Journal Article

Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients–A prospective controlled study

Agerbaek, Mads, Hosseini, SM Hadi, Buskbjerg, Cecilie R., Amidi, Ali, Zachariae, Robert, Gravholt, Claus H.

2021

Overview

Objective Previous research has indicated cognitive decline (CD) among testicular cancer patients (TCPs), even in the absence of chemotherapy, but little is known about the underlying pathophysiology. The present study assessed changes in cognitive functions and structural brain connectomes in TCPs and explored the associations between cognitive changes and endocrine status and hypothesized risk genotypes. Methods Thirty‐eight newly orchiectomized TCPs and 21 healthy controls (HCs) comparable to TCPs in terms of age and years of education underwent neuropsychological testing, structural MRI, and a biological assessment at baseline and 6 months later. Cognitive change was assessed with a neuropsychological test battery and determined using a standardized regression‐based approach, with substantial change defined as z‐scores ≤−1.64 or ≥1.64. MRI scans and graph theory were used to evaluate changes in structural brain connectomes. The associations of cognitive changes with testosterone levels, androgen receptor gene (AR) CAG repeat length, and genotypes (APOE, COMT, and BDNF) were explored. Results Compared with HCs, TCPs showed higher rates of substantial decline on processing speed and visuospatial ability and higher rates of substantial improvement on verbal recall and visuospatial learning (p < 0.05; OR = 8.15–15.84). Brain network analysis indicated bilateral thalamic changes in node degree in HCs, but not in TCPs (p < 0.01). In TCPs, higher baseline testosterone levels predicted decline in verbal memory (p < 0.05). No effects were found for AR CAG repeat length, APOE, COMT, or BDNF. Conclusions The present study confirms previous findings of domain‐specific CD in TCPs following orchiectomy, but also points to domain‐specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of CD. Further studies evaluating the mechanisms underlying CD in TCPs, including the possible role of the dynamics of the hypothalamic–pituitary–gonadal axis, are warranted. The present study confirms previous findings of domain‐specific cognitive decline in testicular cancer patients following orchiectomy, but also points to domain‐specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of cognitive changes.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adult / Age / Androgen receptors / Androgens / Apolipoprotein E / Apolipoproteins / Brain - diagnostic imaging / Brain - physiopathology / Brain research / Brain-derived neurotrophic factor / Breast cancer / Cancer therapies / Case-Control Studies / Chemotherapy / Clinical Cancer Research / Cognition / Cognition & reasoning / Cognitive ability / Cognitive Dysfunction - diagnosis / Cognitive Dysfunction - genetics / Cognitive Dysfunction - metabolism / Cognitive Dysfunction - physiopathology / Connectome / genetic variants / Genotypes / Healthy Volunteers / Humans / Hypothalamus / Intelligence / Magnetic Resonance Imaging / Male / Measuring techniques / Memory / Middle Aged / Neuropsychological Tests - statistics & numerical data / Neuropsychology / Orchiectomy - adverse effects / Pituitary / Polyglutamine / Prospective Studies / Psychology / Quantitative psychology / Questionnaires / Receptors, Androgen - genetics / survival / Testes / Testicular cancer / Testicular Neoplasms - blood / Testicular Neoplasms - genetics / Testicular Neoplasms - psychology / Testicular Neoplasms - surgery / Testis - metabolism / Testis - pathology / Testis - surgery / Testosterone / Testosterone - blood / Testosterone - metabolism / Thalamus / Trinucleotide repeats / urological oncology / Young Adult