Influence of Exercise on Neurocognitive Function in Breast Cancer

运动对乳腺癌神经认知功能的影响

基本信息

批准号：
9102293
负责人：
CATHERINE M. BENDER
金额：
$ 60.91万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9102293
关键词：
Adherence Adjuvant Therapy Aerobic Exercise Affect Aftercare Anxiety Architecture Aromatase Aromatase Inhibitors Attention Behavioral Biological Biological Markers Brain Breast Breast Cancer therapy Clinical Trials Cognitive Decision Making Dendritic Spines Development Diagnosis Elderly Estradiol Estrogens Exercise Fatigue Hippocampus (Brain)Hormone Receptor IL8 gene Impaired cognition Inflammatory Interleukin-10 Interleukin-6 Link Maintenance Malignant Neoplasms Mediating Memory Mental Depression Methods Monitor Natural regeneration Neurocognitive Pathway interactions Patients Personal Satisfaction Physical activity Postmenopause Prefrontal Cortex Randomized Randomized Clinical Trials Research Severities Short-Term Memory Site Sleep Disorders Staging Sum Symptoms TNF gene Withdrawal Woman Work base brain health cognitive function cost effective cytokine depressive symptoms executive function exercise intensity exercise intervention experience gray matter hormone therapy improved malignant breast neoplasm neuroimaging primary outcome programs psychologic public health relevance treatment as usual white matter

项目摘要

DESCRIPTION (provided by applicant): Nearly 61% of women with breast cancer experience a decline in cognitive function with adjuvant therapy. We found declines in attention and working memory with aromatase inhibitor (AI) therapy in women with breast cancer and poorer executive function compared to healthy controls. Multiple biological mechanisms likely underlie this cognitive decline including estrogen (E2) reduction and cytokine dysregulation. AI therapy provides near complete E2 withdrawal and we found that lower E2 levels were related to poorer psychomotor efficiency, attention and executive function with breast cancer therapy. Increases in pro- inflammatory cytokines occur with cancer and persist up to 5 years post-treatment. We found that higher IL-6 levels are related to poorer executive function and reduced gray matter volume. The effect of AIs on cognitive function may also be mediated by symptoms experienced by women with breast cancer including fatigue, sleep problems, depression and anxiety. A promising method for improving cognitive and brain function in older adults is moderate intensity aerobic exercise. Our neuroimaging studies have shown that only modest amounts of aerobic exercise increase hippocampal volume and modify intrinsic connectivity and task-related functional dynamics in the prefrontal cortex and hippocampus. We also found that exercise reduces pro- inflammatory cytokines that are directly linked to hippocampal size and memory formation. Exercise also reduces depression and anxiety and the severity of fatigue and sleep problems in women with breast cancer. We propose a clinical trial in which post-menopausal women with early stage breast cancer are randomized to receive a 6-month, moderate-intensity aerobic exercise intervention or usual care. We will examine whether a well-controlled and monitored site-based exercise intervention, initiated before AI therapy, improves cognitive function and explore whether neuroimaging metrics of brain health, pro-inflammatory biomarkers (IL-6, CRP, TNF-α), and symptoms (fatigue, sleep problems, depression, anxiety) mediate the effects of exercise on cognitive function. Furthermore, we will explore whether the magnitude of the improvements in cognitive function are modified by E2. The specific aims include: 1) Compared to usual care, examine whether the 6-month exercise intervention improves cognitive function over the first six months of AI therapy in postmenopausal women with early stage breast cancer. 2) Compared to usual care, examine the direct effects of exercise on neuroimaging metrics of brain health including regional gray matter volume, white matter architecture and functional dynamics of the brain and pro-inflammatory biomarkers (IL-6 and CRP as primary outcomes; TNF-α as secondary) and explore the direct effects of exercise on symptoms (fatigue, sleep problems, depression, anxiety). 3) Compared to usual care, explore whether the effects of exercise on cognitive function are mediated by neuroimaging metrics of cognitive function, pro-inflammatory cytokines and symptoms and moderated by E2.

描述（由申请人提供）：近 61% 的乳腺癌女性在辅助治疗后出现认知功能下降。我们发现，与芳香酶抑制剂 (AI) 治疗相比，乳腺癌女性的注意力和工作记忆能力下降，且执行功能较差。多种生物机制可能是这种认知能力下降的原因，包括雌激素 (E2) 减少和细胞因子失调，AI 疗法几乎完全停止 E2，我们发现较低的 E2 水平与较差的精神运动效率、注意力和执行力有关。癌症治疗时促炎细胞因子会增加，并持续长达 5 年。我们发现，IL-6 水平升高与执行功能较差和灰质体积减少有关。认知功能也可能由乳腺癌女性经历的症状介导，包括疲劳、睡眠问题、抑郁和焦虑。我们的神经影像学研究表明，中等强度的有氧运动是改善老年人认知和大脑功能的一种有前景的方法。有氧量运动可以增加海马体积，改变前额皮质和海马的内在连接性和任务相关的功能动态。我们还发现，运动可以减少与海马大小和记忆形成直接相关的促炎细胞因子。我们提出了一项临床试验，其中患有早期乳腺癌的绝经后妇女被随机接受为期 6 个月的中等强度有氧运动干预或常规干预。我们将检查在人工智能治疗之前启动的良好控制和监测的基于现场的运动干预是否可以改善认知功能，并探讨大脑健康、促炎生物标志物（IL-6、CRP、TNF-α）的神经影像学指标是否可以改善。，以及症状（疲劳、睡眠问题、抑郁、焦虑）介导运动对认知功能的影响。此外，我们将探讨 E2 是否会改变认知功能的改善程度。具体目标包括：1）与相比。平时护理，检查是否6 个月的运动干预可改善患有早期乳腺癌的绝经后女性在 AI 治疗的前六个月的认知功能。 2) 与常规护理相比，检查运动对大脑健康神经影像指标（包括区域灰质体积）的直接影响。大脑白质结构和功能动态以及促炎生物标志物（IL-6 和 CRP 作为主要结果；TNF-α 作为次要结果）并探索运动对症状（疲劳、睡眠问题、抑郁、焦虑）的直接影响。 3）比较与常规护理相比，探索运动对认知功能的影响是否由认知功能、促炎细胞因子和症状的神经影像学指标介导，并由 E2 调节。