Subcortical Vascular Cognitive Impairment-A Longitudinal Perfusion Imaging Study

描述（由申请方提供）：老年人的小血管缺血性疾病，其磁共振成像（MRI）特征为T2和FLAIR序列上的白色高信号（WMH），推测是由慢性灌注不足引起的。WMH变化几乎无处不在，对非痴呆个体的认知和运动处理产生负面影响，对阿尔茨海默病病理学具有协同作用，并增加功能下降和痴呆的风险。小血管脑血管病导致的认知功能下降被称为皮质下血管性认知功能障碍（VCI），这可能是老年人轻度认知功能障碍的一个未被认识到的原因。尽管我们最近在了解WMH变化对老年人认知和运动健康的影响方面取得了进展，但这些变化的潜在机制和功能轨迹，以及伴随的皮质下VCI和痴呆的风险在很大程度上仍然未知。本研究的目的是调查随着时间的推移WMH负荷积累的脑血流量的变化的影响，确定WMH病变是否是一个更广泛的病理过程的局灶性体征，并确定解剖和灌注MRI标记，赋予认知和运动障碍的风险增加。具体目标是：1）确定灌注改变在老年人WMH蓄积形成中的作用，2）表征正常外观白色物质（NAWM）和胼胝体中的WMH和灌注相关微结构白色物质变化，3）确定认知和运动衰退的MRI生物标志物。65岁以上的非痴呆老年人将被要求参加。除了每年常规的心理测量和神经功能测试外，还将对受试者进行纵向随访，并对家庭步态和运动活动进行非侵入性评估。80例受试者将每年接受一次高场（3和7特斯拉）MRI。将使用动脉自旋标记（一种定量脑血流量的无创方法）获得灰质和白色物质灌注的纵向测量值。将使用扩散张量成像和定量T1弛豫成像评价NAWM和胼胝体中白色物质完整性微结构下降的证据。将获得所有受试者的WMH病变负荷的体积定量。本研究拟采用高场先进成像技术，在一个特征明确的老年队列中研究WMH相关认知障碍和运动功能下降的机制。这项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功能障碍和痴呆风险的老年人的认知和运动功能的影响，并建立CBF和常见的WMH变化之间的因果关系。此外，本研究还将确定WMH病变患者NAWM和胼胝体广泛微结构损伤的程度和功能影响。最终，该提案的目标是确定VCI背后的机制，并识别有认知和运动障碍风险的老年人，以便制定早期治疗和预防措施。

DESCRIPTION (provided by applicant): 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 underrecognized 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.