Determinants of Alzheimer's Disease in Atrial Fibrillation apart from Stroke: The NOMINATE Study

除中风之外的房颤中阿尔茨海默病的决定因素：提名研究

• 批准号: 10433238
• 负责人: Michelle C. Johansen
• 金额: $ 26.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10433238
• 关键词: Accounting; Alleles; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer’s disease biomarker; American; Amyloid; Amyloid Proteins; Amyloid beta-42; Amyloid beta-Protein; Anticoagulation; Area; Atrial Fibrillation; Biological Markers; Blood; Blood Vessels; Brain; Cerebral Infarction; Cerebrovascular Disorders; Cerebrum; Characteristics; Clinical; Cognition; Cognitive; Consent; Control Groups; Data; Dementia; Development; Disease; Future; Goals; Grant; Hippocampus (Brain); Image; Impaired cognition; Infarction; Ischemic Stroke; Lead; Lesion; Life; Light; Link; Magnetic Resonance Imaging; Mediating; Memory; Myocardial dysfunction; Nerve Degeneration; Neuronal Injury; Outcome; Outpatients; Participant; Pathologic; Pathology; Pathway interactions; Patient risk; Patients; Plasma; Population; Public Health; Recording of previous events; Research; Risk; Risk Factors; Spinal Puncture; Stroke; Symptoms; Techniques; Testing; Time; Vascular Diseases; White Matter Disease; abeta deposition; apolipoprotein E-4; base; brain volume; cardiovascular risk factor; cerebral atrophy; cerebral hypoperfusion; cerebrovascular; clinical development; cohort; comorbidity; cost; dementia risk; demographics; disorder risk; high reward; high risk; high risk population; innovation; insight; interest; neurofilament; neuroinflammation; non-demented; prevent; recruit; screening; secondary analysis; specific biomarkers; stroke patient; stroke risk; stroke survivor; tau Proteins; treatment effect; vascular cognitive impairment and dementia; vascular contributions; vascular injury; vascular risk factor

PROJECT SUMMARY Dementia poses a significant public health problem, and over 2 million American stroke survivors suffer from dementia. Atrial fibrillation (AF), which is a particular type of irregular heartbeat, is the most common cause of cardioembolic stroke, and studies have demonstrated that, among stroke patients, cardioembolic stroke patients are at the greatest risk for cognitive decline. However, AF, even independent of clinical stroke, has been associated with cognitive decline and dementia. The mechanisms linking AF and cognitive impairment are likely multifactorial, but the cerebral pathology that underlies this independent pathway between AF and dementia, apart from clinical stroke, is poorly understood. It is known that the cerebral pathology that leads to dementia precedes the development of clinical symptoms, suggesting that such pathology may already be present in patients with AF, but without prevalent dementia. Rapid developments in the dementia field have led to the ability to use blood-based (plasma) biomarkers, rather than the previous, more invasive, techniques, such as a lumbar puncture, to determine the presence of disease-causing pathology that contribute to the development of clinical Alzheimer’s disease (AD). Such plasma biomarkers of AD pathology include phosphorylated-tau181 (pTau181), plasma beta Amyloid (Aβ42/Aβ40) and neurofilament light (NFL), which has been suggested as the three primary pathologic components (A/T/N; Amyloid/Tau/Neurodegeneration) by which to guide AD-specific research. In this proposal, we aim to (Aim 1) compare the mean level of AD- associated plasma biomarkers (p-tau181, Aβ42/Aβ40, NFL) in a cohort of stroke-free, non-demented, high-risk cardiovascular (CVD) outpatients with AF to those in a control group of high-risk CVD patients without AF. We also will determine the potential for differences in the levels of these biomarkers based on characteristics of the AF patient, such as the type of AF a patient has or the possibility of an anticoagulation (AC) associated treatment effect. Finally, (Aim 2) we will determine in a sub-set of those patients if AD associated brain atrophy is present in CVD patients with AF versus in control patients without AF, accounting for silent cerebrovascular disease. This proposal embodies the goals of the R21 high-risk, high-reward grant mechanism by representing an innovative project that will begin to establish an understanding of the cerebral pathology in AF patients underlying the associated risk for cognitive decline, distinct from prevalent clinical stroke. It also has the potential for great public health impact by facilitating future research on potential targets to prevent, postpone or treat AF-related dementia.

项目摘要 痴呆症具有重大的公共卫生问题，超过200万美国中风生存遭受 失智。心房颤动（AF）是一种特殊类型的不规则心跳，是最常见的原因 心脏符号中风和研究表明，在中风患者中，心脏骨骼中风 患者的认知能力下降风险最大。但是，AF，甚至与临床中风无关 我们与认知能力下降和痴呆有关。连接AF和认知障碍的机制 可能是多因素的，但是是AF和AF之间这种独立途径的基础的脑病理学 痴呆症除了临床中风外，人们对痴呆症的了解很少。众所周知，导致的大脑病理 痴呆症先于临床症状的发展，这表明这种病理可能已经是 存在于AF患者中，但没有普遍的痴呆。痴呆症领域的快速发展已导致 具有使用基于血液（等离子体）生物标志物的能力，而不是以前的，更具侵入性的技术 例如腰椎穿刺，以确定导致疾病的病理的存在 临床阿尔茨海默氏病（AD）的发展。这种AD病理学的等离子体生物标志物包括 磷酸化-TAU181（PTAU181），血浆β淀粉样蛋白（Aβ42/Aβ40）和神经丝（NFL）（NFL） 已被认为是三种主要的病理成分（A/T/N;淀粉样蛋白/TAU/神经变性） 这是为了指导广告特定的研究。在此提案中，我们的目标是（目标1）比较AD的平均水平 相关的血浆生物标志物（P-TAU181，Aβ42/Aβ40，NFL）在一系列无冲程，不痴呆的高风险的队列中 具有AF的心血管（CVD）门诊患者对对照组的高风险CVD患者的患者没有AF。我们 还将根据特征来确定这些生物标志物水平差异的潜力 AF患者，例如患者具有的AF类型或相关的抗凝（AC）的可能性（AC） 治疗效果。最后，（AIM 2）如果AD相关的脑萎缩，我们将在这些患者的子集中确定 存在于具有AF的CVD患者与没有AF的对照患者中 疾病。该建议通过代表R21高风险，高回报机制的目标来体现 一个创新的项目，该项目将开始对AF患者的脑病理有所了解 与普遍的临床中风不同的认知下降风险的基础。它也有 通过促进对预防潜在目标的未来研究，推迟对潜在目标的未来研究，从而产生巨大的公共卫生影响 或治疗与AF相关的痴呆症。