Sleep and Circadian Rhythm Regulation in Early Parkinson Disease
Open accessAbstract
IMPORTANCE: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE: To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS: Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES: Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα). RESULTS: Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE: Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.
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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 [255]
In a cohort of 239 individuals with Parkinson's disease, sleep latency is significantly increased, sleep efficiency and REM are reduced, melatonin levels are reduced, and BMAL1 serum expression rhythms are lost.
“This study shows significantly increased sleep latency, reduced sleep efficiency and reduced REM, along with reduced melatonin levels and a loss of BMAL1 serum expression rhythms, in a cohor of 239 individuals with PD.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [255]
A lack of time-dependent variation in Bmal1 expression in Parkinson's disease patients was recently confirmed in another study.
“A lack of time-dependent variation in Bmal1 expression in PD patients was recently confirmed in another study (Breen et al., 2014).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Breen et al., 2014
Both studies reported decreased amplitude of melatonin secretion in Parkinson's disease.
“However, both studies reported decreased amplitude of melatonin secretion.”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Breen et al., 2014
Two other recent studies did not show alterations in the circadian phase of melatonin secretion in Parkinson's disease.
“Two other recent studies did not show alterations in the circadian phase of melatonin secretion (Breen et al., 2014, Videnovic et al., 2014a, Videnovic et al., 2014b).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Breen et al., 2014
Parkinson's disease patients had elevated cortisol levels and reduced melatonin levels.
“PD patients had elevated cortisol levels and reduced melatonin levels.”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Breen et al., 2014
While Parkinson's disease patients exhibit a preserved circadian rhythm of cortisol, the amount of cortisol secreted is elevated in early PD.
“While PD patients exhibit a preserved circadian rhythm of cortisol, the amount of cortsiol secreted is elevated in early PD (Breen et al., 2014).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Breen et al., 2014
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- Authors
- Breen, D. P., Vuono, R., Nawarathna, U., Fisher, K., Shneerson, J. M., Reddy, A. B., & Barker, R. A.
- Affiliations
- University of Cambridge (GB)
- Royal Papworth Hospital (GB)
- Corresponding author
- Breen, David P.
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2014-05-01
- Volume
- 71
- Issue
- 5
- Pages
- 589
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4119609
- OpenAlex
- W1996955271
- Cited by
- 440
- References
- 35
- Citations by year
- 2026: 31 · 2025: 37 · 2024: 42 · 2023: 42 · 2022: 44 · 2021: 47 · 2020: 36 · 2019: 31 · 2018: 35 · 2017: 36 · 2016: 35 · 2015: 11 · 2014: 12
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Wellcome Trust (100574, 100333/Z/12/Z, 100333)
- Parkinson's UK (J-0801)
- 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
- Parkinson's disease, sleep disorders, circadian rhythm, early-stage Parkinson's disease, sleep architecture, sleep latency, REM sleep, serum cortisol, melatonin, clock genes, Bmal1, Per2, NR1D1, non-motor symptoms, quality of life
- MeSH terms
- Aged, Circadian Rhythm, Female, Humans, Male, Middle Aged, Parkinson Disease, Sleep, Cohort Studies, Case-Control Studies, Sleep Disorders, Circadian Rhythm, Early Diagnosis
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