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

摘要 黑人患阿尔茨海默病和相关痴呆(ADRD)的风险仍然高于其他人群 种族/民族群体。这可能至少部分是由于积累的劣势加速了 心血管(CV)危险因素的进展，这反过来可能有助于临床的发展 沉默的阿尔茨海默氏病，早在中年就出现了。我们的团队已经证明，暴露在简历风险之下 肥胖、血糖升高、血脂和血压等因素会通过以下方式影响血管系统 童年，甚至是在子宫里。而早期的血管改变又可能导致大脑健康的改变。 几十年后。尽管有记录的社会经济和地理劣势更多地出现在 促进个人健康差距的黑人(例如，在食品安全、绿地、教育质量、污染物方面) 在童年时期，很少有数据研究这种对中年或中年阿尔茨海默氏症相关大脑健康的影响 后来。这主要是由于预期收集的关于黑人的生活过程数据有限。解决这个问题 随着越来越多的黑人和白人儿童出现不利的简历，知识差距变得越来越紧迫 与前几代人相比，现在。我们建议利用NIH在以下方面的重大投资 前瞻性收集的数据，来自参与博加卢萨心脏研究的黑人和白人男性和女性 (BHS)、NHLBI生长与健康研究(NGHS)和普林斯顿脂质研究(PLRS)。这些独特的 生命历程研究有很强的合作和数据协调的历史，自2009年以来通过 国际儿童履历队列联盟(I3C)，自2015年以来对履历活动进行联合后续行动。 共享的暴露数据包括儿童时期(3-19岁)的地理、社会经济和简历风险因素 年)，并进行了40多年的随访。在这些队列中测量大脑健康指标将第一次允许 时间，探索早期生命周期健康差异和既往劣势对中年大脑的影响 黑人和白人的健康。在这项拟议的研究中，儿童简历暴露的差异和公平性 阿尔茨海默氏症(I3C十年)，我们将收集结构、功能、认知和血液基础 中年(40-55岁)与ADRD相关的大脑健康过程的指标，这是一个微妙影响的时期 亚临床血管改变对大脑健康的影响最先开始出现，通常比ADRD早几十年 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来建立和 共享一个新的数据资源，它促进了早期生命风险因素的开放科学，并将这一努力扩展到 阿德勒。这项工作的影响将是提供可通过以下方式减少ADRD健康差距的战略 在黑人和白人男孩和女孩中识别和干预他们的简历负担增加 几十年后出现ADRD的风险，并有可能导致儿科临床实践指南的变化。 拟议的I3C十年研究代表着一个独特的，也可以说是唯一的机会来研究 中年关键期儿童心血管疾病风险及差异对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.