权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mindfulness-Based Stress Reduction to Improve Cognitive Function During Aromatase Inhibitor Therapy

在芳香酶抑制剂治疗期间，基于正念的减压可改善认知功能

基本信息

批准号：
9499504
负责人：
John D. Merriman
金额：
$ 24.9万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9499504
关键词：
Adverse effects Amygdaloid structure Anxiety Aromatase Inhibitors Basic Science Biological Markers Brain Brain imaging Brain region Breast Cancer therapy Cancer Survivorship Clinical Cognitive Communication Control Groups Cytokine Gene Data Deterioration Diffusion Magnetic Resonance Imaging Discipline Discipline of Nursing Education Environment Estrogen Antagonists Fostering Foundations Functional Magnetic Resonance Imaging Funding Future Gene Expression Genes Genetic Genetic Variation Goals Hippocampus (Brain)Hormone Receptor Image Individual Individual Differences Inflammation Inflammatory International Intervention Intervention Studies Laboratories Learning Magnetic Resonance Magnetic Resonance Imaging Measures Medical center Memory Mentors Methods Moods Nature Neuraxis Neurons Neuropsychological Tests Neuropsychology Nurses Nursing Societies Oncology Nurse Oxidative Stress Parents Patient Self-Report Peripheral Phase Pilot Projects Postmenopause Prefrontal Cortex Reporting Research Resources Rest Risk Risk Factors Role Sample Size Sampling School Nursing Secure Severities Short-Term Memory Structure Symptoms Techniques Testing Training Universities Vagus nerve structure Variant Verbal Learning Woman Women&apos s Group Work age group anastrozole breast surgery cancer diagnosis cancer therapy career cognitive ability cognitive change cognitive function comparison group cytokine depressive symptoms executive function experience improved interest intervention effect malignant breast neoplasm mindfulness-based stress reduction modifiable risk neuroimaging post-doctoral training pre-doctoral prevent programs public health relevance relating to nervous system skills success tau Proteins visual learning visual memory white matter

项目摘要

DESCRIPTION (provided by applicant): Aromatase inhibitor (AI) therapy is the standard anti-estrogen treatment for postmenopausal women with hormone receptor-positive breast cancer. Among the potential side effects of AI therapy is poorer cognitive function. Studies using objective neuropsychological tests found subtle deteriorations in cognitive domains including verbal and visual learning and memory-as well as concentration, working memory, and executive function. However, two trials found no objective cognitive changes. Although women with breast cancer may report that they experience poorer cognitive abilities, these self-reported cognitive changes often do not correlate with scores on objective tests. Neuroimaging techniques may help explain inconsistent relationships between cancer therapy and cognitive changes by describing underlying alterations in brain function and structure. Functional magnetic resonance imaging (fMRI) evaluates brain activation during tasks. Diffusion tensor imaging (DTI) evaluates the extent and integrity of white matter connections. Together, fMRI and DTI evaluate brain function and structure. Alterations in brain function and structure (i.e., brain alterations) may explain disparate findings using subjective and objective measures of cognitive function. The proposed mentored K99 study leverages the mentor's R01 (CA107408), which is evaluating the neuropsychological effects of AI therapy. This application leverages the pilot study to add a crucial long-term imaging assessment, describe resting state functional connectivity (fcMRI) between neural regions, augment sample size, and build capacity to evaluate inter-individual differences in peripheral inflammation using gene expression techniques early in the R00-phase study. The purposes of the K99 study are to describe long-term relationships between AI therapy and brain alterations, and to explore relationships between brain alterations and cognitive and mood changes. Two groups will be studied: a sample of women evaluated 18 months after the initiation of AI therapy for breast cancer and a comparison group of age- and education-matched women without breast cancer. The primary aim of the K99 study is to (1) describe trajectories of alterations in brain function and structure during AI therapy. The exploratory, hypothesis-generating aim of the K99 study, using the same sample, is to (2a) describe long-term relationships between brain alterations and cognitive changes, and (2b) describe long-term relationships of mood changes with cognitive changes and brain alterations. The R00 study first will explicate the risk profile for brain alterations duing AI therapy with analyses of inter-individual differences in expression of inflammatory genes. Then, it will evaluate the effect of an intervention targeted at improving modifiable risk factors or brain alterations underlying cognitive and mood changes. Clinical and academic experiences led the applicant to focus his research on understanding inter-individual differences in cognitive changes after a diagnosis of cancer and on developing targeted interventions to prevent or alleviate cognitive changes. Pre-doctoral training provided a foundational understanding of subjective assessment and the role of genetic variation in inter-individual variability in cognitiv changes. However, two important pieces were missing that are necessary to build the applicant's program of research: (1) objective neuropsychological testing and neuroimaging methods must be incorporated into his research, and (2) these methods must be integrated with past training in genetics and subjective symptom assessment. The applicant currently lacks the expertise to direct an independent program of research that integrates his past training with new skills in neuroimaging, neuropsychology, and gene expression methods that are necessary to launch an independent research career. The K99 training plan was carefully developed with his mentoring team to fill these gaps. The University of Pittsburgh and University of Pittsburgh Medical Center (UPMC) provide the ideal environment for the applicant to integrate training and research in these multiple disciplines. The mentoring team includes experts in each of these disciplines who are committed to the applicant's success and future independent research career. The primary facilities and resources available (i.e., University of Pittsburgh School of Nursing, UPMC Magnetic Resonance Research Center, Mood and Brain Laboratory, Nursing Basic Science Laboratory) are known nationally and internationally for their outstanding environments. The applicant is completing the first year as a postdoctoral scholar. Training in cancer survivorship research (T32NR011972) with his mentor, Dr. Catherine Bender, is focused on the addition of brain imaging into his emerging program of research. Among other accomplishments in this first year, the applicant secured funding from the Oncology Nursing Society-Sigma Theta Tau International Foundation for Nursing for a pilot study using imaging to evaluate brain function and structure early during AI therapy. The K99 will leverage the pilot study, provide the necessary training in new methods, and integrate his pre-doctoral and postdoctoral training into a coordinated program of research that will begin with the R00 phase. Ultimately, the integrated program of research fostered by the K99/R00 has the potential to uncover biomarkers of alterations in brain function and structure, which could explain inter-individual differences in cognitive changes during cancer therapy and provide targeted intervention to prevent or alleviate these changes.

