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

This manuscript presents a rigorous causal framework integrating IPUMS complete-count U.S. Census linkages (1940) with the Health and Retirement Study (HRS) to quantify how early-life socioeconomic status (SES), childhood health, and geographic exposures program late-life cerebrovascular outcomes. We formalize the life-course pathway using directed acyclic graphs (DAGs) and structural causal models, synthesizing published HRS-linked analyses demonstrating persistent effects of low childhood SES on stroke risk (HR=1.271; 95% CI: [1.093, 1.478]) and white matter hyperintensity (WMH) burden (\( \rho = -0.18 \), \( p<0.01 \)) independent of adult confounders. To establish biological plausibility, we develop a mechanistic model linking early-life adversity to persistent alterations in perineuronal nets (PNNs) and extracellular matrix (ECM) dynamics via chondroitin sulfate proteoglycan (CSPG) accumulation. We propose enzymatic degradation via chondroitinase ABC (ChABC) as a targeted regenerative intervention, formalizing its kinetic action through Michaelis-Menten dynamics and diffusion-reaction equations. All quantitative claims—including mediation proportions, E-values, and dose-response parameters—are derived from reproducible Monte Carlo simulations (\( n=5000 \) iterations, seed=42). This framework bridges population-scale causal inference with developmental glycomics, advancing testable hypotheses for equitable, precision regenerative medicine.