PROJECT 4 Autonomic Disorders in Parkinson Disease Idiopathic Parkinson disease (PD) is a heterogeneous disorder containing subgroups that have been differentiated by age of onset;occurrence of cognitive impairment;predominance of tremor or of rigidity and hypokinesia;and genetic factors. Identifying patients by subgroup has proved helpful in predicting the rate of disease progression. Multiple autonomic disorders occur in PD, including constipation, sweating dysfunction, urinary difficulty, and orthpstatic hypotension. Cardiac postganglionic sympathetic fibers become degenerated in the early to middle stages of PD, and the stage at which this occurs varies widely. Other nonmotor disorders in PD include difficulties with color discrimination, contrast sensitivity, and olfaction. This project will evaluate the relationship of cardiac denervation to the severity of other autonomic disorders, motor, visual and olfactory functioning in the disease and the rate of progression of these components of the disorder. The overarching hypothesis is that a greater degree of cardiac denervation is associated with greater baseline impairment of autonomic, visual and olfactory functions, and predicts a more rapid decline of these functions as well as motor performance and a more rapid loss of nigrostriatal projections. This hypothesis will be tested by evaluating PD patients at modified Hoehn and Yahr stages 1.0 through 2.0 utilizing positron emission tomography (PET) with [11C]hydroxyephedrine ([11C]HED) to examine cardiac innervation and [11C]dihydrptetrabenazine ([11C]DTBZ) to measure monoaminergic presynaptic nigrostriatal projections, along with specific tests of autonomic function, color discrimination, contrast sensitivity, olfaction, and motor performance. A total of 60 patients will be evaluated at baseline with PET studies of [11C]HED and [11C]DTBZ, along with motor, autonomic, visual, and olfactory performance. The PET studies will be repeated after two years and the results analyzed together with evaluations of motor, autonomic, visual and olfactory functioning. It is predicted that at baseline, early PD patients with cardiac denervation will have greater impairment of other elements of the autonomic nervous system, vision, and olfaction than patients with preserved cardiac innervation, and that these impairments will worsen more rapidly. It is also predicted that in PD patients with cardiac denervation at baseline, decline in motor function and loss of nigrostriatal innervation will occur more rapidly than in patients with preserved cardiac innervation at baseline. The results of this investigation will provide a novel means of characterizing subgroups of patients with PD and of predicting the rate of progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS015655-29
Application #
8289691
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
29
Fiscal Year
2011
Total Cost
$90,373
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Bohnen, Nicolaas I; Kanel, Prabesh; Müller, Martijn L T M (2018) Molecular Imaging of the Cholinergic System in Parkinson's Disease. Int Rev Neurobiol 141:211-250
Rektor, Ivan; Bohnen, Nicolaas I; Korczyn, Amos D et al. (2018) An updated diagnostic approach to subtype definition of vascular parkinsonism - Recommendations from an expert working group. Parkinsonism Relat Disord 49:9-16
Kim, Kamin; Bohnen, Nicolaas I; Müller, Martijn L T M et al. (2018) Compensatory dopaminergic-cholinergic interactions in conflict processing: Evidence from patients with Parkinson's disease. Neuroimage :
Beaulieu, Mélanie L; Müller, Martijn L T M; Bohnen, Nicolaas I (2018) Peripheral neuropathy is associated with more frequent falls in Parkinson's disease. Parkinsonism Relat Disord 54:46-50
Bohnen, Nicolaas I; Grothe, Michel J; Ray, Nicola J et al. (2018) Recent advances in cholinergic imaging and cognitive decline-Revisiting the cholinergic hypothesis of dementia. Curr Geriatr Rep 7:1-11
Nejad-Davarani, Siamak; Koeppe, Robert A; Albin, Roger L et al. (2018) Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV. Mol Psychiatry :
Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M et al. (2018) Cardiovascular Risk Factor Burden in Veterans and Non-Veterans with Parkinson Disease. J Parkinsons Dis 8:153-160
Bohnen, Nicolaas I; Müller, Martijn L T M; Frey, Kirk A (2017) Molecular Imaging and Updated Diagnostic Criteria in Lewy Body Dementias. Curr Neurol Neurosci Rep 17:73
Chou, Kelvin L; Gilman, Sid; Bohnen, Nicolaas I (2017) Association between autonomic dysfunction and fatigue in Parkinson disease. J Neurol Sci 377:190-192
Kim, Kamin; Müller, Martijn L T M; Bohnen, Nicolaas I et al. (2017) The cortical cholinergic system contributes to the top-down control of distraction: Evidence from patients with Parkinson's disease. Neuroimage :

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