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

摘要 认知困难在接受化疗的乳腺癌幸存者中非常常见 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 指导癌症幸存者认知管理的证据有限。一个有希望的干预措施正在增加 身体活动，因为它在改善非癌症人群的认知方面是有效的;然而，很少有人 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 治疗后，总体上身体活动水平非常低。认知障碍与 更大的焦虑和抑郁，而增加体力活动已被证明可以减少焦虑 和抑郁症，这表明心理变量可以调解身体之间的联系， 活动和认知障碍。生物学机制也可能将身体活动与认知联系起来 包括突触可塑性和细胞老化。该项目建立在我们以前的工作基础上， 增加身体活动可以提高客观测量的处理速度和自我报告的认知 在乳腺癌幸存者中。目前的建议将审查是否身体活动干预 改善了250名治疗后乳腺癌幸存者的认知能力（I-III期，治疗后<5年， 接受化疗）的患者。我们建议进行为期六个月的 干预与12个月随访，2组RCT，比较使用个体的身体活动干预 咨询和Fitbit活动跟踪器（运动臂），具有健康的老龄化注意力比较条件 （健康老化组），以检查干预对客观测量的处理速度和自我- 报告了认知（在3个月和6个月时），并在12个月时维持效果。主要目的是（1） 研究锻炼臂与健康老龄化臂相比对认知变化的影响。 次要目的是（1）研究锻炼臂对维持认知变化的影响 与健康老龄化臂相比;（2）检查候选生物机制和心理机制 干预相关认知变化的介质。此外，我们将探索剂量反应 身体活动变化与处理速度变化和自我报告认知的关系， 探索运动臂与健康老龄化臂相比对其他认知变化的影响， 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 科学，公共卫生和干预文献，提供有关物理影响的新信息， 乳腺癌幸存者的认知障碍活动，并帮助确定弱势群体， 干预目标。这项研究的结果将为身体活动剂量和强度提供指导， 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.