Surface-based brain age index reflects hematological impacts on cognitive development in children with beta-thalassemia major

<h2>Summary</h2> Children with beta-thalassemia major (β-TM) are at risk of neurodevelopmental or cognitive impairment. In this study, we developed SurfGNN, a surface-based graph neural network model, to estimate brain age from cortical morphological features extracted via structural MRI, to a cross-sectional cohort of 25 β-TM patients and 40 age- and sex-matched healthy controls (ages 6–15 years). A brain age index (BAI)—the difference between predicted and chronological age—was computed and analyzed in relation to cognitive performance (Wechsler Intelligence Scale scores) and hematological parameters. Results showed that β-TM children had significantly lower cognitive scores and more delayed brain age (lower BAI) compared to healthy controls. Furthermore, BAI significantly correlated with hemoglobin and ferritin levels and mediated their association with cognitive performance, as demonstrated by mediation analysis. The SurfGNN model outperformed conventional machine learning baselines and provided interpretable insights into regional cortical alterations. Our findings suggest that BAI may serve as a sensitive biomarker for detecting early brain developmental delays in β-TM.