ADT and brain dysfunction in prostate ca: the effects of age & neural plasticity

该提案的目标是将联合收割机神经认知测试、临床评估和 神经影像学检查早期前列腺癌患者的认知功能障碍 接受雄激素剥夺治疗（ADT）。具体来说，年龄和基线的影响 睾酮水平对ADT引起的认知缺陷及其神经基础的影响 将研究赤字。 ADT已被证明在许多前列腺癌患者的治疗中有效。但 在早期前列腺癌中ADT的需要或适应症方面缺乏共识。 越来越多的证据表明，ADT会导致认知缺陷，这可能会产生负面影响。 影响生活质量。另一方面，很少有人知道是否或何时这些 接受ADT的患者会出现认知缺陷，或者这些缺陷是否取决于年龄 和治疗前的睾酮水平系统性纵向研究，调查神经 ADT引起认知功能障碍的基础缺乏。 在早期的一项使用脑成像的初步研究中，我们发现6个月的ADT与 老年前列腺癌患者的大脑结构和功能变化， 显示出神经心理学测试表现的明显下降。这些发现 提示脑成像是识别脑结构早期变化有用工具， 功能与ADT相关，老年患者可能会补偿任务表现 神经可塑性。另一方面，更精确的神经认知测试可能是 需要检测认知的变化。此外，尚不清楚年轻患者是否 前列腺癌患者会表现出类似的大脑结构和功能变化， ADT导致的睾酮下降比例大于治疗前基线 可能对认知功能和生活质量产生更不利的影响， 老年患者 本申请提出采用集中于执行控制的神经认知测试， 注意力、工作记忆、临床访谈和多种脑成像模式， 在96名患有ADT的患者中识别认知功能障碍和大脑变化模式 早期前列腺癌96例未接受ADT的年龄匹配患者将 作为对照组进行研究。研究结果将与生活质量评估相关， 相同个体报告的主观认知症状以及年龄和治疗前 患者的睾丸激素水平。这项研究的结果将加强我们对 ADT对认知功能的影响，与接受ADT治疗的年轻患者高度相关。 非转移性前列腺癌的辅助激素治疗，因为大多数这些 患者有望从前列腺癌中治愈，并继续在社会中发挥作用。 可能同样重要的是ADT对不断扩大的老年人口的潜在影响， 其中ADT可能加重认知功能障碍并损害生活质量。

The goal of this proposal is to combine neurocognitive testing, clinical assessments, and neuroimaging to examine cognitive dysfunction in patients with early stage prostate cancer undergoing androgen deprivation therapy (ADT). Specifically, the effects of age and baseline testosterone level on ADT-elicited cognitive deficits and the neural bases underlying these deficits will be studied. ADT has proven efficacy in the treatment of many patients with prostate cancer. However, there is a lack of consensus in the need or indications for ADT in early stage prostate cancer. Evidence grows to suggest that ADT causes cognitive deficits which may have a negative impact on the quality of life. On the other hand, little is known about whether or when these cognitive deficits will occur in patients undergoing ADT or whether these deficits depend on age and pre-treatment testosterone level. Systematic longitudinal studies investigating the neural bases of cognitive deficits induced by ADT are lacking. In an earlier pilot study using brain imaging we showed that 6 months of ADT was associated with both structural and functional brain changes in elderly prostate cancer patients without demonstrating an explicit decline in neuropsychological test performance. These findings suggest brain imaging as a useful tool to identify early changes in cerebral structure and function in association with ADT and that elderly patients may compensate for task performance with neural plasticity. On the other hand, it is likely that more precise neurocognitive testing is needed to detect changes in cognition. Further, it remains unclear whether younger patients with prostate cancer will exhibit similar structural and functional brain changes and whether a greater proportional drop in testosterone as result of ADT compared to pre-treatment baseline could have a more detrimental impact on cognitive function and quality of life, as compared to older patients. This application proposes to employ neurocognitive tests focusing on executive control, attention, and working memory, clinical interviews, and multiple brain imaging modalities to identify cognitive dysfunction and pattern of cerebral changes due to ADT in 96 patients with early stage prostate cancer. Ninety-six age matched patients who do not undergo ADT will be studied as a control group. The findings will be correlated with quality of life assessments and subjective cognitive symptoms reported by the same individuals and the age and pre-treatment testosterone level of the patient. The results from this study will enhance our understanding of the effects of ADT on cognitive function and are highly relevant to younger patients undergoing adjuvant hormonal treatment for non-metastatic prostate cancer, as the majority of these patients are expected to be cured from prostate cancer and continue to be productive in society. Probably just as important is the potential impact of ADT on the expanding elderly populations, in which ADT may potentiate cognitive dysfunction and compromise quality of life.