title: 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.
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.
authors.affiliation: Unit for Psychooncology and Health Psychology, Department of Oncology and Department of Psychology and Behavioural Sciences, Aarhus University Hospital & Aarhus University, Bartholins Allé 9, bygn. 1340, DK-8000, Aarhus C, Denmark. ali@psy.au.dk.
authors.forename: Ali
authors.initials: A
authors.lastname: Amidi
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Agerbæk
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Wu
authors.affiliation: Vejlefjord Rehabilitation, Stouby, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Pedersen
authors.affiliation: Unit for Psychooncology and Health Psychology, Department of Oncology and Department of Psychology and Behavioural Sciences, Aarhus University Hospital & Aarhus University, Bartholins Allé 9, bygn. 1340, DK-8000, Aarhus C, Denmark.
authors.forename: Mimi
authors.initials: M
authors.lastname: Mehlsen
authors.affiliation: Unit for Psychooncology and Health Psychology, Department of Oncology and Department of Psychology and Behavioural Sciences, Aarhus University Hospital & Aarhus University, Bartholins Allé 9, bygn. 1340, DK-8000, Aarhus C, Denmark.
authors.forename: Cecilie R
authors.initials: CR
authors.lastname: Clausen
authors.affiliation: Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Demontis
authors.affiliation: Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Harbøll
authors.affiliation: Unit for Psychooncology and Health Psychology, Department of Oncology and Department of Psychology and Behavioural Sciences, Aarhus University Hospital & Aarhus University, Bartholins Allé 9, bygn. 1340, DK-8000, Aarhus C, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Zachariae
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging*; D002097:C-Reactive Protein / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009919:Orchiectomy; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D001057:Apolipoproteins E; D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: APOE; Cancer; Cognition; Cortisol; Cytokine; Germ cell tumor; MRI; Neurocognitive function; Neuropsychological function; Testicular cancer; Voxel-based morphometry