Idiopathic REM sleep behaviour disorder in the development of Parkinson's disease
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.
SourceAvailable from: Raymond Chong[Show abstract] [Hide abstract]
ABSTRACT: Background Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson’s disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin is also thought to be involved in the regulation of circadian rhythm. Here we evaluated the relationships among the receptor, niacin levels and EEG night-sleep in individuals with PD. Methods and Findings GPR109A expression (blood and brain), niacin index (NAD-NADP ratio) and cytokine markers (blood) were analyzed. Measures of night-sleep function (EEG) and perceived sleep quality (questionnaire) were assessed. We observed significant up-regulation of GPR109A expression in the blood as well as in the substantia nigra (SN) in the PD group compared to age-matched controls. Confocal microscopy demonstrated co-localization of GPR109A staining with microglia in PD SN. Pro and anti-inflammatory cytokines did not show significant differences between the groups; however IL1-β, IL-4 and IL-7 showed an upward trend in PD. Time to sleep (sleep latency), EEG REM and sleep efficiency were different between PD and age-matched controls. Niacin levels were lower in PD and were associated with increased frequency of experiencing body pain and decreased duration of deep sleep. Conclusions The findings of associations among the GPR109A receptor, niacin levels and night-sleep function in individuals with PD are novel. Further studies are needed to understand the pathophysiological mechanisms of action of niacin, GPR109A expression and their associations with night-sleep function. It would be also crucial to study GPR109A expression in neurons, astrocytes, and microglia in PD. A clinical trial to determine the symptomatic and/or neuroprotective effect of niacin supplementation is warranted.PLoS ONE 10/2014; 9(10):e109818. DOI:10.1371/journal.pone.0109818 · 3.53 Impact Factor
Article: Malattia a corpi di Lewy[Show abstract] [Hide abstract]
ABSTRACT: La malattia a corpi di Lewy fu descritta per la prima volta nel 1984 come una demenza neurodegenerativa associata, sul piano istologico, a dei corpi di Lewy osservati principalmente nella sostanza nera della via nigrostriatale, come nella malattia di Parkinson, ma anche nelle regioni corticali. Le alterazioni neuropsicologiche che si possono osservare allo stadio del disturbo cognitivo leggero, ben prima dello stadio demenziale, sono caratterizzate da una sindrome disesecutiva con una ripercussione sulle capacità di memorizzazione e da una riduzione delle prestazioni spaziali. Sono classicamente associati dei disturbi del sonno paradosso, delle allucinazioni visive precoci, una sindrome parkinsoniana, delle fluttuazioni motorie e cognitive, una disautonomia e un’ipersensibilità ai neurolettici. Gli inibitori dell’acetilcolina-esterasi possono mostrare una certa efficacia sui disturbi cognitivi, mentre la L-dopa può fornire dei benefici riguardo alla sindrome parkinsoniana, se la sindrome allucinatoria e la disautonomia non ne impediscono l’utilizzo. Sono, d’altra parte, fortemente consigliate delle misure non farmacologiche, in particolare la gestione dei disturbi del comportamento e la fisioterapia.11/2014; 14(4). DOI:10.1016/S1634-7072(14)68870-X
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ABSTRACT: Parkinson's disease (PD) is a neurobehavioral disorder characterized by motor symptoms and signs, and non-motor abnormalities such as olfactory dysfunction, pain, sleep disorders and cognitive impairment. Amongst these alterations, sleep disturbances play an important role in the pathology, but presence of disturbed sleep is not currently considered in diagnosis. However, sleeping problems may precede by many years the classic motor abnormalities of PD and should be clinically evaluated as a potential marker before disease onset. The first disturbance reported with this potential was the disorder REM sleep behaviour and currently several other disturbances have gained importance as potential markers, such as excessive daytime sleepiness, restless legs syndrome and new evidence also points to changes in circadian rhythms. Here we present a brief review of the major evidence indicating that sleep disturbances precede the motor symptoms in PD and neurodegeneration occurs in regions that could underlie these phenomena in order to provide support for the conclusion that disturbances of sleep should be considered as valuable preclinical markers for PD.Neurochemical Research 11/2014; 40(3). DOI:10.1007/s11064-014-1488-7 · 2.55 Impact Factor