The Clinical Profile of Parkinson's Disease (PD) Pathology

描述（由申请人提供）：帕金森病（PD）病理学临床概况的总体目标是描述未诊断为PD的老年人的PD病理临床概况。显示PD病理与没有临床诊断的PD患者的独特和进展性疾病相关，将对PD研究产生变革性影响。尽管到85岁时，PD仅影响5%的人，但令人信服的初步数据显示，PD病理指标，包括神经变性和路易体，在近20%的无PD的老年人中存在，并且与帕金森病的严重程度接近死亡有关。这表明PD病理是常见的，并且在不符合PD临床标准的人中引起临床症状。与最近对AD的重新分类一样，PD也可能有一个无症状的PD病理阶段，随后是PD病理导致轻度运动和非运动损伤的阶段，其严重程度不足以保证PD的诊断，PD的临床诊断是该疾病的后期。为此，我们将采用类似的方法，成功地改变了我们对AD的看法。拟议的研究将利用两个正在进行的队列研究，即Rush宗教秩序研究（P30AG10161）和记忆与衰老项目（R01AG17917），其参与者都同意在死亡时进行年度临床检查和器官捐赠。针对没有临床PD的成年人，我们建议描述PD在脑和脊髓的病理程度和负担。接下来，我们建议确定运动和非运动行为与PD病理的广泛联系。最后，我们建议开发一种具有高灵敏度和特异性的PD病理检测的临床概况。这一建议提供了极大地扩展我们对PD临床阶段知识的潜力，并在显性临床疾病之前识别PD患者进行早期干预。

DESCRIPTION (provided by applicant): The overall goal of The Clinical Profile of Parkinson's Disease (PD) Pathology, is to characterize the clinical profile of PD pathology in older person's without a diagnosis of PD. Showing that PD pathology is associated with a distinct and progressive condition among persons without a clinical diagnosis of PD, would have a transformative effect on PD studies. Although, PD only affects up to 5% of persons by age 85, compelling preliminary data shows that indices of PD pathology including nigral degeneration and Lewy bodies are present in nearly 20% of older persons without PD and are associated with the severity of parkinsonism proximate to death. This suggests that PD pathology is common and causes clinical signs in persons who do not meet clinical criteria for PD. Like the recent reclassification of AD, PD may also have an asymptomatic PD pathology phase, followed by a stage in which PD pathology results in mild motor and non-motor impairments not severe enough to warrant a diagnosis of PD, and a clinical diagnosis of PD is a later stage of the disease. Toward this end, we will apply a similar approach to that which has succeeded in transforming our ideas of AD. The proposed study will take advantage of two ongoing cohort studies, the Rush Religious Orders Study (P30AG10161) and the Memory and Aging Project (R01AG17917), whose participants have all agreed to annual clinical examination and organ donation at the time of death. Focusing on adults without clinical PD, we propose to delineate the extent and burden of PD pathology in both brain and spinal cord. Next, we propose to determine the associations of a wide range of motor and non- motor behaviors to PD pathology. Finally, we propose to develop a clinical profile for the detection of PD pathology with high sensitivity and specificity. This proposal offers the potential to greatly expand our knowledge of the clinical phase of PD and to identify people with PD for early intervention prior to overt clinial disease. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to characterize the clinical profile of Parkinson's disease (PD) pathology in older person's without a diagnosis of PD. Showing that PD pathology is associated with a distinct and progressive condition among persons without a clinical diagnosis of PD, would have a transformative effect on PD studies, in terms of potential biomarkers, early detection and interventions to delay the onset of PD.