Amyloid PET and blood biomarker supplement to the Delirium Program Project

淀粉样蛋白 PET 和血液生物标志物对谵妄计划项目的补充

• 批准号: 10430721
• 负责人: SHARON K. INOUYE
• 金额: $ 22.73万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10430721
• 关键词: Achievement; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Biological Assay; Biological Markers; Blood; Brain; Cells; Cerebrospinal Fluid; Cerebrum; Cessation of life; Classification; Clinical; Clinical Trials; Cognitive; Cognitive aging; Cytometry; Data; Delirium; Dementia; Development; Doctor of Medicine; Doctor of Philosophy; Early identification; Elderly; Electroencephalography; Electrophysiology (science); Enrollment; Ensure; Functional disorder; Future; Glial Fibrillary Acidic Protein; Goals; Grant; Health Care Costs; Hospitalization; Immune; Impaired cognition; Impairment; Incidence; Individual; Inflammation; Inflammatory; Knowledge; Life; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Modeling; Modification; Monitor; Nerve Degeneration; Nursing Homes; Operative Surgical Procedures; Outcome; Parents; Participant; Pathway interactions; Patients; Pattern; Phenotype; Physiology; Plasma; Positron-Emission Tomography; Postoperative Period; Prevention strategy; Probability; Probability Samples; Proteins; Proteomics; Recording of previous events; Risk; Risk Marker; Role; Sampling; Scanning; Series; Severities; Spinal Anesthesia; Surgeon; Testing; Text; Validation; amyloid imaging; base; cerebral atrophy; cognitive performance; cohort; cost; crosslink; disability; effective intervention; follow-up; high risk; imaging biomarker; indexing; inflammatory marker; innovation; magnetic resonance imaging biomarker; multimodality; network dysfunction; neuroimaging; neuroimaging marker; neuropathology; neurophysiology; novel; novel marker; postoperative delirium; pre-clinical; predictive modeling; predictive test; preference; preventive intervention; programs; prospective; tau Proteins; tau-1; treatment response

Abstract Delirium is a common, costly, life-threatening, and potentially preventable problem for older persons. The development of delirium is considered to be a marker of brain vulnerability; however, its relationship to dementia and Alzheimer’s disease and related dementias (AD/ADRD) remains unclear. In the parent Program Project renewal grant, we are now conducting a series of 5 interlinked projects applying innovative approaches to deepen our exploration of pathophysiologic pathways potentially contributing to delirium and its associated cognitive decline. We are examining the role of amyloid markers in primary aims of Projects 1, 3, and 5, and in cross-linking aims across all projects. In our original proposal, we proposed using cerebrospinal fluid (CSF) biomarkers to quantify amyloid status in a subsample (n=128) of the SAGES I cohort, and in all of the new SAGES II cohort (n=350-400); however, about 25-30% of the participants are either medically ineligible or will not receive CSF sampling (due to their own or their surgeon’s preference). We will be completing SAGES II cohort enrollment in the next year, and anticipate about 80-90 participants where CSF amyloid status will not have been determined. In this supplement, we request support for 2 Sub-Projects: (1) addition of 30 [F18] Florbetapir (“Amyloid”) Positron Emission Tomography (PET) scans to measure amyloid status in SAGES II participants who did not receive CSF sampling; (2) measurement of novel biomarkers for neurodegeneration (p-tau 181 and GFAP) in stored plasma from the entire SAGES I cohort (n=560). This supplement will enhance the impact of the Program Project in several ways. First, amyloid-PET will allow us to assure we can assess amyloid status for most high-risk participants who do not receive CSF sampling, and to achieve the original aims. Second, PET imaging allows abnormally elevated cerebral amyloid to be localized, which will offer opportunities to relate amyloid imaging measures to the variety of MRI and electrophysiological measures we are obtaining. Third, the biomarker assays would allow us to validate additional potential blood-based predictors of delirium, delirium severity, and post-operative cognitive decline (aligned with our original aims), which would provide risk markers to stratify future patients for clinical trials and to monitor response to treatment. Thus, obtaining the additional scans and assays will ensure the achievement of our original aims and will also magnify the overall impact of the Program Project, through modifications that are well-aligned with the original aims. This supplement will truly bolster the Program Project, and allow it to achieve its goals of advancing our understanding of delirium and its relationship to AD/ADRD, and ultimately, to develop more effective strategies for prevention and treatment.

抽象的 对于老年人来说，del妄是一个常见，昂贵的，威胁生命的和可能可预防的问题。 ir妄的发展被认为是大脑脆弱性的标志。但是，它与 痴呆症和阿尔茨海默氏病和相关痴呆症（AD/ADRD）尚不清楚。在父级程序中 项目更新赠款，我们现在正在进行一系列5个相互联系的项目，采用创新方法 为了加深我们对病理生理途径的探索，可能导致del妄及其相关的探索 认知能力下降。我们正在研究淀粉样蛋白标记在项目1、3和5的主要目标中的作用，以及 在所有项目中的交联。在我们的原始建议中，我们提出了使用脑脊液（CSF）的建议 生物标志物量化鼠尾草的子样本中的淀粉样蛋白状态（n = 128），以及在所有新的 SAGES II队列（n = 350-400）;但是，大约25-30％的参与者在医学上没有资格或将 没有收到CSF抽样（由于他们自己或外科医生的偏好）。我们将完成圣人II 明年的队列入学人数，预计大约有80-90名参与者CSF淀粉样蛋白会不会 已经确定。 在此补充中，我们要求对2个子项目的支持：（1）添加30 [F18] Florbetapir（“淀粉样蛋白”） 正电子发射断层扫描（PET）扫描以测量未经 接受CSF抽样； （2）在神经退行性的新生物标志物（p-tau 181和GFAP）中的测量 从整个鼠尾草I队列中存储了血浆（n = 560）。这种补充将增强 程序项目以几种方式。首先，淀粉样蛋白宠物将使我们能够确保我们可以评估淀粉样蛋白状态 大多数没有接受CSF抽样并实现最初目标的高风险参与者。第二，宠物 成像使绝对升高的大脑淀粉样蛋白可以定位，这将提供与之相关的机会 淀粉样蛋白成像测量我们正在获得的多种MRI和电生理测量。第三， 生物标志物的阿萨斯将使我们能够验证del妄的其他潜在基于血液的预测因子， ir妄的严重程度和术后认知下降（与我们的最初目标保持一致），这将提供风险 标记以分层未来的患者进行临床试验并监测对治疗的反应。 那，获得其他扫描和测定将确保我们原始目标的实现，并将 还通过与该计划的整体影响，通过与该计划的整体影响 原始目标。这种补充剂将真正加强计划项目，并允许其实现其目标 促进我们对del妄及其与AD/ADRD的关系的理解，并最终发展更多 预防和治疗的有效策略。