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Relationship between functional network integrity, cognition and fatigue at long-term follow-up in patients with IDH-mutated gliomas

AI Summary
  • Preserved cognitive performance associates with functional network organisation closely matching healthy brain templates at long-term follow-up in IDH-mutated glioma patients.
  • Distinct cognitive domains map to specific networks: auditory for language and verbal memory, default mode for visual memory, executive and frontoparietal for attention and control.
  • Mental fatigue correlates with executive, processing speed and language deficits; combined fatigue and executive impairment show greatest network reorganisation and highest anxiety and depression.
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Front Hum Neurosci. 2026 Jul 16;20:1860966. doi: 10.3389/fnhum.2026.1860966. eCollection 2026.

ABSTRACT

BACKGROUND: Many patients with IDH-mutated gliomas struggle with cognitive dysfunction and mental fatigue at long-term follow-up. Here, we investigate the relationship between functional network re-organization and long-term cognitive outcomes in patients treated for IDH mutated glioma.

METHODS: We examined 61 patients at 5-21 years post-surgery using resting-state fMRI and neuropsychological testing. Individual-level network maps were obtained by regressing each patient’s resting-state time series against reference template networks via dual regression, and network integrity was quantified as the spatial correspondence between these maps and the corresponding healthy templates. The Mental Fatigue Scale and Hospital Anxiety and Depression Scale were used to assess fatigue, depression and anxiety.

RESULTS: Tests of executive function, processing speed/attention, and language showed significant associations with auditory, executive control, and frontoparietal network-template similarity. Memory domains displayed distinct patterns: visual memory correlated with network-template similarity of the default mode network, and verbal memory with the auditory network. Mental fatigue correlated with executive function, processing speed/attention, and language performance. Three cognition-fatigue profiles emerged, distinguished by depression/anxiety levels and auditory/sensorimotor network integrity.

CONCLUSION: In patients with IDH mutated gliomas at long-term follow-up, preserved cognitive performance is associated with functional network organization resembling healthy brain templates. For patients with cognitive impairment, different networks were linked to distinct cognitive domains. Patients with a combination of mental fatigue and executive impairment were characterized by most pronounced network re-organization and highest symptoms of anxiety and depression. These findings suggest network-specific rehabilitation approaches targeting the interplay between fatigue, mood, and executive control may improve patient outcomes.

PMID:42534736 | PMC:PMC13422171 | DOI:10.3389/fnhum.2026.1860966

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