This application describes a Program Project with research plan focused on neurochemical positron emission tomography (PET) studies of Parkinson disease (PD). PD is the most common neurodegenerative movement disorder, and considerable progress has been made in understanding and treating the """"""""typical"""""""" movement abnormalities of resting tremor, bradykinesia and rigidity. These cardinal PD features are all initially responsive to dopamine replacement therapy, and have been investigated intensively with respect to their relationships to degeneration of the nigrostriatal dopamine projection. More recently, increased attention has focused on the """"""""non-motor"""""""" clinical aspects of PD, including cognitive, mood, chronobiological and peripheral autonomic defects. These clinical features are less reliably affected by dopaminergic therapy, and are likely to be associated with other, non-dopaminergic neural degenerations. Indeed, detailed postmortem assessments of PD brain reveal substantial neuronal losses in a variety of chemically-defined neurons, including brainstem serotonin and norepinepherine neurons and basal forebrain cholinergic neurons. Projects in our proposal will focus on dementia, depression, sleep-apnea and dysautonomia in PD patients, employing PET measures of presynaptic dopaminergic, serotoninergic and cholinergic CNS neurons and of peripheral sympathetic neurons. Results of our investigations may identify associations of non-motor PD signs and symptoms with the non-dopamiergic neuronal losses. These findings will establish additional therapeutic targets for symptomatic, but also for potential neuroprotective PD therapies. In addition, a majority of patients will be characterized with all 3 CNS PET measures. The availability of multiple markers of distinct neuronal populations involved in PD neurodegeneration will permit exploratory analyses to assess whether the degenerations are correlated (possibly manifestations of a common pathophysiology) or apparently independent (possibly a manifestation of multiple PD subtypes or pathophysiologies). Ultimately, better understanding of these non-motor features will be essential to developing future treatments that address the entire PD patient.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZNS1-SRB-E (26))
Program Officer
Sutherland, Margaret L
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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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
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 :
Bohnen, Nicolaas I; Haugen, Jacob; Ridder, Andrew et al. (2017) Color discrimination errors associate with axial motor impairments in Parkinson's disease. Mov Disord Clin Pract 4:864-869

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