White matter and small vessel disease in older adults

随着人口的不断老龄化，认知能力下降和痴呆症正成为越来越重要的公共问题。 健康问题。虽然阿尔茨海默病是痴呆症最常见的原因，但它正变得越来越多。 显然，脑血管机制是认知障碍的基础，混合病理学占 至少一半的痴呆症患者大多数临床研究将脑血管机制与认知功能联系起来， 损伤集中在小血管疾病的神经影像学证据，如白色物质 高信号（WMH）和无症状腔隙性梗死。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学上明显脑血管疾病证据的前兆。 我们建议利用现有的本地队列，范德比尔特记忆与衰老项目，检查 与认知功能和神经影像学标记物相关的非侵入性血清和CSF生物标志物 血管疾病、白色物质完整性和老年人微循环。自从范德比尔特记忆& 老龄化项目队列于2012年开始，我们已经完成了系列访视（基线，18个月，36个月） 关键协变量确定、神经心理学评估、多模式3T脑MRI和空腹血 和CSF采集，包括维持无临床卒中的老年人的生物样本库， 老年痴呆症因此，我们非常有能力检查蛋白质组血清和CSF生物标志物， 与横截面和纵向神经影像学和认知结果的关系。结果从这个 协作努力将提供对轴突损伤、淀粉样蛋白沉积、tau聚集 以及与小血管疾病、白色物质完整性和微循环相关的神经变性 健康结果将产生重要的应用调查研究的自然历史，分析 流行病学、预防、临床诊断、预后和与年龄相关的疾病管理， 小血管、白色物质的病理变化和微循环健康。

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.