Active clinical trials for "REM Sleep Behavior Disorder"

Up to 60% of Parkinson's Disease (PD) patients suffer from REM sleep behavior disorder (RBD), a parasomnia. This disorder is thought to be related to a dysfunction of limbic system and brainstem. Impulse control disorders (ICD) are found in about 14% of PD patients taking dopaminergic drugs. These disorders are thought to be related to a dysfunction of meso-cortico-limbic pathways which belong to the so-called "reward system". A strong link was found between these two disorders and therefore the investigators believe that RBD is associated with impaired reward system. The main objective of this study is to evaluate differences in brain activation between PD patients with and without RBD. The investigators hypothesize that PD patients with RBD have a more severe dysfunction of the reward system (hypoactivation of the meso-cortico-limbic pathway) than patients without RBD, explaining their susceptibility to ICD when exposed to high doses of dopaminergic treatment.

This is a prospective cohort study to evaluate degenerative changes in the brain by performing functional imaging analysis in patients with RBD and its correlations with clinical symptoms and dopaminergic degeneration. This study also evaluates cognitive changes with functional imaging measures and olfactory and other premotor symptoms of Lewy body disease. This study also collects gene extracts and sera to develop a biomarker for early detection of neurodegeneration.

Background: Previous studies have confirmed that most patients with idiopathic REM sleep behaviour disorder (iRBD) eventually develop neurodegenerative diseases. In addition, REM sleep without atonia (RSWA), a hallmark of RBD feature, is a significant predictor of development of neurodegenerative diseases in patients with iRBD. Some preliminary studies have implied that isolated RSWA in the absence of RBD symptoms may also indicate neurodegeneration. However, this speculation needs to be confirmed by more refined study with sophisticated measures in both RSWA and markers of neurodegeneration Objectives: 1) to determine the differences in striatal dopamine transmission and other markers of neurodegeneration among individuals with isolated RSWA and healthy controls; 2) to examine the correlation of severity of RSWA with striatal dopamine transmission. Design: Case-control study Setting: Community-based sample Participants: 1) iRBD first degree relatives with isolated RSWA (n=18) 2) iRBD first degree relatives without isolated RSWA (n=18) 3) Community-based health controls without isolated RSWA (n=18) Main outcome measures: The dopamine transmission as measured by triple-tracer PET/ CT imaging protocol including 18F-DOPA, 11C-Raclopride and 18F-FDG images; Brain glucose metabolism and neurocognitive measures; Severity of EMG activity during REM sleep

To determine whether retinal abnormalities, as measured by high definition optical coherence tomography (HD-OCT) and visual electrophysiology techniques can be used as a clinical biomarker to monitor disease progression overtime in patients with Parkinson disease. To establish whether these measures can be used to identify patients with PD in the premotor phase. To define the rate of progression of retinal abnormalities in PD (both in the motor and premotor stages) for potential use as a clinical outcome measure

With the global ageing population, neurodegenerative disorders including synucleinopathy are major burdens to patients, carers and society. Synucleinopathy refers to a group of neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein protein in the central nervous system (CNS). Common examples of synucleinopathy are Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Among all the premotor clinical markers that have been identified, a sleep disorder known as REM sleep behavior disorder (RBD) is associated with the highest likelihood ratio of developing PD. In addition, it has been shown that almost all RBD patients (over 80%) eventually developed neurodegenerative diseases after 14 years follow-up. Gut microbiota and synucleinopathy In recent years, several key studies have advanced our understanding regarding the roles that brain-gut-microbiota axis plays in the pathogenesis of brain diseases, including PD. It has been shown that gut microbiota is implicated in a series of pathophysiological changes in PD, including motor deficits, microglia activation, and αSyn pathology in mice model with overexpression of αSyn. Furthermore, some microbiotas, such as enterobacteriaceae, have been shown to be positively associated with the severity of PD symptoms, including postural instability and gait difficulty. Limitations in previous studies and knowledge gaps Nonetheless, the answers for several key questions regarding the roles of gut microbiota in the progression of synucleinopathy are still unclear. First, whether these microbiotas found in previous studies are the causes or the effects of PD. For example, medications treating PD may also affect the gut microbiome. Moreover, the microbiota may be affected by a number of factors commonly found in PD, such as constipation per se and diet. In this regard, an influential hypothesis of synucleinopahy was proposed by Braak et al at which the early premotor features including gastro-enterology symptoms, such as constipation and RBD would predate the onset of PD by some years. Thus, it is crucial to compare the microbiota among individuals at different stages of synucleinopathy. In view of slow progression of synucleinopathy and a relatively low prevalence of synucleinopathy in the general population, it is impractical to run a prospective study to examine this research question. Finally, gut microbiota is determined by both genetic and environmental factors. A family cohort design will help to understand the genetic and environmental influences on the association between microbiota and synucleinopathy.

