Subcortical Vascular Cognitive Impairment-A Longitudinal Perfusion Imaging Study

项目摘要：老年人小血管缺血性疾病的磁共振征象 磁共振成像(MRI)是T2和FLAIR序列上的白质高信号(WMH)，推测 是由慢性低灌注量引起的。WMH变化几乎无处不在，对认知和 非痴呆者的运动处理对阿尔茨海默病的病理有协同作用，并且 增加功能衰退和痴呆症的风险。小血管导致的认知功能减退 脑血管疾病被称为皮质下血管认知障碍(VCI)，可能是一种 老年人轻度认知障碍的公认原因。尽管最近我们对 WMH改变对老年人认知和运动健康的影响、潜在机制和 这些变化的功能轨迹以及伴随而来的皮质下VCI和痴呆症的风险仍然存在 很大程度上是未知的。这项研究的目的是调查脑血流变化的影响。 WMH负荷累积的时间，判断WMH病变是否为局灶性征象更弥漫 病理过程，并确定可增加认知风险的解剖和灌注MRI标记物 以及运动障碍。具体目的是：1)确定血流灌注改变在WMH形成中的作用 老年人脑积聚；2)WMH和脑血流灌注相关脑白质微结构改变的特征 在正常外观白质(NAWM)和胼胝体，以及3)测定MRI生物标志物 认知和运动能力下降。65岁以上的非痴呆症老年人将被要求参加。除了……之外 一年一度的常规心理测量和神经学测试，受试者还将接受纵向 对居家步态和运动活动进行不显眼的评估。80名受试者将接受年度高场(3和 7特斯拉)核磁共振。灰质和白质灌注量的纵向测量将使用动脉自旋 标记，一种非侵入性的量化脑血流量的方法。白色中微结构下降的证据 物质完整性将使用弥散张量成像和弥散张量成像在NAWM和穹隆中进行评估 定量T1弛豫造影术。将获得所有受试者的WMH损伤负荷的体积量化。 这项研究建议使用高场高级成像技术来研究背后的机制 WMH相关的认知障碍和运动功能下降在一个具有良好特征的老年人队列中。本研究 将是第一个前瞻性地研究随着时间的推移大脑低灌流对认知和 认知损害和痴呆症高危老年人的运动功能，并建立因果关系 CBF与通常观察到的WMHs变化之间的关系。此外，这项研究将确定 广泛性微结构损伤对WMH患者NAWM和胼胝体的功能影响 损伤。最终，这项提案的目标是确定VCI背后的机制，并在 对认知和运动损伤的风险进行评估，以便及早采取治疗和预防措施。

PROJECT SUMMARY: Small vessel ischemic disease in the elderly whose signature on Magnetic Resonance Imaging (MRI) is white matter hyperintensities (WMH) on T2 and FLAIR sequences is presumed to be caused by chronic hypoperfusion. WMH change is nearly ubiquitous, negatively impacts cognitive and motor processing in nondemented individuals, has synergistic effects on Alzheimer disease pathology, and increases the risk of functional decline and dementia. Cognitive decline that occurs as a result of small vessel cerebrovascular disease has been termed subcortical vascular cognitive impairment (VCI), a likely under- recognized cause of mild cognitive impairment in the elderly. Despite recent advances in our understanding of the impact of WMH changes on cognitive and motor health in the elderly, the underlying mechanisms and functional trajectory of these changes, as well as the attendant risks of subcortical VCI and dementia remain largely unknown. The goals of this study are to investigate the effects of changes in cerebral blood flow over time on WMH burden accumulation, determine whether WMH lesions are focal signs of a more diffuse pathological process, and identify anatomical and perfusion MRI markers that confer increased risk of cognitive and motor impairment. Specific aims are to: 1) Identify the role of altered perfusion in the formation of WMH accumulation in the elderly, 2) Characterize WMH and perfusion-related microstructural white matter changes in normal appearing white matter (NAWM) and the corpus callosum, and 3) Determine MRI biomarkers of cognitive and motor decline. Non-demented seniors over age 65 will be asked to participate. In addition to annual conventional psychometric and neurologic testing, subjects will also be followed longitudinally with unobtrusive assessment of in-home gait and motor activity. Eighty subjects will undergo yearly high-field (3 and 7 Tesla) MRI. Longitudinal measures of grey and white matter perfusion will be obtained using arterial spin labeling, a non-invasive means of quantifying cerebral blood flow. Evidence of microstructural decline in white matter integrity will be evaluated in NAWM and the corpus callosum using diffusion tensor imaging and quantitative T1 relaxography. Volumetric quantification of WMH lesion burden will be obtained for all subjects. This study proposes to use high-field advanced imaging techniques to investigate the mechanisms behind WMH-related cognitive impairment and motor function decline in a well-characterized elderly cohort. This study would be one of the first to prospectively study the effects of cerebral hypoperfusion over time on cognitive and motor function in elderly at risk for cognitive impairment and dementia, and establish a causal relationship between CBF and commonly observed WMHs changes. In addition, this study will determine the extent and functional effects of widespread microstructual damage to the NAWM and corpus callosum in those with WMH lesions. Ultimately, the goal of this proposal is to determine the mechanisms behind VCI and identify elderly at risk for cognitive and motor impairment, so that early treatment and preventative measures can be instituted.