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.

随着人口持续老龄化，认知能力下降和痴呆症对公众变得越来越重要健康问题。虽然阿尔茨海默氏病是痴呆症最常见的原因，但它的发病率正变得越来越高显然，脑血管机制是认知障碍的基础，其混合病理学解释至少有一半的痴呆症病例。大多数临床研究将脑血管机制与认知联系起来损伤主要集中在小血管疾病的神经影像学证据上，例如白质高信号（WMH）和无症状腔隙性梗塞。对血清或脑脊液的关注较少脑脊液（CSF）生物标志物可能是神经影像学上明显脑血管疾病证据的先兆。我们建议利用现有的本地队列，即范德比尔特记忆与衰老项目，来检查与认知功能和神经影像标记相关的无创血清和脑脊液生物标记物老年人的血管疾病、白质完整性和微循环。自范德比尔特记忆与老龄化项目队列于2012年启动，我们已完成系列访问（基线、18个月、36个月）包括关键协变量确定、神经心理学评估、多模式 3T 脑部 MRI 和空腹血液脑脊液采集，包括维护没有临床中风的老年人的生物样本库入学时患有痴呆症。因此，我们非常有能力检查蛋白质组血清和脑脊液生物标志物与横断面和纵向神经影像和认知结果的关系。结果由此协作努力将提供对轴突损伤、淀粉样蛋白沉积、tau 聚集、神经退行性变与小血管疾病、白质完整性和微循环的关系健康。结果将为自然历史、分析等研究提供重要的应用。与年龄相关的流行病学、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。