BRAIN-ICU-2 Study: Bringing to Light the Risk Factors And Incidence of Neuropsychological Dysfunction (Dementia) in ICU Survivors, 2nd Study

BRAIN-ICU-2 研究：揭示 ICU 幸存者神经心理功能障碍（痴呆）的危险因素和发生率，第二项研究

• 批准号: 10356009
• 负责人: E Wesley ELY
• 金额: $ 353.25万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356009
• 关键词: Acute; Address; Admission activity; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Apolipoprotein E; Atrophic; Autopsy; Axon; Biological Markers; Brain; Brain Diseases; Brain Injuries; Caring; Cerebrospinal Fluid; Cerebrovascular Disorders; Cessation of life; Climacteric; Clinical; Cognitive; Confusion; Consensus; Consent; Data; Delirium; Dementia; Development; Diagnosis; Diagnostic; Disease; Drug Exposure; Education; Endothelium; Enrollment; Family; Functional disorder; Funding; Future; HMGB1 gene; Healthcare; Hippocampus; Histopathology; Hospitals; Immobilization; Impaired cognition; Incidence; Infarction; Inflammation; Injury; Intensive Care Units; Intervention; Investigation; Knowledge; Leadership; Learning; Length of Stay; Life; Link; Location; Magnetic Resonance Imaging; Maintenance; Measures; Mediating; Medical; Memory; Nerve Degeneration; Neurofibrillary Tangles; Neuropsychology; Occupations; Outcome; Pathologic; Pathology; Pathway interactions; Patients; Perfusion; Persons; Phenotype; Plasma; Plasminogen Activator Inhibitor 1; Population; Preventive; Proteins; Publishing; Quality of life; Recovery; Rehabilitation therapy; Research; Respiratory Failure; Risk; Risk Factors; Sampling; Science; Sepsis; Shock; Structure; Surgical Intensive Care; Survivors; Synapses; Testing; Time; Universities; Ventilator; White Matter Disease; Work; brain abnormalities; cerebral atrophy; clinical risk; cognitive recovery; cognitive rehabilitation; cognitive reserve; cognitive testing; cohort; comorbidity; confusion assessment method; cost; diagnostic tool; executive function; follow-up; frailty; frontal lobe; functional outcomes; health care settings; imaging biomarker; microvascular pathology; modifiable risk; mortality; neuroimaging; neuroinflammation; neuropathology; participant enrollment; programs; protein TDP-43; public health relevance; repository; resilience; response; secondary analysis; survivorship; tau Proteins; vascular injury; white matter; Acute; Address; Admission activity; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Apolipoprotein E; Atrophic; Autopsy; Axon; Biological Markers; Brain; Brain Diseases; Brain Injuries; Caring; Cerebrospinal Fluid; Cerebrovascular Disorders; Cessation of life; Climacteric; Clinical; Cognitive; Confusion; Consensus; Consent; Data; Delirium; Dementia; Development; Diagnosis; Diagnostic; Disease; Drug Exposure; Education; Endothelium; Enrollment; Family; Functional disorder; Funding; Future; HMGB1 gene; Healthcare; Hippocampus; Histopathology; Hospitals; Immobilization; Impaired cognition; Incidence; Infarction; Inflammation; Injury; Intensive Care Units; Intervention; Investigation; Knowledge; Leadership; Learning; Length of Stay; Life; Link; Location; Magnetic Resonance Imaging; Maintenance; Measures; Mediating; Medical; Memory; Nerve Degeneration; Neurofibrillary Tangles; Neuropsychology; Occupations; Outcome; Pathologic; Pathology; Pathway interactions; Patients; Perfusion; Persons; Phenotype; Plasma; Plasminogen Activator Inhibitor 1; Population; Preventive; Proteins; Publishing; Quality of life; Recovery; Rehabilitation therapy; Research; Respiratory Failure; Risk; Risk Factors; Sampling; Science; Sepsis; Shock; Structure; Surgical Intensive Care; Survivors; Synapses; Testing; Time; Universities; Ventilator; White Matter Disease; Work; brain abnormalities; cerebral atrophy; clinical risk; cognitive recovery; cognitive rehabilitation; cognitive reserve; cognitive testing; cohort; comorbidity; confusion assessment method; cost; diagnostic tool; executive function; follow-up; frailty; frontal lobe; functional outcomes; health care settings; imaging biomarker; microvascular pathology; modifiable risk; mortality; neuroimaging; neuroinflammation; neuropathology; participant enrollment; programs; protein TDP-43; public health relevance; repository; resilience; response; secondary analysis; survivorship; tau Proteins; vascular injury; white matter

