Imaging the effects of androgen deprivation therapy on cognitive functions in pat

摘要/摘要前列腺癌是美国男性最常见的癌症（非黑色素瘤性皮肤癌除外）。许多前列腺癌患者将接受多年的雄激素剥夺治疗（ADT）。ADT的许多副作用和风险在过去已经被描述过，包括一系列的体质症状，性欲丧失和阳痿。然而，ADT对认知功能（生活质量的主要决定因素）的影响尚不清楚。认知能力的改变已经被报道过，但之前仅使用神经心理学测试的研究结果是模棱两可的。我们假设ADT导致认知功能受损，而神经心理学测试无法充分识别这一点，因为许多神经心理学测试是用来检测相对严重的认知功能下降的，比如阿尔茨海默氏痴呆症或创伤性脑损伤后。这项初步研究建议使用功能性脑成像结合行为任务，检查关键额叶执行功能，以评估ADT对认知的影响。无明显转移性疾病的前列腺癌患者在ADT开始前后的功能脑成像结果将与传统的神经认知测试和生活质量问卷结果相关。年龄匹配且从未接受过ADT治疗的前列腺癌患者将被纳入对照组。拟议的研究旨在为进一步研究激素治疗对认知的影响及其潜在的可预防性或可逆性的更大规模研究准备关键数据。了解ADT导致的潜在认知障碍的神经基础可以帮助识别高危人群，并制定新的策略来最大限度地减少ADT相关的认知变化。这将提高对未来前列腺癌患者的护理质量。此外，本研究的结果可以强调功能性脑磁成像在评估其他癌症药物治疗对认知的影响方面的效用。

DESCRIPTION (provided by applicant): Abstract/Summary Prostate cancer is the most frequently diagnosed cancer in US men (except for non-melanomatous skin cancer). Many patients with prostate cancer will undergo years of androgen deprivation therapy (ADT). A multitude of side effects and risks of ADT have been described in the past and include a range of constitutional symptoms, loss of libido and impotence. However, the impact of ADT on cognitive functions, a major determinant of quality of life, remains unclear. Changes in cognitive performance have been reported but results of previous studies using neuropsychological tests alone have been equivocal. We hypothesize that ADT leads to impaired cognitive function that are not sufficiently recognized by neuropsychological testing as many of these test were developed to detect relatively severe cognitive decline, such as in Alzheimer's Dementia or after traumatic brain injury. This pilot study proposes to use functional brain imaging in combination with a behavioral task that examines critical frontal executive function to evaluate the effects of ADT on cognition. The results of functional brain imaging before and after initiation of ADT in prostate cancer patients without overt metastatic disease will be correlated to results of traditional neurocognitive tests and quality-of-life questionnaires. Age-matched subjects with prostate cancer who have never been treated with ADT will be enrolled to the control arm. The proposed study aims to obtain critical data in preparation for larger scale studies that further examine the effects of hormonal treatments on cognition and their potential preventability or reversibility. Understanding the neural basis of potential cognitive impairment as a result of ADT can help to identify individuals at highest risk and lead to new strategies to minimize cognitive changes related to ADT. This would result in improved quality of care for future prostate cancer patients. Furthermore, results of this study could underscore the utility of functional magnetic brain imaging to assess the impact on cognition of other pharmacological cancer treatments. PUBLIC HEALTH RELEVANCE: Narrative Many men with prostate cancer will be affected by side effects of hormonal therapy. The impact of hormonal therapy for prostate cancer on cognitive function, a major determinant of quality of life, remains unclear. This study proposes to use brain imaging to directly measure the effects of hormonal therapy on cognition in patients with prostate cancer before and after initiation of hormonal therapy. [The results of brain imaging will be correlated with scores obtained by neurocognitive testing and quality-of-life-questionnaires.]