ICAM-1 and IL-10 are associated with cognitive dysfunction in glioma: findings from the NCI neuro-oncology branch natural history study cohort

Authors

• VA Guedes
• T Mendoza
• K Slattery
• MC Kauss
• D Raval
• E Hsieh
• ML Wright
• TS Davis
• Ann Choi
• K Reinhart
• H Miller
• E Vera
• M Penas-Prado
• MR Gilbert
• TS Armstrong

Abstract

Background: Cognitive dysfunction is common among glioma patients, but the contribution of specific mechanisms to the development of cognitive symptoms is unclear. Circulating levels of proteins linked to neurodegeneration, inflammation, and vascular damage have been associated with cognitive symptoms in neurological diseases and aging, but their prognostic value in glioma is unknown. Here, we examined associations between cognitive symptoms and a panel of blood-based protein biomarkers in glioma patients.
Methods: Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA, scores ≤ 25 = cognitive dysfunction). Serum levels of 17 proteins were measured using ultrasensitive assays.
Results: Patients (n=73) were predominantly male (58%), white (74%), with a median age of 44 (range=24,74). Levels of neurofilament light chain, (p=0.035), interleukin-6 (IL-6) (p=0.006), IL-10 (p=0.007), tumor necrosis factor-α (p=0.035), interferon-γ (p=0.011), C-reactive protein (p=0.016), vascular cell adhesion molecule 1 (VCAM-1) (p=0.012), and intercellular adhesion molecule 1 (ICAM-1) (p<0.001) were higher in patients with cognitive dysfunction (n=39) when compared to those with normal cognition (n=34). After adjusting for isocitrate dehydrogenase (IDH) tumor mutation status, age, tumor grade, and number of surgeries, higher levels of ICAM-1 and IL-10, but not other markers, remained associated with cognitive dysfunction. MoCA scores were negatively correlated with IL-10 (r=-0.24, p=0.039) and ICAM-1 (r=-0.39, p<0.001).
Conclusions: Cognitive dysfunction and tumor IDH wildtype status were associated with protein markers linked to vascular damage and inflammation. Our findings shed light on pathophysiological mechanisms linked to cognitive dysfunction in glioma, suggesting an association with a heightened systemic inflammatory state.

Scientific Focus Area: Clinical Research

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