ICAM-1 and IL-10 are associated with cognitive dysfunction using the MoCA test in glioma: Findings from the NCI Neuro-Oncology Branch Natural History Study.

Background: Cognitive dysfunction is common among patients with malignant glioma, yet the underlying mechanisms of this dysfunction remain unclear. Protein markers of neurodegeneration, inflammation, and vascular damage have been associated with central nervous system pathology and with cognitive changes in neurological diseases, but their clinical utility in gliomas is unknown. This study examined the relationships between cognitive dysfunction, tumor isocitrate dehydrogenase (IDH) mutation status in gliomas, and a panel of blood-based protein biomarkers.

Methods: This retrospective cohort study included 73 glioma patients with either IDH-mutant (n = 45) or IDH-wildtype tumors (n = 28) enrolled in a natural history study. Cognitive function was assessed using the Montreal Cognitive Assessment (scores <26 indicated cognitive dysfunction). Serum levels of 17 proteins were measured using ultrasensitive assays.

Results: Cognitive dysfunction was present in 53% of participants (n = 39), and more frequently in the IDH-wildtype group (75%) than in the IDH-mutant group (40%). Patients with wildtype tumors had higher levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin-6 (IL-6), and tumor necrosis factor-α than patients with IDH-mutant tumors, which remained in multivariate analysis. ICAM-1 and IL-10 were higher in patients with cognitive dysfunction compared to those with normal cognition, even after adjusting for tumor IDH-mutation status, age, tumor grade, and surgery history.

Conclusions: Cognitive dysfunction was associated with protein markers linked to vascular damage and inflammation regardless of tumor IDH status. Our findings suggest an association of cognitive dysfunction with heightened systemic inflammatory status that requires further interrogation for its role in pathophysiologic mechanisms.