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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: APOE ε4; brain tumor; cognitive functioning; glioma; meningioma.

FIGURE 1

Flow chart of patient inclusion and attrition. NPA, neuropsychological assessment; T, time.

FIGURE 2

Proportions of cognitive impairment at baseline (T0) in the sample. Bars represent proportions (%) of impaired (light) and non‐impaired (dark) performances on each test. The p values refer to statistical testing of impairment proportions between non‐ε4 carriers and ε4 carriers. CPT, Continuous Performance test; DSBW, Digit Span Backward; DSFW, Digit Span Forward; SAT, Shifting Attention test; SDC, Symbol Digit Coding test; VEM, Verbal Memory test; VIM, Visual Memory test. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Depiction of mean Z‐scores (status) at each measurement ± SE stratified by ε4 carrier (light) versus non‐carrier (dark). CPT, Continuous Performance test; DSBW, Digit Span Backward; DSFW, Digit Span Forward; SAT, Shifting Attention test; SDC, Symbol Digit Coding test; VEM, Verbal Memory test; VIM, Visual Memory test. [Colour figure can be viewed at wileyonlinelibrary.com]