Pre-operative Neurocognitive Function Was More Susceptible to Decline in Isocitrate Dehydrogenase Wild-Type Subgroups of Lower-Grade Glioma Patients

Abstract

Background: Neuropsychological deficits frequently occur in diffuse lower-grade glioma (DLGG) patients, but their relationship with molecular subgroups based on the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) is unclear.Methods: All patients enrolled for this study were divided into different subgroups according to the molecular-integrated 2016 CNS WHO and morphology-centric 2007 CNS WHO to compare their neurocognitive function (NCF) dysfunction. Univariate and multivariate analyses were used to assess the independent factors for NCF decline. The performance of NCF changes for discrimination of IDH and 1p19q status was evaluated by receiver operating characteristic (ROC).Results: There was no significant difference in the clinical characteristics among the molecular and morphologic subgroups. In the molecular subgroups, significant differences in NCF alterations were found in terms of attention function, working memory and executive function in grade II glioma patients; in addition to these changes in NCF, memory function and abstract thinking were also significantly different in grade III glioma patients. The pairwise comparison further confirmed that patients with astrocytoma (A)/anaplastic astrocytoma (AA) with isocitrate dehydrogenase wild-type (IDHwt) glioma were more susceptible to severe cognitive decline in terms of the NCF performance described above. For the morphologic subgroups, only working memory was significantly different in grade III glioma patients. The distribution proportion was significantly different among each subgroup of DLGG (grade II, P = 0.001; grade III, P = 0.002). The proportion of extensive NCF decline (≥5 tests) was 4, 12, and 50% in the IDH mutant oligodendroglioma (IDHm-O), IDHm-A, and IDHwt-A subgroups, and this proportion was 33, 60, and 93% in the IDHm-AO, IDHm-AA, and IDHwt-AA subgroups, respectively. In multivariate regression analysis, molecular types were independent factors for NCF alterations after adjusted the factors of tumor and demographics (p < 0.05). ROC curves suggested combined NCF tests model showed an advantage in the differentiation of IDH status.Conclusions: NCF alteration is closely related to molecular-integrated subgroups with varying degrees and frequencies in DLGG. Patients with IDHwt gliomas are more susceptible to suffer from severe and extensive NCF decline than other subgroups.

The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment

“…For abstraction domain, we did not observe any significant improvement during the whole hospitalization and 3-month follow-up. According to Zhang et al, the scores of memory function and abstract thinking were significantly different presented for grade III glioma patients, and their results implied that patients with IDHwt-astrocytoma/anaplastic astrocytoma are more susceptible to suffering from neurocognitive function decline than those with other subgroups of grade II and III gliomas (43). Our current data did not further support the relationship between the cognitive status of MoCA scores and the pathological classification (Supplementary Figures 3-5).…”

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification

“…Emma van Kessel et al found that IDH status is associated with psychomotor speed, memory performance, and executive functioning (van Kessel et al 2022 ). Also, Zhe Zhang et al, summarizing data from a total of 104 patients with primary supratentorial diffuse lower-grade glioma (DLGG), similarly found severe cognitive decline in terms of neurocognitive function performance in patients with IDHwt (Zhang et al 2020 ). To explain this phenomenon, previous studies pointed out that IDH mutations lead to the production of 2-hydroxyglutarate, which is associated with good cognition (Venkatesh et al 2019 ).…”

The Montreal Cognitive Assessment (MoCA) in neuro-oncology: A pilot study of feasibility and utility in telehealth and in-person clinical assessments

“…Although this was a cross-sectional study, analyzing the effects of education on MoCA scores longitudinally may provide more insight into cognitive reserve in this patient population. A recent study has found that patients with isocitrate dehydrogenase ( IDH )-wildtype gliomas may have worse cognitive decline than those with IDH -mutant gliomas, 36 and other studies suggest an association between APOE alleles and cognitive function among brain tumor patients. 37 This suggests further genomic analysis in addition to neurocognitive testing may be necessary to understand the patient’s overall cognitive profile and provide appropriate treatment.…”