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

项目总结/摘要 化疗相关的认知功能障碍（CRCI）与生活质量降低相关， 生存使其成为一个尚未充分研究的重要问题。我们小组和其他人的研究 已经证明CRCI与治疗前脑结构和功能的改变有关， 后处理。化疗作用和生理作用之间存在显著重叠， 参与衰老的过程。神经认知已经在患者中发现， 我们小组和其他人的治疗和工作表明，乳腺癌患者的大脑老化表型加速， 接受化疗的癌症幸存者我们还观察到，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 癌症和认知的研究，包括我们自己的，一直局限于相对短期的后， 治疗随访（例如6-12个月）。为了开始解决这些限制，我们的目标是扩展我们的 目前的前瞻性研究（CA 172145），纵向检查认知功能和大脑 术前、化疗后1个月和化疗后1年的结构/功能。我们将 继续评估接受化疗的女性、化疗初治患者队列， 健康对照组，每年一次，持续5年（最多10年）。使用非侵入性 神经影像学方法，我们将推进我们最初的目标，从最初的项目，以衡量很长的- 长期神经生物学结果，重点是评估神经连接，而不是 具体区域变化（目标1）。我们还将研究非常长期的认知结果， 通过标准化神经心理学测试（Aim 2）测量。最后，我们将探索不同的 损伤的轨迹或亚型及其神经表型（目标3）。拟议项目将 通过扩大对化疗相关认知障碍的认识， 我们对不同亚型的非常长期的神经生物学结果沿着的知识 乳腺癌化疗后的认知障碍和相关神经特征。

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.