Very-long Term Neurocognitive Outcomes in Breast Cancer Survivors (ProbC2)

项目摘要/摘要 化疗相关认知障碍(CRCI)与生活质量下降和 生存使其成为一个仍未得到充分研究的重大问题。我们团队和其他人的研究 已经证明CRCI与治疗前大脑结构和功能的改变有关 去做后处理。化疗作用和生理作用之间有明显的重叠。 与衰老有关的过程。在20年后的患者中发现了神经认知 我们小组和其他人的治疗和工作表明，乳房的大脑老化表型加速 癌症幸存者接受了化疗。我们还观察到，患者可能会表现出 认知障碍的独特轨迹需要进一步研究。现有的前瞻性、纵向 对癌症和认知的研究，包括我们自己，一直局限于相对较短的后 治疗随访(如6-12个月)。为了开始解决这些限制，我们的目标是扩大我们的 当前的前瞻性研究(CA172145)，纵向检查认知功能和大脑 结构/功能：术前、化疗后1个月、化疗后1年。我们会 继续评估接受化疗的妇女、化疗幼稚患者和 健康对照组每年间隔5年(最多10年)。使用非侵入性 神经成像方法，我们将把我们最初的目标从最初的项目提前到很长时间的测量- 术语神经生物学结果，强调对神经连通性的评估，而不是 具体的区域变化(目标1)。我们还将研究非常长期的认知结果，如 通过标准化的神经心理测试(目标2)进行测量。最后，我们将探索不同的 损害的轨迹或亚型及其神经表型(目标3)。拟议的项目将 通过扩展扩展显著促进对化疗相关认知障碍的理解 我们对非常长期的神经生物学结果以及不同亚型的知识 乳腺癌化疗后的认知障碍和相关的神经特征。

PROJECT SUMMARY/ABSTRACT Chemotherapy-related cognitive impairment (CRCI) is associated with reduced quality of life and survival making it a significant problem that remains understudied. Research by our group and others has demonstrated that CRCI is associated with altered brain structure and function from pretreatment to post treatment. There is significant overlap between chemotherapy actions and physiologic processes involved in aging. Neurocognitive have been found in patients up to 20+ years post- treatment and work by our group and others suggests an accelerated brain aging phenotype in breast cancer survivors treated with chemotherapy. We have also observed that patients may demonstrate unique trajectories of cognitive impairment that require further study. Existing prospective, longitudinal studies of cancer and cognition, including our own, have been limited to relatively short-term post- treatment follow-ups (e.g. 6-12 months). To begin addressing these limitations, we aim to extend our current prospective study (CA172145), which longitudinally examines cognitive function and brain structure/function pre-surgery, 1-month post chemotherapy, and 1-year post chemotherapy. We will continue to assess cohorts of women treated with chemotherapy, chemotherapy naïve patients, and healthy controls at yearly intervals for 5 additional years (up to 10 years). Using non-invasive neuroimaging methods, we will advance our original aims from the initial project to measure very long- term neurobiologic outcomes with an emphasis on the assessment of neural connectivity rather than specific regional changes (Aim 1). We will also examine very long-term cognitive outcomes as measured by standardized neuropsychological testing (Aim 2). Finally, we will explore different trajectories or subtypes of impairment and their neural phenotypes (Aim 3). The proposed project will significantly advance the understanding of chemotherapy-related cognitive impairments by extending our knowledge on very long-term neurobiological outcomes along with the different subtypes of cognitive impairments and associated neural profiles following breast cancer chemotherapy.