Understanding the association between fatigue and neurocognitive functioning in patients with glioma: a cross-sectional multinational study

Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data. We analyzed data on self-reported fatigue and neurocognitive outcomes from postoperative patients with glioma from the University of California San Francisco (n = 100, UCSF) and Amsterdam University Medical Center (n = 127, Amsterdam UMC). We used multiple linear regression models to assess associations between fatigue and seven (sub)domains of neurocognitive functioning and latent profile analysis to identify distinct patterns of fatigue and neurocognitive functioning. UCSF patients were older (median age 49 vs. 43 years, p = 0.002), had a higher proportion of grade 4 tumors (32% vs. 18%, p = 0.03), and had more neurocognitive deficits (p = 0.01). While the number of clinically fatigued patients was similar between sites (64% vs. 58%, p = 0.12), fatigue and the number of impaired neurocognitive domains were not correlated (p = 0.16-0.72). At UCSF, neurocognitive domains were not related to fatigue, and at Amsterdam UMC attention and semantic fluency explained only 4 to 7% of variance in fatigue. Across institutions, we identified four distinct patterns of neurocognitive functioning, which were not consistently associated with fatigue. Although individual patients might experience both fatigue and neurocognitive impairment, the relationship between the two is weak. Consequently, both fatigue and neurocognitive functioning should be independently assessed and treated with targeted therapies.