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.

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

“…In addition, cognitive dysfunction, GM reduction in the left anterior cingulate cortex and the bilateral parahippocampal gyri and insula, as well as focally decrease WM integrity in bilateral inferior longitudinal fasciculi and left cingulum were found in chemotherapy-exposed subjects compared to healthy controls. A few other recent publications of structural MRI of testicular cancer [27] as well as fMRI studies of prostate [28] and various cancers [29], including breast, colorectal, Hodgkin’s lymphoma, leukemia and myeloma, similarly support the presence of structural/functional neuroimaging and cognitive abnormalities in these malignancies following treatment.…”

“…Structural [15, 19, 34] and functional MRI [23, 24, 35] studies have found that abnormalities may already exist in the absence of chemotherapy for breast cancer patients. More recent neuroimaging studies of other types of cancer including lung [26] and testicular cancer [27] also suggest that structural abnormalities exist without chemotherapy. This is further supported by neuropsychological data in breast [36, 37], testicular [27] and lung cancer [26] patients not treated with chemotherapy.…”

“…More recent neuroimaging studies of other types of cancer including lung [26] and testicular cancer [27] also suggest that structural abnormalities exist without chemotherapy. This is further supported by neuropsychological data in breast [36, 37], testicular [27] and lung cancer [26] patients not treated with chemotherapy.…”

Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

“…Not only the number of behavioral studies remains limited for these patients, neuroimaging studies in childhood non-CNS solid tumor survivors have not been performed yet. Still, adult studies have reported alterations of the WM microstructure in solid tumor patients (including breast and testicular cancer; Ahles et al, 2014;Amidi et al, 2016;Deprez et al, 2011;Deprez, Billiet, Sunaert, & Leemans, 2013;McDonald et al, 2010). Nowadays, MR diffusion-weighted neuroimaging is used to characterize the WM microstructure, and assess possible changes after treatments.…”

Cognitive impairment following hormone therapy: current opinion of research in breast and prostate cancer patients

“…Indeed, in men with prostate cancer, Gonzalez et al [43■■] examined a number of these factors and found that a genetic variant on the G protein subunit beta 3 region was associated with cognitive decline in those on ADT. There has also been promising research examining genetic variants in breast and other cancer patients, showing that individuals carrying specific genetic polymorphisms of the Apoliprotein (APOE) and catechol-O-methyltransferase (COMT) genes may be at greater risk of cognitive impairment [51–53]. An additional well known issue is that cognitive impairment may exist prior to the onset of systemic treatments such as hormone therapy and chemotherapy [54, 55] posing methodological challenges as hormone therapy-related effects may be confounded by other treatment and disease-related effects.…”