A Randomized Trial of Physical Activity for Cognitive Functioning in Breast Cancer Survivors

摘要 接受化疗的乳腺癌存活者中认知障碍极为普遍 并可显著影响生活质量、日常功能和重返工作岗位的能力。不幸的是，有 指导癌症存活者认知管理的证据有限。一种有希望的干预正在增加 体育锻炼在改善非癌症人群的认知方面是有效的；然而，很少有 干预试验包括癌症幸存者。乳腺癌幸存者经常减少体力活动 在接受治疗后，总体体力活动水平很低。认知障碍与 更多的焦虑和抑郁，而增加体力活动被证明可以减少焦虑 和抑郁之间的关系，这表明心理变量可以中介生理上的联系 活动和认知障碍。生物机制也可能将体力活动与认知联系起来。 包括突触可塑性和细胞衰老。这个项目建立在我们以前工作的基础上，表明 增加体力活动可以提高客观测量的处理速度和自我报告的认知能力 在乳腺癌幸存者中。目前的提案将审查是否进行体力活动干预 改善250名治疗后乳腺癌幸存者的认知(治疗后5年，I-III期和Lt； 接受化疗的患者)，他们报告有认知障碍。我们建议进行为期6个月的 干预，为期12个月的随访，双臂随机对照试验，比较个人的体力活动干预 咨询和Fitbit活动跟踪器(锻炼手臂)，具有健康的衰老注意力比较条件 (Healthy Aging Arm)考察对客观测量的处理速度和自我调节的干预效果 报告认知(3个月和6个月)，并在12个月时维持效果。主要目的是(1) 与健康衰老的手臂相比，研究运动手臂对认知变化的影响。这个 第二个目标是(1)调查运动手臂对维持认知变化的影响 与健康衰老手臂进行比较；(2)考察候选生物机制和心理机制 干预相关认知变化的调节因子。此外，我们还将探索剂量反应 体力活动变化与加工速度和自我报告认知功能变化的关系 探讨运动手臂与健康衰老手臂相比对其他认知功能变化的影响 受化疗影响的领域(记忆、执行功能和注意力)。这项研究将有助于 通过提供有关身体健康影响的新信息，科学、公共卫生和干预文献 乳腺癌幸存者的认知障碍活动，并帮助识别易感人群和 干预目标。这项研究的发现将为身体活动剂量和强度的指南提供参考 改善数百万乳腺癌幸存者的生活。

ABSTRACT Difficulties with cognition are extremely common among breast cancer survivors treated with chemotherapy and can significantly impact quality of life, daily functioning, and ability to return to work. Unfortunately, there is limited evidence to guide management of cancer survivors' cognition. One promising intervention is increasing physical activity as it has been effective in improving cognition in non-cancer populations; however, few intervention trials have included cancer survivors. Breast cancer survivors often decrease physical activity following treatment and have very low levels of physical activity overall. Cognitive impairments are associated with greater anxiety and depression, while increasing physical activity has been shown to decrease anxiety and depression, suggesting that psychological variables could mediate the association between physical activity and cognitive impairment. Biological mechanisms may also link physical activity with cognition including synaptic plasticity and cellular aging. This project builds upon our previous work indicating that increased physical activity can improve objectively-measured processing speed and self-reported cognition among breast cancer survivors. The current proposal will examine whether a physical activity intervention improves cognition among 250 post-treatment breast cancer survivors (Stages I-III, <5 years post-treatment, treated with chemotherapy) who are reporting cognitive difficulties. We propose to conduct a 6-month intervention with a 12-month follow-up, 2-arm RCT comparing a physical activity intervention using individual counseling and Fitbit activity trackers (Exercise Arm), with a healthy aging attention-comparison condition (Healthy Aging Arm) to examine intervention effects on objectively measured processing speed and self- reported cognition (at 3 and 6 months) and maintenance of the effect at 12 months. The primary aim is to (1) investigate the impact of the Exercise arm on changes in cognition compared to the healthy Aging arm. The secondary aims are to (1) investigate the impact of the Exercise arm on maintenance of changes in cognition compared to the Healthy Aging arm; (2) examine candidate biological mechanisms and psychological mediators of intervention-related changes in cognition. Additionally, we will explore a dose response relationship of changes in physical activity with change in processing speed and self-reported cognition and explore the effects of the Exercise arm compared to the Healthy Aging arm on changes to other cognitive domains (memory, executive function, and attention) affected by chemotherapy. This study will contribute to the scientific, public health, and intervention literature by providing new information on the impact of physical activity for cognitive impairment in breast cancer survivors and help identify vulnerable populations and intervention targets. Findings from this study will inform guidelines for physical activity dose and intensity to improve the lives of millions of breast cancer survivors.