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 #
5P01NS015655-30
Application #
8376381
Study Section
Special Emphasis Panel (ZNS1-SRB-E)
Project Start
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
30
Fiscal Year
2012
Total Cost
$90,373
Indirect Cost
$31,878
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Haugen, Jacob; Müller, Martijn L T M; Kotagal, Vikas et al. (2016) Prevalence of impaired odor identification in Parkinson disease with imaging evidence of nigrostriatal denervation. J Neural Transm (Vienna) 123:421-4
Chou, Kelvin L; Kotagal, Vikas; Bohnen, Nicolaas I (2016) Neuroimaging and clinical predictors of fatigue in Parkinson disease. Parkinsonism Relat Disord 23:45-9
Kotagal, Vikas; Bohnen, Nicolaas I; Müller, Martijn L T M et al. (2015) Educational attainment and motor burden in Parkinson's disease. Mov Disord 30:1143-7
Müller, Martijn L T M; Bohnen, Nicolaas I; Kotagal, Vikas et al. (2015) Clinical markers for identifying cholinergic deficits in Parkinson's disease. Mov Disord 30:269-73
Albin, Roger L; Fisher-Hubbard, Amanda; Shanmugasundaram, Krithika et al. (2015) Post-Mortem evaluation of amyloid-dopamine terminal positron emission tomography dementia classifications. Ann Neurol 78:824-30
Snider, Jonathan; Müller, Martijn L T M; Kotagal, Vikas et al. (2015) Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration. Parkinsonism Relat Disord 21:1227-31
do Couto-Filho, Carlos Eduardo Gomes; de Moraes, Paulo Hemerson; Alonso, Maria Beatriz Carrazzone et al. (2015) Accuracy in the Diagnosis of the Mental Nerve Loop. A Comparative Study Between Panoramic Radiography and Cone Beam Computed Tomography. International journal of morphology = Revista internacional de 33:327-332
Frey, Kirk A; Petrou, Myria (2015) Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes. Clin Transl Imaging 3:57-64
Bohnen, Nicolaas I; Albin, Roger L; Müller, Martijn L T M et al. (2015) Frequency of cholinergic and caudate nucleus dopaminergic deficits across the predemented cognitive spectrum of Parkinson disease and evidence of interaction effects. JAMA Neurol 72:194-200

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