Objective/Rationale:
Sleep related problems are a major cause of impairment in Parkinson's disease. Recent studies indicate a high incidence of a disabling sleep disorder – sleep disordered breathing (SDB; known also as obstructive sleep apnea) in Parkinson's disease. Brain systems using the neurotransmitter serotonin are involved in control of breathing during sleep. Degeneration of serotonin systems occurs in Parkinson's disease. We will determine if loss of serotonin brain systems underlies sleep disordered breathing in Parkinson disease.
Project Description:
Our hypothesis is that loss of brain serotonin-using nerve cells regulating breathing during sleep causes sleep disordered breathing in Parkinson's disease. We will study 60 Parkinson's disease patients; 30 with sleep disordered breathing and 30 without sleep disordered breathing. These Parkinson's disease patients will undergo careful clinical characterization of their Parkinson's disease and sleep-related symptoms. Sleep problems will be measured objectively with overnight sleep studies. Minimally invasive positron emission tomography (PET) imaging will be used to quantify brain serotonin neurons in different brain regions. We predict that Parkinson's disease patients with sleep disordered breathing will have marked loss of serotonin-using nerve cells regulating breathing. We predict that the magnitude of the sleep disordered breathing will correlate with the magnitude of serotonin-using nerve cell loss.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Sleep and sleep related problems such as excessive daytime somnolence are major causes of impaired quality of life in Parkinson's disease. Perhaps 20 – 30 % of Parkinson's disease patients suffer from sleep disordered (obstructive sleep apnea). By determining the cause of sleep disordered breathing in Parkinson's disease, we hope to lay the foundation for developing better Symptoms & Side Effects treatments for sleep problems in Parkinson's disease.
Anticipated Outcome:
We anticipate that we will establish the basis for sleep disordered breathing (obstructive sleep apnea) in Parkinson's disease by correlating loss of serotonin-using nerve cells with sleep disordered breathing.
Progress Report
We have studied over 50 PD subjects with a combination of laboratory evaluations of sleep behavior and positron emission tomography (PET) imaging to assess the integrity of brain serotonin neurons. Participating PD subjects undergo systematic clinical and behavioral evaluations, motor performance evaluations, and PET imaging of dopamine and acetylcholine brain systems. We found that over 50% of PD subjects studied exhibited at least moderate SDB. There was no correlation with PET measures of either brain serotonin or dopamine changes. Preliminary analysis suggests that changes in some brain acetylcholine pathways are related to another sleep disorder, REM sleep behavior disorder. Analysis is proceeding to compare changes in brain serotonin, dopamine, and acetylcholine systems with a spectrum of disabling features of PD.
Papers:
Bohnen NI, Müller MLTM, Kotagal V, Koeppe RA, Kilbourn MA, Albin RL, Frey KA. Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson disease. Brain, 133:1747-1754, 2010. PMCID: PMC2877903
Chotinaiwattarakul W, Dayalu P, Chervin RD, Albin RL. Risk of sleep-disordered breathing in Parkinson’s disease. Sleep Breath. 2010 May 16. [Epub ahead of print] PMCID: PMC2978748 [Available on 2011/11/1]
Müller MLTM, Albin RL, Bohnen NI. Association of cardinal motor symptoms in mild to moderate Parkinson disease with region-specific dopaminergic transporter activity. Eur Neurol J, In Press, 2010.
Abstracts (Accepted for American Academy of Neurology Annual Meeting, 4/11):
Bohnen N, Muller M, Lelieveld I, Frey K, Albin R (2011) Raphe and Limbic Cortical Serotonergic Denervation, Depressive Symptoms, and Mental Rigidity in Parkinson Disease. Neurology: Accepted.
Gallagher G, Muller M, Lelieveld I, Frey K, Albin R, Bohnen N (2011) Cortical Serotonergic Innervation Is a Determinant of Cognitive Flexibility in Non-Demented Patients with Parkinson Disease. Neurology: Accepted.