Depression, Inflammation, Biological Age and Cognitive Function

抑郁、炎症、生物年龄和认知功能

• 批准号: 10333619
• 负责人: CHRISTOPHER G ENGELAND
• 金额: $ 66.03万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-29 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10333619
• 关键词: Address; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Anhedonia; Apolipoprotein E; Behavioral; Biological; Biological Aging; Biological Markers; Black race; Blood; Cause of Death; Classification; Cognitive; Cognitive aging; DNA Methylation; Data; Data Collection; Dementia; Development; Dimensions; Ecological momentary assessment; Elderly; Ethnic Origin; Future; Gender; Hispanic; Immune; Impaired cognition; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Length; Major Depressive Disorder; Measures; Mediating; Mediation; Mental Depression; Modeling; Nerve Degeneration; Neuropsychology; Outcome; Pathway interactions; Plasma; Population; Predictive Value; Prevalence; Psychosocial Factor; Public Health; Race; Recording of previous events; Research; Risk; Risk Factors; Role; Socioeconomic Status; Stress; Structure; Testing; Time; Variant; Woman; Work; aged; base; biopsychosocial; cognitive function; cognitive performance; cognitive testing; cohort; dementia risk; depressive symptoms; ethnic diversity; experience; functional outcomes; health disparity; inflammatory marker; innovation; men; mild cognitive impairment; novel strategies; perceived discrimination; preventive intervention; psychosocial; racial disparity; racial diversity; sex; symptomatology; systemic inflammatory response; telomere

ABSTRACT - PROJECT 2 The incidence of Alzheimer’s disease and related dementias (ADRD) are rapidly rising as the world population is aging. The majority of past research to identify risk factors for dementia has focused on the predictive value of one factor at a time. This has resulted in a long list of factors that relate to the precursors of ADRD (i.e., cognitive decline and mild cognitive impairment [MCI]) with little guidance as to which to prioritize or which targets might be most suitable for intervention. Our approach will address this problem by considering many factors simultaneously and in interaction. This project will focus on the role of three interrelated factors: major depressive disorder (and depressive symptomatology), systemic inflammation, and accelerated biological aging (e.g., DNA methylation age, telomere length). All three are known to be risk factors for MCI and subsequent ADRD, but the degree to which they have unique impact is unclear, as is the degree to which they accumulate or interact to confer risk. In addition, this project will help unpack underpinnings of cognitive health disparities by examining how race and gender moderate connections between depressive symptoms and biological measures with ADRD, and the relevance of perceived discrimination, lifetime adversity, and socioeconomic status (SES). Rich assessment at multiple time points in older adults, and determination of inter-relationships between multiple key risk factors, will enable greater ability to predict not only who is at greatest risk but also to illuminate specific targets for future intervention. The proposed project is part of a renewal of the Einstein Aging Study (EAS). For this renewal, 767 racially diverse men and women aged 60 and older will complete up to 5 annual waves of data collection. Each wave will include a two week “burst” of daily and ecological momentary assessments (EMAs) to examine psychosocial and behavioral factors as they are experienced, as well as an in-depth assessment of cognitive function level, mild cognitive impairment (MCI), and depression. A blood draw will occur at the end of each EMA burst to capture inflammatory load and enable classification of biological age, as well as plasma-based neurodegenerative biomarkers that will further inform study endpoints. This project will help clarify the effects of depression, inflammation, and biological age on individual risk for cognitive decline and MCI, using more nuanced and integrative models than in past research. Innovation includes leveraging an existing cohort of diverse older adults to explore disparities in ADRD risk attributable to race, ethnicity, SES, and psychosocial factors (e.g., perceived discrimination), and the use of multiple biological measures that have not previously been integrated in biopsychosocial models. This work will ultimately pave the way for tailored interventions to reduce risk of cognitive aging and decline.

摘要 - 项目 2 随着世界人口的增长，阿尔茨海默病和相关痴呆症 (ADRD) 的发病率正在迅速上升 正在老化。过去识别痴呆症危险因素的大多数研究都集中在以下因素的预测价值上： 一次只考虑一个因素。这导致了与 ADRD 前兆相关的一长串因素（即， 认知衰退和轻度认知障碍 [MCI]），但对于优先考虑哪些或哪些 目标可能最适合干预。我们的方法将通过考虑许多因素来解决这个问题 因素同时存在且相互作用。该项目将重点关注三个相互关联因素的作用： 抑郁症（和抑郁症状）、全身炎症和加速生物 衰老（例如 DNA 甲基化年龄、端粒长度）。已知这三者都是 MCI 的危险因素， 随后的 ADRD，但它们具有独特影响的程度尚不清楚，正如它们在多大程度上 累积或相互作用以赋予风险。此外，该项目将有助于揭示认知健康的基础 通过研究种族和性别如何调节抑郁症状和抑郁症之间的联系来发现差异 ADRD 的生物测量，以及感知到的歧视、一生逆境和 社会经济地位（SES）。对老年人进行多个时间点的丰富评估，并确定 多个关键风险因素之间的相互关系，不仅能够提高预测谁处于危险状态的能力 最大的风险，同时也阐明了未来干预的具体目标。 拟议的项目是爱因斯坦衰老研究（EAS）更新的一部分。第767章 种族歧视 60 岁及以上的不同男性和女性将完成最多 5 波年度数据收集。每波 将包括为期两周的每日和生态瞬时评估（EMA）“爆发”，以检查 所经历的心理社会和行为因素，以及对认知的深入评估 功能水平、轻度认知障碍 (MCI) 和抑郁症。每次结束时都会进行抽血 EMA 爆发以捕获炎症负荷并实现生物年龄分类以及基于血浆的分类 神经退行性生物标志物将进一步告知研究终点。 该项目将有助于阐明抑郁、炎症和生物年龄对个体风险的影响 认知衰退和 MCI，使用比过去的研究更细致和综合的模型。创新 包括利用现有的多元化老年人群体来探索 ADRD 风险的差异 种族、族裔、社会经济地位和社会心理因素（例如，感知到的歧视），以及使用多种 以前尚未整合到生物心理社会模型中的生物测量。这项工作将 最终为量身定制的干预措施降低认知老化和衰退的风险铺平道路。