This competing revision adds a venous blood component to the fieldwork protocols for the 2021-2022 follow-up of the High School and Beyond (HSB) cohort. HSB is a nationally representative and diverse sample of 26,820 Americans who have been followed since they were high school students in 1980 with exceptionally high rates of retention. Adding the collection of venous blood to our already funded survey, genomic, microbiome, and administrative data collection plans has massive potential to revolutionize understanding of the risk and resilience factors that shape cognitive impairment. The resulting HSB biomarker data and biorepository will enable transformative and highly innovative research on the life course social and biological forces that intersect to shape the evolution of cognitive impairment and AD/ADRD over the life course. HSB will become the first cohort study with the requisite social, biological, and cognitive measures that has followed a large, nationally representative and racially/ethnically diverse sample of Americans from adolescence through middle age. This project brings together an interdisciplinary team of leading neurologists, sociologists, education scientists, neuropathologists, and survey methodologists who in 2021-2022 will re-contact all 25,517 surviving members of the HSB cohort and use the resulting survey, genomic, microbiome, and administrative data to conduct transformative analyses of the effects of education and early life conditions on cognitive function and risk for impairment at midlife. This competing revision proposal has three aims:
(Aim 1) Obtain samples of whole blood, plasma, and serum from the entire HSB Cohort in 2021-2022.
(Aim 2) Conduct assays most useful for research on cognitive impairment and AD/ADRD and store the rest of the blood for future assays.
(Aim 3) Disseminate biomarker data and facilitate access to the HSB Biorepository. By adding biomarkers of neuropathology found in blood, HSB will become vastly more useful for studying the risk and resilience factors that shape the evolution of cognitive impairment and AD/ADRD. Neuropathologies are already accumulating in the brain by middle-age. While some people with neuropathologies will go on to develop cognitive impairments or dementias, others will remain cognitively resilient into old age. HSB data collected between 1980 and 2021-2022 will provide a wealth of prospectively measured indicators of the educational, social, and other forces from adolescence through midlife that may promote cognitive resilience to neuropathology. These forces may also affect the accumulation of neuropathology in the first place. In either case, measuring the degree of blood-based neuropathology at this stage of sample members? lives is critical.
This project will yield biological data and a biorepository that will make possible highly innovative and transformative research on the neuropathological pathways through which education and early life conditions impact cognitive impairment at midlife. Understanding the social, economic, and biological pathways through which education and early life conditions impact cognitive functioning and impairment will inform efforts to use educational and other social interventions to improve the midlife cognitive functioning of future cohorts of Americans.
