Offspring Study of Mechanisms for Racial Disparities in Alzheimer's Disease

项目摘要 本研究的总体目的是确定事件的种族/民族差异的社会和生物学途径， 轻度认知障碍（MCI）/阿尔茨海默病及相关疾病（ADRD）和认知下降， 出现在中年。我们招募了1,500多名中年人，他们都是华盛顿的参与者。 Heights/Inwood哥伦比亚老龄化项目（WHICAP），并在基线时使用以下指标对其进行表征： 神经心理学和心理社会功能，社会和环境决定因素的生命过程措施， 健康，储存的血液样本，和大脑结构与MRI。后代研究在其他队列中是独一无二的， 有大量的拉丁裔和非洲裔美国人参与者在中年谁不是一个方便的样本 他们的年龄和文化群体的代表，其父母的特点是直接 观察临床和生物学数据。我们之前在后代队列中的研究发现：1）记忆力和执行力较低 在父母患有MCI/AD的中年人中发挥作用，特别是在非拉丁裔白人中 与非拉丁裔黑人和拉丁裔相比，2）在白人中，父母的认知对 后代海马体积，在黑人中，父母的认知对后代WMH有更强的影响， 3)年龄对认知功能和皮质厚度的负面影响在黑人中不成比例地大， 和拉丁裔参与者与白人相比，4）早期生活的社会因素，如父母的SES促进认知 对父母AD史的适应力，以及5）种族歧视对认知能力有不成比例的负面影响。 黑人和讲西班牙语的拉丁裔后代相对于白色后代的测试表现。在未来 5年后，我们建议招募额外的后代，总样本量为2,500例， 另外1，000名参与者，获得基线血液中AD风险和神经退行性变的血浆生物标志物 样本，并获得两个认知，心理和医疗功能的重复评估。我们的总体 一种假说认为，血管和炎症途径在父母AD风险的传递中起着更大的作用 与白人相比，黑人和拉丁裔老年人的社会经济地位，教育质量， 和歧视的经验将缓和父母的AD状态和生物标志物之间的关系， AD关于后代认知。具体来说，该项目将1）检查血管生物标记物的影响， 和炎症健康，AD病理生理学，神经退行性变，生物衰老，以及认知功能的遗传风险 不同人种/种族和性别的衰退和事件损伤，以及2）确定生命过程 父母AD风险的教育、经济和社会调节因素以及认知衰退的AD生物标志物， 不同种族/民族和性别的事件损害。

PROJECT SUMMARY The overall aim of this study is to identify social and biological pathways of racial/ethnic disparities for incident Mild Cognitive Impairment (MCI)/ Alzheimer's Disease and Related Disorders (ADRD) and cognitive decline that emerge in middle age. We have recruited over 1,500 middle-aged offspring of participants in the Washington Heights/Inwood Columbia Aging Project (WHICAP), and characterized them at baseline using measures of neuropsychological and psychosocial function, lifecourse measures of social and environmental determinants of health, stored blood samples, and brain structure with MRI. The Offspring study is unique among other cohorts, with large numbers of Latinx and African American participants in middle age who are not a convenience sample and are representative of their age and cultural groups, and whose parents are well-characterized with directly observed clinical and biological data. Our prior work in the Offspring cohort found 1) lower memory and executive function among middle aged people whose parents have MCI/AD, particularly among non-Latinx Whites compared with non-Latinx Blacks and Latinx, 2) among Whites, parental cognition had a stronger impact on offspring hippocampal volume, and among Blacks, parental cognition had a stronger impact on offspring WMH, 3) the negative impact of age on cognitive function and cortical thickness is disproportionately large among Black and Latinx participants compared with Whites, 4) early life social factors such as parental SES promote cognitive resilience to parental AD history, and 5) racial discrimination has a disproportionate negative impact on cognitive test performance among Black and Spanish-speaking Latinx offspring relative to White offspring. Over the next 5 years, we propose to recruit additional offspring for a total sample of 2,500, obtain baseline MRI scans on an additional 1,000 participants, obtain plasma biomarkers for AD risk and neurodegeneration on baseline blood samples, and obtain two repeat assessments of cognitive, psychosocial, and medical function. Our overarching hypothesis is that vascular and inflammatory pathways of transmission of parental AD risk play a greater role among Black and Latinx older adults compared with Whites, and that socioeconomic status, educational quality, and experience of discrimination will moderate the relationship between parental AD status and biomarkers of AD on Offspring cognition. Specifically, the project will 1) examine the impact of biological markers of vascular and inflammatory health, AD pathophysiology, neurodegeneration, biological aging, and genetic risk on cognitive decline and incident impairment across race/ethnicity and sex/gender and 2) determine the lifecourse educational, economic, and social moderators of parental AD risk and AD biomarkers on cognitive decline and incident impairment across race/ethnicity and sex/gender.