conditions such as RA are lacking, resulting in a substantial knowledge gap. Chronic inflammation precedes the onset of dementia. Furthermore, growing evidence suggests a protective effect of anti-rheumatic medications on AD. We propose to utilize data from existing cohorts of patients with RA and matched comparators without RA (R01 AR046849) to quantify and compare the risk of dementia in RA vs. non-RA participants and to define the role of chronic systemic inflammation in cognitive decline using RA as a prototype. We will determine the impact of chronic systemic inflammation and anti-rheumatic treatments on dementia in RA patients, adjusting for important confounders (age, sex, education, socio-economic status, smoking, obesity, cardiovascular disease, depression). Additionally, using the Mayo Clinic Study of Aging resources (U01 AG006786), we will define change of cognitive function and neuroimaging markers in patients with RA according to the level of inflammation and use of anti-rheumatic treatments. Successful completion of the proposed series of studies will be a key step towards understanding whether chronic exposure to systemic inflammation has adverse cognitive effects and whether tight control of systemic inflammation with anti-rheumatic treatments has protective effects. Our existing cohorts offer a rare opportunity to efficiently address this knowledge gap. Potential downstream effects are significant, including new strategies for prevention and management of dementia in patients with RA and new insights for future studies on prevention of dementia in the general population.

项目摘要/摘要 与年龄有关的全身感染燃烧相关的增加是关键参与者，也是潜在的治疗目标 阿尔茨海默氏病（AD）和其他与年龄有关的痴呆症。类风湿关节炎（RA）是一种自身免疫性高 - 炎症性疾病和理解慢性炎症和 自身免疫性在认知能力下降和抗风湿疗法的调节作用中。纵向研究 缺乏慢性炎症条件（例如RA）的痴呆症的风险和时机的大小， 导致大量知识差距。 慢性炎症先于痴呆症的发作。此外，越来越多的证据表明受保护 抗震颤药物对AD的影响。我们建议利用现有RA患者同类群的数据 并匹配没有RA的比较器（R01 AR046849），以量化和比较RA VS中的痴呆风险。 非RA参与者，并定义慢性系统性炎症在使用RA作为A的认知下降中的作用 原型。我们将确定慢性全身注射和抗风湿治疗对 RA患者的痴呆症，调整重要的混杂因素（年龄，性别，教育，社会经济地位， 吸烟，肥胖，心血管疾病，抑郁症）。另外，使用蛋白诊所的衰老研究 资源（U01 AG006786），我们将定义患者的认知功能和神经成像标记的变化 根据感染水平和使用抗风湿治疗的水平。 拟议的一系列研究成功完成将是了解是否是否 长期暴露于全身性炎症会产生不良的认知效果，以及对全身性的严格控制 抗震荡治疗的炎症具有​​保护作用。我们现有的队列提供了难得的机会 有效解决这一知识差距。潜在的下游效果很重要，包括新策略 用于预防和管理RA患者的痴呆症和新见解，以将来研究 预防普通人群的痴呆症。