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; 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，阿尔茨海默氏病（AD），共享重叠 病理生理学。血管合并症和脑动脉疾病极大地有助于冒险 中风和广告；更重要的是，AD经常与脑血管疾病共存。应用程序 现在，超急性中风的MRI提供了一个前所未有且独特的机会来研究急性 缺血性中风（AIS）影响已经诊断为AD的患者的ADRD的进展。我们 提案对50例轻度AD/MCI患者的前瞻性观察研究，他们出现在紧急情况下 纪念赫尔曼医院的部门在符号发作24小时内，拥有AIS。这些患者会 在急诊室进行超急性的多模式MRI，然后随后24-48小时 通过连续认知，生物标志物和成像评估长达1年。作为特定目标1的一部分，我们将 测量AI对轻度ADRD患者临床疾病进展率的影响。我们将 创建精心匹配的对照患者的同类阶段AD，但没有中风。 安慰剂组最近的随机临床试验测试AD的新疗法，以确定AIS如何 在认知测试中加速疾病进展。在特定目标2中，我们将衡量AIS对 通过测量区域的各种成像标记，轻度ADRD患者的神经退行性率 和总脑大量分析以及定量MRI的选择性白质管的变性。 子HOC分析将重点关注梗塞生长和超急性中风的灌注变化的影响 随后的灰质变性和选定的白质区。对于比较分析，我们将 创建一个来自阿尔茨海默氏病神经影像学（ADNI）数据集的匹配的队列对照组。 在AIM 3中，我们将测量AIS和轻度AD/MCI患者的神经变性生物标志物：等离子体β- 淀粉样蛋白比（42:40），Total Tau和P-Tau18，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个广告 中风后，患者的疾病进展和神经退行性的轨迹将更加加速。 结果对于随后的研究至关重要，以鉴定预测疾病进展的生物标志物 这些患者。