Early-Life Socioeconomic and Environmental Exposures as Predictors of Late-Life Cerebrovascular Outcomes: A Theoretical Framework Linking IPUMS/HRS Insights with Glycomics-Informed Regenerative Interventions

This manuscript integrates evidence from existing IPUMS complete-count U.S. Census linkages (e.g., 1940) with the Health and Retirement Study (HRS) to synthesize how early-life socioeconomic status (SES), childhood health, and geographic exposures program late-life cerebrovascular outcomes, including stroke incidence and white matter hyperintensities (WMH). We draw on published HRS-linked analyses demonstrating persistent effects of low childhood SES (HR=1.27–1.31 for stroke risk; ρ = -0.18 for WMH burden) independent of adult confounders. To establish biological plausibility, we link early-life adversity to persistent alterations in perineuronal nets (PNNs) and extracellular matrix (ECM) components, proposing enzymatic degradation via chondroitinase ABC (ChABC) as a targeted regenerative intervention to restore neural plasticity in chronic post-stroke states among socioeconomically disadvantaged older adults. This theoretical framework bridges population-scale linked data with developmental glycomics, advancing hypotheses for equitable, precision regenerative medicine.