Moderating effects of educational inequality on education polygenic scores, attained education and dementia-risk relationships

While education is among the most consistent predictors of cognitive health and dementia risk, it is unclear whether this reflects the benefits of schooling itself or other factors such as underlying genetic predispositions or family-based inequality. Further, the benefits of education to cognitive health may be dependent on larger structures of inequality. Using data from the IGEMS Consortium of over 4500 twins from seven cohorts in the USA, Sweden, Denmark, and Australia, we examine how genetic propensity for education and national/historical contexts of inequality shape dementia risk in later life. Dementia risk was measured with the Latent Dementia Index, a validated continuous indicator of likelihood of dementia, while key predictors included both attained education, a polygenic score for educational attainment (PGS-ED), and cohort- and country-specific Gini indices of educational inequality (GINI-ED). Ordinary least squares and within-between twin models were estimated to separate between-family from within-family effects. Results confirm that higher education is associated with lower likelihood of dementia; PGS-ED also predicts likelihood of dementia, although both associations are attenuated when comparing twins within families. Country-level educational inequality moderated these effects; education-and to a lesser extent PGS-ED-were stronger predictors of cognition in more egalitarian contexts. Our findings emphasize the interplay of both genes and social factors in potentially shaping dementia.