A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the underlying pathophysiology. The present study assessed CI in newly orchiectomized TCPs and explored the structural brain networks, endocrine status, and selected genotypes. Forty TCPs and 22 healthy controls (HCs) underwent neuropsychological testing and magnetic resonance imaging, and provided a blood sample. CI was defined as a z-score ≤ -2 on one neuropsychological test or ≤ -1.5 on two neuropsychological tests, and structural brain networks were investigated using graph theory. Associations of cognitive performance with brain networks, endocrine status (including testosterone levels and androgen receptor CAG repeat length), and genotypes (APOE, BDNF, COMT) were explored. Compared with HCs, TCPs performed poorer on 6 out of 15 neuropsychological tests, of which three tests remained statistically significant when adjusted for relevant between-group differences (p < 0.05). TCPs also demonstrated more CI than HCs (65% vs. 36%; p = 0.04). While global brain network analysis revealed no between-group differences, regional analysis indicated differences in node degree and betweenness centrality in several regions (p < 0.05), which was inconsistently associated with cognitive performance. In TCPs, CAG repeat length was positively correlated with delayed memory performance (r = 0.36; p = 0.02). A COMT group × genotype interaction effect was found for overall cognitive performance in TCPs, with risk carriers performing worse (p = 0.01). No effects were found for APOE, BDNF, or testosterone levels. In conclusion, our results support previous findings of a high incidence of CI in newly orchiectomized TCPs and provide novel insights into possible mechanisms.
Brain imaging and behavior. 2021 Aug 15 [Epub ahead of print]
Cecilie R Buskbjerg, Robert Zachariae, Mads Agerbæk, Claus H Gravholt, Lene Haldbo-Classen, S M Hadi Hosseini, Ali Amidi
Unit for Psychooncology and Health Psychology, Department of Psychology and Behavioral Sciences, Aarhus University, Bartholins Allé 11, building 1351, 8000, Aarhus C, Denmark. ., Unit for Psychooncology and Health Psychology, Department of Psychology and Behavioral Sciences, Aarhus University, Bartholins Allé 11, building 1351, 8000, Aarhus C, Denmark., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark., Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA.