Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment

Ali Amidi*, Mads Agerbæk, Lisa M. Wu, Anders D. Pedersen, Mimi Mehlsen, Cecilie R. Clausen, Ditte Demontis, Anders D. Børglum, Anja Harbøll, Robert Zachariae

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Evidence suggests that testicular cancer (TC) and its treatment are associated with cognitive impairment. However, the underlying neural substrate and biological mechanisms are poorly understood. This study aimed to investigate changes in cognition and brain grey matter (GM) morphology in TC patients undergoing treatment, and to explore associations with immune markers, endocrine markers, and genotype. Sixty-five patients with stage I-III TC underwent assessment after surgery but prior to further treatment and again 6 months after. Twenty-two patients received chemotherapy (+CT), while 43 did not (−CT). Assessments included neuropsychological testing, whole-brain magnetic resonance imaging, and blood samples. Twenty-five healthy controls (HCs) underwent neuropsychological testing with a matching time interval. A regression-based approach was used to determine cognitive changes and longitudinal voxel-based morphometry (VBM) was performed to investigate changes in GM density in the TC groups. Compared with the HCs, both TC groups showed higher rates of cognitive decline (p < 0.05). A trend towards greater decline was observed in + CT (63.6 %) compared with -CT patients (39.5 %) (p = 0.07). VBM revealed widespread GM reductions in both TC groups, but a group-by-time interaction analysis revealed prefrontal reductions specific to the + CT group (p = 0.02), which were associated with poorer cognitive performance. Poorer cognitive performance was also associated with an increase in tumor necrosis factor alpha in + CT patients. Furthermore, an interaction effect was found between the APOE ε4 genotype and chemotherapy on cognitive performance with ε4 carriers performing significantly worse. These findings provide novel evidence of changes in cognition and brain morphology in TC patients undergoing treatment.

Original languageEnglish (US)
Pages (from-to)769-783
Number of pages15
JournalBrain Imaging and Behavior
Volume11
Issue number3
DOIs
StatePublished - Jun 1 2017

Keywords

  • APOE
  • Cancer
  • Cognition
  • Cortisol
  • Cytokine
  • Germ cell tumor
  • MRI
  • Neurocognitive function
  • Neuropsychological function
  • Testicular cancer
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Cognitive Neuroscience
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience

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