描述(申请人提供)：芳香酶抑制剂(AI)治疗是激素受体阳性乳腺癌绝经后妇女的标准抗雌激素治疗。人工智能治疗的潜在副作用之一是认知功能下降。使用客观神经心理学测试的研究发现，包括语言和视觉学习和记忆在内的认知领域以及注意力、工作记忆和执行功能都有轻微的恶化。然而，两项试验没有发现客观的认知变化。尽管患有乳腺癌的女性可能会报告她们的认知能力较差，但这些自我报告的认知变化通常与客观测试的分数无关。神经成像技术通过描述大脑功能和结构的潜在变化，可能有助于解释癌症治疗和认知变化之间的不一致关系。功能磁共振成像(FMRI)评估任务期间的大脑激活。弥散张量成像(DTI)评估白质连接的范围和完整性。FMRI和DTI一起评估大脑的功能和结构。大脑功能和结构的改变(即大脑改变)可能会解释使用认知功能的主观和客观测量方法得出的不同结果。拟议的Mentor K99研究利用了Mentor的R01(CA107408)，该R01正在评估人工智能治疗的神经心理影响。这项应用利用试点研究增加了关键的长期成像评估，描述了神经区域之间的静息状态功能连接(FcMRI)，扩大了样本量，并建立了在R00阶段研究早期使用基因表达技术评估外周炎症的个体间差异的能力。K99研究的目的是描述人工智能治疗与大脑改变之间的长期关系，并探索大脑改变与认知和情绪变化之间的关系。将对两组进行研究：一组是在乳腺癌人工智能治疗开始18个月后进行评估的女性样本，另一组是年龄和教育程度匹配的非乳腺癌女性的对照组。K99研究的主要目的是(1)描述大脑功能和结构变化的轨迹在人工智能治疗期间。K99研究的探索性和假设生成目的是使用相同的样本，目的是(2a)描述大脑变化和认知变化之间的长期关系，以及(2b)描述情绪变化与认知变化和大脑变化之间的长期关系。R00研究将首先通过分析炎症基因表达的个体差异来阐明人工智能治疗过程中大脑变化的风险概况。然后，它将评估旨在改善可改变的风险因素或认知和情绪变化背后的大脑变化的干预措施的效果。临床和学术经验使申请人将研究重点放在了解癌症诊断后认知变化的个体间差异，并开发有针对性的干预措施来预防或缓解认知变化。博士前培训提供了对主观评估和遗传变异在认知变化的个体间变异中的作用的基础理解。然而，为了建立申请人的研究计划，两个重要的部分被遗漏了：(1)客观的神经心理测试和神经成像方法必须被纳入他的研究中，以及(2)这些方法必须与过去的遗传学培训和主观症状评估相结合。申请人目前缺乏指导独立研究计划的专业知识，该计划将他过去的培训与启动独立研究生涯所必需的神经成像、神经心理学和基因表达方法方面的新技能相结合。K99的培训计划是与他的指导团队一起精心制定的，以填补这些空白。匹兹堡大学和匹兹堡大学医学中心(UPMC)为申请者提供了理想的环境，以整合这些多学科的培训和研究。指导团队包括这些学科的专家，他们致力于申请者的成功和未来的独立研究生涯。现有的主要设施和资源(即匹兹堡大学护理学院、UPMC磁共振研究中心、心境和脑实验室、护理基础科学实验室)因其卓越的环境而闻名全国和国际。申请者将完成第一年的博士后研究。与他的导师凯瑟琳·本德尔博士一起接受癌症生存研究(T32NR011972)方面的培训，重点是将脑成像添加到他新兴的研究计划中。在第一年的其他成就中，申请者获得了肿瘤护理学会-西格玛·西塔国际护理基金会的资助，用于一项试点研究，使用成像来评估人工智能治疗期间早期的大脑功能和结构。K99将利用试点研究，提供必要的新方法培训，并将他的博士前和博士后培训整合到一个协调的研究计划中，该计划将从R00阶段开始。最终，K99/R00培育的综合研究计划有可能发现大脑功能和结构变化的生物标记物，这可能解释癌症治疗期间认知变化的个体差异，并提供有针对性的干预措施来预防或缓解这些变化。