Idiopathic REM sleep behaviour 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: 21.82). 04/2013; 12(5). DOI: 10.1016/S1474-4422(13)70054-1
Source: PubMed

ABSTRACT 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.

  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    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 · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Study Objectives: Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed. Design: Between-groups, single time point imaging. Setting: UTHSC-H 3 telsa MRI center. Participants: Ten patients with RBD, 11 patients with PD, and 10 age-matched controls. Interventions: NA. Measurements and Results: We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and agematched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD. Conclusions: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.
    Sleep 12/2013; 36(12):1885-92. DOI:10.5665/sleep.3222 · 5.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The major neurodegenerative diseases are characterised by a disabling loss of the daily pattern of sleep and wakefulness, which may be reflective of a compromise to the underlying circadian clock that times the sleep cycle. At a molecular level, the canonical property of neurodegenerative diseases is aberrant aggregation of otherwise soluble neuronal proteins. They can thus be viewed as disturbances of proteostasis, raising the question whether the two features - altered daily rhythms and molecular aggregation - are related. Recent discoveries have highlighted the fundamental contribution of circadian clocks to the correct ordering of daily cellular metabolic cycles, imposing on peripheral organs such as the liver a strict programme that alternates between anabolic and catabolic states. The discovery that circadian mechanisms are active in local brain regions suggests that they may impinge upon physiological and pathological elements that influence pro-neurodegenerative aggregation. This review explores how introducing the dimension of circadian time and the circadian clock might refine the analysis of aberrant aggregation, thus expanding our perspective on the cell biology common to neurodegenerative diseases.
    Current opinion in neurobiology 06/2013; 23(5). DOI:10.1016/j.conb.2013.05.004 · 6.77 Impact Factor
Show more

Brad Boeve