White Matter Connectivity and PD Cognitive Phenotypes

描述（由申请人提供）：帕金森病（PD）仅在美国就影响至少150万人。PD最严重的非运动症状之一是认知功能障碍，包括处理速度/工作记忆和/或情景记忆降低。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能力下降的神经解剖学相关性知之甚少。在初步工作中，我们检查了一组特发性非痴呆性PD患者相对于非PD年龄匹配的同龄人与认知相关的大脑连通性。观察到三种不同的认知表型：a)信息加工速度慢，保留情景记忆；b)情景记忆困难，信息加工速度轻微缓慢；c)功能正常，与同龄人相比没有缺陷。高角分辨率弥散成像的初步结果显示了独特的白质和灰质特征：患有情景记忆缺陷的PD表现出中颞叶电路中断（即内咽-海马连通性）；初级加工速度缺陷的PD在背外侧前额叶皮层和尾状核之间的额皮层-皮层下白质回路（DLPFcircuit）中表现出畸变；而没有认知缺陷的帕金森病患者的神经回路与年龄匹配的对照组相似。本研究将招募

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.