REM sleep behavior disorder (typical or 'idiopathic' RBD, iRBD) is a novel and distinct parasomnia characterized by recurrent dream enactment behaviours and polysomnographic features of loss of normal REM-sleep related muscle atonia, with a male predominance commonly occurring at the age of 60's. A majority of the patients with iRBD will eventually develop α-synucleinopathy (e.g., Parkinson's disease). On the other hand, growing evidence reveals a specific group of psychiatric patients demonstrating comparable clinical RBD features (pRBD) (e.g., abnormal REM-related electromyographic (EMG) activities) as found in typical iRBD, but with less male predominance occurring at the age of mid 40's to early 50's. Although recent findings from both cross-sectional and prospective studies have suggested that pRBD is likely to be a persistent parasomnia with close association with clinical and neuroimaging biomarkers related to neurodegeneration, the nosology of the development of RBD symptoms among patients with psychiatric disorders, notably major depressive disorder, remains unclear as to whether they are simply antidepressants related, or represent a part of the early phase of α-synucleinopathy neurodegeneration. Family studies on iRBD have confirmed a significant familial aggregation of iRBD with a higher rate of RBD cases and presence of prodromal neurodegenerative biomarkers (e.g. tonic EMG activity during REM sleep, constipation, and motor function impairments) of α-synucleinopathy neurodegeneration among first-degree relatives (FDRs) of patients with iRBD. Thus, the investigators propose this family study to examine the following hypotheses: 1) FDRs of patients with pRBD have a higher rate of RBD symptoms and its core features when compared to FDRs of controls with and without psychiatric disorders; 2) FDRs of pRBD are more likely to exhibit the features associated with prodromal markers of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders; 3) FDRs of patients with pRBD have a higher rate of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders. A total of 176 FDRs from each group (e.g., pRBD cases, psychiatric controls, and healthy controls) will be recruited to undergo a face-to-face clinical interview and a series of assessments on prodromal markers of Parkinson's diseases (as according to the International Parkinson and Movement Disorder Society research criteria) respectively. All FDRs with possible RBD and a subset of FDRs without possible RBD will be invited to undergo one-night video-polysomnographic assessment to confirm the clinical diagnosis of RBD and to assess the abnormal REM-related EMG muscle activities.

We hypothesise that a real-time quaking induced conversion assay for the detection of pathological alpha-synuclein (α -syn RTQuIC) can be used to differentiate between cases of idiopathic REM-sleep behaviour disorder (RBD) and RBD that is symptomatic of prodromal α-synucleinopathies.

This study is a prospective study with a mean of 5-year follow-up interval, aims to monitor the progression of α-synucleinopathy neurodegeneration by the evolution of prodromal markers and development of clinical disorders in first-degree relatives (FDRs) of idiopathic REM Sleep Behavior Disorder (RBD) patients and healthy controls.

Up to 50% of Narcolepsy-cataplexy (NC) patients suffer from REM sleep behavior disorder (RBD), a parasomnia. A strong link was found between RBD and impulse control disorders (ICD) in Parkinson disease (PD) patients. ICD are thought to be related to a dysfunction of meso-cortico-limbic pathways which belong to the so called ''reward system''. A recent study in IRMf shows that RBD is associated with impaired reward system. A strong link was found between these two disorders and therefore we believe that RBD is associated with impaired reward system in NC The main objective of this study is to evaluate differences in brain activation between NC patients with and without RBD. The investigators hypothesize that NC patients with RBD have a more severe dysfunction of the reward system (hypoactivation of the meso-cortico-limbic pathway) than patients without RBD.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is characterized by nocturnal violence, increased muscle tone during REM sleep and the lack of any other neurological disease. However, iRBD can precede parkinsonism and dementia by several years. The causes of the loss of muscle atonia during REM sleep in these patients are unclear. Using 3 T MRI and neuromelanin- sensitive sequences, the signal intensity was previously found to be reduce in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and RBD. Here, the investigators aimed at studying the integrity of the locus coeruleus/ subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with iRBD and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects will undergo a clinical examination, motor, cognitive, autonomous, psychological, olfactory and color vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging.