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）有重叠之处 病理生理学。血管合并症和脑动脉疾病在很大程度上增加了风险。 中风和AD；更重要的是，AD经常与脑血管疾病并存。 超急性中风的 MRI 技术现在提供了前所未有的独特机会来研究急性中风的急性程度 缺血性中风 (AIS) 会影响已诊断为 AD 的患者的 ADRD 进展。 提议对 50 名就诊的轻度 AD/MCI 患者进行一项前瞻性观察研究 患有 AIS 的患者将在症状出现后 24 小时内前往纪念赫尔曼医院的科室就诊。 在急诊科接受超急性多模式 MRI，然后 24-48 小时后进行随访 作为具体目标 1 的一部分，我们将进行长达 1 年的连续认知、生物标志物和影像评估。 我们将测量 AIS 对轻度 ADRD 患者临床疾病进展率的影响。 创建一个仔细匹配的对照组患者队列，该患者患有早期 AD，但没有因 AD 引起的中风 最近随机临床试验的安慰剂组测试 AD 新疗法以确定 AIS 加速认知测试中的疾病进展 在具体目标 2 中，我们将测量 AIS 对认知测试的影响。 通过测量区域的各种影像学标志物来评估轻度 ADRD 患者的神经退行性变率 和全脑体积分析以及定量 MRI 上选择性白质束的变性。 亚组分析将重点关注梗塞生长和灌注变化对超急性卒中的影响 随后的灰质和选定的白质束的退化，为了进行比较分析，我们将进行比较。 创建源自阿尔茨海默病神经影像 (ADNI) 数据集的匹配队列对照组。 在目标 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：血浆 β- 我们将评估淀粉样蛋白比率 (42:40)、总 tau 和 P-tau18、神经丝轻链和 GFAP。 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。 中风后，患者的疾病进展和神经退行性疾病将加速。 该结果对于后续研究确定预测疾病进展的生物标志物至关重要 这些病人。