Idiopathic REM sleep behavior disorder in the development of Parkinson's disease

Department of Neurology and Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: .
The Lancet Neurology (Impact Factor: 21.9). 04/2013; 12(5). DOI: 10.1016/S1474-4422(13)70054-1
Source: PubMed


Parkinson's disease is a progressive neurodegenerative disorder associated with Lewy body disease pathology in central and peripheral nervous system structures. Although the cause of Parkinson's disease is not fully understood, clinicopathological analyses have led to the development of a staging system for Lewy body disease-associated pathological changes. This system posits a predictable topography of progression of Lewy body disease in the CNS, beginning in olfactory structures and the medulla, then progressing rostrally from the medulla to the pons, then to midbrain and substantia nigra, limbic structures, and neocortical structures. If this topography and temporal evolution of Lewy body disease does occur, other manifestations of the disease as a result of degeneration of olfactory and pontomedullary structures could theoretically begin many years before the development of prominent nigral degeneration and the associated parkinsonian features of Parkinson's disease. One such manifestation of prodromal Parkinson's disease is rapid eye movement (REM) sleep behaviour disorder, which is a parasomnia manifested by vivid dreams associated with dream enactment behaviour during REM sleep. Findings from animal and human studies have suggested that lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause REM sleep behaviour disorder phenomenology, and degeneration of these structures might explain the presence of REM sleep behaviour disorder years or decades before the onset of parkinsonism in people who develop Parkinson's disease.

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    • "Several non-motor features including REM sleep behavioral disorder, olfactory dysfunction, depression, and bowel dysfunction often precede the classic motor features of PD, sometimes by many years. REM sleep behavior disorder in particular is associated with a higher risk for development of subsequent parkinsonism and dementia [26]. Depression, personality traits, and reduced interest in new experiences have been associated with early PD, and olfactory dysfunction is present in over 90% of patients. "
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    ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.
    Parkinsonism & Related Disorders 09/2015; DOI:10.1016/j.parkreldis.2015.09.048 · 3.97 Impact Factor
    • "For instance, the proposed circuitry underlying RBD [70] [71] [157] is not yet confirmed. "
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    ABSTRACT: Parkinson disease is one of the neurodegenerative diseases that benefited the most from the use of non-human models. Consequently, significant advances have been made in the symptomatic treatments of the motor aspects of the disease. Unfortunately, this translational success has been tempered by the recognition of the debilitating aspect of multiple non-motor symptoms of the illness. Alterations of the sleep/wakefulness behavior experienced as insomnia, excessive daytime sleepiness, sleep/wake cycle fragmentation and REM sleep behavior disorder are among the non-motor symptoms that predate motor alterations and inevitably worsen over disease progression. The absence of adequate humanized animal models with the perfect phenocopy of these sleep alterations contribute undoubtedly to the lack of efficient therapies for these non-motor complications. In the context of developing efficient translational therapies, we provide an overview of the strengths and limitations of the various currently available models to replicate sleep alterations of Parkinson's disease. Our investigation reveals that although these models replicate dopaminergic deficiency and related parkinsonism, they rarely display a combination of sleep fragmentation and excessive daytime sleepiness and never REM sleep behavior disorder. In this light, we critically discuss the construct, face and predictive validities of both rodent and non-human primate animals to model the main sleep abnormalities experienced by patients with PD. We conclude by highlighting the need of integrating a network-based perspective in our modeling approach of such complex syndrome in order to celebrate valid translational models. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Sleep Medicine Reviews 02/2015; DOI:10.1016/j.smrv.2015.02.005 · 8.51 Impact Factor
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    • "The pathological reason for the link between RWA and PD severity is not clear. One possibility is that RWA is related to the temporal sequence of synuclein deposition described by Braak's staging hypothesis (Braak et al., 2004; Boeve, 2013); however, the mechanisms underlying RWA remain poorly understood. A recent study using neuromelanin-sensitive magnetic resonance "
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    ABSTRACT: Objective The aim of the present study was to investigate the relationship between rapid eye movement (REM) sleep without atonia (RWA) and Parkinson’s disease (PD) progression. Methods We quantified tonic and phasic RWA by performing polysomnography in 198 PD patients. We then correlated the extent of RWA with clinical patient characteristics. Results PD patients were categorized into quartiles of tonic and phasic RWA. We found that patients with more RWA tended to be older and have longer PD duration, a greater likelihood of REM sleep behavior disorder (RBD), more advanced Hoehn & Yahr (H&Y) stage, a higher dose of parkinsonian medication, poorer cognitive performance, worse quality of life, and more severe sleep disturbance. After adjusting for age, sex, and PD duration, patients in the highest two RWA quartile were more likely to have severe PD (H&Y stage⩾3.0) than those in the lowest RWA quartile. Conclusions These findings provide evidence that RWA, especially with regard to tonic muscle activity, is associated with PD severity. Significance Further studies are warranted to determine the importance and utility of assessing RWA to evaluate sleep in PD patients.
    Clinical Neurophysiology 09/2014; 126(6). DOI:10.1016/j.clinph.2014.09.014 · 3.10 Impact Factor
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Brad Boeve