Distinct and Reproducible Neurocognitive Profiles in Stable Diffuse Glioma: A Data-Driven Approach to Understanding Cognitive Heterogeneity

Background Glioma patients often exhibit neurocognitive deficits across multiple domains, yet studies typically assess these impairments separately. This study explores aggregated neurocognitive functioning (NCF), identifying distinct profiles and their clinical correlates. Methods NCF in glioma patients with stable disease (≥ 2 months after treatment without clinical or radiological progression) was assessed across five domains: attention, information processing speed, verbal memory, working memory, and flexibility. We used hierarchical cluster analysis to distinguish neurocognitive profiles and replicated these profiles in an independent glioma cohort. Associations between neurocognitive profiles and clinical characteristics were examined using multinomial logistic regression. Results Four distinct neurocognitive profiles were identified in both the study (N = 108) and the validation cohort (N = 185): a preserved, memory, processing/attention, and multi-domain profile. In both cohorts, 40% of patients exhibited impaired NCF, with deficits in at least one domain observed in 44% in the study cohort and 38% in the validation cohort. In the study cohort, tumor hemisphere and prior treatment with radiotherapy or combined radio- and chemotherapy were associated with processing/attention and multi-domain profiles. In both the cohorts, the multi-domain profile showed a weak association with self-perceived NCF. No other significant associations with patient, tumor, or treatment characteristics were observed. Conclusions NCF in glioma patients can be classified in four reproducible neurocognitive profiles. Importantly, concurrent problems in NCF are highly prevalent. Neurocognitive profiles are associated with tumor laterality, previous oncological treatment, and self-perceived NCF, but not with other clinical characteristics.