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

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).

项目概要 因呼吸衰竭或休克被紧急送往重症监护室 (ICU) 的患者中，50% 至 70% 出现谵妄（迄今为止在所有医疗保健环境中最高）。这种谵妄的持续时间独立 每年预测更早的死亡、更长的住院时间和更高的医疗费用。 ICU 患者出现谵妄 已被证明是长期认知能力发展的最强的潜在可改变风险因素 损害，类似于中度至重度阿尔茨海默病和相关痴呆症（ADRD）。 因此，使用呼吸机或休克的内科和外科 ICU 患者是研究该疾病的主要人群。 谵妄与痴呆之间的关系。我们的 NIA 资助、NEJM 发表、PAR-18-029 引用了 BRAIN- ICU-1研究【揭示ICU神经心理功能障碍的危险因素和发生率 幸存者，第一项研究]表明，三分之一的 ICU 幸存者（没有先前存在的痴呆症）出现了 1 年时出现新的认知障碍或 ADRD。一些 BRAIN-ICU-1 患者对 BRAIN-ICU-1 具有认知弹性 ADRD，但其他人则出现了持续性或进行性痴呆样疾病。我们渴望发展 针对这种与 ICU 相关的痴呆症的干预措施，但在不了解更多关于这种形式的脑损伤的情况下，我们 非常有限。现在，我们的试点神经影像 (MRI) 数据显示，急性 ICU 谵妄与 全脑、额叶、海马体萎缩，但这个问题需要深入研究。 我们知道异常的脑蛋白（淀粉样蛋白、tau 蛋白）与阿尔茨海默病有关，但是，我们几乎知道 没有任何关于蛋白质病理学或这种 ICU 相关痴呆症的其他原因的信息。了解原因至关重要 重症监护病房的幸存者正在失去工作，以及作为家庭家长的领导权。这 BRAIN-ICU-2 研究【揭示神经心理功能障碍的危险因素和发生率 ICU 幸存者中的（痴呆），第二项研究]是对 PAR-18-029 的直接回应，并将确定 ICU 患者的 大脑功能衰退、维持或恢复的主要途径。我们将回答有关知识的空白 通过跟踪原始 ICU 幸存者，了解 ICU 后脑部疾病的长期结果 14 年来首次进行完整认知测试的 BRAIN-ICU-1 研究 (AIM 1)。我们会同意 并在范德比尔特大学和拉什大学招募 567 名新的 ICU 患者（即新的 ICU 队列），并确定如何 详细的神经影像和脑脊液样本有助于揭示损伤的位置和机制 超出了我们从原始研究 (AIM 2) 中收集的临床信息中了解到的信息。重要的是，我们 正在与世界著名的拉什阿尔茨海默病研究中心脑库项目合作，以便 所有参与目标 1 和 2 的患者都将能够将他们的大脑捐献给科学，这是有史以来第一次深入的研究 对那些在 ICU 后患上和未患上痴呆症的人进行病理研究，以正式定义这种疾病 (AIM 3)。