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

项目摘要。 这项研究的总体目标是确定事件中种族/民族差异的社会和生物途径 轻度认知障碍(MCI)/阿尔茨海默病和相关疾病(ADRD)和认知功能下降 出现在中年。我们已经招募了1500多名华盛顿参与者的中年后代 高地/因伍德哥伦比亚老龄化项目(WHICAP)，并使用以下测量方法在基线上对它们进行表征 神经心理和心理社会功能，社会和环境决定因素的生命周期测量 健康，储存的血液样本，以及核磁共振的大脑结构。关于后代的研究在其他队列中是独一无二的， 有大量拉丁裔和非裔美国人的中年参与者，他们不是方便的样本 他们代表了他们的年龄和文化群体，他们的父母直接 观察临床和生物学资料。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 父母患有MCI/AD的中年人，特别是非拉丁裔白人的功能 与非拉丁裔黑人和拉丁裔相比，2)在白人中，父母的认知对 在黑人中，父母的认知对后代WMH的影响更大， 3)在黑人中，年龄对认知功能和皮质厚度的负面影响不成比例地大 4)早期生活的社会因素，如父母的社会地位促进认知 对父母AD病史的适应能力，以及5)种族歧视对认知的负面影响不成比例 测试黑人和讲西班牙语的拉丁裔后代相对于白人后代的表现。在接下来的时间 5年内，我们建议招募额外的后代，总样本为2,500人，获得基线MRI扫描 另外1,000名参与者，在基线血液中获得AD风险和神经变性的血浆生物标志物 样本，并获得认知、心理社会和医学功能的两次重复评估。我们最重要的是 假设血管和炎症途径在父母AD风险的传播中起着更大的作用 在黑人和拉丁裔老年人中与白人相比，社会经济地位，教育质量， 而歧视的经历将调节父母AD状态与 《关于后代认知的广告》。具体地说，该项目将1)检查血管生物标志物的影响 以及炎症健康、阿尔茨海默病的病理生理学、神经退变、生物老化和遗传风险对认知的影响 跨种族/民族和性别/性别的衰退和事故损害；2)决定生命历程 父母AD风险和AD生物标志物的教育、经济和社会调节因素对认知能力下降和 跨种族/民族和性别/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.