Cerebral Autoregulation, Brain Perfusion, and Neurocognitive Outcomes After Traumatic Brain Injury (CAPCOG-TBI)

脑外伤后的大脑自动调节、脑灌注和神经认知结果 (CAPCOG-TBI)

• 批准号: 10733565
• 负责人: KAN DING
• 金额: $ 83.97万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733565
• 关键词: Accounting; Acute; Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Attention; Axon; Bilateral; Blood Flow Velocity; Blood Pressure; Blood Vessels; Brain; Brain Injuries; Brain imaging; Brain region; Cephalic; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Physiology; Cerebrum; Chronic; Clinical; Cognition; Cognitive; Data; Dementia; Development; Disease; Elderly; Episodic memory; Etiology; Fingers; Goals; Health; Homeostasis; Impaired cognition; Impairment; Individual; Injury; Internal carotid artery structure; Knowledge; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Memory impairment; Near-Infrared Spectroscopy; Nerve Degeneration; Neurobehavioral Manifestations; Neurocognitive; Nonpharmacologic Therapy; Orthopedics; Outcome; Perfusion; Photoplethysmography; Population; Quality of life; Recovery; Recovery of Function; Research; Research Priority; Severities; Structure; Sum; Survivors; Time; Trauma; Traumatic Brain Injury; Traumatic Brain Injury recovery; Ultrasonography; United States National Institutes of Health; axon injury; brain tissue; brain volume; cerebrovascular; clinical care; cognitive performance; cognitive recovery; crosslink; diagnostic strategy; disability; economic cost; epidemiology study; experience; functional outcomes; hemodynamics; hypoperfusion; imaging approach; imaging biomarker; improved; individual variation; injury recovery; multimodality; neuroimaging; noninvasive diagnosis; pharmacologic; primary outcome; processing speed; sex; symposium; targeted treatment; tissue oxygenation; vascular contributions; vertebral artery; white matter

PROJECT SUMMARY Traumatic brain injury (TBI) is a leading cause of disability in adults and the quality of life of TBI survivors is highly dependent on the adequacy of cognitive recovery. TBI is also a risk factor for Alzheimer’s disease (AD) and AD-related dementias (ADRD). Mounting evidence indicates that cerebrovascular dysfunction occurs in both TBI and AD/ADRD and can be a cross-link between the two diseases. The 2019 ADRD Summit called for further studies to understand vascular contributions to progressive cognitive impairment/dementia associated with TBI and develop non-invasive diagnostic approaches5,9. The following important knowledge gaps exist: 1) What is the impact of early cerebrovascular dysfunction after TBI on short and long-term cognitive outcomes after accounting for age, sex, and pre-existing health conditions? 2) What is the temporal relationship between the cerebrovascular function recovery and cognitive outcome after TBI? and 3) Is there a relationship between cerebrovascular dysfunction and post-TBI neurodegeneration? The overarching goal of this proposal is to determine whether acute cerebrovascular dysfunction and its recovery within the first year postinjury are associated with cognitive outcomes and neurodegeneration 12 months after moderate to severe TBI (msTBI). Our central hypothesis is that cerebrovascular function measured by dynamic cerebral autoregulation (CA) and brain perfusion during acute stage and its recovery during the first year are inversely associated with cognitive outcomes and brain volume loss at 12 months postinjury. We propose a longitudinal study with 100 adults who sustained a single msTBI and 30 controls with non-TBI orthopedic trauma in the first week after the initial injury. We will follow them at 3 months, 6 months, and 12 months after injury. The primary outcome will be the NIH Toolbox Cognitive battery fluid composite score supplemented with sensitive episodic memory and processing speed measures at 12 months postinjury. To address the overarching goal, we aim to 1) determine the association of cerebrovascular dysfunction during the acute stage of msTBI (<1-week postinjury) with cognitive outcome at 1 year. CA will be quantified by dynamic changes in arterial blood pressure and cerebral blood flow velocity or brain tissue oxygenation. Brain perfusion will be determined by the sum of cerebral blood flow measured from the bilateral internal carotid artery and vertebral artery. 2) To determine the temporal association between the recovery of cerebrovascular function and cognitive outcomes after TBI. CA and brain perfusion will be measured at 3, 6 and 12 months postinjury. 3) To determine the temporal associations of acute cerebrovascular dysfunction and its recovery with the imaging biomarkers of neurodegeneration after TBI over time. Multimodal MRI studies will be performed at 3 months and 12 months postinjury. The findings from this study will improve our understanding of cerebrovascular contributions to cognitive outcome and neurodegeneration after TBI. The knowledge obtained will provide critical data to inform the development of strategies based on vascular mechanisms to improve cognition and slow neurodegeneration after TBI.

项目总结 创伤性脑损伤是成人致残的主要原因，而脑损伤幸存者的生活质量是 高度依赖认知康复的充分性。脑外伤也是阿尔茨海默病(AD)的危险因素 和AD相关痴呆(ADRD)。越来越多的证据表明，脑血管功能障碍发生在 颅脑损伤和AD/ADRD都可能是这两种疾病之间的交叉链接。2019年亚洲复兴开发银行峰会呼吁 进一步研究了解血管对进行性认知障碍/痴呆症的影响 并开发非侵入性诊断方法5，9.存在以下重要知识空白： 1)颅脑损伤后早期脑血管功能障碍对短期和长期认知结果有何影响 在考虑了年龄、性别和既往健康状况后？2)时间关系是什么？ 颅脑损伤后脑血管功能恢复及认知结局？3)两者之间有没有关系？ 脑血管功能障碍与脑外伤后神经变性？这项提议的首要目标是 确定急性脑血管功能障碍及其在受伤后一年内的恢复情况 与中到重度脑外伤(MsTBI)后12个月的认知结果和神经退行性变有关。 我们的中心假设是通过动态脑自动调节(CA)来测量脑血管功能 急性期的脑血流灌注和第一年的恢复呈负相关 损伤后12个月的认知结果和脑体积损失。我们建议对100人进行一项纵向研究 成年患者和30名对照组在术后第一周遭受单一msTBI和30名非TBI骨科创伤的对照。 最初的伤势。我们将在受伤后3个月、6个月和12个月进行随访。主要结果将是 是NIH工具箱认知电池液综合评分，补充了敏感的情景记忆和 在损伤后12个月测量加工速度。为了解决总体目标，我们的目标是1)确定 重型颅脑损伤急性期脑血管功能障碍与伤后1周的关系 1岁时的认知结果。CA将通过动脉血压和脑组织的动态变化来量化 血流速度或脑组织氧合。脑血流灌注量将由脑血总量决定。 从双侧颈内动脉和椎动脉测量的血流。2)确定时态 颅脑损伤后脑血管功能恢复与认知结局的关系CA与脑 分别于伤后3、6、12个月测量血流灌注。3)确定以下各项的时间关联 神经退行性变的影像生物标志物与急性脑血管功能障碍的恢复 随着时间的推移，TBI。在损伤后3个月和12个月进行多模式MRI检查。调查结果 这项研究将提高我们对脑血管对认知结果的贡献的理解 脑外伤后神经退行性变。所获得的知识将提供关键数据，为制定 基于血管机制的策略，以改善认知和减缓脑外伤后的神经变性。