Contribution of cognitive function and fatigue to health-related quality of life in patients with IDH -mutant gliomas from diagnosis to long-term follow-up

Abstract Background Cognitive impairment, fatigue, and reduced health-related quality of life (HRQoL) are common in patients with IDH-mutant gliomas. However, it remains unclear which cognitive domains are most relevant for global HRQoL, how fatigue relates to these associations, and whether this differs across disease stages. This cross-sectional study examined associations between impairments in cognitive domains and global HRQoL across the disease trajectory. Methods Objective neuropsychological test results from patients with IDH-mutant gliomas were evaluated preoperatively, at 1 year, and long-term (≥ 5 years). Results were classified into 6 cognitive domains. HRQoL was assessed using the EORTC QLQ-C30 global health score. Hierarchical regression models were applied at each time point, adjusting for age and sex. Sensitivity analyses examined the contribution of fatigue and anxiety/depression. Results Preoperatively (n = 106 patients), impairments in cognitive domains significantly explained additional variance beyond demographic variables (ΔR² = 0.20, p < .001), with impairments in learning/memory associated with lower global HRQoL (p < .001). At 1 year (n = 106 patients), cognitive domains also explained additional variance (ΔR ² = 0.16, p < .01), with language (p < .05) and executive impairments (p < .01) as significant predictors. In the long-term cohort (n = 82 patients), cognitive domains explained additional variance (ΔR² = 0.31, p < .001), with executive impairments showing the strongest association (p < .001). Fatigue was strongly associated with global HRQoL across time points (p < .001). Anxiety/depression showed weaker associations. Conclusions Associations between cognitive functioning and global HRQoL differ across time points, with executive impairments showing the strongest associations. Fatigue represents an important co-occurring factor. These symptoms are potentially modifiable, indicating that rehabilitation may improve patients’ HRQoL.