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Updated: May 27, 2025

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Cachexia Alters Central Nervous System Morphology and Functionality in Cancer Patients.

Estefania Simoes1,2,3, Ricardo Uchida4, Mariana P Nucci5

  • 1Cancer Metabolism Research Group (LIM26-HCFMUSP), Department of Surgery, São Paulo, Brazil.

Journal of Cachexia, Sarcopenia and Muscle
|February 17, 2025
PubMed
Summary

Cancer cachexia alters the brain’s structure and function, impacting grey matter volume, connectivity, and causing neuroinflammation. These central nervous system (CNS) changes in cachectic cancer patients may explain metabolic and behavioral issues.

Keywords:
central nervous systemgrey matterhuman cachexianeuroimagingneuroinflammationneuropathology

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Area of Science:

  • Neuroscience
  • Oncology
  • Radiology

Background:

  • Cachexia is a complex cancer-related syndrome causing inflammation, appetite loss, and CNS dysfunction.
  • Mechanisms of cachexia-induced neuroinflammation and CNS changes in humans are not well understood.

Purpose of the Study:

  • To investigate the structural and functional changes in the central nervous system (CNS) of cancer patients experiencing cachexia.

Main Methods:

  • Utilized in vivo MRI (structural and functional) and postmortem neuropathological analyses.
  • Compared cachectic cancer (CC) patients with weight-stable cancer (WSC) patients.

Main Results:

  • Identified regional grey matter (GM) structural differences in CC patients, including augmented orbitofrontal cortex and increased caudate/putamen volumes.
  • Observed disrupted functional connectivity in networks like the salience network and evidence of neuroinflammation, abnormal neuronal morphology, and glial changes in postmortem analyses.

Conclusions:

  • Cachexia significantly alters CNS morphology and function, affecting GM, connectivity, and inducing neuroinflammation.
  • These CNS alterations in cachectic cancer patients likely contribute toHomeostasis disruption, information processing deficits, and metabolic/behavioral changes.
  • This study provides the first human map of CNS responses to cachexia, opening avenues for therapeutic interventions.