Depression, Inflammation, Biological Age and Cognitive Function

摘要--项目2 随着世界人口的增加，阿尔茨海默病和相关痴呆(ADRD)的发病率正在迅速上升 是在变老。过去大多数确定痴呆症危险因素的研究都集中在以下方面的预测价值 一次只考虑一个因素。这导致了与ADRD前兆有关的一长串因素(即， 认知衰退和轻度认知障碍[MCI])，几乎没有关于优先顺序或优先顺序的指导 目标可能是最适合干预的。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。本项目将重点关注三个相互关联的因素的作用：主要 抑郁障碍(和抑郁症状)、全身性炎症和加速生物反应 衰老(如DNA甲基化年龄、端粒长度)。这三种因素都是MCI和MCI的危险因素 随后的ADRD，但它们产生独特影响的程度尚不清楚，它们在多大程度上 积累或相互作用以赋予风险。此外，这个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缓和抑郁症状和 与ADRD的生物学测量，以及感知的歧视、终身逆境和 社会经济地位(SES)。老年人在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，将不仅能够更好地预测谁在 最大的风险，也是为了阐明未来干预的具体目标。 这项拟议的项目是爱因斯坦老化研究(EAS)更新的一部分。对于这次更新，767个种族 年龄在60岁及以上的不同男性和女性将完成最多5次年度数据收集。每一波 将包括为期两周的日常和生态瞬时评估(EMA)以供检查 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。每次结束时都会抽血 EMA突发捕获炎性负荷并实现生物年龄分类以及基于血浆的 神经退行性生物标记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人罹患糖尿病风险的影响。 认知衰退和MCI，使用了比过去研究更细微和综合的模型。创新 包括利用现有的不同老年人队列来探索可归因于以下因素的ADRD风险差异 种族、族裔、社会地位和心理社会因素(例如，感觉到的歧视)，以及使用多重 以前没有整合到生物心理社会模型中的生物措施。这项工作将 最终为量身定做的干预措施铺平道路，以降低认知老化和衰退的风险。

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.