Stroke Connectome MRI biomarkers for VCID risk assessment

用于 VCID 风险评估的中风连接组 MRI 生物标志物

• 批准号: 10887028
• 负责人: Nagesh Adluru
• 金额: $ 11.51万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10887028
• 关键词: Administrative Supplement; Adult; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Apolipoproteins; Attention; Biological; Biological Assay; Biological Markers; Biology; Blood; Blood Vessels; Brain; Cerebrovascular Disorders; Characteristics; Clinical Data; Clinical Research; Cognition; Cognitive; Complement; Complex; Data; Dementia; Development; Disease; Disease Progression; Economic Burden; Foundations; Funding; Future; Genes; Genetic Markers; Genetic Risk; Goals; Health; Impaired cognition; Ischemic Stroke; Language; Life; Link; Location; Magnetic Resonance Imaging; Measures; Memory; Microvascular Dysfunction; Monitor; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Neuropsychology; Parents; Pathology; Patients; Persons; Plasma; Positron-Emission Tomography; Procedures; Prognosis; Recurrence; Reporting; Research; Research Project Grants; Risk; Risk Assessment; Risk Factors; Severities; Spinal Puncture; Stroke; Survivors; Testing; Time; United States; Vascular Diseases; Visuospatial; Work; accurate diagnosis; blood-based biomarker; brain health; burden of illness; cognitive function; cognitive reserve; connectome; cost; dementia risk; diagnostic tool; digital; disability; early onset; executive function; genetic risk factor; human old age (65+); improved; magnetic resonance imaging biomarker; molecular marker; neighborhood disadvantage; neuroimaging; post stroke; post stroke cognitive impairment; post stroke dementia; prognostic tool; resilience; stroke cognitive outcome; stroke patient; stroke survivor; tau-1; tool; vascular cognitive impairment and dementia; vascular risk factor; β-amyloid burden

PROJECT SUMMARY Vascular Contributions to Cognitive Impairments and Dementia (VCID) is one of the four Alzheimer’s Disease and Related Dementias (ADRDs). VCID research investigates the effects of a range of vascular disease and vascular risk factors on cognition. Every year 610,000 people in the US have first-time strokes and three-quarters of strokes occur in people aged 65 and older. Post-stroke cognitive impairment and dementia is highly prevalent (~30%) and is a major cause of adult disability in the US, with economic burden in the billions. Post-stroke dementia is defined as an immediate and or delayed cognitive decline that begins within 6 months after a stroke. Therefore, post-stroke cognitive impairments and dementia is recognized as a major VCID. However, the underlying disease biology linked to stroke is not fully understood. There is robust evidence that AD pathology often coexists with cerebrovascular disorders such as stroke, with many risk factors being shared, resulting in additive or synergistic effects on cognitive decline. However, there is also a distinction made between ‘early- onset post-stroke dementia’ which depends on the complex interplay between stroke and brain resilience, versus ‘late-onset post-stroke dementia’ which depends on severe small vessel disease, rather than by recurrent stroke or concurrent AD pathology. However no biological biomarkers have yet been reported to reliably differentiate between neurodegenerative and cerebrovascular disease. Understanding the relationships between the two diseases therefore remains a high priority to enable targeting of underlying mechanisms and reducing the overall burden of VCID. The specific goal of this project is to investigate the utility of blood-plasma based phosphorylated-tau (p-tau) and apolipoprotein 𝜖𝜖-4 gene (APOE4) in predicting progression to post-stroke VCID. p-tau represents the extent of amyloid burden in the brain and APOE4 is linked to risk for developing AD. Our central hypothesis is that interactions between amyloid burden, APOE4 genetic risk, and stroke would better explain the underlying pathology of why a subset of stroke patients go on to develop VCID. Specific Aim: Characterize specific relationships between VCID risk factors, cognitive reserve, blood plasma biomarkers (p- tau, APOE4), brain health and cognitive function at 6 and 12-months after stroke. Successful completion of the project will provide currently lacking scientific understanding of the intricate biological relationships among VCID risk factors, blood, and stroke MRI biomarkers, which underlie the biology of cognitive decline after a stroke. Blood-based biomarker testing is more accessible, and less complex compared to PET scan or lumbar puncture for assessing amyloid burden in the brain. Therefore, the proposed project is expected to exert a significant influence on the field of molecular and genetic biomarkers of post stroke VCID. The results will lay a strong foundation for building accurate diagnosis, prognosis, and future clinical studies that can aid in positively altering disease progression and reducing the burden of illness on patients due to post stroke VCID.

项目摘要 对认知障碍和痴呆（VCID）的血管贡献是四个阿尔茨海默氏病之一 和相关痴呆症（ADRDS）。 VCID研究调查了一系列血管疾病和 认知的血管风险因素。每年有610,000人在美国有初次中风和四分之三 中风发生在65岁及以上的人中。中风后认知障碍和痴呆症非常普遍 （〜30％），是美国成人残疾的主要原因，经济焚烧数十亿。冲程后 痴呆被定义为中风后6个月内开始的立即和 /或延迟的认知下降。 因此，中风后认知障碍和痴呆被认为是主要的VCID。但是， 与中风相关的潜在疾病生物学尚不完全了解。有强有力的证据表明AD病理 经常与脑血管疾病（例如中风）共存，并共享许多风险因素，从而导致 对认知下降的添加剂或协同作用。但是，“早期 - 中风后痴呆症取决于中风和大脑弹性之间的复杂相互作用， “中风后痴呆症”依赖于严重的小血管疾病，而不是复发性中风 或并发的AD病理学。但是，尚无据报道的生物学生物标志物可靠地分化 在神经退行性和脑血管疾病之间。了解两者之间的关系 因此，疾病仍然是高度优先事项，以实现潜在机制并减少整体 VCID的负担。该项目的具体目标是调查基于血压的实用性 磷酸化的-TAU（p-TAU）和载脂蛋白𝜖𝜖-4基因（APOE4）在预测势后VCID的发展中。 p-tau代表大脑中淀粉样蛋白伯恩的程度，APOE4与发展AD的风险有关。我们的 中心假设是淀粉样蛋白伯嫩，APOE4遗传风险和中风之间的相互作用会更好 解释为什么中风患者继续发展为VCID的基本病理。具体目的： 表征VCID风险因素，认知储备，血浆生物标志物（P-）之间的特定关系 tau，apoE4），中风后6和12个月时的脑健康和认知功能。成功完成 项目将提供当前缺乏对VCID复杂生物学关系的科学理解 危险因素，血液和中风MRI生物标志物，这是中风后认知能力下降的生物学。 与PET扫描或腰椎相比 用于评估大脑中的淀粉样蛋白。因此，预计拟议的项目将发挥重要作用 对后中风后VCID的分子和遗传生物标志物的影响。结果将使很强 建立准确的诊断，预后和未来临床研究的基础，这些研究可以帮助积极改变 疾病进展并减少由于中风后VCID引起的患者疾病的燃烧。