Characterization of brain dysfunction during development in survivors of childhood acute lymphoblastic leukemia

儿童急性淋巴细胞白血病幸存者发育过程中脑功能障碍的特征

• 批准号: 10360657
• 负责人: PETER D. COLE
• 金额: $ 93.79万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360657
• 关键词: Acute Lymphocytic Leukemia; Age; Attention; Attentional deficit; Behavioral; Brain; Child; Childhood; Childhood Acute Lymphocytic Leukemia; Chronic; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Data; Development; Discrimination; Electrophysiology (science); Event; Exhibits; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impaired cognition; Impairment; Inferior; Intervention; Leukemia Acute Lymphoblastic Chemotherapy; Light; Link; Long-Term Effects; Longitudinal Studies; Measurable; Measures; Memory; Memory impairment; Modeling; Neurocognitive; Neurologic Process; Neuropsychological Tests; Occupational; Outcome Measure; Pathway interactions; Patients; Pattern; Performance; Pharmacotherapy; Play; Prevention strategy; Process; Protocols documentation; Public Health; Quality of life; Research; Role; Schools; Sensory; Sensory Process; Severities; Short-Term Memory; Specificity; Standardization; Structure; Survivors; Testing; Therapeutic Index; base; behavior measurement; behavior test; brain dysfunction; cancer therapy; causal model; chemotherapy; clinical outcome measures; cognitive ability; cognitive development; cognitive function; cognitive skill; curative treatments; design; efficacy testing; executive function; improved; indexing; leukemia treatment; multimodal data; neural patterning; neuroimaging; neurophysiology; neurotoxicity; novel; prevent; public health relevance; relating to nervous system; sensory discrimination; sex; skills; targeted treatment; tool; treatment effect; treatment strategy

Project Summary Between 40-70% of children treated for acute lymphoblastic leukemia (ALL) on contemporary protocols exhibit measurable deficits in cognitive functioning, which negatively impacts school and occupational performance, and diminishes quality of life. However, the specific processing deficits contributing to poor cognitive functioning in survivors of childhood ALL and the implications for ongoing brain development are poorly understood. The goal of this project is to characterize treatment-related effects on brain functions (Aim 1), identify abnormal patterns of neural connectivity (Aim 2), and assess chronic effects of chemotherapy treatment on the development of cognitive skills (Aim 3) in childhood survivors. We achieve these aims by using a combination of behavioral, electrophysiological, and neuroimaging measures to demonstrate effects on neurocognitive function, brain activity and brain development following chemotherapy compared to healthy, matched controls. Our study is designed to identify the relative contributions of sensory processes, memory, and attentional mechanisms, and cortical-maturation delays to poor performance on standardized tests of cognition function. Our approach will lead to the development of a powerful set of tools for identifying children with persistent treatment-related changes in cognitive functioning due to exposure to toxic therapy. Results will differentiate the level at which processing deficits occur (Aims 1 and 2), and longitudinally assess cognitive development (Aim 3) and the associated development in brain function and pathways in survivors of childhood ALL. This contribution is significant because defining the loci of neurocognitive dysfunction caused by ALL treatment would guide the development of novel preventive, treatment, and intervention strategies.

项目概要 40-70% 接受现代方案治疗急性淋巴细胞白血病 (ALL) 的儿童表现出 认知功能可测量的缺陷，这会对学校和职业表现产生负面影响， 并降低生活质量。然而，特定的处理缺陷会导致认知能力差 儿童 ALL 幸存者的功能及其对持续大脑发育的影响很差 明白了。该项目的目标是表征治疗相关的对大脑功能的影响（目标 1）， 识别神经连接的异常模式（目标 2），并评估化疗的慢性影响 对儿童幸存者认知技能发展（目标 3）的治疗。我们通过以下方式实现这些目标 结合行为学、电生理学和神经影像学测量来证明对 与健康人相比，化疗后的神经认知功能、大脑活动和大脑发育 匹配的控件。我们的研究旨在确定感觉过程、记忆、 和注意力机制，以及皮质成熟延迟导致标准化测试表现不佳 认知功能。我们的方法将导致开发一套强大的工具来识别儿童 由于接触有毒治疗而导致认知功能持续发生与治疗相关的变化。结果将 区分处理缺陷发生的水平（目标 1 和 2），并纵向评估认知能力 儿童幸存者的大脑功能和通路的发育（目标 3）以及相关发育 全部。这一贡献意义重大，因为定义了 ALL 引起的神经认知功能障碍的位点 治疗将指导新的预防、治疗和干预策略的制定。