Parkinsons REM disorder

BACKGROUND: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added. OBJECTIVE: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group. METHODS: In this cross-sectional, case-control study, in a first set of analyses, we performed extensive cognitive testing on people with (n = 76) and a control group without (n = 195) probable RBD and hyposmia...

BACKGROUND: In early-stage Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) predicts poor cognitive and motor outcome. However, the baseline significance and disease evolution associated with isolated REM sleep without atonia (iRWA, ie, enhanced muscle tone during 8.7% of REM sleep, but no violent behavior) are not well understood. OBJECTIVES: The objective is to determine whether iRWA was a mild form of RBD and progressed similarly over time...

Rapid eye movement sleep behavior disorder is a parasomnia characterized by excessive muscle activity during rapid eye movement sleep (rapid eye movement sleep without atonia), along with dream enactment behavior. Isolated rapid eye movement sleep behavior disorder tends to occur in older males and is of concern due to the known link to Parkinson's disease and other synucleinopathies. When rapid eye movement sleep behavior disorder occurs in association with other neurological or general medical conditions, or resulting from the use of various substances, it is called secondary rapid eye movement sleep behavior disorder; the most common cause is neurodegenerative illness, specifically the synucleinopathies...

STUDY OBJECTIVES: A growing body of literature suggests that deep brain stimulation (DBS) to treat motor symptoms of Parkinson's disease (PD) may also ameliorate certain sleep deficits. Many foundational studies have examined the impact of stimulation on sleep following several months of therapy, leaving an open question regarding the time course for improvement. It is unknown whether sleep improvement will immediately follow onset of therapy or accrete over a prolonged period of stimulation...

BACKGROUND: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. OBJECTIVE: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. METHODS: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years...

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD...

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) may precede or follow motor symptoms in Parkinson's disease (PD). While over 70% of idiopathic RBD cases phenoconvert within a decade, a small subset develops PD after a more extended period or remains nonconverted. These heterogeneous manifestations of RBD in PD prompt subtype investigations. Premotor RBD may signify "body-first" PD with bottom-up, symmetric synucleinopathy propagation. OBJECTIVE: Explore brainstem and nigrostriatal monoaminergic degeneration pattern differences based on premotor RBD presence and duration in de novo PD patients...

BACKGROUND AND OBJECTIVES: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive. METHODS: Combining magnetic resonance (MR) spectroscopy and [11 C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD...

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III)...

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI...

Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson's disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood...

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. OBJECTIVES: To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. METHODS: Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing...

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. OBJECTIVE: The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods...

BACKGROUND: Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alpha-synucleinopathies such as Parkinson's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed in PD. However, relatively little is known about whole-brain functional brain alterations in iRBD. Here, we characterize the functional brain connectome of iRBD compared with PD patients and healthy controls (HC) using resting-state functional MRI (rs-fMRI)...

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The "body-first subtype" is associated with a prodrome of isolated REM-sleep Behavior Disorder (iRBD) and a relatively symmetric brain degeneration. The "brain-first subtype" is suggested to have a more asymmetric degeneration and a prodromal stage without RBD. This study aims to investigate the proposed difference in symmetry of the degeneration pattern in the presumed body and brain-first PD subtypes...

BACKGROUND: Adaptive immune dysfunction may play a crucial role in Parkinson's disease (PD) development. Isolated rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of synucleinopathies, including PD. Elucidating the peripheral adaptive immune system is crucial in iRBD, but current knowledge remains limited. OBJECTIVE: This study aimed to characterize peripheral lymphocyte profiles in iRBD patients compared with healthy control subjects (HCs)...

INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) have been found to have changes in cerebral perfusion and overlap of some of the lesioned brain areas. However, a consensus regarding the specific location and diagnostic significance of these cerebral blood perfusion alternations remains elusive in both iRBD and PD. The present study evaluated the patterns of cerebral blood flow changes in iRBD and PD. MATERIAL AND METHODS: A total of 59 right-handed subjects were enrolled, including 15 patients with iRBD, 20 patients with PD, and 24 healthy controls (HC)...

We recently proposed a new disease model of Parkinson's disease - the a-Synuclein Origin site and Connectome model. The model posits that the initial pathology starts either in the olfactory bulb or amygdala leading to a brain-first subtype, or in the enteric nervous system leading to a body-first subtype. These subtypes should be distinguishable early in the disease course on a range of imaging, clinical, and neuropathological markers. Here, we review recent original human studies, which tested the predictions of the model...

During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function)...

BACKGROUND: Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) represents the prodromal stage of Lewy body disorders (Parkinson's disease (PD) and dementia with Lewy bodies (DLB)) which are linked to variations in circulating cell-free mitochondrial DNA (cf-mtDNA). Here, we assessed whether altered cf-mtDNA release and integrity are already present in IRBD. METHODS: We used multiplex digital PCR (dPCR) to quantify cf-mtDNA copies and deletion ratio in cerebrospinal fluid (CSF) and serum in a cohort of 71 participants, including 1) 17 patients with IRBD who remained disease-free (non-converters), 2) 34 patients initially diagnosed with IRBD who later developed either PD or DLB (converters), and 3) 20 age-matched controls without IRBD or Parkinsonism...