Cognitive impairments are independently associated with shorter survival in diffuse glioma patients

Emma van Kessel*, Irene Huenges Wajer, Carla Ruis, Tatjana Seute, Susanne Fonville, Filip De Vos, Joost Verhoeff, Pierre Robe, Martine van Zandvoort, Tom Snijders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Diffuse gliomas (WHO grade II–IV) are progressive primary brain tumors with great variability in prognosis. Cognitive deficits are of important prognostic value for survival in diffuse gliomas. Until now, few studies focused on domain-specific neuropsychological assessment and rather used MMSE as a measure for cognitive functioning. Additionally, these studies did not take WHO 2016 diagnosis into account. We performed a retrospective cohort study with the aim to investigate the independent relationship between cognitive functioning and survival in treatment-naive patients undergoing awake surgery for a diffuse glioma. Methods: In patients undergoing awake craniotomy between 2010 and 2017, we performed pre-operative neuropsychological assessments in five cognitive domains, with special attention for the domains executive functioning and memory. We evaluated the independent relation between these domains and survival, in a Cox proportional hazards model that included state-of-the-art integrated histomolecular (‘layered’ or WHO-2016) classification of the gliomas and other known prognostic factors. Results: We included 197 patients. Cognitive impairments (Z-values ≦ − 2.0) were most frequent in the domains memory (18.3%) and executive functioning (25.9%). Impairments in executive functioning and memory were significantly correlated with survival, even after correcting for the possible confounders. Analyses with the domains language, psychomotor speed, and visuospatial functioning yielded no significant results. Extensive domain-specific neuropsychological assessment was more strongly correlated to survival than MMSE. Conclusion: Cognitive functioning is independently related to survival in diffuse glioma patients. Possible mechanisms underlying this relationship include the notion of cognitive functioning as a marker for diffuse infiltration of the tumor and the option that cognitive functioning and survival are determined by overlapping genetic pathways and biomarkers.

Original languageEnglish
Pages (from-to)1434-1442
Number of pages9
JournalJournal of Neurology
Publication statusPublished - Apr 2021


  • Brain Neoplasms/complications
  • Cognition
  • Cognitive Dysfunction/etiology
  • Glioma/complications
  • Humans
  • Neuropsychological Tests
  • Retrospective Studies
  • Wakefulness


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