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

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. This prospective longitudinal study found no evidence for worse pretreatment cognitive function in APOE ε4‐carrying as compared to non‐carrying primary brain tumor patients. Cognitive performances over time up to 12 months after surgery also showed no statistically significant differences between carriers and non‐carriers. APOE ε4’s effects on cognition should be further studied in large primary brain tumor samples with long‐term follow‐ups, where possible interactions with other genetic, clinical and behavioral factors should also be investigated.