PROJECT 3 SEROTONIN AND SLEEP DISORDERED BREATHING IN PARKINSON DISEASE Sleep disturbance and excessive daytime somnolence are important non-motor/non-dopaminergic features of Parkinson disease (PD). Sleep disruption in PD is likely multifactorial but recent evidence suggests a high prevalence of sleep disordered breathing in PD, a surprising finding in view of the tendency for PD subjects to lose weight during their illness. PD is clearly a multisystem neurodegeneration with evidence indicating degeneration of central serotoninergic systems. Caudal brainstem serotoninergic neurons are key actors in controlling upper airway patency during sleep and degeneration of this group of neurons would be a plausible cause of sleep disordered breathing in PD. Our hypothesis is that loss of caudal brainstem serotoninergic neurons causes SDB in PD. We will evaluate this hypothesis by comparing the caudal brainstem [11C]DASB binding, a measure of serotoninergic neurons, in PD subjects with and without SDB. We predict greater loss of caudal brainstem [11C]DASB binding in PD subjects with SBD than in PD subjects without SDB. We predict an inverse correlation between indices of SDB and caudal brainstem [11C]DASB binding in PD subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS015655-30
Application #
8376380
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
$91,212
Indirect Cost
$32,174
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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