Early and life course socioeconomic adversity and dementia risk in Hispanics/Latinos

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Although the clinical manifestations of Alzheimer’s disease and related dementias (ADRD) typically emerge in late life, early life/childhood risk factors play a role in their etiology. Because childhood is a period of brain plasticity and sensitivity to enduring environmental influences, early socio-economic adversities can affect brain development and maturation, fostering adverse cognitive changes later in life. Persisting poverty over the life course may exacerbate these effects. Furthermore, genomic research in ADRDs does not fully consider the social determinants of health that are robust causes of racial and ethnic ADRDs disparities. This research gap is particularly important for Hispanics, who experience widespread socio-economic adversities, and are at high risk of ADRD despite modest effect of ApoE4 on ADRD risk. The Study of Latinos Investigation of Neurocognitive Aging (SOL INCA) and its MRI neuroimaging study are ideally suited to elucidating health effects of life course socio-economic conditions given the large and richly characterized cohort with repeated neurocognitive, vascular, and socio-cultural assessments. We will leverage these unparalleled resources to understand how early and sustained adverse socioeconomic conditions shape risk of ADRD and the biological mechanisms that may explain these effects. We posit that early socio-economic adversity will be related to lower gray matter and hippocampal volumes, as a result of poverty-related exposures during key periods of brain development and maturation. Later, these early adversities can foster steeper aging-related trajectories of cognitive decline. Persisting adversities over the life course may also result in greater white matter hyperintensity (WMH), due to poor cardiometabolic control arising from social determinants common in disadvantaged populations. Longitudinal DNA methylation (DNAm) markers will provide novel insights about the biological mechanisms linking early and sustained socio-economic adversities and indicators of ADRD risk. ADRD-related biomarkers (MRI, plasma Amyloid, Tau and Neurodegeneration [ATN] and DNAm) will inform whether the pathways linking socio-economic adversity are related to neurodegeneration, vascular injury, and accelerated aging. The study will directly address NIA research priorities related to understanding the pathways by which socio-economic, socio-cultural and behavioral factors affect neurocognitive aging.