Project Summary Of people admitted emergently to the Intensive Care Unit (ICU) in respiratory failure or shock, 50% to 70% develop delirium (by far the highest in any healthcare setting). The duration of this delirium independently predicts earlier death, longer hospital stay, and higher healthcare expenses annually. Delirium in ICU patients has been shown to be the strongest potentially modifiable risk factor for development of a long-term cognitive impairment, which resembles moderate to severe Alzheimer’s Disease and Related Dementias (ADRDs). Thus, medical and surgical ICU patients on ventilators or in shock are a prime population in whom to study the relationship between delirium and dementia. Our NIA-funded, NEJM published, and PAR-18-029 cited BRAIN- ICU-1 study [Bringing to light the Risk factors And Incidence of Neuropsychological dysfunction in ICU Survivors, 1st Study] showed over that one-third of ICU survivors (without preexisting dementia) emerged with new cognitive impairments or ADRD at 1 year. Some BRAIN-ICU-1 patients had cognitive resilience against ADRD, but others developed a persistent or progressive dementia-like illness. We are eager to develop interventions against this ICU-related dementia, but without knowing more about this form of brain injury, we are very limited. Now, we have pilot neuroimaging (MRI) data show that acute ICU delirium is associated with atrophy of the whole brain, frontal lobe, and hippocampus, but this problem requires an in-depth investigation. We know abnormal brain proteins (amyloid, tau) relate to Alzheimer’s disease, however, we know nearly nothing about protein pathology or other causes of this ICU-related dementia. It is critical to understand why ICU survivors are losing their jobs, and the leadership as matriarchs and patriarchs of their families. This BRAIN-ICU-2 study [Bringing to light the Risk factors And Incidence of Neuropsychological dysfunction (dementia) in ICU Survivors, 2nd Study] is in direct response to PAR-18-029 and will determine ICU patients’ main paths to decline, maintenance, or recovery of brain function. We will answer gaps in knowledge about long-term outcome of post-ICU brain disease by following the remaining ICU survivors from the original BRAIN-ICU-1 study with complete cognitive testing for the first time ever to 14 years (AIM 1). We will consent and enroll 567 new ICU patients at Vanderbilt and Rush Universities (i.e., new ICU cohort) and determine how detailed neuroimaging and cerebrospinal fluid samples can help reveal locations and mechanisms of injury beyond what we learned from the clinical information collected in our original study (AIM 2). Importantly, we are partnering with the world-renowned Rush Alzheimer's Disease Research Center brain bank program so that all patients enrolled in Aims 1 and 2 will able to donate their brains to science for the first-ever in-depth pathological study of those who do and do not get post-ICU dementia to define this disease formally (AIM 3).

项目摘要 在呼吸衰竭或冲击的重症监护室（ICU）紧急接纳的人中，有50％至70％ 发展ir妄（到目前为止，在任何医疗保健环境中最高）。独立的del妄的持续时间 预测较早的死亡，更长的住院时间和每年更高的医疗费用。 ICU患者的ir妄 已被证明是长期认知发展的强大潜在可修改风险因素 损害，类似于中度至重度阿尔茨海默氏病和相关痴呆症（ADRDS）。 那是呼吸机或令人震惊的医疗和外科ICU患者是主要人群 del妄与痴呆症之间的关系。我们的NIA资助的NEJM出版了，Par-18-029引用了大脑 ICU-1研究[揭示ICU中神经心理功能障碍的危险因素和事件 幸存者，第一项研究]表明，三分之一的ICU幸存者（不存在痴呆症）出现了 1年的新认知障碍或ADRD。一些Brain-ICU-1患者对 ADRD，但其他人患有持久或渐进的痴呆症样疾病。我们渴望发展 针对这种与ICU相关痴呆的干预措施，但在没有更多关于这种形式的脑损伤的情况下，我们 非常有限。现在，我们有飞行员神经影像学（MRI）数据表明，急性ICU deli妄与 整个大脑，额叶和海马的萎缩，但是这个问题需要深入研究。 我们知道脑蛋白异常（淀粉样蛋白，tau）与阿尔茨海默氏病有关，但是，我们几乎知道 与这种与ICU相关的痴呆症的蛋白质病理或其他原因无关。了解为什么 ICU奔波者正在失去工作，领导层是其家庭的族长和族长。这 Brain-ICU-2研究[揭示神经心理功能障碍的危险因素和事件 （痴呆症）在ICU幸存者中，第二项研究是直接回应PAR-18-029的，将确定ICU患者的患者。 衰落，维护或恢复大脑功能的主要途径。我们将回答有关知识的差距 遵循原始的剩余的ICU冲浪者，后ICU大脑疾病的长期结局 Brain-ICU-1研究首次进行完全认知测试至14年（AIM 1）。我们将同意 并在Vanderbilt和Rush大学（即新ICU队列）招募567名新的ICU患者，并确定如何 详细的神经影像学和脑脊液样品可以帮助揭示损伤的位置和机制 除了我们从原始研究中收集的临床信息中学到的知识（AIM 2）。重要的是，我们 正在与世界知名的阿尔茨海默氏病研究中心脑库计划合作，所以 所有参加AIMS 1和2的患者都将能够将其大脑捐赠给科学，以深入了解 对那些做和没有得到ICU后痴呆症的人的病理研究（AIM 3）。