Multimodal MRI Biomarker of Mild Cognitive Impairment in Breast Cancer

乳腺癌轻度认知障碍的多模态 MRI 生物标志物

• 批准号: 8690626
• 负责人: SHELLI R KESLER
• 金额: $ 52.93万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-27 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690626
• 关键词: Adjuvant Chemotherapy; Affect; Aftercare; Age; Aging; Atrophic; Behavior; Biological Markers; Brain; Brain region; Cancer Patient; Cancer Survivor; Chemotherapy-Oncologic Procedure; Clinical; Cognition; Cognitive; Comorbidity; Dementia; Diagnosis; Disease; Epidemiology; Episodic memory; Fatigue; Female; Frequencies; Genetic; Genotype; Imaging Techniques; Impaired cognition; Impairment; Incidence; Individual; Integration Host Factors; Life; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Memory; Mental Depression; Methods; Modeling; Moods; Nerve Degeneration; Pathway interactions; Pattern; Performance; Population; Problem Solving; Public Health; Quality of life; Reporting; Research; Research Design; Risk; Role; Short-Term Memory; Societies; Testing; Time; Woman; cancer therapy; chemotherapy; cognitive control; cognitive function; cognitive reserve; disability; executive function; gray matter; high risk; improved; innovation; malignant breast neoplasm; mild cognitive impairment; neuroimaging; neuropsychological; older women; predictive modeling; processing speed; prospective; public health relevance; satisfaction; skills; therapy development; time interval; white matter

DESCRIPTION (provided by applicant): Women with breast cancer, particularly those who are older and who receive adjuvant chemotherapy, are at significantly increased risk for mild cognitive impairment (MCI). Our previous research shows persistent and progressive MCI long after cancer treatment has ended. This cognitive impairment tends to involve difficulties with memory and executive function (i.e. multi-tasking, problem solving) that interfere with daily livin skills and reduce quality of life. The default mode network (DMN) is a brain circuit important for normal cognitive function. The connections between the DMN brain regions tend to naturally decrease in strength as we age. DMN functional connectivity has been demonstrated to be a highly promising neuroimaging biomarker of MCI in non-cancer populations. Disruption of DMN functional connectivity is strongly associated with conversion to dementia and has even been show to precede other biomarkers of neurodegeneration. Previous studies, including our own, show atrophy of DMN regions and damage to the white matter pathways that connect these regions following breast cancer chemotherapy. We believe that chemotherapy treatment accelerates DMN decline resulting in increased frequency of MCI following breast cancer. However, no studies to date have directly assessed the DMN or its relationship to MCI in breast cancer. The specific aims of the proposed study are therefore to 1) determine the frequency of MCI in older breast cancer subjects who receive chemotherapy, 2) identify DMN neuroimaging biomarkers in older breast cancer subjects treated with chemotherapy, and 3) develop models that predict vulnerability to MCI in this population. We will accomplish these aims by integrating longitudinal multidimensional neuropsychological assessments of cognitive function, mood and behavior with advanced, non-invasive multimodal magnetic resonance imaging techniques and APOE genotyping. We will evaluate 55 women with primary breast cancer prior to chemotherapy, one month following chemotherapy and six months following chemotherapy. We will compare the chemotherapy-treated group to 55 women with breast cancer who do not receive chemotherapy and 55 healthy females, all matched on important demographic and clinical factors. All groups will be assessed at the same time intervals. We will emphasize the assessment of memory and executive function as well as DMN functional connectivity. We will incorporate clinical, demographic, psychiatric (e.g. depression, fatigue) and genetic (e.g. APOE) factors with DMN connectivity into our predictive models of MCI. Identifying neuroimaging biomarkers underlying chemotherapy-related MCI will improve identification of individuals at highest risk for neurodegeneration and aid the development of treatments for these impairments. This is of critical importance given an aging society and the increased incidence of and vulnerability to both breast cancer and MCI.

描述（由申请人提供）：患有乳腺癌的妇女，尤其是年龄较大和接受辅助化疗的女性，其轻度认知障碍的风险显着增加了（MCI）。我们先前的研究表明，在癌症治疗结束很久之后，持续性和进行性MCI。这种认知障碍往往涉及在记忆和执行功能（即多任务处理，解决问题）方面遇到困难，这些困难会干扰日常的生活技能并降低生活质量。默认模式网络（DMN）是对正常认知功能重要的大脑电路。随着年龄的增长，DMN大脑区域之间的连接自然会降低强度。 DMN功能连接已被证明是非癌症人群中MCI的高度有希望的神经影像学生物标志物。 DMN功能连通性的破坏与痴呆症的转化密切相关，甚至已被证明是在神经变性的其他生物标志物之前。先前的研究，包括我们自己的研究表明，DMN区域的萎缩以及对乳腺癌化疗后连接这些区域的白质途径的损害。我们认为，化学疗法治疗会加速DMN的下降，导致乳腺癌后MCI的频率增加。但是，迄今为止，尚无研究直接评估DMN或其与MCI在乳腺癌中的关系。因此，拟议研究的具体目的是1）确定接受化学疗法的老年乳腺癌受试者中MCI的频率，2）确定在接受化学疗法治疗的老年乳腺癌受试者中识别DMN神经影像标志物，3）开发模型可以预测该人群中对MCI的脆弱性。我们将通过将纵向多维神经心理心理学评估与先进的非侵入性多模式磁共振成像和APOE基因分型结合在一起来实现这些目标。我们将在化疗之前评估55名原发性乳腺癌的女性，化疗后一个月和化疗后六个月。我们将将接受化疗治疗的组与55例未接受化学疗法和55名健康女性的乳腺癌妇女进行比较，所有这些女性都与重要的人口统计学和临床​​因素相匹配。所有组将在同一时间间隔进行评估。我们将强调记忆和执行功能以及DMN功能连接的评估。我们将将临床，人口统计学，精神病学（例如抑郁症，疲劳）和遗传（例如APOE）因子与DMN连接性结合到我们的MCI预测模型中。确定与化疗相关的MCI的神经影像学生物标志物将改善对神经变性风险最高风险的个体的识别，并有助于对这些障碍的治疗发展。鉴于社会的老龄化以及对乳腺癌和MCI的脆弱性的增加和脆弱性，这至关重要。