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.

项目总结