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

描述（由申请人提供）：帕金森病（PD）病理学临床特征的总体目标是描述未诊断为PD的老年人的PD病理学临床特征。表明PD病理学与没有临床诊断PD的人中的独特和进行性病症相关，将对PD研究产生变革性影响。虽然PD仅影响85岁以上人群的5%，但令人信服的初步数据显示，包括黑质变性和路易体在内的PD病理学指标存在于近20%的无PD的老年人中，并且与帕金森症的严重程度接近死亡相关。这表明PD病理学是常见的，并在不符合PD临床标准的人中引起临床体征。与最近对AD的重新分类一样，PD也可能具有无症状PD病理学阶段，随后是PD病理学导致轻度运动和非运动损伤的阶段，这些损伤不足以保证PD的诊断，并且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，成功地改变了我们对AD的看法。这项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），其参与者都同意在死亡时进行年度临床检查和器官捐赠。针对无临床PD的成人，我们建议描述脑和脊髓中PD病理的程度和负担。接下来，我们建议确定广泛的运动和非运动行为与PD病理的关联。最后，我们建议开发一种具有高灵敏度和特异性的PD病理检测的临床特征。这一建议提供了潜力，大大扩大我们的知识，PD的临床阶段，并确定与PD的人进行早期干预之前，明显的临床疾病。

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.