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)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1-SRB-E (26))
Program Officer
Sutherland, Margaret L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Albin, Roger L (2014) Nourish the roots while picking the fruit. Neurology 83:1473-5
Bohnen, Nicolaas I; Kotagal, Vikas; Müller, Martijn L T M et al. (2014) Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease. Parkinsonism Relat Disord 20:1394-8
Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M et al. (2014) Modifiable cardiovascular risk factors and axial motor impairments in Parkinson disease. Neurology 82:1514-20
Bohnen, Nicolaas I; Frey, Kirk A; Studenski, Stephanie et al. (2014) Extra-nigral pathological conditions are common in Parkinson's disease with freezing of gait: an in vivo positron emission tomography study. Mov Disord 29:1118-24
Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M et al. (2014) Advanced age, cardiovascular risk burden, and timed up and go test performance in Parkinson disease. J Gerontol A Biol Sci Med Sci 69:1569-75
Weathers, Shiao-Pei S; Kotagal, Vikas; Bohnen, Nicolaas I et al. (2014) Risky driving and pedunculopontine nucleus-thalamic cholinergic denervation in Parkinson disease. Parkinsonism Relat Disord 20:13-6
Chou, Kelvin L; Lenhart, Adrienne; Koeppe, Robert A et al. (2014) Abnormal MoCA and normal range MMSE scores in Parkinson disease without dementia: cognitive and neurochemical correlates. Parkinsonism Relat Disord 20:1076-80
Shao, Xia; Fawaz, Maria V; Jang, Keunsam et al. (2014) Ethanolic carbon-11 chemistry: the introduction of green radiochemistry. Appl Radiat Isot 89:125-9
Soileau, Michael J; Persad, Carol; Taylor, Jennifer et al. (2014) Caregiver burden in patients with Parkinson disease undergoing deep brain stimulation: an exploratory analysis. J Parkinsons Dis 4:517-21
Armstrong, Melissa J; Duff-Canning, Sarah; Tang-Wai, David F et al. (2013) The meaning of a "hippo" response on the Montreal Cognitive Assessment in Parkinson's disease. Parkinsonism Relat Disord 19:463-5

Showing the most recent 10 out of 101 publications