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.

Highlights

  • Diffuse lower-grade gliomas (DLGGs, World Health Organization grade II and grade III) are common infiltrative neoplasms in the central nervous system (CNS) of adults

  • Patients suspected of having primary supratentorial diffuse lower-grade glioma (DLGG) on preoperative magnetic resonance imaging (MRI) and who received a preoperative neurocognitive function (NCF) assessment in neurosurgical oncology 6 ward of Beijing Tiantan Hospital, Capital Medical University between December 2018 and January 2020 were considered for inclusion

  • To the best of our knowledge, this study is the first to represent neurocognitive dysfunction in molecular-integrated subgroups according to the 2016 CNS World Health Organization (WHO) classification for DLGG

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Summary

Introduction

Diffuse lower-grade gliomas (DLGGs, World Health Organization grade II and grade III) are common infiltrative neoplasms in the central nervous system (CNS) of adults. A recent study further elaborated that IDHwt was a risk factor for neurocognitive dysfunction in diffuse glioma (grade IIIV) [3] These results illustrate that IDH status is a potent molecular marker for NCF subgrouping due to its ability to reflect the inherent characteristics of diffuse glioma. 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

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