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Original Investigation |

Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease

Aleksandar Videnovic, MD, MSc1,2; Charleston Noble, BA2,3; Kathryn J. Reid, PhD2; Jie Peng, MSc4; Fred W. Turek, PhD5; Angelica Marconi, BS2; Alfred W. Rademaker, PhD4; Tanya Simuni, MD2; Cindy Zadikoff, MD, MSc2; Phyllis C. Zee, MD, PhD2
[+] Author Affiliations
1Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
2Department of Neurology, Northwestern University, Chicago, Illinois
3Department of Physics, Lund University, Lund, Sweden
4Department of Preventive Medicine, Northwestern University, Chicago, Illinois
5Department of Neurobiology, Northwestern University, Chicago, Illinois
JAMA Neurol. 2014;71(4):463-469. doi:10.1001/jamaneurol.2013.6239.
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Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Interventions  Twenty-four hour monitoring of serum melatonin secretion.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

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Figure.
Plasma Melatonin Concentration During 24-Hour Modified Constant Routine Monitoring

A, Patients with Parkinson disease (PD) and controls. B, Patients with PD with and without excessive daytime sleepiness (EDS). Circadian time is measured as the time since awaking. Data markers and whiskers indicate mean (SE).

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