The APOE ε4 allele in relation to pre- and postsurgical cognitive functioning of patients with primary brain tumors

Elke Butterbrod*, Margriet Sitskoorn, Marjan Bakker, Bernadette Jakobs, Ruth Fleischeuer, Janine Roijers, Geert-Jan Rutten, Karin Gehring

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Recent studies suggest a relationship between the APOE ε4 allele and cognitive outcome in patients treated for malignant brain tumors. Still, longitudinal investigations that include a pretreatment cognitive assessment are lacking and APOE's effects in patients with benign tumors are understudied. This study investigated presurgical cognitive performance and postsurgical change in ε4-carrying and non-carrying patients with glioma and meningioma.


Neuropsychological test scores (CNS Vital Signs battery [seven measures], Digit Span Forward/Backward, Letter Fluency test) were obtained as part of a prospective study in which patients with meningioma and glioma underwent cognitive assessment 1 day before (T0, n = 505) and 3 (T3, n = 418) and 12 months after (T12, n = 167) surgery. APOE isoforms were identified retrospectively. ε4 carriers and non-carriers were compared with regard to pretreatment cognitive performance on the group and individual level. Changes in performances over time were compared with longitudinal mixed model analysis in the total sample and the subgroup receiving adjuvant treatment.


Carriers and non-carriers did not differ with regard to pretreatment performance. No significant main effect of ε4 carrier status or interaction between time (T0-T12) and carrier status was found on any of the tests in the whole sample nor in the sample receiving adjuvant treatment.


This study found no evidence of increased vulnerability for pretreatment cognitive dysfunction or cognitive decline within 1 year after surgery in APOE ε4-carrying meningioma and glioma patients. Investigations that include larger samples at longer-term follow-up are recommended to investigate potential late treatment effects.

Original languageEnglish
Pages (from-to)1665-1676
Number of pages12
JournalEuropean Journal of Neurology
Issue number5
Early online date2021
Publication statusPublished - 2021


  • APOE ε4
  • brain tumor
  • cognitive functioning
  • glioma
  • meningioma

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