The Impact of Social, Genetic and Neuroimaging Factors on Cognitive Functioning in the Black Community

项目总结 申请者希望获得K01奖项，以获得整合社会因素和神经心理学的专业知识。 评估以检查种族内的异质性，以确定黑人社区中认知衰退的风险因素。至 为了实现这些目标，申请者计划利用她的优势是生物标志物的定量方法学 在四个关键培训领域获得专门知识的数据：(1)研究、神经心理测试和社区 参与；(2)健康差距和生命周期因素；(3)遗传学；和(4)专业培训。与 在她的专家指导团队的指导下，通过详细的培训计划，申请者将制定 在这些培训领域有深入的知识，并使申请者能够很好地成功 完成K01的拟议目标。这个K01应用程序的总体研究目标是确定如何 社会、神经成像标记物和遗传风险因素导致非痴呆老年人认知能力下降 黑人个体。研究表明，目前“公认的”认知能力下降的危险因素 阿尔茨海默病(AD)主要在白人社区被发现，它不会表现出 黑人个人也是如此。因此，探索黑人内部风险因素的潜在异质性是至关重要的 以准确预测认知功能衰退的风险。《目标1》的第一部分考察了 先前与认知相关的神经成像测量的早期和现代社会因素 (例如，结构磁共振成像措施和以白质衡量的血管负荷 高强度)在自我认同的非西班牙裔黑人参与者中。目标1的第二部分将决定是否 这些神经成像标记物在社会因素和认知衰退之间的联系中起中介作用。我们假设 更多的社交劣势将与AD特有的大脑区域和更快的 认知能力下降。我们还假设，神经成像方法将部分地调节 社会因素对认知衰退的影响。种族群体的差异可能是由于社会因素，其中的成员 黑人社区受到的影响不成比例。最后，重要的是要记住，种族是一种社会 构建并依赖于自我认同，没有生物根源。此外，最近的研究表明， 遗传背景可能影响AD的风险，影响衰老的病理特征。目前还不清楚基因是否 血统和社会因素是相关的，或者它们是否对认知衰退有独特的贡献。因此，我们的决赛 AIM将确定遗传血统和/或社会因素是否对载脂蛋白4对 认知能力下降。主要的假设是，在整个过程中，具有更多社会劣势的黑人参与者 生活，会对这些风险因素产生相反的影响，并有更快的认知衰退速度。我们还将调查是否 这种关联会影响从轻度认知障碍到阿尔茨海默病的转化。完成这些目标， 与来自经验丰富的多学科指导团队的培训一起，将生成数据和支持 未来的R01应用程序，收集洛杉矶县黑人社区成员的数据。

PROJECT SUMMARY The applicant seeks this K01 award to gain expertise on integrating social factors and neuropsychological assessments to examine within race heterogeneity for cognitive decline risk factors in the Black community. To achieve these goals, the applicant plans to leverage her strength is quantitative methodology for biomarker data to gain expertise in four critical areas of training: (1) research neuropsychological testing and community engagement; (2) health disparities and lifecourse factors; (3) genetics; and (4) professional training. With the guidance from her expert mentorship team and through a detailed training plan, the applicant will develop an in-depth knowledge in these training areas and enable the applicant to be well positioned to successfully complete the proposed aims of the K01. The overall research goal of this K01 application is to determine how social, neuroimaging markers, and genetic risk factors contribute to cognitive decline in non-demented older Black individuals. Research suggests current “well-established” risk factors for cognitive decline and Alzheimer’s disease (AD), which have been identified primarily in the white community, do not behave the same in Black individuals. Thus, it is critical to explore potential heterogeneity in risk factors within the Black community in order to accurately predict risk for cognitive decline. The first part of aim 1 examines the effect of early and current social factors on neuroimaging measures that have previously been associated with cognition (e.g. structural magnetic resonance imaging measures and vascular burden measured as white matter hyperintensities) in self-identified non-Hispanic Black participants. The second part of aim 1 will determine if these neuroimaging markers mediate the association of social factors and cognitive decline. We hypothesize that more social disadvantage will be inversely associated with AD-specific brain regions and faster rates of cognitive decline. We also hypothesize that neuroimaging measures will partially mediate the association of social factors on cognitive decline. Differences in racial groups may be due to social factors, which members of the Black community are disproportionately impacted. Finally, it is important to remember that race is a social construct and is dependent on self-identification, with no biological root. Moreover, recent studies suggest that genetic ancestry may influence risk for AD and impact pathological features of aging. It is unclear if genetic ancestry and social factors correlate, or if they have unique contributions to cognitive decline. Thus, our final aim will determine if genetic ancestry and/or social factors differentially influence the effect of APOE4 on cognitive decline. The primary hypothesis is that Black participants with more social disadvantage throughout life, will inversely effect these risk factors and have a faster rate of cognitive decline. We will also investigate if this association impacts conversion from mild cognitive impairment to AD dementia. Completion of these aims, along with the training from an experienced multidisciplinary mentoring team, will generate data and support for a future R01 application collecting data from members of the Black community in Los Angeles County.