White Matter Connectivity and PD Cognitive Phenotypes

描述(申请人提供)：帕金森氏症(PD)仅在美国就至少影响150万人。帕金森病最严重的非运动性症状之一是认知功能障碍，涉及处理速度/工作记忆和/或情景记忆减慢。相对于其他伴有认知障碍的神经退行性疾病，我们对帕金森病认知功能下降的神经解剖学相关性知之甚少。在前期工作中，我们检查了一组特发性非痴呆性帕金森病患者与非帕金森病年龄匹配的同龄人的大脑连接与认知的关系。观察到了三种不同的认知表型：a)信息处理速度慢，但保留了情景记忆；b)情景记忆困难，信息处理速度微乎其微；c)相对于年龄匹配的同龄人，功能正常，没有缺陷。高角分辨率弥散成像的初步结果提示有独特的白质和灰质轮廓：有发作性记忆缺陷的帕金森病患者表现为内侧颞叶环路中断(即，内嗅海马连通)；有初级处理速度缺陷的帕金森病患者表现为额叶-皮质下白质环路(DLPF环路)的异常；无认知障碍的帕金森病患者表现出与年龄匹配的对照组相似的环路。本研究将招募 来自该国最大的运动障碍数据库之一，以调查关于记忆和处理速度/执行困难以及分别在颞区和额叶-皮质下区域内的区域白质连接的工作假说。将解决三个具体目标。目的1：证明记忆功能与内嗅皮层和海马区之间的连通性；目标2：研究加工速度/工作记忆减慢与DLPF皮质至尾状回的完整性之间的关系；以及目标3：揭示脑局部连通性在基线后一年和两年内对记忆或执行功能下降的意义。一个专门从事运动障碍、功能和扩散成像、神经心理学评估、可靠变化分析和纵向统计建模的研究小组将实现这些目标。研究方法将来自独特的帕金森病患者数据库，最先进的成像技术，以及来自临床和翻译科学研究所内的综合临床研究中心的资源。

DESCRIPTION (provided by applicant): Parkinson's Disease (PD) affects at least 1.5 million people in the United States alone. One of the most severe non-motor symptoms of PD is cognitive dysfunction involving reduced processing speed/working memory, and/or episodic memory. Relative to other neurodegenerative disorders with cognitive impairment, we know little about the neuroanatomical correlates of cognitive decline in PD. In preliminary work, we have examined brain connectivity associated with cognition in a group of idiopathic non-dementia PD relative to non- PD age-matched peers. Three distinct cognitive phenotypes were observed: a) slow information processing speed with preserved episodic memory, b) episodic memory difficulty with subtle slow information processing speed; and c) normal functioning with no deficits relative to age matched peers. Preliminary results of high angular resolution diffusion imaging suggest unique white matter and gray matter profiles: PD with episodic memory deficits exhibited mesial temporal circuit disruption (i.e., entorhinal-hippocampal connectivity); PD with primary processing speed deficits displayed aberration in the frontal-subcortical white matter circuitry (DLPFcircuit) between the dorsolateral prefrontal cortex and caudate; and PD without cognitive deficits showed circuitry similar to age-matched controls. The present study will recruit from one of the largest movement disorder databases in the country to investigate working hypotheses regarding memory and processing speed/executive difficulties and regional white matter connectivity within the temporal and frontal-subcortical regions, respectively. Three specific aims will be addressed. Aim 1: to demonstrate the association between memory function and the connectivity between the entorhinal cortex and hippocampus; Aim 2: to examine the relation between reduced processing speed/working memory and integrity within the DLPF cortex to caudate; and Aim 3: to reveal the significance of regional brain connectivity on memory or executive function decline at one and two years post-baseline. A research team specialized in movement disorders, functional and diffusion imaging, neuropsychological assessment, reliable change analyses, and longitudinal statistical modeling will carry out these aims. Study methods will draw from unique PD patient database, state-of-the art imaging techniques, and resources from the General Clinical Research Center within the Clinical and Translational Science Institute.