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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS078009-03
Application #
8688372
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Sieber, Beth-Anne
Project Start
2012-09-15
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Li, Peng; Yu, Lei; Lim, Andrew S P et al. (2018) Fractal regulation and incident Alzheimer's disease in elderly individuals. Alzheimers Dement 14:1114-1125
Dawe, Robert J; Leurgans, Sue E; Yang, Jingyun et al. (2018) Association Between Quantitative Gait and Balance Measures and Total Daily Physical Activity in Community-Dwelling Older Adults. J Gerontol A Biol Sci Med Sci 73:636-642
Buchman, Aron S; Nag, Sukriti; Leurgans, Sue E et al. (2018) Spinal Lewy body pathology in older adults without an antemortem diagnosis of Parkinson's disease. Brain Pathol 28:560-568
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Buchman, Aron S; Dawe, Robert J; Yu, Lei et al. (2018) Brain pathology is related to total daily physical activity in older adults. Neurology 90:e1911-e1919
Chu, Yaping; Buchman, Aron S; Olanow, C Warren et al. (2018) Do subjects with minimal motor features have prodromal Parkinson disease? Ann Neurol 83:562-574
Sohail, Shahmir; Yu, Lei; Schneider, Julie A et al. (2017) Sleep fragmentation and Parkinson's disease pathology in older adults without Parkinson's disease. Mov Disord 32:1729-1737
Buchman, Aron S; Bennett, David A (2017) Author response: Incident parkinsonism in older adults without Parkinson disease. Neurology 88:919-920
Buchman, Aron S; Leurgans, Sue E; Nag, Sukriti et al. (2017) Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism. Stroke 48:2792-2798

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