Enhancing cognitive function in breast cancer survivors through community-based aerobic exercise training

项目摘要 50岁以上的女性占乳腺癌诊断的77%，占所有乳腺癌幸存者（BCS）的93%。 不幸的是，癌症治疗和正常衰老之间的相互作用往往导致一些健康问题。 后遗症高达75%的BCS患者在治疗期间会出现认知变化，超过45%的患者会出现临床症状。 治疗前后认知能力显著下降。癌症相关认知障碍的最佳治疗 认知障碍（CRCI）可能是一种已知可改善类似人群认知的综合干预措施， 作为老年人。我们之前的研究支持中等强度有氧运动训练对 改善无癌症老年人的认知功能。这项工作表明，心肺健康（即， 峰值VO 2）和脑结构和功能完整性（例如，白色物质微观结构，静息状态功能 连接）可能是运动引起的认知功能变化的基础。我们最近应用了一种老化 框架，以获得初步信息的影响，身体活动对认知功能的BCS。我们 这一领域的研究表明，有氧运动训练可能同样改善癌症引起的认知能力下降。 癌症相关的疲劳也可能是运动对认知有益的机制， 癌症。我们在衰老和癌症方面的初步数据，沿着有据可查的运动的益处， 建议的CRCI机制（例如，心肺健康，疲劳），提供了一个令人信服的论点， 有氧运动训练对改善BCS患者认知功能的支持。虽然有证据表明， 这一领域正在增长，很少有大型试验已经进行，没有，据我们所知，考虑到 传播和实施的先验。我们提出了一项临床试验，其中绝经后BCS（3-24 主要辅助治疗后3个月）将被随机分配到基于社区的有氧运动计划，或 注意力控制本研究采用混合I型有效性-实施设计来研究临床 有效性，同时收集与我们的新的，社区- 基于方法。我们的运动方案是基于我们以前的研究，在老年人中证明了有效性。 成年人，我们的社区为基础的方法是基于我们以前的研究表明， 在BCS和绝经后无癌症妇女中的实施成功。具体目标是：（1）检查 与对照组相比，为期6个月的社区有氧运动计划对指标的有效性 认知功能（即，认知表现，大脑健康的神经影像学指标，自我报告的认知 损伤）;以及2）收集有关干预措施的可扩展性潜力的信息， 由RE-AIM框架定义（即，覆盖面、有效性、采用、实施、维护）。我们将 还探索干预与临床变量的相互作用（例如，调节剂：化疗治疗方案， 肥胖状态）和有氧运动与对照组相比影响认知能力的潜在途径， 函数（即，介质：神经影像学结果、心肺适应性、疲劳）。

Project Summary Women aged 50+ years comprise 77% of breast cancer diagnoses and 93% of all breast cancer survivors (BCS). Unfortunately, the interaction between cancer treatment and normal aging often results in a number of health sequelae. Up to 75% of BCS suffer cognitive changes during treatment, and over 45% experience clinically significant cognitive decline pre- to post-treatment. An optimum treatment for cancer-related cognitive impairment (CRCI) is likely one integrating interventions known to improve cognition in similar populations, such as older adults. Our previous research supports the efficacy of moderate-intensity aerobic exercise training for improving cognitive function in older adults without cancer. This work suggests that cardiorespiratory fitness (i.e., peak VO2) and brain structural and functional integrity (e.g., white matter microstructure, resting state functional connectivity) may underlie exercise-induced changes in cognitive function. We recently applied an aging framework to gain preliminary information on the effects of physical activity on cognitive function in BCS. Our work in this area suggests that aerobic exercise training may similarly ameliorate cognitive decline due to cancer and that cancer-related fatigue may also represent a mechanism of exercise’s cognitive benefits in the context of cancer. Our preliminary data in aging and cancer, along with the well-documented benefits of exercise relative to proposed CRCI mechanisms (e.g., cardiorespiratory fitness, fatigue), provide a compelling argument in support of aerobic exercise training for improving cognitive function in BCS. While evidence toward efficacy in this area is growing, few large trials have been conducted and none, to our knowledge, with consideration of dissemination and implementation a priori. We propose a clinical trial in which post-menopausal BCS (3-24 months post primary adjuvant therapy) will be randomized to a community-based aerobic exercise program or attentional control. This study utilizes a Hybrid Type I effectiveness-implementation design to investigate clinical effectiveness while gathering information on implementation success associated with our novel, community- based approach. Our exercise protocol is based upon our previous studies with demonstrated efficacy in older adults, and our community-based approach is based upon our previous studies with demonstrated implementation success in BCS and post-menopausal women without cancer. The specific aims are: 1) Examine the effectiveness of a 6-month, community-based aerobic exercise program, compared to control, on indicators of cognitive function (i.e., cognitive performance, neuroimaging metrics of brain health, self-reported cognitive impairment) in post-menopausal BCS; and 2) Gather information on the intervention’s potential for scalability as defined by the RE-AIM framework (i.e., reach, effectiveness, adoption, implementation, maintenance). We will also explore intervention interactions with clinical variables (e.g., moderators: chemotherapy treatment regimen, obesity status) and potential pathways by which aerobic exercise, compared to control, influences cognitive function (i.e., mediators: neuroimaging outcomes, cardiorespiratory fitness, fatigue).