Aging Brain: DTI, Subcortical Ischemia and Behavioral

描述（由申请人提供）：我们将使用弥散张量成像（DTI）研究皮质下缺血性血管病（SIVD）患者的额叶白色物质完整性与执行功能和行为之间的关系。SIVD的特征在于腔隙性梗死和深部白色物质变化，并且可引起认知损害，占血管性痴呆病例的约50%，并且与执行认知和行为的损害相关，推测是由于额叶-皮质下回路的中断。执行和行为障碍导致老年人功能下降，并可能加速向痴呆症的转化。 本提案的目的是（1）使用DTI证明SIVD患者与正常老年人对照组相比白色物质完整性的丧失，（2）证明SIVD患者与正常老年人相比，使用DTI测量的额叶白色物质完整性与执行认知和行为功能之间的关联，以及（3）使用创新的DTI纤维束成像工具来识别特定的白色物质通路并确定它们与认知和行为的关联，j我们将招募一个CADASIL（伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病）受试者亚组（一种相对纯粹的SIVD形式）作为“金标准”对照组，以增强任何显著相关性与SIVD相对于其他病理学相关的信心。 我们专注于行为和使用DTI纤维束成像来探索离散纤维束的关联是新颖的。本研究的结果将有助于我们了解额叶系统中断对SIVD和其他影响白色物质的疾病的认知和行为的影响。这些结果可能导致使用DTI作为脑血管损伤易感性和向痴呆转化的预测因子，并有助于发展DTI作为旨在降低脑血管风险的治疗试验的结果指标。此外，Aim 3将产生创新的自动纤维束成像方法，该方法可能导致开发整个生命周期的白色物质连接的规范图，该图可用于检测白色物质疾病的最早迹象。

DESCRIPTION (provided by applicant): We will use diffusion-tensor imaging (DTI) to investigate the relationship between frontal white matter integrity and executive function and behavior in patients with subcortical ischemic vascular disease (SIVD). SIVD is characterized by lacunar infarcts and deep white matter changes and can cause cognitive impairment, accounts for approximately 50% of vascular dementia cases, and is associated with impairment in executive cognition and behavior presumably due to interruption of frontal-subcortical circuits. Executive and behavioral impairment leads to functional decline in the elderly and may hasten conversion to dementia. The aims of this proposal are (1) to demonstrate loss of white matter integrity in patients with SIVD vs. normal elderly controls using DTI, (2) to demonstrate an association between frontal white matter integrity measured with DTI and executive cognition and behavioral functioning in SIVD vs. normal elderly, and (3) to use innovative DTI tractography tools to identify specific white matter pathways and determine their association with cognition and behavior, j We will recruit a subgroup of subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy) - a relatively pure form of SIVD - to serve as a "gold standard" comparison group to strengthen confidence that any significant associations are related to SIVD vs. other pathology. Our focus on behavior and the use of DTI tractography to explore associations in discrete fiber tracts is novel. The results of this study will contribute to our understanding of the impact of frontal systems disruption on cognition and behavior in SIVD and other disorders affecting white matter. The results could lead to the use of DTI as a predictor of susceptibility to cerebrovascular injury and of conversion to dementia, and help develop DTI as an outcome measure in treatment trails aimed at reducing cerebrovascular risk. Further, Aim 3 will produce innovative automated tractography methods that could lead to the development of a normative map of white matter connectivity across the lifespan which could be used to detect the earliest signs of white matter disease.