PDF(Pubmed)
Abstract：
Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT leads to altered testosterone levels that may affect brain morphology as well as cognition. Considering the reliability of cortical thickness (CT) as a marker of cognitive and brain changes, e.g., in Alzheimer\'s disease, we assessed the impacts of ADT on CT and working memory. Thirty men with non-metastatic prostate cancer receiving ADT and 32 patients not receiving ADT (controls or CON), matched in age and years of education, participated in N-back task and quality-of-life (QoL) assessments as well as brain imaging at baseline and prospectively at 6 months. Imaging data were processed with published routines to estimate CT and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. ADT and CON did not differ in N-back performance or QoL across time points. Relative to CON, patients receiving ADT showed significantly higher frontopolar cortex (FPC) CT at 6-month follow-up vs. baseline. Follow-up vs. baseline FPC CT change correlated negatively with changes in 2-back correct response rate and in testosterone levels across all participants. In mediation analysis, FPC CT change mediated the association between testosterone level change and 2-back accuracy rate change. Increases in FPC CT following 6 months of ADT may reflect early neurodegenerative changes in response to androgen deprivation. While no significant impact on working memory or QoL was observed over 6 months, further research of longer duration of treatment is warranted to unravel the full spectrum of cognitive and neural consequences of ADT in prostate cancer patients.
摘要：
雄激素剥夺疗法（ADT）与对大脑的不利影响有关。ADT导致睾酮水平改变，可能影响大脑形态和认知。考虑到皮质厚度（CT）作为认知和大脑变化标志的可靠性，例如，在阿尔茨海默病中，我们评估了ADT对CT和工作记忆的影响.30名接受ADT的非转移性前列腺癌患者和32名未接受ADT的患者（对照或CON），年龄和受教育年限相匹配，在基线和6个月时参与了N-back任务和生活质量(QoL)评估以及脑成像。使用已发布的例程处理成像数据以估计CT，并通过时间灵活的因素分析以校正的阈值评估一组的结果。ADT和CON在不同时间点的N-back性能或QoL上没有差异。相对于CON,接受ADT的患者在6个月随访时显示额极皮质（FPC）CT明显高于基线。后续行动与所有参与者的基线FPCCT变化与2-back正确应答率和睾酮水平的变化呈负相关.在调解分析中，FPCCT变化介导了睾酮水平变化与2回准确率变化之间的关联。ADT6个月后FPCCT的增加可能反映了对雄激素剥夺的早期神经退行性变化。虽然在6个月内没有观察到对工作记忆或QoL的显著影响，有必要进一步研究更长的治疗时间,以揭示前列腺癌患者ADT的认知和神经后果.
