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）

• 批准号: 8887591
• 负责人: HEATHER M CONKLIN
• 金额: $ 58.9万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 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/8887591
• 关键词: Address; Adult; 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; 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; Relative (related person); 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; improved; medulloblastoma; memory process; neurogenesis; neuroimaging; novel; post intervention; preference; processing speed; programs; prophylactic; public health relevance; response; social; synergism; therapy development

 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（由申请人提供）：接受脑肿瘤放射治疗的儿童始终表现出智力功能下降，这与学业失败和生活质量下降有关。髓母细胞瘤是儿童最常见的恶性脑肿瘤，目前的多模式治疗存活率接近 80%。随着幸存者人数的不断增加，改善长期认知结果的努力变得势在必行。该研究计划的主要目标是开发干预措施，减轻中枢神经系统导向疗法对儿童癌症幸存者生活质量的影响。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（WM；信息的在线维护和操作）受损可能是脑肿瘤幸存者智力下降的直接原因。基于计算机的 WM 干预已证明对患有发育性和后天性注意力障碍的个体有效。注意力、工作管理和执行功能方面均取得了进步，并且在培训后数月内仍能持续受益。 WM 训练前后进行的功能性神经影像 (fMRI) 表明支持大脑系统的神经可塑性。最近，这种干预措施被证明对儿童癌症幸存者是可行且有效的，并有证据表明相关的大脑变化。现在至关重要的是，确定我们是否可以在迟发效应出现之前通过预防性干预来保留认知功能，并结合干预措施来优化结果。针对患有慢性疾病的儿童的新研究表明，有氧运动可以带来认知益处。此外，动物模型揭示了受伤后与运动相关的恢复，并提示了潜在的大脑机制（例如新神经细胞的形成）。在拟议的研究中，我们将招募接受新诊断的髓母细胞瘤治疗的儿童进行一线治疗，其中包括放射治疗期间的随机运动试验。治疗后，我们将立即将患者随机分配到计算机化 WM 干预组或时间和注意力对照组（通用社会支持）。两组都将完成干预前和干预后的认知测试和功能磁共振成像。研究目的包括：测试预防性计算机化 WM 干预的功效（具体目标 1），比较计算机化 WM 干预与有氧运动干预相结合的认知影响（具体目标 2），并使用 fMRI 检查与 WM 训练相关的神经可塑性（具体目标 3）。假设：1. 随机接受 WM 干预的参与者将表现出相对于对照组较少的 WM 下降，其益处可推广到高阶认知技能，并且随着时间的推移可持续，2. 同时接受有氧运动和 WM 干预的参与者将表现出比单独接受任一干预的参与者更好的认知结果，以及 3. 随机接受 WM 干预的参与者将表现出 WM 后大脑激活模式的有意义的变化 训练。