Depression, Inflammation, Biological Age and Cognitive Function

摘要-项目2 随着世界人口的增加，阿尔茨海默病及相关痴呆（ADRD）的发病率迅速上升 就是衰老过去大多数识别痴呆症风险因素的研究都集中在以下方面的预测价值： 一次一个因素。这导致了一长串与ADRD前体相关的因素（即， 认知衰退和轻度认知障碍[MCI]），很少有指导，以优先考虑或 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。 同时，相互作用。本项目将侧重于三个相互关联的因素的作用： 抑郁症（和抑郁症），全身性炎症，和加速生物学 老化（例如，DNA甲基化年龄、端粒长度）。所有这三种都是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，因为它们在多大程度上 积累或相互作用以产生危险。此外，这个项目将有助于解开认知健康的基础， 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， ADRD的生物学措施，以及感知歧视，终身逆境， 社会经济地位（SES）。在老年人的多个时间点进行丰富的评估，并确定 多个关键风险因素之间的相互关系，将使更大的能力，不仅预测谁是在 这不仅是最大的风险，也是未来干预的具体目标。 该拟议项目是爱因斯坦衰老研究（EAS）更新的一部分。在这次更新中，767个种族 年龄在60岁及以上的不同男子和妇女将完成每年最多5次的数据收集。每个波 将包括为期两周的每日和生态瞬时评估（EMA）， 心理社会和行为因素，因为他们是经验丰富，以及深入评估的认知 功能水平，轻度认知障碍（MCI）和抑郁症。每次结束时抽血 EMA爆发以捕获炎症负荷并实现生物学年龄分类，以及基于血浆的 神经退行性生物标志物将进一步为研究终点提供信息。 该项目将有助于澄清抑郁症，炎症和生物年龄对个体风险的影响， 认知下降和MCI，使用比过去的研究更细致和综合的模型。创新 包括利用现有的不同老年人队列，探索ADRD风险的差异， 种族、民族、社会经济地位和社会心理因素（例如，歧视），以及使用多重 生物措施，以前没有被纳入生物心理社会模型。这项工作将 最终为量身定制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.