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患者的生存率