Ncog-04. whole-brain structural connectivity predicts cognitive deficits in pretreated patients with cns who grade 3 or 4 gliomas

Abstract BACKGROUND Glioma patients frequently suffer from cognitive dysfunction potentially caused by tumor invasion or treatment effects. We hypothesized that cognitive functioning in pretreated glioma patients critically depends on the maintained structural connectivity of multiple brain networks. PATIENTS AND METHODS The study included 121 pretreated glioma patients (median age, 52 years; median ECOG score, 1; CNS WHO grade, 3 or 4) who had biopsy or resection plus chemoradiation as first-line therapy. Cognitive performance was assessed by ten tests in five main cognitive domains after a median time of 14 months (range, 1-214 months) after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography tools were used to generate whole-brain fiber count-weighted connectivity matrices. These matrices were applied to a machine learning-based model to identify predictive fiber connections, essential cortical nodes, and the networks underlying cognitive performance in the evaluated domains. RESULTS Compared to healthy controls (n=121), the cognitive scores were significantly lower in nine cognitive tests. For each test, a subset of connections between nodes (median number, 254; range, 32-542) was identified whose fiber count sum was related to the actual scores in a linear model (median R2, 0.37; range, 0.16-0.44). Leave-one-out cross-validation confirmed the model's generalizability in 7 of 10 tests (median correlation coefficient for predicted vs. observed scores, 0.47; range, 0.39-0.57). Critically involved cortical regions (≥ 10 adjacent predictive edges) included predominantly left-sided cortical nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥ 15-20 edges) included the default-mode network’s left temporal and bilateral posterior cingulate cortex. CONCLUSION These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders.