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

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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.