Prophylactic Multimodal Cognitive Intervention for Children with Medulloblastoma (Resubmission)

髓母细胞瘤儿童的预防性多模式认知干预（重新提交）

基本信息

批准号：
9109597
负责人：
HEATHER M CONKLIN
金额：
$ 53.3万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-13 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9109597
关键词：
Address Adult Aerobic Aerobic Exercise Animal Model Attention Base of the Brain Bilateral Brain Brain Neoplasms Child Childhood Brain Neoplasm Chronic Chronic Disease Cognitive Cognitive deficits Combined Modality Therapy Computers Control Groups Cranial Irradiation Development Disease Exercise Exhibits Failure Functional Magnetic Resonance Imaging Generic Drugs Goals Health Impairment Individual Injury Intervention Late Effects Life Light Longitudinal Studies Maintenance Malignant Neoplasms Malignant neoplasm of brain Measures Medical Memory Loss Memory impairment Neuronal Plasticity Neurons Neurotransmitters Newly Diagnosed Outcome Parietal Participant Patients Pattern Performance Pharmaceutical Preparations Population Prefrontal Cortex Protocols documentation Provider Quality of life Radiation therapy Randomized Recovery Recruitment Activity Research Secondary to Short-Term Memory Social support Survival Rate Survivors Synaptic plasticity System Time Training Unemployment base chemotherapy childhood cancer survivor cognitive function cognitive skill cognitive testing cognitive training computerized efficacy testing executive function exercise intervention exercise training improved medulloblastoma memory process neurogenesis neuroimaging novel post intervention predicting response preference processing speed programs prophylactic social synergism therapy development

项目摘要

DESCRIPTION (provided by applicant): Children treated with radiation therapy for brain tumors consistently demonstrate a decline in intellectual functioning that is associated with academic failure and reduced quality of life. Medulloblastoma is the most common malignant brain tumor in children and survival rates approach 80% with current multimodal therapy. With a growing survivor population, efforts to improve long-term cognitive outcomes become imperative. A primary goal of this research program is development of interventions that mitigate the impact of CNS-directed therapies on the quality of life of childhood cancer survivors. While efficacious, pharmacological and therapist- delivered interventions are limited by medical contraindications and availability of local providers. Recent research suggests impairments in attention and working memory (WM; online maintenance and manipulation of information) may be proximal contributors to intellectual declines among brain tumor survivors. A computer- based WM intervention has demonstrated efficacy with individuals with developmental and acquired attention disorders. Improvements have been achieved on measures of attention, WM and executive functions with benefits persisting months after training. Functional neuroimaging (fMRI) conducted before and after WM training suggests neuroplasticity for supporting brain systems. This intervention has recently been shown to be feasible and efficacious for childhood cancer survivors with evidence for associated brain-based changes. It is now crucial to determine whether we can preserve cognitive function by intervening prophylactically, before the emergence of late effects, and combine interventions to optimize outcomes. New research with children with chronic disease indicates aerobic exercise offers cognitive benefits. Further, animal models reveal exercise- related recovery following injury and suggest underlying brain mechanisms (e.g., new nerve cell formation). In the proposed study, we will recruit children treated for newly diagnosed medulloblastoma on a front-line protocol that includes a randomized exercise trial during radiation therapy. Immediately following treatment, we will randomly assign patients to a computerized WM intervention or a time and attention control group (generic social support). Both groups will complete pre- and post-intervention cognitive testing and fMRI. Study aims include: testing the efficacy of a prophylactically administered computerized WM intervention (Specific Aim 1), comparing the cognitive impact of a computerized WM intervention administered in conjunction with an aerobic exercise intervention (Specific Aim 2), and using fMRI to examine neuroplasticity associated with WM training (Specific Aim 3). It is hypothesized that: 1. participants randomized to the WM intervention will demonstrate less WM decline relative to controls, with benefits that are generalizable to higher-order cognitive skills and sustainable over time, 2. participants receiving both aerobic exercise and WM interventions will demonstrate better cognitive outcomes than participants receiving either intervention alone, and 3. participants randomized to the WM intervention will demonstrate meaningful changes in brain activation patterns after WM training.

描述（由适用提供）：接受放射治疗的儿童脑肿瘤始终显示出与学术失败和生活质量降低有关的智力功能下降。髓母细胞瘤是儿童中最常见的恶性脑肿瘤，生存率接近80％的多模式治疗。随着生存人数的增长，必须努力改善长期认知结果。该研究计划的主要目标是开发干预措施，以减轻CNS指导疗法对儿童癌症生存质量的影响。虽然有效，但药物和治疗师提供的干预措施受到医疗禁忌症和当地提供者的可用性的限制。最近的研究表明，注意力和工作记忆的损害（WM；在线维护和信息操纵）可能是脑肿瘤幸存者智力下降的近端贡献者。基于计算机的WM干预已证明了患有发育和获得注意力障碍的人的效率。在训练后几个月，对关注，WM和执行职能的衡量标准进行了改进。 WM训练之前和之后进行的功能性神经影像学（fMRI）提出了支持大脑系统的神经可塑性。最近，该干预措施对儿童癌症生存是可行且有效的，并有证据表明相关的基于大脑的变化。现在，至关重要的是要确定我们是否可以通过预防性介入，在迟到效应的出现以及优化结局的联合干预措施之前保留认知功能。与儿童患有慢性疾病的新研究表明有氧运动具有认知益处。此外，动物模型揭示了损伤后与运动相关的恢复，并暗示了潜在的脑机制（例如，新的神经细胞形成）。在拟议的研究中，我们将根据一条前线方案招募接受新诊断的髓母细胞瘤治疗的儿童，其中包括放射治疗期间的随机运动试验。治疗后立即将患者随机分配到计算机化的WM干预措施或时间和注意力控制组（通用社会支持）。两组将完成干预前后的认知测试和fMRI。研究目的包括：测试预防性施用的计算机化WM干预措施的有效性（特定目的1），比较与有氧运动干预和有氧运动干预相结合的计算机化WM干预措施的认知影响（特定的AIM AIM 2），并使用FMRI使用FMRI检查与WM训练相关（特定目标3）。假设的是：1。参与者将随机分配到WM干预措施相对于对照组的下降幅度较小，并且可以将其推广到高阶认知能力和随着时间的推移的可持续性，2。参与者同时接受有氧运动和WM干预的参与者将表现出更好的认知模式，而不是单独进行干预的参与者，将表现出更好的认知方式。训练。