Dementia of Parkinson Type: Clinicopathologic Phenotype

帕金森病和路易体痴呆（DLB）一起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。这些疾病中的标志性病理损伤是在皮质（DLB）和黑质（PD）神经元中发现的路易体（Lb）。此外，相当数量的AD患者在疾病过程中出现帕金森症状，并且这些患者中的许多人在尸检时也被发现具有Lbs。先前诊断为PD相关痴呆的患者现在是否会被归类为DLB尚不清楚。目前还不清楚PD单独是否会导致痴呆症，只有在存在严重的Lbs或AD相关病理的情况下才会发生。本项目的目标是描述帕金森型痴呆（DPT）的临床病理表型。本研究拟分析阿尔茨海默病研究中心（ADRC）对尸检确诊的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，以：1）确定区分病理诊断的DLB和PD与AD以及彼此的临床特征，以建立DPT表型; 2）通过探索DPT独特的临床病理学的神经解剖学相关性，确定除用于诊断的病理学特征外的组间差异; 3）确定用于诊断病理学定义的DPT组的最佳临床特征的短集。ADRC和华盛顿大学医学院神经病学系为候选人提供了一个出色的环境，以发展他作为独立临床医生-科学家的技能。该K 08奖将为候选人提供受保护的时间，以完成该项目的具体目标，并完成研究，生物统计学和流行病学研究设计的道德行为的教学课程。候选人的研究职业发展计划是利用辅导期在痴呆症研究领域建立，特别是研究共存的病理在痴呆症的发病，进展和独特特征中的作用。在奖励期结束时，候选人计划开发一个独立的R 01项目，该项目来自本提案中描述的实验产生的数据。

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.