Background: Hodgkin lymphoma (HL) survivors experience neurocognitive impairment despite receiving no central nervous system-directed therapy, though little is known about underlying mechanisms. Methods: HL survivors (n=197) and age-, sex- and race/ethnicity-frequency-matched community controls (n=199) underwent standardized neurocognitive testing, and serum collection. Luminex multiplex or ELISA assays measured markers of inflammation and oxidative stress. Linear regression models compared biomarker concentrations between survivors and controls and with neurocognitive outcomes, adjusting for age, sex, race, body mass index, anti-inflammatory medication, and recent infections. Results: HL survivors (mean[SD] current age 36[8] years, 22[8] years post-diagnosis) demonstrated higher concentrations of interleukin-6 (IL-6), high-sensitivity c-reactive protein (hs-CRP), oxidized low-density lipoprotein, and glutathione peroxidase (GPx), compared to controls (p’s<0.001). Among survivors, higher concentrations of IL-6 were associated with worse visuomotor processing speed (p=0.046). hs-CRP ≥3 mg/L was associated with worse attention, processing speed, memory, and executive function (p’s<0.05). Higher concentrations of malondialdehyde were associated with worse focused attention and visual processing speed (p’s<0.05). Homocysteine was associated with worse short-term recall (p=0.008). None of these associations were statistically significant among controls. Among survivors, hs-CRP partially mediated associations between cardiovascular or endocrine conditions and visual processing speed, while IL-6 partially mediated associations between pulmonary conditions and visuomotor processing speed. Conclusions: Neurocognitive function in long-term survivors of HL appears to be associated with inflammation and oxidative stress, both representing potential targets for future intervention trials.

中文翻译：

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儿童霍奇金淋巴瘤长期幸存者神经认知功能障碍的全身生物学机制

背景：霍奇金淋巴瘤（HL）幸存者尽管没有接受中枢神经系统定向治疗，但仍会经历神经认知障碍，但对其潜在机制知之甚少。方法：HL 幸存者 (n=197) 和年龄、性别和种族/民族频率匹配的社区对照 (n=199) 接受标准化神经认知测试和血清采集。Luminex 多重检测或 ELISA 检测可测量炎症和氧化应激的标志物。线性回归模型比较了幸存者和对照组之间的生物标志物浓度以及神经认知结果，并根据年龄、性别、种族、体重指数、抗炎药物和近期感染进行了调整。结果：HL 幸存者（平均[SD]当前年龄 36[8] 岁，诊断后 22[8] 岁）表现出较高浓度的白细胞介素 6 (IL-6)、高敏 C 反应蛋白 (hs-CRP) )、氧化低密度脂蛋白和谷胱甘肽过氧化物酶(GPx)，与对照相比(p＜0.001)。在幸存者中，较高浓度的 IL-6 与较差的视觉运动处理速度相关（p=0.046）。hs-CRP ≥3 mg/L 与注意力、处理速度、记忆力和执行功能较差相关（p<0.05）。较高浓度的丙二醛与较差的注意力集中和视觉处理速度相关(p＜0.05)。同型半胱氨酸与较差的短期记忆相关（p=0.008）。这些关联在对照组中均不具有统计学显着性。在幸存者中，hs-CRP 部分介导心血管或内分泌状况与视觉处理速度之间的关联，而 IL-6 部分介导肺部状况与视觉运动处理速度之间的关联。结论：HL 长期幸存者的神经认知功能似乎与炎症和氧化应激相关，两者都是未来干预试验的潜在目标。