Subcortical Vascular Cognitive Impairment-A Longitudinal Perfusion Imaging Study

描述(申请人提供)：老年人的小血管缺血性疾病，其磁共振成像(MRI)的特征是T2和FLAIR序列上的白质高信号(WMH)，推测是由慢性低灌注引起的。WMH的变化几乎无处不在，对非痴呆者的认知和运动处理产生负面影响，对阿尔茨海默病的病理有协同作用，并增加功能下降和痴呆的风险。小血管脑血管疾病导致的认知功能下降被称为皮质下血管认知障碍(VCI)，这可能是老年人轻度认知障碍的一种被低估的原因。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，以及伴随而来的皮质下VCI和痴呆症的风险在很大程度上仍不清楚。本研究的目的是研究脑血流随时间的变化对WMH负荷累积的影响，确定WMH病变是否是更弥漫的病理过程的局灶性信号，并确定解剖和灌注MRI标志物增加认知和运动损伤的风险。其具体目的是：1)确定血流灌注改变在老年人WMH积聚形成中的作用；2)表征WMH及其在正常外观白质(NAWM)和胼胝体中与血流灌注相关的微结构白质变化；3)确定认知和运动功能下降的MRI生物标志物。65岁以上的非痴呆症老年人将被要求参加。除了一年一度的常规心理测量和神经学测试外，受试者还将接受纵向跟踪，对家庭步态和运动活动进行不引人注目的评估。80名受试者将接受每年3特斯拉和7特斯拉的高场磁共振成像。灰质和白质灌注的纵向测量将使用动脉自旋标记，这是一种量化脑血流量的非侵入性手段。脑白质完整性微结构下降的证据将通过扩散张量成像和定量T1弛豫造影术在NAWM和穹隆体内进行评估。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先进的成像技术来研究WMH相关的认知损害和运动功能下降的机制，在一个特征良好的老年人队列中。这项研究将是第一个前瞻性地研究随着时间的推移脑低灌流对认知损害和痴呆高危老年人认知和运动功能的影响，并建立CBF与通常观察到的WMHs变化之间的因果关系。此外，这项研究还将确定WMH患者NAWM和胼胝体广泛的微结构损伤的程度和功能影响。最终，这项建议的目标是确定VCI背后的机制，并确定有认知和运动障碍风险的老年人，以便能够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.