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.

项目摘要 创伤性脑损伤（TBI）是成年人残疾的主要原因，并且TBI幸存者的生活质量是 高度依赖于认知恢复的充分性。TBI也是阿尔茨海默病（AD）的危险因素 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 TBI和AD/ADRD两者，并且可以是两种疾病之间的交叉联系。2019年ADRD峰会呼吁 进一步研究，以了解血管对进行性认知障碍/痴呆相关的影响 与TBI和开发非侵入性诊断方法5，9.存在以下重要的知识差距： 1)TBI后早期脑血管功能障碍对短期和长期认知结果的影响是什么 在考虑了年龄性别和之前的健康状况之后2)什么是时间关系 脑外伤后脑血管功能恢复及认知功能的转归？（3）是否存在关系 脑血管功能障碍和脑外伤后神经退行性变本提案的总体目标是 确定急性脑血管功能障碍及其在伤后第一年内的恢复是否 与中度至重度TBI（msTBI）后12个月的认知结果和神经退行性变相关。 我们的中心假设是通过动态脑自动调节（CA）测量脑血管功能， 急性期脑灌注及第1年脑灌注恢复与脑缺血程度呈负相关， 损伤后12个月的认知结果和脑容量损失。我们提出了一项纵向研究， 在术后第一周内，接受单次msTBI的成年人和30名非TBI骨科创伤的对照者， 最初的伤害。我们将在受伤后3个月、6个月和12个月对他们进行随访。主要成果将 是补充了敏感情景记忆的NIH认知电池液综合评分， 在伤后12个月测量加工速度。为了实现总体目标，我们的目标是1）确定 msTBI急性期（伤后<1周）脑血管功能障碍与 1年时的认知结果。CA将通过动脉血压和脑动脉压的动态变化来量化。 血流速度或脑组织氧合。脑灌注将通过脑血流量总和确定 从双侧颈内动脉和椎动脉测量的流量。2)为了确定时间 脑血管功能恢复与TBI后认知结果之间的相关性。CA和大脑 将在损伤后3、6和12个月测量灌注。3)要确定的时间关联 急性脑血管功能障碍及其恢复与神经变性的成像生物标志物， 随着时间的推移，将在伤后3个月和12个月进行多模态MRI研究。这些发现 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，为发展 基于血管机制的策略，以改善TBI后的认知和减缓神经退行性变。