Integration of Socio-Spatial Data for Neighborhoods with Multi-omic profiles to Identify and Mitigate Factors Affecting Risk of ALzheimer's Disease

阿尔茨海默病（AD）影响西班牙裔的比例比白人高，而西班牙裔是美国增长最快的老年人群体，而且年龄较小。造成这些差异的原因尚不清楚，部分原因是西班牙裔在阿尔茨海默病研究中的代表性不足。揭示这种差异的原因可能有助于深入了解AD的原因，并有助于开发解决方案，这是本项目的目标。强有力的研究结果将社区的社会和身体特征与认知健康联系起来，而社区- el barrio -对西班牙裔人口来说是很重要的。然而，确定影响AD风险的特定环境和个体因素是一个复杂的问题。本项目旨在通过一种新的方法来确定社区因素对西班牙裔美国人ad样认知轨迹的影响，该方法整合了1)高维多组学（遗传和代谢分子标记）揭示的个体差异和2)家庭和社区动态的调解/调节。我们对墨西哥裔美国人群体的访问——圣安东尼奥墨西哥裔美国人家庭研究（SAFS）——将使我们能够测试跨社区的类似广告的认知轨迹的变化是否完全由个人特征来解释，或者至少部分取决于社区的社会和物理因素。近30年来，SAFS参与者已被深入表征，包括临床（心脏代谢和认知轨迹）、结构神经成像和环境数据；全基因组测序（WGS）和其他组学（例如，代谢谱、表观基因组学、蛋白质和RNA表达模式）。该项目的具体目标是：1)确定与非ad类认知衰退相比，墨西哥裔美国人的家族性是否提供了对ad类认知衰退的保护；2)通过对17个社区（每个社区至少有30名SAFS参与者）的在线街道图像分析，分析不同社区的社会环境和建筑环境与类广告认知轨迹之间的关联；3)检测邻里和家庭水平的环境（社会和空间）信号，这些信号反映在我们发现与ad样认知衰退风险相关的任何高维代谢组学/脂质组学、表观基因组学和转录组学生物标志物中；4)利用研究结果为基于社区的项目提供指导，旨在通过开发战略沟通工具包，并召开一个论坛，让不同的利益相关者（特别是社区设计师和城市规划者）参与进来，从而降低类似广告的认知能力下降的风险。总的来说，结果将阐明社区特定因素导致西班牙裔AD样认知能力下降的途径，为缓解AD提供新的方法。

Alzheimer’s disease (AD) affects a higher proportion of Hispanics - the fastest growing group of older adults in the U.S. - than Caucasians, and at younger ages. The causes of these differences are unknown, partly due to underrepresentation of Hispanics in AD research. Uncovering the reasons for this disparity may provide insight into the causes of AD and help to develop solutions and is this project's goal. Robust findings have linked the social and physical characteristics of neighborhoods to cognitive health, and the neighborhood - el barrio - is known to be important to Hispanic populations. However, identifying specific contextual and individual factors that affect risk of AD is a complex problem. This project aims to determine the effects of neighborhood factors on AD-like cognitive trajectories in Hispanic Americans, by a novel approach that integrates 1) individual differences revealed by high-dimensional multi-omics (genetic and metabolic molecular markers) and 2) mediation/moderation by family and neighborhood dynamics. Our access to a Mexican American cohort - the San Antonio Mexican American Family Study (SAFS) - will enable us to test if variations in AD-like cognitive trajectories across neighborhoods are explained exclusively by individual characteristics, or depend at least partly on social and physical elements of neighborhoods. SAFS participants have been deeply characterized for almost 30 years, including clinical (cardiometabolic and cognitive trajectories), structural neuroimaging, and environmental data; whole-genome sequencing (WGS), and other -omics (e.g., metabolic profiles, epigenomics, protein and RNA expression patterns). The specific aims of this project are to 1) determine if familism provides protection from AD-like cognitive decline compared to non-AD like cognitive decline in Mexican Americans; 2) analyze the associations between social and built environments of different neighborhoods and AD-like cognitive trajectories, by using online street imagery analysis of 17 neighborhoods within each of which at least 30 SAFS participants reside; 3) detect environmental (social and spatial) signals at neighborhood and family levels, reflected in any high-dimensional metabolomic/lipidomic, epigenomic, and transcriptomic biomarkers we find correlated with risk of AD-like cognitive decline; and 4) exploit the results to provide guidance for neighborhood-based projects aimed at decreasing the risk of AD-like cognitive decline, by developing a strategic communication toolkit, and convening a forum that will engage diverse stakeholders, particularly neighborhood designers and city planners. Overall, the results will elucidate pathways through which neighborhood-specific factors contribute to AD-like cognitive decline in Hispanics, offering new approaches to mitigation of AD.