Prefrontal cortex abnormalities associated with breast cancer chemotherapy

描述(申请人提供)：我们的实验室以及其他实验室已经显示出与乳腺癌化疗相关的大脑结构和功能的异常，最一致的是在前额叶皮质。前额叶皮质对多任务处理、注意力、处理速度和记忆力等技能至关重要，而这些技能在接受乳腺癌化疗的患者中往往会受到损害。由于化疗前以及接受放射和/或激素阻断治疗的患者也观察到了前额叶皮质的变化，因此化疗对前额叶皮质的具体影响尚不清楚。目前也不清楚为什么一些接受化疗的患者随着时间的推移表现出认知功能的改善，而另一些患者则没有。这项拟议的研究将检查50名计划接受化疗的乳腺癌患者的前额叶皮质结构和功能以及认知状态。这些患者将在从手术前到化疗后12个月的整个治疗过程中接受评估。我们会将化疗组与50名未接受化疗的患者和50名健康女性进行比较，这些患者都在与化疗组相同的时间间隔接受评估。我们将利用非侵入性神经成像(MRI)方法来测量前额叶皮质的体积和功能激活，并结合执行功能、记忆、处理速度和注意力的神经心理学测量。我们还将探索个人结果的可能预测因素，如人口统计、疾病、精神疾病和治疗因素。增加我们对化疗相关认知障碍潜在的神经生物学机制的了解，可能会改善对认知障碍高危患者的识别，并有助于开发针对这些障碍的治疗方法。

DESCRIPTION (provided by applicant): Our laboratory, as well as others, has demonstrated abnormalities in brain structure and function associated with breast cancer chemotherapy, most consistently in the prefrontal cortex. The prefrontal cortex is critical for skills such as multi-tasking, attention, processing speed and memory; skills that are often impaired in patients who have undergone breast cancer chemotherapy. Because prefrontal cortex changes have also been observed in patients prior to chemotherapy treatment as well as in those treated with radiation and/or hormonal blockade, the specific effects of chemotherapy on prefrontal cortex remain unclear. It is also currently unknown why some patients treated with chemotherapy show improvement in cognitive function over time while others do not. The proposed research will examine prefrontal cortex structure and function as well as cognitive status in 50 patients with primary breast cancer scheduled for chemotherapy. These patients will be evaluated across the treatment course, from pre-surgery to 12 months post-chemotherapy. We will compare the chemotherapy-treated group to 50 patients who do not receive chemotherapy and to 50 healthy females who are all assessed at the same time intervals as the chemotherapy-treated group. We will utilize non-invasive neuroimaging (MRI) methods to measure prefrontal cortex volume and functional activation in combination with neuropsychological measures of executive function, memory, processing speed and attention. We will also explore possible predictors of individual outcome such as demographic, disease, psychiatric and treatment factors. Increasing our understanding regarding the neurobiologic mechanisms underlying chemotherapy-related cognitive impairments may improve identification of patients at highest risk for cognitive deficit and aid the development of treatments for these impairments.