Brain age prediction from structural and functional connectivity across the lifespan using connectome-based predictive modeling

Abstract

Brain maturation and aging are characterized by widespread changes in structural and functional brain organization. The extent to which these modalities capture shared versus distinct signatures of lifespan development and aging remains unclear. In this study, we applied connectome-based predictive modeling (CPM) to connectomes derived from diffusion MRI and resting-state functional MRI in Human Connectome Project Development, Young Adult, Aging, and combined Lifespan cohorts to predict chronological age. Both structural and functional connectomes significantly predicted age across cohorts, demonstrating that age-related information is distributed throughout whole-brain connectivity patterns. Prediction performance varied across lifespan stages, with generally stronger performance in the Development, Aging, and Lifespan cohorts than in Young Adulthood. Structural and functional models produced significantly correlated predicted ages in several cohorts, indicating shared age-related information across modalities. Structural-functional convergence analyses revealed limited and variable correspondence between modality-specific predictive features, suggesting that structural and functional connectomes capture both shared and complementary aspects of brain maturation and aging. Network-level analyses demonstrated that age-predictive information was distributed across canonical brain networks, including cerebellar, frontoparietal, salience, somatomotor, and subcortical networks, with patterns varying across cohorts and modalities. Multimodal CPM improved prediction relative to unimodal models in several cohorts, supporting the complementary contribution of structural and functional connectivity to age prediction. Cross-cohort, cross-sex, and cross-modality analyses further characterized the generalizability and shared information of predictive models across lifespan stages, sexes, and imaging modalities. This work demonstrates the utility of CPM for characterizing distributed structural and functional connectivity patterns associated with chronological age across the lifespan and provides a foundation for future studies of individual variability in brain maturation and aging.