White matter and small vessel disease in older adults

随着人口的持续老龄化，认知能力下降和痴呆症正变得越来越重要 健康问题。虽然阿尔茨海默氏症是痴呆症最常见的原因，但它正变得越来越多 显然，脑血管机制是认知损害的基础，混合病理可解释AT 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 损害集中在小血管疾病的神经成像证据上，如白质 高信号(WMH)和无症状性腔隙梗死。对血清或脑脊液的关注较少。 脑脊液(CSF)生物标志物，可能是神经影像上显性脑血管疾病证据的先兆。 我们建议利用现有的本地队列，Vanderbilt Memory&Aging Project，来研究 无创性血清和脑脊液生物标志物与小鼠认知功能和神经影像标志物的关系 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& 老龄项目队列自2012年开始以来，我们已经完成了连续访问(基线、18个月、36个月) 关键的协变量确定、神经心理评估、多模式3T脑MRI和空腹血液 和脑脊液采集，包括维护老年人的生物样本库，避免临床中风和 注册时患有痴呆症。因此，我们能够很好地检测蛋白质组血清和脑脊液生物标记物。 与横断面和纵向神经影像和认知结果的关系。由此产生的结果 合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有关 健康。结果将产生重要的应用于考察自然历史、分析 年龄相关和疾病管理的流行病学、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。

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.