Research Infrastructure for the study of Alzheimer's Disease and Alzheimer's Disease-related dementias in older Asian Americans

项目摘要 老年亚裔美国人人口一直在上升，患老年痴呆症和老年痴呆症的风险 疾病相关性痴呆（AD/ADRD）也在增加。然而，大多数健康结果的差异 因为老年亚裔美国人在临床研究中的代表性明显不足。社会 健康的决定因素（SDOH）是一个人的个人情况，影响他们的健康和良好的- 存在。SDOH导致了广泛的健康差距和不平等。AD/ADRD与SDOH相关的研究是 虽然这一疾病正在迅速扩大，但仍需要在年长的亚裔美国人中获得大量证据。此外，相对 少数研究纳入了与健康相关的风险，如血管疾病和生物标志物，以了解 SDOH和AD/ADRD之间的联系;尚不清楚血管风险因素和/或生物标志物是否介导了这种联系。 关系使用经过验证的英汉认知测试和文化相关的测量方法， 社会人口因素，研究MPI（李）成功地招募了200多名老年亚裔美国人在临床 西奈山阿尔茨海默病研究中心（ADRC）的研究。在这里，研究团队将成长为 包括多学科成员，提出了一项为期5年的研究，以建立一个研究基础设施， 在老年亚裔美国人中的AD/ADRD。SDOH评估将提供英语，普通话和 广东话-亚裔美国老年人中最常见的口语。本研究将回答 以下问题：（1）SDOH措施的中文翻译和文化适应是否有效地招募 新的和现有的老年亚裔美国人在AD/ADRD研究？(2)我们能识别行为，环境， 与AD/ADRD相关的社会、遗传和神经生物学因素？(3)神经生物学过程 与环境、社会文化、行为和其他人口因素交叉影响AD/ADRD 成果？研究小组将成立一个科学咨询委员会，为 拟议的研究，特别是在（1）社会科学领域;（2）AD/ADRD的临床表型;（3）痴呆 在亚裔美国人中的研究;和（4）AD/ADRD的危险因素和生物标志物。该团队还将与 与关键的社区利益相关者，以确保SDOH评估是文化和语言上适当的。 招募目标设定为300名老年亚裔美国人完成全面的痴呆症评估， 包括SDOH测量。新的，基于理论的SDOH指数将被开发来描述老年亚洲人的特征 正常、MCI和AD/ADRD组的美国人。在300名参与者中，研究小组的目标是重新评估 100名参与者进行为期1年的随访，并收集200份生物标志物样本进行分子分析，包括全 基因组测序、RNA测序和蛋白质组学。网络生物学与机器学习的整合 将采用基于的方法来开发高度预测性的诊断和预后分子生物标志物 AD/ADRD。UH 2阶段将用于开发研究基础设施和评估工具 在UH 3阶段结束时，需要申请更大的RO 1项目。

PROJECT SUMMARY The older Asian American population has been rising, with the risk of Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) also increasing. However, most of the disparities in health outcomes are masked because older Asian Americans are significantly underrepresented in clinical research. Social determinants of health (SDOH) are an individual’s personal circumstances that influence their health and well- being. SDOH contribute to wide health disparities and inequities. Research linking AD/ADRD to SDOH is expanding rapidly, yet much evidence is still needed in older Asian Americans. Additionally, there are relatively few studies incorporating health related risks, such as vascular conditions, and biomarkers to understand the link between SDOH and AD/ADRD; it remains unclear if vascular risk factors and/or biomarkers mediate such a relationship. Using validated cognitive tests in English/Chinese and culturally relevant measures of sociodemographic factors, the study MPI (Li) successfully enrolled over 200 older Asian Americans in clinical research at the Alzheimer’s Disease Research Center (ADRC) at Mount Sinai. Here, the study team will grow to include multidisciplinary members, proposing a 5-year study to develop a research infrastructure for studying AD/ADRD in older Asian Americans. The SDOH assessment will be available in English, Mandarin, and Cantonese – the most common spoken languages among Asian American older adults. This study will answer the following questions: (1) Do Chinese translation and cultural adaptation of SDOH measures effectively recruit new and existing older Asian Americans in AD/ADRD research? (2) Can we identify behavior, environmental, social, genetic, and neurobiological factors associated with AD/ADRD? (3) How neurobiological processes intersect with environmental, sociocultural, behavioral, and other demographic factors to affect AD/ADRD outcomes? The study team will establish a scientific advisory board to provide scientific perspectives for the proposed study, particularly in the areas of (1) Social science; (2) Clinical phenotypes of AD/ADRD; (3) Dementia research in Asian Americans; and (4) Risk factors and biomarkers for AD/ADRD. The team will also collaborate with key community stakeholders to ensure that the SDOH assessment is culturally and linguistically appropriate. Recruitment goal is set to be 300 older Asian Americans to complete a comprehensive dementia evaluation that includes SDOH measurement. Novel, theory based SDOH indices will be developed to characterize older Asian Americans in the normal, MCI, and AD/ADRD groups. Of the 300 enrollees, the study team aims to re-evaluate 100 participants for a 1-year follow-up and collect 200 biomarker samples for molecular profiling, including whole genome sequencing, RNA-sequencing and proteomics. An integrative network biology and machine learning based approach will be employed to develop highly predictive diagnostic and prognostic molecular biomarkers of AD/ADRD. The UH2 phase will be used to develop the research infrastructure and assessment tools necessary to apply for a larger RO1 project at the end of the UH3 phase.