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

摘要/摘要 这项建议的目标是检查认知障碍的组成部分和神经过程 前列腺癌患者接受雄激素剥夺治疗(ADT)。我们将结合神经认知 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 并确定预测认知缺陷严重程度的大脑结构和功能变化。早些时候 检测ADT的认知副作用将有助于临床决策治疗和护理 前列腺癌患者。 ADT已被证明对许多转移性前列腺癌患者有效。然而， 前列腺癌患者ADT的适应证和最佳持续时间尚缺乏共识 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，这种缺陷可能会 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 神经心理测试组合并没有始终如一地表征ADT引起的认知障碍。它 目前尚不清楚接受ADT的患者是否或何时会出现这些认知缺陷，这些 缺陷广泛地或仅与特定的认知领域有关，以及这些缺陷是否可逆。 此外，目前还没有已建立的生物标志物可以预测ADT引起的认知障碍。我们的 初步研究结果表明，脑部改变可能先于ADT的临床表现 认知障碍。据报道，许多前列腺癌患者将接受ADT多年或终身治疗 根据目前的治疗方案，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所致的认知损害及其对生活质量的影响，以检查 这些变化取决于治疗持续时间，并且在短期治疗后是可逆的，并且 在一大群前列腺癌患者中研究可能预测认知障碍的脑标志物 接受ADT的患者和未接受ADT的对照患者。我们的首要目标是彻底评估 ADT对治疗早期认知功能的影响接受药物治疗的女性认知功能障碍的研究 化疗影响了我们对乳腺癌早期治疗的想法。同样，来自 这项研究可以加深我们对ADT相关风险的理解，并为临床管理提供参考 患有前列腺癌的男性。

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.