Microbiome Composition and Function Contributes to Cognitive Impairment and Neuroinflammation in...
Parkinson DiseaseCognitive impairment is a common non-motor symptom among individuals living with Parkinson's disease (PD). Traditionally, cognitive impairment is thought to reflect disruptions in dopaminergic frontal-striatal systems. However, the current conceptualization does not thoroughly explain the heterogeneous profiles or trajectories of cognitive impairment in PD; suggesting that alternative mechanisms may contribute to cognitive impairments. Identification of alternative mechanisms of cognitive impairment may lead to better prognostic prediction and yield novel treatment targets. The gut is implicated as a site of early pathology in PD. Early signs of PD pathology (alpha synuclein and Lewy body aggregates) are detected in the gastrointestinal tract years before motor symptoms manifest. Recent studies provide evidence that individuals with PD have an altered gut-bacterial composition (termed dysbiosis) relative to controls. To date, dysbiosis is linked to more severe motor symptoms and certain non-motor symptoms (constipation, REM behavioral sleep disorder) in PD, but the relationship between dysbiosis and cognitive impairment remains unknown. Animal studies support the hypothesis that microbiota composition play a direct role in cognitive impairment. Germ free (GF) mice demonstrate deficits in cognition. Specifically, findings suggest that a disrupted gut- microbial environment in conjunction with elevated stress hormones may create an imbalance of pro- inflammatory vs. anti-inflammatory cytokines that induces potentially reversible cognitive impairments. In human studies among individuals with PD, neuroinflammatory markers are associated with cognitive impairment. However, the relationship between dysbiosis, neural inflammation and cognitive functioning remains unknown. This model has incredible clinical implications, as microbiota dysbiosis may represent a reversible risk factor for cognitive impairment. The proposed study will examine the hypothesis that dysbiosis contributes to increased neuroinflammation and cognitive impairment. Microbiota composition/function, neuroinflammatory markers and cognitive functioning will be examined in 100 participants with PD. Analyses of microbiota composition/function will examine abundance of amplicon sequence variants (ASVs; 16s), bacterial species/strains (metagenomics), microbial genes, and functional pathways. We hypothesize that microbiota composition/function will be associated with inflammatory markers (e.g. interleukin-6, tumor necrosis factor-alpha, c-reactive protein) and cognitive impairment.
Diaphragmatic Thickness and Pulmonary Function in Parkinson's Disease
Parkinson's Disease and ParkinsonismUltrasound can give important information about the morphology of the diaphragm and the amount of contraction. Our aim, with the prediction that a restrictive pathology will occur in the pulmonary function with the addition of camptocormia in Parkinson's patients; to compare respiratory functions in Parkinson's patients with and without camptocormia, to investigate the correlation between ultrasonographically measured diaphragmatic thickness and pulmonary function test values.
Earlier Diagnosis and Better Treatment Mission Related to the Cohort Programme
Parkinson DiseaseThe Luxembourg Parkinson's Study is an ongoing longitudinal nationwide monocentric observational study. It collects extensive clinical, molecular, genetic, and digital device-based longitudinal data, as well as foreseen post-mortem diagnostic validation (Hipp et al., 2018). The cohort consists of more than 1,600 participants from Luxembourg and the Greater Region, comprising patients with typical PD or atypical parkinsonism - irrespective of disease stage, age, cognitive status, comorbidities, or linguistic background - followed-up annually and age- and sex-matched healthy control subjects followed-up every 4 years. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, the investigators have implemented an open-source digital platform that has been partly harmonized with other international PD cohort studies. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies (including blood, urine, stool, saliva, hair, skin biopsy and cerebrospinal fluid). All data and samples are stored, curated, and integrated into state-of-the-art data and biobank facilities.
Flexible Reaching Control in Parkinson Disease
Parkinson DiseaseCurrent research and theories have highlighted that the parameters linked to movement planning, e.g. the decision to select a movement goal, and adaptation, e.g. the ability to update control dependent on a novel dynamical context, are update quickly and within an ongoing movement in the general population. In parallel, it has been suggested that the evaluation of movement costs is a function of the basal ganglia, and it is impaired in Parkinson disease (PD). Here the investigators want to test whether these mechanisms also alter the ability of patients to update control during an ongoing action. A positive result would confirm that movement-related costs and dynamical representations depend on the integrity of the basal ganglia, in contrast a negative result would indicate that the deficit in PD is more specifically related to movement initiation, which would invite one to reconsider the cause of bradykinesia in this population.
Gait Control in Parkinson Disease
Parkinson DiseasePrevious work has shown that a statistical property of gait characterised by long-range autocorrelation functions is altered in Parkinson disease (PD). On the other hand it has been suggested that the same property is linked to the ability in healthy humans to co-regulate the amplitude and cadence of strides towards maintaining a constant speed. Here the investigators want to better understand why it is altered in PD by measuring the transitions between gait instructed by a metronome, and gait without metronome. The experimental conditions will allow the comparisons between these transitions across PD and healthy groups of volunteers, and assess differences based on statistical and computational modelling. The link with potential freezing episodes will also be studied to assess whether the statistical determinants of gait control in this population can be used as a proxy or predictor of the occurence of freezing episodes.
Visualization of the STN and GPi for DBS
Deep Brain StimulationParkinson DiseaseThe purpose of the study is to determine if using SIS System for DBS planning results in less distance between the planned target location and the actual implanted lead location than DBS planning without SIS System.
Clinical Outcomes for Deep Brain Stimulation
Parkinson DiseaseEssential Tremor1 moreThe object of this study is to longitudinally collect clinical outcomes of patients receiving deep brain stimulation for movement disorders with the objective of making retrospective comparisons and tracking of risks, benefits, and complications.
Clinical Laboratory Evaluation of Chronic Autonomic Failure
Parkinson's DiseaseMultiple System Atrophy1 moreBackground: The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure. Objective: To improve testing for conditions that cause autonomic nervous system failure. Eligibility: People ages 18 and older in one of these categories: Their blood pressure drops when they get up. They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation Design: All participants will be screened with: Medical history Physical exam Blood and urine tests Some participants will be screened with: Heart and breathing tests IV placement into an arm vein Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood. Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and: Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture. Lumbar puncture: A needle is inserted between the bones in the back to collect fluid. MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical. Bladder catheter placement to collect urine Skin biopsies: A punch tool removes a small skin sample. Tests to see how the pupils react to light Smelling tests Thinking and memory tests Questionnaires Participants may have a visit about 2 years later to repeat tests.
Cohort Study to Identify Predictor Factors of Onset and Progression of Parkinson's Disease
Parkinson DiseaseObservational, prospective, monocentric study to assess clinical features, imaging and biologic biomarkers in Parkinson disease (PD) patients and rate of progression compared to healthy controls (HC) and subjects at risk to develop PD. The primary objective of this study is to identify clinical, imaging and biologic markers of PD onset and progression for use in clinical trials of disease-modifying therapies.
Registry of Deep Brain Stimulation With the VERCISE™ System: Vercise DBS Registry
Parkinson's DiseaseThe purpose of this registry is to compile characteristics of world-wide outcomes for the use of Boston Scientific's commercially available Vercise DBS System in the treatment of Parkinson's disease. The utilization of Image Guided Programming (IGP), and other commercially available programming features, used as planning tools for the programming of patients with Boston Scientific's Vercise DBS System are also evaluated. Additionally, the utilization of the DBS Illumina 3D feature that may be used for the programming of patients with Boston Scientific's Vercise DBS Systems is also evaluated.