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Sleep and circadian rhythm regulation in early Parkinson disease.

ABSTRACT: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood.To define the sleep and circadian phenotype of patients with early-stage Parkinson disease.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).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-Erb?).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.Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.

SUBMITTER: Breen DP

PROVIDER: S-EPMC4119609 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Sleep and circadian rhythm regulation in early Parkinson disease.

Breen David P DP Vuono Romina R Nawarathna Upekshani U Fisher Kate K Shneerson John M JM Reddy Akhilesh B AB Barker Roger A RA

JAMA neurology 20140501 5

<h4>Importance</h4>Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood.<h4>Objective</h4>To define the sleep and circadian phenotype of patients with early-stage Parkinson disease.<h4>Design, setting, and participants</h4>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-c ...[more]

PMID: 24687146

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Project description:Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72?h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns.

Dataset Information

Sleep and circadian rhythm regulation in early Parkinson disease.

Publications

Sleep and circadian rhythm regulation in early Parkinson disease.

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