Dementia of Parkinson Type: Clinicopathologic Phenotype

帕金森病和路易体痴呆（DLB）共同构成了仅次于阿尔茨海默病（AD）的第二种最常见的痴呆形式。这些疾病的典型病理病变是在皮层（DLB）和黑神经（PD）神经元中发现的路易体（Lbs）。此外，相当数量的AD患者在疾病过程中出现帕金森症状，其中许多患者在尸检时也被发现有Lbs。以前诊断为PD相关痴呆的患者现在是否会被归类为DLB尚不清楚。目前尚不清楚PD是否仅在存在关键的Lbs或ad相关病理时才会导致痴呆。该项目的目的是表征帕金森型痴呆（DPT）的临床病理表型。我们建议对阿尔茨海默病研究中心（ADRC）关于尸检确定的AD、PD和DLB病例的临床、运动、认知、行为和病理特征的纵向研究进行分析，以便：1)确定病理诊断的DLB和PD与AD以及彼此区分的临床特征，以建立DPT表型；2)通过探索DPT独特临床症状的神经解剖学相关性，识别各组间除诊断中使用的病理特征外的差异；3)确定诊断病理定义的DPT组的最佳临床特征短集。ADRC和华盛顿大学医学院神经学系为候选人提供了一个优秀的环境，以发展他作为独立临床医生和科学家的技能。该K08奖将为候选人提供保护时间，以完成项目的具体目标，并完成研究伦理行为，生物统计学和流行病学研究设计的教学课程。候选人的研究生涯发展计划是利用指导期在痴呆症研究领域建立，具体考察共存病理在痴呆症的发病、发展和独特特征中的作用。在奖励期结束时，候选人计划根据本提案中描述的实验产生的数据开发一个独立的R01项目。

Parkinson's disease and Dementia with Lewy bodies (DLB) together comprise the second most common form of dementia after Alzheimer's Disease (AD). The signature pathologic lesions in these disorders are Lewy bodies (Lbs) found in cortical (DLB) and nigral (PD) neurons. Furthermore, a significant number of AD patients develop parkinsonian signs during the course of disease and many of these patients also are found to have Lbs on autopsy. Whether previously diagnosed with PD- associated dementia now would be classified as DLB is unknown. It is also unclear that PD alone can cause dementia occurs only in the presence of critical Lbs or AD-related pathology. The goal of this project is to characterize the clinicopathologic phenotypes of Dementia of the Parkinson Type (DPT). We propose to analyze the longitudinal studies of the Alzheimer's Disease Research Center (ADRC) for the clinical, motor, cognitive, behavioral, and pathologic characteristics of autopsy defined case of AD, PD and DLB in order to: 1) determine those clinical features that differentiate pathologically diagnosed DLB and PD from AD and from each other to establish the DPT phenotype; 2) identify differences between groups in pathologic features other than those used in the diagnosis by exploring the neuroanatomical correlates of the unique clinical symptomatology of DPT; and 3) to determine the best short set of clinical features for the diagnosis of pathologically defined DPT groups. The ADRC and the Department of Neurology at Washington University School of Medicine provide the candidate with an outstanding environment to develop his skills as an independent clinician-scientist. This K08 award will make available to the candidate protected time to complete the Specific Aims of the project and complete didactic courses in the ethical conduct of research, biostatistics and epidemiological study design. The research career development plan of the candidate is to use the mentored period to establish in the field of dementia research, specifically examining the role co-existent pathologies play in the onset, progression and unique characteristics of dementing disorders. At the completion of the award period, candidate plans to develop an independent R01 project derived from the data generated by the experiments described in this proposal.