MINDS Imaging Ancillary Study

MINDS 影像辅助研究

• 批准号: 10413144
• 负责人: Michelle Gurvitz
• 金额: $ 39.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413144
• 关键词: Address; Adolescent; Adult; Alzheimer' s Disease; Ancillary Study; Behavioral; Biological; Blood Vessels; Brain; Brain Diseases; Brain Injuries; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Trauma; Child; Childhood; Clinical; Clinical Data; Cognitive deficits; Common Ventricle; Complex; Cross-Sectional Studies; Crystallization; Data; Dementia; Development; Educational Background; Executive Dysfunction; Exhibits; Fostering; Funding; Future; Habits; Heart; Hemosiderin; Image; Impaired cognition; Impairment; Infarction; Knowledge; Lesion; Life Style; Longevity; Machine Learning; Measures; Modeling; Molecular Abnormality; Multicenter Studies; National Heart, Lung, and Blood Institute; Network Infrastructure; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Outcome; Parents; Patients; Physiological; Physiology; Population; Prevention strategy; Protocols documentation; Proxy; Quality of life; Research; Rest; Risk; Risk Factors; Role; Sampling; Shapes; Site; Social Interaction; Statistical Models; Strategic vision; Structure; Techniques; Thick; Translational trial; United States National Institutes of Health; White Matter Hyperintensity; aged; brain abnormalities; brain magnetic resonance imaging; cerebrovascular; cognitive reserve; cohesion; cohort; congenital heart disorder; connectome; cost effective; environmental enrichment for laboratory animals; executive function; hypoxic ischemic injury; imaging study; improved; insight; multimodal neuroimaging; neuroimaging; neuroimaging marker; prevent; protective factors; randomized trial; reconstruction; recruit; response; social; translational study; white matter; young adult

Dramatic advances in management of congenital heart disease (CHD) have improved survival to adulthood from <10% in the 1960's to nearly 90% in the current era. With this shifting demographic, adult CHD (ACHD) patients now outnumber pediatric CHD patients.1 ACHD patients demonstrate domain-specific neurocognitive deficits such as impairment in executive function, associated with reduced quality of life that includes deficits in educational attainment and social interaction.2-7 These deficits are related to risk factors that can occur across the lifespan, including genetic abnormalities, cumulative hypoxic/ischemic injury, and, adult-onset atherosclerotic cerebrovascular disease. Our overarching hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits, including executive dysfunction, which are modified by behavioral and environmental enrichment proxies of CR (e.g., level of education and lifestyle/social habits). We propose an ancillary study to the NHLBI-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD).” We will leverage the MINDS-ACHD parent study data (i.e., NIH Toolbox neuropsychological battery/clinical data/biological samples) and our established neuroimaging harmonization, which we currently use for the PHN Single Ventricle Reconstruction (SVRIII) multi-center brain connectome study (R01-HL128818; PI-Panigrahy), to measure neuroimaging biomarkers in ACHD patients at the same PHN sites. Our specific aims are: Specific Aim #1 (brain injury): To determine if vascular-related brain injury (cortical infarcts, hemosiderin lesions, and white matter hyperintensity) is associated with specific neurocognitive deficits (e.g. NIH Toolbox total composite score) in ACHD patients. Specific Aim #2 (brain structure): To determine if reduced fronto-temporal cortical thickness and white matter connectivity are associated with specific neurocognitive deficits (e.g. NIH Toolbox frontal executive sub-score) in ACHD patients. Specific Aim #3 (brain physiology): To determine if reduced cerebrovascular reserve (regional cerebral blood flow/ resting BOLD imaging) is associated with specific neurocognitive deficits (e.g. NIH Toolbox crystallized composite score) in ACHD patients. Specific Aim #4 (cognitive reserve): To determine if the associations between neuroimaging biomarkers and neurocognitive outcomes in ACHD patients are modified by behavioral and environmental enrichment proxies of CR, using traditional statistical models and machine learning techniques. Given the paucity of multi-modal neuroimaging studies in ACHD, our proposed study addresses a major knowledge gap in the ACHD population by providing insight into the mechanism underlying impaired neurocognitive outcomes. Our study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging study to be performed in ACHD. Importantly, other behavioral and environmental enrichment data will be integrated with these neuroimaging and neurocognitive outcome data to model cognitive reserve. Results from this research will help shape the care of ACHD patients, and further our understanding of the interplay between brain injury and cognitive reserve. The proposed ancillary study is thus both feasible and cost-effective by leveraging the NHLBI-PHN infrastructure As such, the proposed research is well aligned with the NHLBI's Strategic Vision.

先天性心脏病（CHD）治疗的巨大进步提高了存活率， 成年人从20世纪60年代的<10%到当今时代的近90%。随着人口结构的变化，成人CHD ACHD患者现在超过了儿童CHD患者。1 ACHD患者表现出领域特异性 神经认知缺陷，如执行功能受损，与生活质量降低相关， 包括教育程度和社会交往方面的缺陷。2 -7这些缺陷与风险因素有关 这可能发生在整个生命周期，包括遗传异常，累积缺氧/缺血性损伤，和， 成人型动脉粥样硬化性脑血管病。我们的总体假设是ACHD患者 表现出血管性脑损伤和结构/生理性脑改变， 神经认知缺陷，包括执行功能障碍，这是由行为和环境改变， CR的富集代理（例如，教育水平和生活方式/社会习惯）。我们建议进行辅助研究， NHLBI资助的儿科心脏网络（PHN）“多机构神经认知发现研究（MINDS） 成人先天性心脏病（ACHD）。我们将利用MINDS-ACHD母研究数据（即，NIH 神经心理学成套测验/临床数据/生物样本）和我们建立的神经成像 协调，我们目前将其用于PHN单脑重建（SVRIII）多中心脑 连接组研究（R 01-HL 128818; PI-Panigrahy），以测量ACHD患者的神经影像学生物标志物， 相同的PHN网站。我们的具体目标是：具体目标#1（脑损伤）：确定是否与血管相关 脑损伤（皮质梗死、含铁血黄素病变和白色高信号）与特异性 ACHD患者的神经认知缺陷（如NIH神经功能缺损综合评分）。具体目标#2（大脑 结构）：为了确定是否减少额颞叶皮质厚度和白色物质连接是 与ACHD中的特定神经认知缺陷（例如NIH额叶执行子评分）相关 患者具体目标#3（脑生理学）：确定脑血管储备（局部）是否减少 脑血流/静息BOLD成像）与特定的神经认知缺陷（如NIH神经功能缺损）相关 结晶综合评分）。具体目标#4（认知储备）：确定 ACHD患者神经影像学生物标志物和神经认知结果之间的关系被修改 通过行为和环境富集代理的CR，使用传统的统计模型和机器 学习技巧由于缺乏对ACHD的多模态神经影像学研究， 通过提供对潜在机制的深入了解，解决了ACHD人群中的一个主要知识缺口。 神经认知结果受损。我们的研究将提供神经认知的结构-生理相关性 结果，代表了第一个多中心的神经影像学研究将在ACHD。重要的是，其他 行为和环境富集数据将与这些神经成像和神经认知 结果数据来模拟认知储备。这项研究的结果将有助于塑造ACHD的护理 患者，并进一步了解脑损伤和认知储备之间的相互作用。的 因此，通过利用NHLBI-PHN基础设施，拟议的辅助研究既可行又具有成本效益 因此，拟议的研究与NHLBI的战略愿景保持一致。