Factors associated with cognitive impairment in long-term IDH-mutant glioma survivors

Cognition is a critical patient-relevant outcome in IDH-mutant (IDHm) glioma; however, there is a limited understanding of long-term neurocognition in this population and its implications for quality of life (QoL), especially in the modern era of molecular classification. We sought to evaluate long-term neurocognitive outcomes in patients with IDHm glioma.

We identified a cohort of adult patients with molecularly defined IDHm glioma treated at Massachusetts General Hospital who underwent neuropsychological assessment 3 + years from initial diagnosis.

This cohort included 63 patients with pathologically proven IDH-mutant gliomas (46% female, median age 45, median 16 years of education, and underwent testing a median 7 years from diagnosis). 40% had oligodendroglioma, and 60% had astrocytoma, with 44, 49, and 6% WHO grade 2, 3, and 4 tumors, respectively. Cognitive impairment (defined as z-score ≤ -1.5 on at least 2 tests in different cognitive domains) was present in 30 patients (48%) and was associated with higher grade (p = 0.03 for grade 3 vs. 2), L-sided laterality (p = 0.02), female sex (p = 0.04), less education (p = 0.02), older age at testing (p = 0.03), longer disease duration (p = 0.01), prior chemotherapy (p = 0.03), and prior radiotherapy (p = 0.03). Cognitive impairment predicted lower scores on a cognitive-focused QoL measure (p < 0.001). This cohort was more impaired compared to a previously reported cohort who were tested at disease onset.

In this population of long-term survivors of IDHm glioma, neurocognitive deficits were common, occurred more frequently than in a comparable newly diagnosed cohort, related to QoL, and associated with clinical and demographic factors. These findings emphasize the need for future research on interventions to support these patients' neurocognitive abilities and QoL.