I3C DECADE: Disparities and Equity in Childhood Cardiovascular Exposures and Alzheimer's Dementia

总结 阿尔茨海默病和相关痴呆症（ADRD）的风险在黑人人群中仍然高于其他人群。 这可能至少部分是由于积累的不利条件加速了种族/族裔群体的 心血管（CV）风险因素的进展，进而可能导致临床 早在中年时就已经患有老年痴呆症我们的团队已经证明， 肥胖、血糖、血脂和血压升高等因素会影响血管系统， 童年甚至在子宫里。反过来，早期的血管变化可能会导致大脑健康的变化 几十年后。尽管有文件记载的社会经济和地理劣势， 黑色（例如，食品安全、绿色空间、教育质量、污染物），这些因素导致CV健康差异 在童年时期，很少有数据研究这种影响阿尔茨海默氏症相关的大脑健康在中年或 后这主要是由于有限的前瞻性收集，黑人的生命历程数据。解决这一 随着越来越多的黑人和白色儿童将发展出不良的CV特征，知识差距日益紧迫 与前几代人相比。我们建议利用NIH的重大投资， 从参与博加卢萨心脏研究的黑人和白色男性和女性中前瞻性收集数据 (BHS)NHLBI生长和健康研究（NGHS）和普林斯顿脂质研究（PLRS）。这些独特 自2009年以来，生命历程研究具有很强的合作和数据协调历史， 国际儿童CV队列联盟（I3 C），自2015年以来对CV事件进行联合随访。 共享的暴露数据包括儿童期（3-19岁）的地理、社会经济和CV风险因素 年），并进行了40多年的随访。测量这些队列中的大脑健康指标将允许， 时间，探索早期生活CV健康差异和中年大脑的先前缺点的影响 黑人和白人的健康在拟议的研究中，儿童CV暴露的差异和公平性， 阿尔茨海默氏痴呆症（I3 C DECADE），我们将收集结构，功能，认知和血液为基础的 在中年（40-55岁）与ADRD相关的大脑健康过程的指标，这一时期的微妙影响 亚临床血管变化对大脑健康的影响开始出现，通常在ADRD之前几十年 在临床上变得明显。这些队列研究的PI将利用他们正在进行的合作， 分享一个新的数据资源，推动早期生命风险因素的开放科学，并将这一努力扩展到 ADRD。这项工作的影响将是为可能减少ADRD健康差异的战略提供信息， 确定和干预黑人和白色男孩和女孩，他们的简历负担使他们在增加 几十年后ADRD的风险，并有可能导致儿科临床实践指南的变化。 拟议的I3 C十年研究代表了一个独特的，可以说是唯一的机会，调查 儿童期CV风险和差异对中年关键期ADRD相关脑健康的影响。

SUMMARY Risk for Alzheimer’s Disease and related dementias (ADRD) remains higher in black populations than in other race/ethnic groups.This may be due at least in part to accumulated disadvantage which accelerates the progression of cardiovascular (CV) risk factors, that in turn may contribute to the development of clinically silent Alzheimer’s pathology as early as middle age. Our team has demonstrated that exposure to CV risk factors such as obesity, elevated glucose, lipids and blood pressure can impact the vascular system by childhood and even in utero. Early vascular changes, in turn, may contribute to changes in brain health decades later. Despite documented socioeconomic and geographic disadvantages more often encountered by blacks (in, e.g., food security, green spaces, education quality, pollutants) that promote CV health disparities in childhood, there is little data examining such influences on Alzheimer’s related brain health in midlife or later. This is primarily due to limited prospectively collected, life-course data on blacks. Addressing this knowledge gap is increasingly urgent, as many more black and white children will develop adverse CV profiles now as compared to previous generations. We propose to leverage the significant NIH investment in prospectively collected data, from black and white men and women participating in the Bogalusa Heart Study (BHS), NHLBI Growth and Health Study (NGHS), and Princeton Lipid Research Study (PLRS). These unique life course studies have a strong history of collaboration and data harmonization formalized since 2009 through the international childhood CV cohort consortium (I3C), with joint follow-up of CV events since 2015. Shared exposure data include geographic, socioeconomic, and CV risk factors in childhood (from ages 3-19 years), with 40+ years of follow-up. Measuring brain health indicators in these cohorts will allow, for the first time, exploration of the impact of early life CV health disparities and antecedent disadvantages on midlife brain health in blacks and whites. In the proposed study, Disparities and Equity in Childhood CV Exposure and Alzheimer’s DEmentia (I3C DECADE), we will collect structural, functional, cognitive and blood-based indicators of ADRD-related brain health processes in mid-life (40-55 years), a period when the subtle impacts of subclinical vascular changes on brain health first begin to emerge, often several decades before ADRD become clinically evident. The PIs of these cohort studies will leverage their ongoing collaboration to build and share a novel data resource that advances open science in early life risk factors, and extends that effort to ADRD. The impact of this work will be to inform strategies that may reduce ADRD health disparities by identifying and intervening among black and white boys and girls whose CV burden places them at increased risk of ADRD decades later and has the potential to lead to changes in pediatric clinical practice guidelines. The proposed I3C DECADE Study represents a unique, and arguably the only opportunity to investigate the influence of childhood CV risk and disparities on ADRD-related brain health in the critical period of midlife.