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.

此前曾报道睾丸切除术患者 (TCPs) 的认知障碍 (CI) 发生率较高，但对其潜在的病理生理学知之甚少。本研究评估了新切除睾丸的 TCP 中的 CI，并探索了大脑结构网络、内分泌状态和选定的基因型。40 名 TCP 和 22 名健康对照 (HC) 接受了神经心理学测试和磁共振成像，并提供了血液样本。CI 定义为 z 分数在一项神经心理学测试中≤-2 或在两项神经心理学测试中≤-1.5，并使用图论研究结构性脑网络。认知能力与大脑网络、内分泌状态（包括睾酮水平和雄激素受体 CAG 重复长度）和基因型（APOE，BDNF, COMT ) 进行了探索。与 HC 相比，TCP 在 15 项神经心理学测试中有 6 项表现较差，其中 3 项测试在调整相关组间差异后仍具有统计学意义（p  < 0.05）。TCP 也显示出比 HC 更多的 CI（65% 对 36%；  p  = 0.04）。虽然全球脑网络分析显示没有组间差异，但区域分析表明几个区域的节点度和中介中心性存在差异（p  <0.05），这与认知表现不一致。在 TCPs 中，CAG 重复长度与延迟记忆性能呈正相关（r = 0.36；  p  = 0.02）。一个COMT在 TCPs 的整体认知表现中发现了组 × 基因型相互作用效应，风险携带者表现更差（p  = 0.01）。没有发现对APOE、BDNF或睾酮水平的影响。总之，我们的结果支持先前关于新睾丸切除的 TCP 中 CI 高发病率的发现，并为可能的机制提供了新的见解。