Abstract

Abstract Cognitive impairment is common in primary brain tumor (PBT) patients, as a result of the disease and secondary damage from directed and systemic therapy. Recently, the risk in patients with IDH-mutant gliomas and role of interconnectivity of the tumor with neurons and the tumor microenvironment has heightened interest in exploration of biomarkers of impairment to inform care. Here, we investigate Montreal Cognitive Assessment (MoCA) scores and peripheral blood levels of C-reactive protein (CRP) in a cross-sectional cohort of 47 adult IDH-mutant PBT patients enrolled in a natural history study (NHS, NCT02851706: PI T. Armstrong). MoCA raw scores (range 0-30) were dichotomized (≤ 25 = cognitive dysfunction). Baseline CRP was quantified in banked serum samples in duplicate using (V-Plex/Vascular Injury Panel-2, Meso Scale Discovery [MSD], Rockville, MD) in a QuickPlex SQ 120 instrument (MSD). Lab personnel were blinded to diagnosis and clinical status. To reduce skewness in CRP raw values, we used log transformation. Descriptive statistics, Pearson’s correlation, and logistic regression were conducted using IBM SPSS and SAS Statistics software. The sample was predominately male (62%), white (70%), with high-grade gliomas (III/IV) (68%) and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The mean MoCA score was 25 (SD: 5; median: 26; range: 11-30). Dichotomizing MoCA scores showed that less than half (43%) of participants exhibited moderate-severe (≤ 25) cognitive impairment. MoCA binary group was negatively correlated with levels of CRP (r=-0.42, p<.003). The log mean concentration of CRP was higher in participants with cognitive impairment (7.99, SD=0.47 vs 7.57, SD=0.45, p<.003) than those without impairment. Finally, when controlling for age and sex, CRP remained predictive of cognitive impairment (OR 8.18, 95% CI 1.70,39.23). Higher levels of CRP were associated with lower MoCA scores in a cross-sectional sample of patients with IDH-mutant gliomas, suggesting an association between the severity of inflammation and cognitive impairment in IDH-mutant glioma patients. Further analysis in large, more diverse longitudinal cohorts will be needed to validate these findings in this population and compare to those with IDH-WT tumors and develop predictive models to inform biomarker development. Citation Format: McKenzie C. Kauss, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, Kaitlynn Slattery, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Association between C-reactive protein and cognitive impairment in IDH-mutant gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7445.

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