Stroke Impact on Progression of Alzheimer's (SIPA)

中风对阿尔茨海默病进展的影响 (SIPA)

• 批准号: 10402113
• 负责人: Sean I Savitz
• 金额: $ 51.43万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402113
• 关键词: Accident and Emergency department; Acute; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Biological Markers; Blood Vessels; Brain; Cerebral Arterial Diseases; Cerebral Ischemia; Cerebral hemisphere; Cerebrovascular Disorders; Clinical; Clinical Trials; Cognitive; Control Groups; Data Set; Dementia; Disease Progression; Enrollment; Evaluation; Failure; Functional disorder; Funding; Glial Fibrillary Acidic Protein; Goals; Growth; Hippocampus (Brain); Hospitals; Image; Immune; Impaired cognition; Infarction; Infrastructure; Intervention Trial; Ischemic Stroke; Light; Location; Magnetic Resonance Imaging; Measures; Medial; Nerve Degeneration; Observational Study; Oxidative Stress; Pathogenesis; Patient-Focused Outcomes; Patients; Perfusion; Plasma; Probability; Randomized Clinical Trials; Reperfusion Therapy; Risk; Serum; Stroke; Students; Symptoms; Temporal Lobe; Testing; Time; cerebral hypoperfusion; cognitive testing; cohort; comorbidity; comparative; gray matter; high risk; imaging biomarker; improved outcome; insight; multimodality; neurofilament; neuroimaging; novel therapeutics; placebo group; predictive marker; prospective; serial imaging; standard of care; stroke therapy; support network; tau Proteins; white matter

Stroke and the most commonly occurring dementia, Alzheimer's disease (AD), share overlapping pathophysiology. Vascular comorbidities and cerebral arterial disease substantially contribute to the risk for both stroke and AD; more importantly, AD frequently co-exists with cerebrovascular disease. The application of MRI for hyperacute stroke now provides an unprecedented and unique opportunity to study how acute ischemic stroke (AIS) impacts the progression of ADRD in patients who already have a diagnosis of AD. We propose a prospective observational study of 50 patients with mild AD/MCI who present to the emergency department at Memorial Hermann hospital with AIS within 24 hrs of symptom onset. These patients will undergo a hyperacute multimodal MRI in the emergency department and then 24-48 hrs afterwards followed by serial cognitive, biomarker, and imaging assessments up to 1 year. As part of specific aim 1, we will measure the effect of AIS on the rate of clinical disease progression in patients with mild ADRD. We will create a carefully matched cohort of control patients with early-stage AD but without stroke derived from the placebo groups of recent randomized clinical trials testing new therapies for AD to determine how AIS accelerates disease progression on cognitive testing. In specific aim 2, we will measure the effect of AIS on the rate of neurodegeneration in patients with mild ADRD by measuring various imaging markers of regional and total brain volumetric analyses as well as degeneration of selective white matter tracts on quantitative MRI. Subhoc analyses will focus on the impact of infarct growth and perfusion changes in hyperacute stroke with subsequent degeneration of grey matter and selected white matter tracts. For comparative analyses, we will create a matched cohort control group derived from the Alzheimer's Disease Neuroimaging (ADNI) dataset. In aim 3, we will measure biomarkers of neurodegeneration in patients with AIS and mild AD/MCI: plasma β- amyloid ratios (42:40), total tau, and P-tau18, neurofilament light chain, and GFAP. We will assess the relationships between serum biomarkers and disease progression. This study will help to identify which AD patients will have a more accelerated trajectory of disease progression and neurodegeneration after a stroke. The results will be critical for subsequent studies to identify biomarkers that predict disease progression in these patients.

中风和最常见的痴呆症，阿尔茨海默病（AD），共享重叠 病理生理学血管合并症和脑动脉疾病显著增加了 中风和AD;更重要的是，AD经常与脑血管疾病共存。应用 MRI用于超急性卒中现在提供了一个前所未有的和独特的机会， 缺血性卒中（AIS）影响已诊断为AD的患者的ADRD进展。我们 提出了一项前瞻性观察性研究，50例轻度AD/MCI患者， 在症状发作的24小时内，在Memorial Hermann医院的AIS科就诊。这些患者将 在急诊室接受超急性多模式MRI，然后在24-48小时后随访 通过长达1年的系列认知、生物标志物和成像评估。作为具体目标1的一部分，我们将 测量AIS对轻度ADRD患者临床疾病进展率的影响。我们将 创建一个精心匹配的对照组，这些对照组患者患有早期AD，但没有中风， 安慰剂组最近随机临床试验测试新的治疗AD，以确定如何AIS 在认知测试中加速疾病进展。在具体目标2中，我们将测量AIS对 轻度ADRD患者神经退行性变的发生率，通过测量区域性神经退行性变的各种影像学标志物， 和全脑体积分析以及定量MRI上选择性白色物质束的变性。 亚组分析的重点是梗死生长和灌注变化对超急性卒中的影响， 随后灰质和选定的白色物质束变性。为了进行比较分析，我们将 从阿尔茨海默病神经成像（ADNI）数据集创建匹配的队列对照组。 在目标3中，我们将测量患有AIS和轻度AD/MCI的患者中神经变性的生物标志物：血浆β- 淀粉样蛋白比率（42：40）、总tau蛋白和P-tau 18、神经丝轻链和GFAP。我们将评估 血清生物标志物与疾病进展之间的关系。这项研究将有助于确定哪些AD 患者在中风后将具有更加速的疾病进展和神经变性的轨迹。 这些结果对于随后的研究至关重要，以确定预测疾病进展的生物标志物。 这些病人。