Stroke Connectome MRI biomarkers for VCID risk assessment

用于 VCID 风险评估的中风连接组 MRI 生物标志物

• 批准号: 10444411
• 负责人: Nagesh Adluru
• 金额: $ 73.69万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444411
• 关键词: Address; Affect; African American population; Alzheimer' s Disease; Amyloid; Atlases; Attention; Biological; Biological Markers; Biology; Blood Vessels; Brain; Cardiovascular system; Categories; Chronic; Clinical; Clinical Research; Cognition; Cognitive; Complex; Data; Dementia; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Distal; Foundations; Functional Magnetic Resonance Imaging; Future; Health; Hispanic Populations; Image; Impaired cognition; Impairment; Ischemic Stroke; Language; Left; Lesion; Life; Location; Machine Learning; Magnetic Resonance Imaging; Maps; Mediating; Memory; Microvascular Dysfunction; Minority Groups; Modeling; Monitor; Native Americans; Neuropsychology; Neurosciences; Outcome; Pathway interactions; Patient Recruitments; Patients; Pattern; Perfusion; Persons; Predisposition; Prognosis; Prospective cohort; Research; Research Project Grants; Rest; Risk; Risk Assessment; Risk Factors; Rural; Stroke; Structure; Survivors; Underrepresented Minority; United States; Validation; Visuospatial; White Matter Hyperintensity; accurate diagnosis; base; brain health; burden of illness; cerebral atrophy; clinical care; cognitive function; connectome; dementia risk; demographics; diagnostic tool; executive function; hypoperfusion; improved; innovation; machine learning method; magnetic resonance imaging biomarker; middle cerebral artery; neighborhood disadvantage; neural network; novel; post stroke; predictive modeling; prognostic tool; prospective; socioeconomic disadvantage; standard of care; stroke patient; stroke survivor; tool; vascular cognitive impairment and dementia; white matter

PROJECT SUMMARY Every year, more than 795,000 people in the United States have a stroke, with currently around 4.7 million survivors. Approximately 20% of survivors develop vascular contributions to cognitive impairments and dementia (VCID) which is second only to Alzheimer’s disease (AD). While several putative biomarkers are known, a considerable gap exists in stroke research in terms of validation and interaction of biomarkers of VCID. There is a critical need to better understand the complex interactions of VCID risk factors, baseline cognitive and brain health, and incident stroke lesion burden on post stroke brain changes and subsequent development of VCID. The specific aims of this project will address this need innovatively by (1) utilizing a novel neighborhood disadvantage atlas to geo-spatially map and quantify socio-economic disadvantage, (2) quantifying vascular risk burden, (3) incorporating baseline brain and cognitive health, (4) leveraging technical advances in state-of-the- art connectome MRI, and (5) applying network neuroscience and machine learning. In addition, we will recruit participants from underrepresented minority groups (African Americans, Hispanics, Native Americans), rural/urban, low/high SES who might be at increased risk for VCID. Our central hypothesis is that VCID risk factors, baseline cognitive and brain health, incident stroke damage, and post stroke brain changes will act in concert through brain perfusion, structure, and connectivity pathways in determining whether a stroke patient develops VCID. We will collect longitudinal connectome MRI and Neuropsychological data from a prospective cohort of patients 55-90 years old with incident ischemic stroke in the left (n=50) or right (n=50) middle cerebral artery territory. We will prospectively collect data on n=50 and retrospectively use n=100 from AD connectome project for matched healthy controls. Aim 1 (Brain changes): Characterize how the interaction of VCID risk factors (e.g., cardiovascular, demographics), baseline brain health and the extent of incident stroke damage will affect post stroke brain changes at 6 months. Aim 2 (Brain-cognition relationships): Characterize specific relationships between VCID risk factors, baseline cognition, brain, incident stroke, post stroke brain changes and post stroke cognitive function at 6 and 12-months across 5 cognitive domains including executive function, attention, language, memory and visuospatial. We will use advanced machine learning to build predictive models that will identify contributory and deleterious brain changes associated with post stroke cognitive outcomes. Successful completion of the project will provide currently lacking scientific understanding of the intricate biological relationships between VCID risk factors, stroke MRI biomarkers, and their interactions, that underlie the biology of cognitive outcomes after an ischemic stroke. The results will lay a strong foundation for building accurate diagnosis, prognosis, disease monitoring tools, and future clinical studies that can aid in positively altering disease progression and reducing illness burden on patients due to post ischemic stroke VCID.

项目总结 美国每年有超过79.5万人中风，目前约有470万人 幸存者。约20%的幸存者发展为认知障碍和痴呆症的血管因素 (VCID)，仅次于阿尔茨海默病(AD)。虽然已知几个假定的生物标志物，但 在VCID生物标志物的验证和相互作用方面，卒中研究中存在着相当大的差距。的确有 迫切需要更好地了解VCID风险因素、基线认知和大脑之间的复杂相互作用 健康、突发卒中损害负担对卒中后脑变化及随后发生的VCID的影响。 该项目的具体目标将通过以下方式创新地满足这一需求：(1)利用一个新的社区 不利地图集，用于绘制和量化社会经济不利因素的地理空间图，(2)量化血管风险 负担，(3)纳入基线大脑和认知健康，(4)利用技术进步-- ART连接体MRI，以及(5)应用网络神经科学和机器学习。此外，我们还将招募 来自代表性不足的少数群体(非洲裔美国人、西班牙裔美国人、印第安人)的参与者， 农村/城市，低/高的社会经济地位者，他们患VCID的风险可能会增加。我们的中心假设是VCID风险 因素、基线认知和脑健康、卒中事件损害和卒中后脑变化将 通过脑灌注、结构和连接路径协同行动，以确定 中风患者患上VCID。我们将收集纵向连接体MRI和神经心理学数据 55-90岁左右发生缺血性卒中的患者的前瞻性队列研究 大脑中动脉区域。我们将前瞻性地收集n=50的数据，并追溯使用n=100 AD连接组项目，用于匹配的健康对照。目标1(大脑变化)：描述相互作用如何 VCID风险因素(例如，心血管、人口统计学)、基线大脑健康和发生中风的程度 损伤会在6个月后影响中风后脑部的变化。目标2(大脑-认知关系)：表征 VCID危险因素与基线认知、脑、卒中事件、卒中后脑的特定关系 卒中后6个月和12个月包括执行功能在内的5个认知领域的变化和认知功能 功能、注意力、语言、记忆和视觉空间。我们将使用高级机器学习来构建 预测模型将确定与中风后相关的促成和有害的脑变化 认知结果。该项目的成功完成将提供目前缺乏的科学理解 VCID危险因素、中风MRI生物标记物及其相互作用之间的复杂生物学关系， 这是缺血性中风后认知结果的生物学基础。这一结果将奠定坚实的基础。 用于建立准确的诊断、预后、疾病监测工具和未来的临床研究，以帮助 积极改变疾病进展，减轻缺血性卒中后VCID患者的疾病负担。