Community Socioeconomic Disadvantage in Midlife Relates to Cortical Morphology via Neuroendocrine and Cardiometabolic Pathways

: Residing in communities of socioeconomic disadvantage confers risk for chronic diseases and cognitive aging, as well as risk for biological factors that negatively affect brain morphology. The present study tested whether community disadvantage negatively associates with brain morphology via 2 biological factors encompassing cardiometabolic disease risk and neuroendocrine function. Participants were 448 midlife adults aged 30-54 years (236 women) who underwent structural neuroimaging to assess cortical and subcortical brain tissue morphology. Community disadvantage was indexed by US Census data geocoded to participants' residential addresses. Cardiometabolic risk was indexed by measurements of adiposity, blood pressure, glucose, insulin, and lipids. Neuroendocrine function was indexed from salivary cortisol measurements taken over 3 days, from which we computed the cortisol awakening response, area-under-the-curve, and diurnal cortisol decline. Community disadvantage was associated with reduced cortical tissue volume, cortical surface area, and cortical thickness, but not subcortical morphology. Moreover, increased cardiometabolic risk and a flatter (dysregulated) diurnal cortisol decline mediated the associations of community disadvantage and cortical gray matter volume. These effects were independent of age, sex, and individual-level socioeconomic position. The adverse risks of residing in a disadvantaged community may extend to the cerebral cortex via cardiometabolic and neuroendocrine pathways.