White matter and small vessel disease in older adults

老年人的白质和小血管疾病

基本信息

批准号：
9565479
负责人：
ANGELA L. JEFFERSON
金额：
$ 63.27万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9565479
关键词：
Academic Medical Centers Accounting Age Aging Alzheimer&apos s Disease Amyloid deposition Anisotropy Attention Biochemistry Biological Assay Biological Markers Biometry Biophysics Blood Brain Cerebrospinal Fluid Cerebrovascular Circulation Cerebrovascular Disorders Clinical Clinical Research Cognition Cognitive Collaborations Core-Binding Factor Data Dementia Detection Diffuse Disease Management Elderly Engineering Enrollment Fasting Foundations Functional disorder Future Health Impaired cognition Incidence Individual Investigation Lacunar Infarctions Light Link Magnetic Resonance Imaging Maintenance Memory Microcirculation Microvascular Dysfunction Natural History Nerve Degeneration Neurobehavioral Manifestations Neuropsychology Neurosciences Outcome Participant Pathologic Pathology Population Positioning Attribute Prevalence Prevention Prevention strategy Process Proteomics Public Health Radial Research Serum Source Specificity Stroke Testing Time Visit White Matter Hyperintensity Work age related analytic epidemiology axon injury cerebrovascular cerebrovascular pathology clinical Diagnosis cognitive function cohort follow-up in vivo multimodality neurofilament neuroimaging neuroimaging marker outcome forecast repository tau Proteins tau-1 translational study treatment strategy vascular cognitive impairment and dementia white matter white matter damage white matter injury

项目摘要

As the population continues to age, cognitive decline and dementia are becoming increasingly important public health issues. While Alzheimer's disease is the most common cause of dementia, it is becoming increasingly evident that cerebrovascular mechanisms underlie cognitive impairment with mixed pathology accounting for at least half of all dementia cases. A majority of clinical research linking cerebrovascular mechanisms to cognitive impairment has focused on neuroimaging evidence of small vessel disease, such as white matter hyperintensities (WMHs) and silent lacunar infarcts. Less attention has been given to serum or cerebrospinal fluid (CSF) biomarkers that may be precursors to overt cerebrovascular disease evidence on neuroimaging. We propose to leverage an existing local cohort, the Vanderbilt Memory & Aging Project, to examine noninvasive serum and CSF biomarkers in relation to cognitive functioning and neuroimaging markers of small vessel disease, white matter integrity, and microcirculation in older adults. Since the Vanderbilt Memory & Aging Project cohort's inception in 2012, we have completed serial visits (baseline, 18-months, 36-months) with key covariate ascertainment, neuropsychological assessment, multimodal 3T brain MRI, and fasting blood and CSF acquisition, including maintaining a biosample repository on older adults free of clinical stroke and dementia at enrollment. Thus, we are very well positioned to examine proteomic serum and CSF biomarkers in relation to cross-sectional and longitudinal neuroimaging and cognitive outcomes. Results from this collaborative effort will provide a dynamic understanding of axonal injury, amyloid deposition, tau aggregation, and neurodegeneration associations with small vessel disease, white matter integrity, and microcirculatory health. Results will yield important applications for investigations examining the natural history, analytic epidemiology, prevention, clinical diagnosis, prognosis, and disease management of age-related and pathological changes in small vessel, white matter, and microcirculatory health.

随着人口的持续年龄，认知能力下降和痴呆症变得越来越重要健康问题。尽管阿尔茨海默氏病是痴呆症的最常见原因，但它变得越来越多显然，脑血管机制是认知障碍及其混合病理学的基础所有痴呆症病例的至少一半。大多数将脑血管机制与认知联系起来的临床研究障碍的重点是神经影像学的小血管疾病的证据，例如白质超强度（WMHS）和无声lacunar梗塞。对血清或脑脊液的关注较少流体（CSF）生物标志物可能是明显的脑血管疾病证据的神经影像学证据。我们建议利用现有的当地队列，即范德比尔特的记忆和老化项目与小的认知功能和神经成像标记有关的无创血清和CSF生物标志物老年人的血管疾病，白质完整性和微循环。由于范德比尔特的记忆＆衰老项目队列的成立于2012年，我们已经完成了连续访问（基线，18个月，36个月）通过关键协变量确定，神经心理学评估，多模式3T脑MRI和空腹血液和CSF获取，包括维持没有临床中风和的老年人的生物样品存储库入学时痴呆症。因此，我们在检查蛋白质组学血清和CSF生物标志物的位置非常好与横断面和纵向神经影像和认知结果有关。结果协作努力将对轴突损伤，淀粉样蛋白沉积，tau聚集，有动态理解，和神经变性与小血管疾病，白质完整性和微循环的关联健康。结果将为研究自然历史，分析的研究产生重要的应用与年龄有关的流行病学，预防，临床诊断，预后和疾病管理小血管，白质和微循环健康的病理变化。