Neurocognitive Changes from Long-Term Androgen Deprivation Therapy in Prostate Cancer Patients

摘要/总结 这项建议的目的是检查认知障碍的组成部分和神经过程， 接受雄激素剥夺治疗（ADT）的前列腺癌患者。我们将联合收割机 测试，临床评估和脑成像，以检查认知障碍及其对质量的影响， 生活和识别结构和功能的大脑变化，预测认知缺陷的严重程度。早期 检测ADT的认知副作用将有助于在治疗和护理中做出临床决策。 前列腺癌患者。 ADT已被证明在治疗许多转移性前列腺癌患者中有效。然而，在这方面， 在前列腺癌患者中ADT的适应症和最佳持续时间方面缺乏共识 没有转移性疾病。越来越多的证据表明，ADT可能会导致认知缺陷， 对这些患者的生活质量产生负面影响。然而，现有的研究使用传统的 神经心理学测试组合并没有一致地表征ADT诱导的认知损害。它 目前尚不清楚接受ADT的患者是否或何时会发生这些认知缺陷，这些认知缺陷是否 缺陷广泛或仅涉及特定的认知领域，以及缺陷是否可逆。 此外，没有确定的生物标志物可以预测ADT诱导的认知缺陷。我们 初步研究结果表明，大脑的变化可能早于ADT引起的临床表现， 认知障碍由于许多前列腺癌患者将接受ADT多年或终身，根据 在目前的治疗方案中，识别有认知障碍风险的个体至关重要。 为此，我们建议采用纵向神经认知和临床评估，以及 脑成像，以确定ADT引起的认知障碍及其对生活质量的影响， 这些变化取决于治疗持续时间，并且在短时间治疗后是可逆的， 在一个大的前列腺癌患者队列中研究可能预测认知障碍的脑标志物 接受ADT治疗的患者和未接受ADT治疗的对照患者。我们的首要目标是彻底评估 ADT在治疗早期对认知的影响。研究认知障碍的妇女接受 化疗影响了我们对乳腺癌早期治疗的想法。同样，来自 这项研究可以提高我们对ADT相关风险的理解，并为临床管理提供信息 前列腺癌的患者。

ABSTRACT/SUMMARY The goal of this proposal is to examine the component and neural processes of cognitive impairment in prostate cancer patients undergoing androgen deprivation therapy (ADT). We will combine neurocognitive testing, clinical assessments, and brain imaging to examine cognitive impairment and its impact on quality of life and identify the structural and functional brain changes that predict the severity of cognitive deficits. Early detection of cognitive side effects of ADT would facilitate clinical decision making in the treatment and care of prostate cancer patients. ADT has proven efficacy in the treatment of many patients with metastatic prostate cancer. However, there is a lack of consensus in the indications for and optimal duration of ADT in prostate cancer patients without metastatic disease. Evidence grows to suggest that ADT may cause cognitive deficits that can have a negative impact on the quality of life in these patients. However, extant studies using traditional neuropsychological testing batteries have not consistently characterized ADT-induced cognitive impairment. It remains unclear whether or when these cognitive deficits will occur in a patient undergoing ADT, whether these deficits pertain broadly or only to specific cognitive domains, and whether the deficits are reversible. Furthermore, there are no established biomarkers that may predict cognitive deficits induced by ADT. Our preliminary findings suggest that cerebral changes may predate clinical manifestations of ADT-induced cognitive impairment. As many prostate cancer patients will receive ADT for many years or for life, according to current treatment protocols, it is of critical importance to identify individuals at risk for cognitive impairment. To this end, we propose to employ longitudinal neurocognitive and clinical assessments, as well as brain imaging, to identify cognitive impairment due to ADT and its impact on quality of life, to examine whether these changes depend on treatment duration and are reversible after a short duration of treatment, and to investigate cerebral markers that may predict cognitive impairment in a large cohort of prostate cancer patients undergoing ADT and control patients not receiving ADT. Our over-arching goal is to thoroughly evaluate the impact of ADT on cognition early during treatment. Studies of cognitive impairment in women receiving chemotherapy have influenced our thoughts about early treatment of breast cancer. Similarly, the findings from this study could enhance our understanding of the risks associated with ADT and inform clinical management of men with prostate cancer.