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Cited by 390Circadian rhythm and melatoninParkinson's Disease Mechanisms and TreatmentsSleep and related disorders

Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease

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Videnovic, Aleksandar, Noble, Charleston, Reid, Kathryn J., Peng, Jie, Turek, Fred W., Marconi, Angelica, Rademaker, Alfred W., Simuni, Tanya +2 more·2014·JAMA Neurology
DOI 10.1001/jamaneurol.2013.6239PMC PMC4078989
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Abstract

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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  • Compared with healthy aged people, individuals with AD or PD show considerably lower melatonin rhythm amplitudes and excessive sleepiness, as well as other sleep-wake cycle disturbances, such as later sleep onsets.

    “Compared with healthy aged people, individuals with AD or PD show considerably lower melatonin rhythm amplitudes and excessive sleepiness, as well as other sleep–wake cycle disturbances, such as later sleep onsets254–258.”

    From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [258]

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Authors
Videnovic, A., Noble, C., Reid, K. J., Peng, J., Turek, F. W., Marconi, A., Rademaker, A. W., Simuni, T., Zadikoff, C., & Zee, P. C.
Affiliations
  • Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts2Department of Neurology, Northwestern University, Chicago, Illinois
  • Northwestern University (US)
ORCID
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2014-04-01
Volume
71
Issue
4
Pages
463
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2013.6239
PMC
PMC4078989
OpenAlex
W1980509662
Cited by
390
References
51
Citations by year
2026: 22 · 2025: 46 · 2024: 33 · 2023: 29 · 2022: 41 · 2021: 43 · 2020: 31 · 2019: 28 · 2018: 27 · 2017: 34 · 2016: 33 · 2015: 11 · 2014: 12
FWCI
14.63
Type
journal article
Language
en
Open access
Locations
  • JAMA Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR000150)
  • National Institute on Alcohol Abuse and Alcoholism (R01AA020216)
  • National Institute on Aging (P01-AG11412., P01AG011412)
  • National Heart, Lung, and Blood Institute (R01HL090873, R01HL105549, UM1HL112856)
  • National Institute of Neurological Disorders and Stroke (K23NS072283, U10NS053377, U01NS050324, U01NS050095)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
excessive daytime sleepiness, melatonin rhythm, circadian dysfunction, sleep-wake disturbances, sleep quality, melatonin secretion, non-motor symptoms, circadian phase, dopaminergic therapy, phototherapy, exercise therapy, melatonin supplementation, melatonin receptor agonists
MeSH terms
Aged, Circadian Rhythm, Cross-Sectional Studies, Female, Humans, Disorders of Excessive Somnolence, Male, Melatonin, Middle Aged, Parkinson Disease, Registries, Severity of Illness Index, Cohort Studies, Biomarkers

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