Aging Brain: DTI, Subcortical Ischemia and Behavioral

描述(申请人提供)：我们将使用弥散张量成像(DTI)来研究皮质下缺血性血管疾病(SIVD)患者额叶白质完整性与执行功能和行为的关系。SIVD以腔隙性脑梗塞和深部白质改变为特征，可导致认知障碍，约占血管性痴呆病例的50%，并与执行认知和行为障碍有关，推测是由于额叶-皮质下回路中断所致。执行和行为障碍会导致老年人的功能下降，并可能加速转化为痴呆症。 这项建议的目的是(1)证明SIVD患者与使用DTI的正常老年人对照组相比，脑白质完整性的丧失，(2)证明用DTI测量的额叶白质完整性与SIVD与正常老年人的执行认知和行为功能之间的关联，以及(3)使用创新的DTI示踪工具来识别特定的白质通路，并确定它们与认知和行为的关联。J我们将招募CADASIL(伴有皮质下梗塞和白质脑病的常染色体显性遗传性脑动脉病)患者的亚组作为SIVD的“黄金标准”对照组，以增强信心，即任何显著的关联都与SIVD和其他病理有关。 我们的重点是行为和使用DTI纤维束成像来探索离散纤维束中的关联，这是新颖的。这项研究的结果将有助于我们理解额叶系统中断对SIVD和其他影响脑白质的疾病的认知和行为的影响。这一结果可能导致使用DTI作为脑血管损伤易感性和转化为痴呆症的预测因子，并有助于将DTI作为旨在降低脑血管风险的治疗试验的结果衡量标准。此外，AIM 3将生产创新的自动化光谱分析方法，这可能会导致开发出一张标准的白质连通性地图，用于检测白质疾病的最早迹象。

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.