LONGITUDINAL PET-LACUNES, COGNITION AND BEHAVIOR

本项目使用纵向正电子发射计算机断层扫描来解决小血管脑血管疾病患者认知功能障碍的诊断、预后和机制方面的重要问题。这项拨款采用纵向设计和成熟的方法来解决一些问题，尽管几十年来科学的关注并没有取得什么进展。例如，目前很难确定脑血管病理和脑血管疾病的相对贡献 阿尔茨海默病患者的认知功能障碍和皮质下小中风(下丘脑)。我们将测试某些PET发现是否可以用作这些不同病理的活体标记物。关于如何预测腔隙患者的认知能力下降，人们知之甚少。我们的初步数据表明，PET可能有助于判断预后，我们将更明确地探索PET的这一应用。这些临床不确定性反映了 关于松果可能导致认知障碍的机制的潜在困惑。皮质下-额叶环路受损导致额叶连接中断并伴随认知功能衰竭是缺血性血管性痴呆的可能机制之一。这一克中的一只山羊将检验这一假设。将纵向PET和MRI研究添加到我们的方案中，提供了以独特的方式测试所有这些问题的机会，从而允许更强的因果关系归因。这是一项前瞻性的纵向研究，最初样本为150名受试者。核磁共振显示，大约一半的受试者会患上脑血管疾病。大约三分之一的人认知正常，三分之一的人有轻度认知障碍，三分之一的人患有痴呆症。受试者用正电子发射断层扫描(PET)测量大脑局部新陈代谢，用核磁共振测量大脑结构，用神经心理测试和行为量表测量症状。DiFusion张量成像被添加到这次更新中，作为一种潜在的更好的测量白质完整性的方法。所有受试者将接受年度临床随访评估，包括临时病史、神经学检查、精神病学评估和神经心理学测试。脑成像研究将在基线研究后两年和四年内重复进行。这一项目有望更好地了解皮质下卒中相关认知障碍的机制，改善临床诊断，并改善对这一人群认知功能进程的预测。

This project uses longitudinal PET to address important questions about diagnosis, prognosis, and the mechanisms of cognitive failure in patients with small vessel cerebrovascular disease. The grant uses a longitudinal design and well established methods to address questions that have yielded little progress despite decades of scientific attention. For example, it is presently extremely difficult to determine the relative contributions of ccrebrovascular pathology and Alzheimer's disease in patients with cognitive dysfunction and small subcortical strokes (iacunes). We will test whether or not certain PET findings can be used as in vivo markers for these different pathologies. Very little is known about how to predict cognitive decline in patients with lacunes. Our preliminary data suggest that PET may be useful in defining prognosis and we will explore this application of PET more definitively. These clinical uncertainties reflect underlying confusion about the mechanisms through which tacunes may cause cognitive failure. Damage to subcortical-frontal loops resulting in disconnection of the frontal lobes and attendant cognitive failure is one possible mechanism of ischemic vascular dementia. One goat of this gram is to test this hypothesis. The addition of longitudinal PET and MRI studies to our protocol offers the opportunity to test all of these questions in unique ways that allow stronger attributions of causality. This is a prospective, longitudinal study with an initial sample of 150 subjects. Approximately half of the subjects will have cerebrovascutar disease as revealed by MRI. About 1/3 will be cognitively normal, 1/3 will have mild cognitive impairment, and 1/3 will be demented. Subjects are studied with positron emission tomography (PET) to measure regional brain metabolism, with MRI to measure brain structures, and with neuropsychological tests and behavioral scales to measure symptoms. Difusion tensor imaging is added in this renewal as a potentially superior way of measuring white matter integrity. All subjects will receive annual clinical follow-up evaluations consisting of interim medical history, neurological exams, psychiatric evaluation, and neuropsychologicat testing. Brain imaging studies will be repeated two and four years after the baseline study. This project is expected to yield better understanding of the mechanisms of cognitive failure associated with subcortical stroke, to improve clinical diagnosis, and to improve the prediction of the course of cognitive function in this population.