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

描述(由申请人提供)：帕金森氏病(PD)病理学临床概况的总体目标是描述没有PD诊断的老年人的PD病理学的临床概况。在没有帕金森病临床诊断的人群中，显示帕金森病的病理与一种明显的进行性疾病有关，这将对帕金森病的研究产生变革性的影响。尽管到85岁时，帕金森病只影响到5%的人，但令人信服的初步数据显示，包括黑质变性和路易小体在内的帕金森病病理指标在近20%的没有帕金森病的老年人中存在，并与濒临死亡的帕金森病的严重程度有关。这表明帕金森病的病理很常见，不符合帕金森病临床标准的人会出现临床症状。就像最近对AD的重新分类一样，PD也可能有一个无症状的PD病理阶段，然后是PD病理导致的轻微运动和非运动障碍，不足以保证诊断为PD，而PD的临床诊断是疾病的后期阶段。为此，我们将采用类似的方法来改变我们对AD的看法。这项拟议的研究将利用两项正在进行的队列研究，即拉什宗教秩序研究(P30AG10161)和记忆与衰老项目(R01AG17917)，这两项研究的参与者都同意在死亡时进行年度临床检查和器官捐赠。聚焦于无临床帕金森病的成人，我们建议描绘帕金森病在脑和脊髓的病理程度和负担。接下来，我们建议确定广泛的运动和非运动行为与帕金森病病理的相关性。最后，我们建议建立一种具有高敏感性和特异性的帕金森病病理检测的临床资料。这一建议有可能极大地扩展我们对帕金森病临床阶段的了解，并识别患有帕金森病的人，以便在临床明确疾病之前进行早期干预。

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.