Dementia of Parkinson Type: Clinicopathologic Phenotype

帕金森氏病和路易体痴呆(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症。这些疾病的标志性病理损害是皮质(DLB)和黑质(PD)神经元中的路易小体(Lbs)。此外，相当数量的AD患者在病程中出现帕金森症状，其中许多患者在尸检中也被发现有LBS。目前尚不清楚以前被诊断为帕金森病相关痴呆的患者现在是否会被归类为DLB。同样不清楚的是，只有在存在严重的LBS或AD相关病理的情况下，帕金森病本身才会导致痴呆。这个项目的目标是描述帕金森型痴呆(DPT)的临床病理表型。我们建议分析阿尔茨海默病研究中心(ADRC)对尸检定义的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)确定那些区分病理诊断的DLB和PD与AD以及彼此之间的临床特征，以建立DPT表型；2)通过探索DPT独特的临床症状的神经解剖学相关性，识别不同组之间在病理特征以外的病理特征的差异；以及3)确定诊断病理定义的DPT组的最佳临床特征。ADRC和华盛顿大学医学院的神经科为候选人提供了一个出色的环境来发展他作为一名独立临床医生兼科学家的技能。这一K08奖项将为候选人提供完成项目具体目标和完成研究、生物统计学和流行病学研究设计伦理行为的教学课程的受保护时间。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，特别是考察共存的病理学在痴呆障碍的发生、发展和独特特征中所起的作用。在获奖期结束时，候选人计划开发一个独立的R01项目，该项目由本建议书中描述的实验产生的数据派生而来。

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.