Administrative Supplement to Establish National Exposome Alzheimer's Disease and Related Dementias (ADRD) Infrastructure (Expo-AD)

暴露，包括生命过程暴露的多样性，并受到结构性不平等的影响，如 系统性种族主义，被理论化为与生物、行为、社会文化和经济机制相互作用 作为影响阿尔茨海默病和相关痴呆症(ADRD)风险和复原力的一个可修改因素。这个 差异对齐的暴露组与生物健康结果最佳地联系在一起，使用参与者的居住史- --被美国隐私法称为“受保护的健康信息”或PHI，并受到严格的监管。这个 PHI-Data带来了复杂的法律、行政和技术研究基础设施挑战 与ADRD一致的暴露组研究存在实质性障碍，导致目前大多数国家的生物 存储库和资源只管理非PHI数据，从而禁止直接差异对齐的曝光组指标 联动。由于数据安全方面的担忧，包括机构在 来自本地机构外部的PHI数据的存储，没有现有资源来链接特定地理位置 在全国范围内暴露于ADRD结果。许多人不了解这项任务的复杂性或 成功所需的努力和专业知识。据我们所知，我们的团队是全国唯一的ADRD团队 作为R01AG070883的一部分，已经在建设这样的基础设施。拟议的补编将扩大覆盖范围 并通过解决所需的基础设施扩展来消除暴露科学方面的障碍 将关键的NIA国家数据和生物库资源连接到PHI-需要公开指标，同时屏蔽 这些NIA研究基础设施摆脱了PHI管理的负担。建议的申请 在母公司R01范围内进行的基础设施补充直接响应NOT-AG-22- 022和导致这些资金分配的国会语言；具体地说，支持 能够将生命过程暴露因素与生物结果联系起来的基础设施，其特征 通过机械的健康差距镜头。我们的研究小组在这些方法方面一直处于领先地位， 包括精确的地理定位。我们的长期目标是建立PHI管理研究基础设施，以 允许非PHI存储NIA核心资源的公开链接和共享，对其进行调整和寻址 NOT-AG-22-022中概述的隐私需求。我们的具体提案目标是在 R01AG070883中的22个ADRC，包括为新的曝光体开发数据获取和链接过程 指标(污染)。我们将加强、完善和建立持久、道德和社区一致的行政管理 和法律协议、流程和协调基础设施，用于正在进行的PHI和暴露的数据流获取 和非PHI暴露组数据流出；制定数据采集、获取、链接和管理流程 其他ADRD差异-一致的暴露指标(例如，污染)；为以下项目开发EXPO-AD数据共享 确保综合曝光研究；并实施符合道德规范的采购、标准化、 以公平、监管和隐私合规的方式对数据进行质量控制、集成和分析。

The exposome, comprising the variety of life-course exposures and influenced by structural inequities such as systematic racism, is theorized to interact with biological, behavioral, sociocultural, and economic mechanisms as a modifiable factor influencing Alzheimer’s Disease and Related Dementias (ADRD) risk and resilience. The disparities-aligned exposome is optimally linked to biologic health outcomes using participant residential history- - denoted by US privacy law as ‘protected health information’ or PHI and subject to stringent regulation. The complicated legal, administrative, and technical research infrastructure challenges with PHI-data have formed substantial barriers to ADRD-aligned exposome study, leading to a present state in which most national biologic repositories and resources curate only non-PHI data thus prohibiting direct disparities-aligned exposome metric linkage. Due to data security concerns including the substantial cybersecurity risk an institution assumes in storage of PHI-data from outside the home institution, there are no existing resources to link geo-specific exposures to ADRD outcomes on a national scale. Many do not understand the complexity of this task or the effort and expertise required to succeed. To our knowledge, our team is the only ADRD group in the nation already building such infrastructure as part of R01AG070883. The proposed supplement will extend the reach of the parent R01 and remove barriers in exposome science by addressing the infrastructure expansion needed to connect key NIA national data and biorepository resources to PHI-requiring exposome metrics while shielding these NIA research infrastructures from the burden of PHI management. The proposed application for an infrastructure supplement conducted within the scope of the parent R01 is directly responsive to NOT-AG-22- 022 and the Congressional language that led to the allocation of these funds; specifically, to support infrastructure that enables the linkage of life-course exposure factors to biological outcomes, characterized through a mechanistic health disparities lens. Our research group has been leading the field in these approaches, including precision geo-targeting. Our long-term goal is to establish PHI-management research infrastructure to allow for exposome linkage and sharing for non-PHI storing NIA core resources, aligning with and addressing the privacy needs outlined in NOT-AG-22-022. Our specific proposal goal is to build such infrastructure across the 22 ADRCs in R01AG070883, including developing data intake and linkage processes for new exposome metrics (pollution). We will enhance, refine and establish enduring, ethical and community-aligned administrative and legal agreement, process and coordination infrastructure for on-going PHI and exposome data flow intake and non-PHI exposome data outflow; enact data acquisition, intake, linkage and management processes for additional ADRD disparities-aligned exposome metrics (e.g., pollution); develop the Expo-AD data commons for secure integrative exposome research; and implement best practices for ethical sourcing, standardization, quality control, integration and analysis of data in a FAIR, regulatory and privacy compliant manner.