Add Health as a Resource for the Science of the Exposome and Risk for AD/ADRD

项目摘要 本U 01 AG 071450补充文件响应了NOT-AG-22-022，该文件列出了“研究的迫切需要 基础设施，解决各种物理，化学，社会，心理和经济的作用 在阿尔茨海默病的病因学和社会差异中， 疾病（AD）和AD相关痴呆（ADRD）。我们的总体目标是更好地定位国家 青少年到成人健康的纵向研究（添加健康）作为科学家的核心资源， 有效地操作和研究这个问题及其对认知功能，认知能力下降， 以及AD/ADRD在整个生命过程中的进展，特别注意不同人群之间的差异 分组。鉴于Add Health的Wave I-V中的当前可用暴露数据和Wave VI的时间 通过实地考察，我们的前两个目标将大大加强Add Health的社会和健康背景数据， 极大地扩展了我们的环境背景数据。这样做是为了直接支持Add Health 成为实施疾病组和了解AD/ADRD相关疾病的关键资源 结果和差距。第三个目标是将SARS CoV-2感染抗体数据添加到我们的检测阵列中。 鉴于目前COVID-19感染在普通人群中广泛流行，以及潜在的长期- 就COVID-19暴露对认知功能和AD/ADRD风险的重要性而言， 这些数据最好的位置添加健康作为一个非常丰富的纵向研究，以操作的麻烦。 补充的具体目标是：1）收集，合并，记录和传播丰富的社会-和健康- 相关的上下文数据，以添加Wave I至Wave VI的健康参与者住所。我们将补充 我们以前和正在进行的努力，在这一领域的重点领域的结构性种族主义，结构性性别歧视， 结构性异性恋，结构性仇外心理和健康不平等。2)评估、记录和传播 在精确地理定位/地理编码的环境中，关键的自然、物理和化学环境暴露 从Wave I到Wave VI的参与者住宅。我们将专注于环境，自然和建筑 特定于参与者位置的域。3)认识到持续的COVID-19大流行的关键作用 以及这种感染对疾病和AD/ADRD相关风险因素的影响，我们将测试7,500个Add Health 第六波参与者对SARS CoV-2感染的抗体。这些感染的生物标志物将增加一个大的， Add Health中现有生物标志物的可访问阵列，包括表观基因组、转录组和 微生物组测量加上AD/ADRD的炎症、感染和神经免疫生物标志物。在一起， 实现这些目标将大大提高AddHealth的研究能力， 健康，环境和生物学为基础的维度的麻烦，以及他们如何有助于认知 功能、认知下降、AD/ADRD风险以及其中的差异。

Project Summary This supplement to U01 AG071450 responds to NOT-AG-22-022, which lays out the “urgent need for research infrastructure that addresses the role of diverse physical, chemical, social, psychological, and economic exposures across multiple levels and across the life course in the etiology and social disparities of Alzheimer’s disease (AD) and AD-related dementias (ADRD).” Our overall objective is to better position the National Longitudinal Study of Adolescent to Adult Health (Add Health) as a central resource for scientists to more effectively operationalize and study the exposome and its consequences for cognitive function, cognitive decline, and the progression of AD/ADRD across the life course, with particular attention to disparities across population subgroups. Given currently available exposure data in Waves I-V of Add Health and the timing of Wave VI fieldwork, our first two aims will substantially strengthen Add Health’s social and health contextual data and vastly expand our environmental contextual data, respectively. Doing so is in direct support of Add Health becoming a key resource for the operationalization of the exposome and for understanding AD/ADRD-related outcomes and disparities. The third aim will add SARS CoV-2 infection antibody data to our array of assays. Given the now widespread prevalence of COVID-19 infection in the general population and the potential long- term importance of COVID-19 exposure for cognitive functioning and risk for AD/ADRD, it is critical to include such data to best position Add Health as an extraordinarily rich longitudinal study to operationalize the exposome. Specific aims of the supplement are: 1) To assemble, merge, document, and disseminate rich social- and health- related contextual data to Add Health participant residences from Wave I through Wave VI. We will complement our previous and ongoing efforts in this realm by focusing on the domains of structural racism, structural sexism, structural heterosexism, structural xenophobia, and health inequality. 2) To estimate, document, and disseminate key natural, physical, and chemical environmental exposures at accurately geopositioned/geocoded Add Health participant residences from Wave I through Wave VI. We will focus on the environmental, natural, and built domains specific to participants’ locations. 3) In recognition of the critical role of the ongoing COVID-19 pandemic and the impact of this infection on the exposome and AD/ADRD-related risk factors, we will test 7,500 Add Health Wave VI participants for antibodies to SARS CoV-2 infection. These biomarkers of infection will augment a large, accessible array of existing biomarkers in Add Health, including arrays of epigenomic, transcriptomic, and microbiome measures plus inflammatory, infectious, and neuroimmune biomarkers of AD/ADRD. Together, accomplishing these aims will greatly enhance the research capacity of Add Health to understand the social, health, environmental, and biologically based dimensions of the exposome and how they contribute to cognitive function, cognitive decline, risk of AD/ADRD, and disparities therein.