Dementia of Parkinson Type: Clinicopathologic Phenotype

帕金森型痴呆：临床病理表型

• 批准号: 6625684
• 负责人: James E Galvin
• 金额: $ 15.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625684
• 关键词: Alzheimer's disease; Lewy body; Parkinson's disease; aging; brain disorder diagnosis; cognition; comorbidity; dementia; diagnosis design /evaluation; functional ability; histology; human data; human tissue; longitudinal human study; neuroanatomy; patient oriented research; postdoctoral investigator; psychometrics; psychomotor function

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.

帕金森病和路易体痴呆 (DLB) 共同构成仅次于阿尔茨海默病 (AD) 的第二常见痴呆形式。这些疾病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 (Lbs)。此外，大量 AD 患者在病程中出现帕金森病症状，尸检时还发现其中许多患者患有帕金森病。先前诊断出的 PD 相关痴呆现在是否会被归类为 DLB 尚不清楚。目前还不清楚仅在存在严重 Lbs 或 AD 相关病理的情况下，PD 本身是否会导致痴呆。该项目的目标是表征帕金森型痴呆 (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，以便：1) 确定那些临床特征将病理诊断的 DLB 和 PD 与 AD 以及彼此区分开来建立 DPT 表型； 2) 通过探索 DPT 独特临床症状的神经解剖学相关性，识别诊断中使用的病理特征以外的组间差异； 3) 确定诊断病理学定义的 DPT 组的最佳短临床特征集。 ADRC 和华盛顿大学医学院神经病学系为候选人提供了良好的环境，以培养他作为独立临床医生科学家的技能。 K08 奖项将为候选人提供受保护的时间来完成项目的具体目标，并完成研究道德行为、生物统计学和流行病学研究设计的教学课程。候选人的研究职业发展计划是利用指导期间建立痴呆症研究领域，专门研究共存病理在痴呆症的发病、进展和独特特征中所起的作用。奖励期结束后，候选人计划根据本提案中描述的实验生成的数据开发一个独立的 R01 项目。