Subcortical Vascular Cognitive Impairment-A Longitudinal Perfusion Imaging Study

项目总结：老年人的小血管缺血性疾病， 共振成像（MRI）在T2和FLAIR序列上显示白色高信号（WMH）， 是由慢性灌注不足引起的WMH变化几乎无处不在，对认知和行为产生负面影响。 在非痴呆个体中的运动处理，对阿尔茨海默病病理学具有协同作用， 增加了功能衰退和痴呆的风险。认知能力下降是由于小血管 脑血管疾病被称为皮质下血管性认知障碍（VCI），可能是一种 老年人轻度认知障碍的公认原因。尽管最近我们在理解上取得了进展， WMH变化对老年人认知和运动健康的影响，潜在的机制， 这些变化的功能轨迹，以及伴随的皮质下VCI和痴呆的风险仍然存在， 大部分未知。本研究的目的是研究脑血流变化对脑缺血的影响。 时间对WMH负荷的积累，确定WMH病灶是否有局灶性征象， 病理过程，并确定解剖和灌注MRI标记，赋予认知风险增加 和运动障碍具体目标是：1）确定灌注改变在WMH形成中的作用 2）表征WMH和灌注相关的显微结构白色物质变化 在正常表现的白色物质（NAWM）和胼胝体中，以及3）确定 认知和运动能力下降65岁以上的非痴呆老年人将被要求参加。除了 每年进行一次常规的心理测量和神经系统测试，受试者还将纵向随访， 对家庭步态和运动活动的非侵入性评估。80名受试者将接受每年一次的高场（3和 7特斯拉）MRI。将使用动脉自旋获得灰质和白色物质灌注的纵向测量值 标记，一种量化脑血流量的非侵入性方法。白色中微观结构下降的证据 将使用扩散张量成像评价NAWM和胼胝体中的物质完整性， 定量T1弛豫图将获得所有受试者的WMH病变负荷的体积定量。 本研究建议使用高场先进的成像技术来调查背后的机制 一个特征明确的老年队列中WMH相关的认知障碍和运动功能下降本研究 将是第一个前瞻性研究脑灌注不足随着时间的推移对认知和 运动功能在老年人的认知障碍和痴呆症的风险，并建立因果关系 CBF和通常观察到的WMH变化之间的关系。此外，这项研究将确定范围和 WMH患者NAWM和胼胝体广泛微结构损伤的功能影响 病变最终，这项提案的目标是确定VCI背后的机制，并确定老年人在 认知和运动障碍的风险，以便可以制定早期治疗和预防措施。

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.