Mayo Advancing Research Equity in ADRD Study in Jacksonville(MAREAS-Jax)

项目摘要/摘要 拉美裔/拉丁裔(HL)和非裔美国人(AA)在美国的比例迅速上升 人口(18.7%HL，12.4%AA-美国2020年人口普查)在以下研究中代表性仍然严重不足 阿尔茨海默病(AD)和AD相关痴呆(ADRD)，尽管痴呆症的患病率高出1.5-2倍 (对非西班牙裔白人美国人)。AD/ADRD研究中代表性不足加剧了健康差距 并对制定和实施有效和安全的减少风险战略提出了挑战 HL/AA中的AD/ADRD。遗传学不能完全解释不同的AD/ADRD风险，强调了一个根本的 关于基因组因素如何与共病和寿命暴露有关的知识差距 结构/社会健康决定因素(SDoH；“暴露组”)，以告知AD/ADRD风险。有一个关键的问题 需要确定导致HL/AA不同风险的临床、SDoH和生物学因素； AD/ADRD结果背后的暴露之间的关系；使用此信息来缓解 通过教育和修改风险因素减轻AD/ADRD负担；并广泛传播这一信息 告知有效生物标记物和治疗方法的发展。ADRD中的梅奥推进研究公平性 在杰克逊维尔的研究(MAREAS-JAX；西班牙语中潮汐的意思)将满足这一需求。目标1将提前招聘 通过制定/部署以下方面的外联、招聘和接洽最佳实践，提高HL/AA队列(UH2) 佛罗里达州杰克逊维尔的HL/AA，通过双语(英语-西班牙语)研究团队，得到社区的支持 大使小组(CAT)和外部咨询委员会(EAC)，包括SDOH和AD/ADRD方面的专家 研究。目标2将确定AD/ADRD负担的相关措施(UH2、►、UH3)。SDoH、认知、临床和 将收集与脑血管、淀粉样蛋白和tau负荷相关的基于血液的生物标记物指标。 通过全面的/文化上适当的年度评估，并与多组学数据相结合， 结构(MR)和分子(淀粉样蛋白和tau)PET神经成像在研究开始时获得，每两年获得一次 然后确定可改变的痴呆危险因素、基于血液的生物标记物和 AD/ADRD负担。数据收集将根据EAC成员的意见进行标准化，以优化可扩展性和 促进样本/数据共享。目标3将向参与者提供有意义的个性化反馈(UH3 通过大脑健康报告，详细说明可操作的风险因素和建议，以减轻个体内部 AD/ADRD负担。AIM 4将使用多组学方法来识别相互作用的分子靶标和签名 在HL/AA(UH3)中使用系统生物学方法与AD/ADRD负担相关 经过验证的分析管道，并根据NIH的可查找性、可访问性、 互操作性和可重用性指南。通过这种方式，MAREAS-JAX将绘制驱动 不成比例地参与AD/ADRD研究和不同的AD/ADRD负担，并将为设计提供参考 以及实施战略，以改变佛罗里达州东北部及更远地区的这些趋势。

PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (HL) and African Americans (AA) represent a rapidly growing proportion of the United States population (18.7% HL, 12.4% AA - US 2020 Census) who remain critically underrepresented in research of Alzheimer disease (AD) and AD-related dementia (ADRD), despite a 1.5-2-fold higher prevalence of dementia (vs non-Hispanic-white Americans). Underrepresentation in AD/ADRD research exacerbates health disparities and challenges the development and implementation of efficacious and safe risk-reduction strategies for AD/ADRD in HL/AA. Genetics do not fully explain disparate AD/ADRD risk, highlighting a fundamental knowledge gap concerning how genomic factors interact with comorbidities and lifespan exposures to Structural/Social Determinants of Health (SDoH; the “exposome”) to inform AD/ADRD risk. There is a critical need to identify clinical, SDoH, and biological factors that contribute to disparate risk in HL/AA; establish the relationship between exposures underlying AD/ADRD outcomes; use this information to mitigate disparities in AD/ADRD burden through education and risk factor modification; and broadly disseminate this information to inform the development of effective biomarkers and therapies. The Mayo Advancing Research Equity in ADRD Study in Jacksonville (MAREAS-JAX; Spanish for tides) will address this need. Aim 1 will advance recruitment of HL/AA cohorts (UH2) by developing/deploying outreach, recruitment, and engagement best practices for HL/AA in Jacksonville, Florida, through a bilingual (English-Spanish) research team, supported by community ambassador teams (CAT) and an external advisory committee (EAC) including experts in SDoH and AD/ADRD research. Aim 2 will identify relevant measures of AD/ADRD burden (UH2►UH3). SDoH, cognitive, clinical, and blood-based biomarker measures associated with cerebrovascular, amyloid, and tau burden, will be collected through comprehensive/culturally appropriate annual assessments and integrated with multi-omics data, structural (MR) and molecular (amyloid and tau) PET neuroimaging obtained at study entry, and every 2 years thereafter to identify modifiable dementia risk factors, blood-based biomarkers, and molecular signatures of AD/ADRD burden. Data collection will be standardized with input from EAC members to optimize scalability and promote sample/data sharing. Aim 3 will provide meaningful individualized feedback (UH3) to participants through a Brain Health Report detailing actionable risk factors and recommendations to mitigate intraindividual AD/ADRD burden. Aim 4 will use multi-omics measures to identify molecular targets and signatures that interact with the exposome and associate with AD/ADRD burden in HL/AA (UH3) using a systems biology approach with validated analytic pipelines and prioritizing broad data sharing following NIH’s findability, accessibility, interoperability, and reusability guidelines. In this way, MAREAS-Jax will chart the currents that drive disproportionate participation in AD/ADRD research and disparate AD/ADRD burden and will inform the design and implementation of strategies to shift these tides in Northeast Florida and beyond.