Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease

Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dy...

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Vydáno v:	JAMA neurology Ročník 71; číslo 4; s. 463
Hlavní autoři:	Videnovic, Aleksandar, Noble, Charleston, Reid, Kathryn J, Peng, Jie, Turek, Fred W, Marconi, Angelica, Rademaker, Alfred W, Simuni, Tanya, Zadikoff, Cindy, Zee, Phyllis C
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.04.2014
Témata:	Aged Biomarkers - blood Circadian Rhythm - physiology Cohort Studies Cross-Sectional Studies Disorders of Excessive Somnolence - epidemiology Disorders of Excessive Somnolence - metabolism Disorders of Excessive Somnolence - physiopathology Female Humans Male Melatonin - secretion Middle Aged Parkinson Disease - epidemiology Parkinson Disease - metabolism Parkinson Disease - physiopathology Registries Severity of Illness Index
ISSN:	2168-6157, 2168-6157
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Abstract	Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.
AbstractList	Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD.IMPORTANCEDiurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD.To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics.OBJECTIVETo determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics.A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University.DESIGN, SETTING, AND PARTICIPANTSA cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University.Twenty-four hour monitoring of serum melatonin secretion.INTERVENTIONSTwenty-four hour monitoring of serum melatonin secretion.Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm.MAIN OUTCOMES AND MEASURESClinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm.Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm.RESULTSPatients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm.Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.CONCLUSIONS AND RELEVANCECircadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD. Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.
Author	Peng, Jie Noble, Charleston Rademaker, Alfred W Turek, Fred W Reid, Kathryn J Zadikoff, Cindy Videnovic, Aleksandar Marconi, Angelica Simuni, Tanya Zee, Phyllis C
Author_xml	– sequence: 1 givenname: Aleksandar surname: Videnovic fullname: Videnovic, Aleksandar organization: Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts2Department of Neurology, Northwestern University, Chicago, Illinois – sequence: 2 givenname: Charleston surname: Noble fullname: Noble, Charleston organization: Department of Neurology, Northwestern University, Chicago, Illinois3Department of Physics, Lund University, Lund, Sweden – sequence: 3 givenname: Kathryn J surname: Reid fullname: Reid, Kathryn J organization: Department of Neurology, Northwestern University, Chicago, Illinois – sequence: 4 givenname: Jie surname: Peng fullname: Peng, Jie organization: Department of Preventive Medicine, Northwestern University, Chicago, Illinois – sequence: 5 givenname: Fred W surname: Turek fullname: Turek, Fred W organization: Department of Neurobiology, Northwestern University, Chicago, Illinois – sequence: 6 givenname: Angelica surname: Marconi fullname: Marconi, Angelica organization: Department of Neurology, Northwestern University, Chicago, Illinois – sequence: 7 givenname: Alfred W surname: Rademaker fullname: Rademaker, Alfred W organization: Department of Preventive Medicine, Northwestern University, Chicago, Illinois – sequence: 8 givenname: Tanya surname: Simuni fullname: Simuni, Tanya organization: Department of Neurology, Northwestern University, Chicago, Illinois – sequence: 9 givenname: Cindy surname: Zadikoff fullname: Zadikoff, Cindy organization: Department of Neurology, Northwestern University, Chicago, Illinois – sequence: 10 givenname: Phyllis C surname: Zee fullname: Zee, Phyllis C organization: Department of Neurology, Northwestern University, Chicago, Illinois
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Snippet	Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian...
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SubjectTerms	Aged Biomarkers - blood Circadian Rhythm - physiology Cohort Studies Cross-Sectional Studies Disorders of Excessive Somnolence - epidemiology Disorders of Excessive Somnolence - metabolism Disorders of Excessive Somnolence - physiopathology Female Humans Male Melatonin - secretion Middle Aged Parkinson Disease - epidemiology Parkinson Disease - metabolism Parkinson Disease - physiopathology Registries Severity of Illness Index
Title	Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease
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