Cortical gradient compression links cognition and transcriptomic signatures in primary angle-closure glaucoma

The cerebral cortex is organized along hierarchical gradients that integrate sensory and cognitive functions, yet whether this organization is disrupted in primary angle-closure glaucoma and contributes to cognitive impairment remains unclear. Here we examine cortical functional gradients in individuals with primary angle-closure glaucoma using resting-state functional magnetic resonance imaging and transcriptomic analyses. We show that patients exhibit compression and reorganization of cortical gradients, particularly within visual and default mode networks, and that these alterations are associated with visual performance and cognitive decline. Genes related to gradient disruption are enriched in synaptic signaling, neurodevelopmental pathways, and astrocyte-associated processes. These findings identify cortical hierarchical remodeling and its molecular correlates in primary angle-closure glaucoma, providing insight into the neural basis of cognitive impairment in this disease.