Parkinson's Disease (PD)

The goal of this observational and interventional study is to understand how therapeutic deep brain stimulation (DBS) affects attention, perception and cognition in participants with Parkinson's disease (PD) and non-PD movement disorders, including essential tremor (ET) and dystonia (DT). The main questions it aims to answer are: * Does impaired control of attention and eye movement in PD alter how social cues are perceived and interpreted? * Does therapeutic DBS improve or worsen attentional and perceptual deficits for social cues in PD, ET and DT? * Can DBS be optimized to restore normal attentional control in PD while remaining an effective therapy for other aspects of the disorder. * What do parts of the brain targeted by DBS contribute to the control of attention? Using an eye tracking camera, investigators will study how participants with PD, ET and DT look at and perceive facial expressions of emotion before and after starting DBS therapy, in comparison to a group of healthy participants without ET, PD, DT or DBS. Participants with PD, ET and DT will see and rate morphed facial expressions on a computer screen in three conditions: * Before starting DBS therapy (over approximately 1 hour). * In the operating room, during the standard procedure to implant DBS electrodes, while the participant is awake (for no more than 15 minutes). * After starting DBS therapy, with brief experimental changes of DBS stimulation level and frequency (over approximately 1 hour).

The goal of this clinical trial is to learn if low-fidelity driving simulator training works to improve cognitive performance, driving behavior, and driving aptitude in individuals with Parkinson's disease. The main questions it aims to answer are: * Does low-fidelity driving simulator training improve cognitive performance? * Does low-fidelity driving simulator training improve driving performance? * Does low-fidelity driving simulator training improve driving aptitude? Researchers will compare driving simulator training to no-training (waitlist control group) to see if the low-fidelity driving simulator is effective in individuals with Parkinson's disease. Participants will: * Undergo 10 sessions of driving simulator training or be placed in the no-training group. * Training group participants will visit the driving simulator lab 2-3 times a week for 4 weeks for training. * Paper-based tests and driving simulator tests will be done before and after 10 sessions of training (or a waiting period).

This clinical trial aims to develop and test a prototype immersive gamification technology system (ImGTS) among healthy volunteers and to determine its acceptability, safety, and usability in a healthy population. The main question it aims to answer is: Does ImGTS provide an acceptable, safe, and usable therapeutic modality for patients with Parkinson's Disease? Researchers will compare a head-mounted display (HMD) system and a semi cave automatic virtual environment (semi-CAVE) system to see if they are acceptable, safe, and usable as therapy for PD. Participants will be will undergoing their assigned ImGTS intervention for four sessions (twice a week for two weeks) supervised by a trained therapist. Afterwards, they will be interviewed based on specific questionnaires used to check for acceptability, safety, and usability.

The goal of this clinical trial is to learn whether a personalized brain stimulation method called repetitive transcranial magnetic stimulation (rTMS), combined with walking exercises, is a practical and tolerable approach to help people with Parkinson's disease who experience freezing of gait (FOG). FOG is a disabling symptom where people temporarily feel stuck and unable to start walking, even though they want to move. The main questions this study aims to answer are: Can people with Parkinson's disease and FOG tolerate this combined rTMS and walking training procedure? Can researchers successfully enroll and retain participants for this multi-visit intervention? Does the combination of rTMS and gait training show early signs of improving gait and reducing freezing episodes? This study does not include a comparison or placebo group. All participants will receive the same intervention. Participants will: Attend up to 15 study visits over about 16 weeks, with the option to combine visits to reduce burden. Complete brain imaging (MRI) before and after the intervention to guide and evaluate treatment. Receive a form of brain stimulation (rTMS) using a safe, non-invasive coil placed over a specific part of the brain called the supplementary motor area (SMA). The target is personalized using each person's MRI data. Participate in walking exercises that include cognitive tasks (dual-task gait training) after each set of brain stimulation sessions. Undergo assessments of walking ability, Parkinson's disease symptoms, and brain response to stimulation. Be videotaped during walking tasks to assess gait changes, while wearing small motion sensors on the body. Complete questionnaires about symptoms, safety, and tolerability. This study is being conducted at the Medical University of South Carolina (MUSC) and includes up to 15 adults between the ages of 50 and 80 who have been diagnosed with Parkinson's disease and experience FOG. Although rTMS is already FDA-cleared for depression and other conditions, it has not been approved for freezing of gait, and its use in this study is considered investigational. The stimulation device used has been determined to be non-significant risk (NSR) by the FDA. The study does not offer direct medical benefit to participants, but results from this trial may help researchers develop future treatments and better understand how brain stimulation affects walking difficulties in Parkinson's disease. Participation is voluntary, and individuals can withdraw from the study at any time without affecting their medical care

The goal of this clinical trial (feasibility study) is to learn if a multimodal lifestyle program can improve adherence to recommended lifestyle changes in people with REM Sleep Behavior Disroder (RBD) or Parkinson's disease (PD). The main question it aims to answer is if individuals with RBD oder PD can follow a combined lifestyle program over six months Participants will take part in a six-month intervention program that includes: Physical training, Mediterranean diet counseling, Sleep counseling and cognitive training. The program will be supported by psychoeducation, skills training, and personalization to make it practical and motivating.

Impulse control disorders (ICDs) are frequently observed in Parkinson's disease (PD) and can have a major functional impact on the quality of life of both the patient and their entourage. The primary risk factor for the emergence of ICDs in PD is long-term dopaminergic treatment, but other risk factors, such as rapid eye movement sleep behavior disorder (RBD), have recently been identified. The mechanisms leading to ICDs in PD remain debated, but it has been shown that the dopaminergic mesocorticolimbic pathways play a key role in reward, learning, and reinforcement processes, as well as in the regulation of impulsivity. PET studies using \[11C\]raclopride, a tracer that allows evaluation of the postsynaptic availability of dopamine D2/D3 receptors, have demonstrated abnormal sensitization of the mesocorticolimbic dopaminergic system (the reward system), particularly in the ventral striatum, in Parkinson's patients with ICDs when presented with appetitive stimuli or during gambling tasks. However, this has never been studied in patients with and without RBD. Parkinson's patients with RBD may present greater impairment of mesocorticolimbic pathways than those without RBD, particularly abnormal sensitization and postsynaptic modifications of the dopaminergic system, which could predispose patients to the emergence of ICDs when exposed to dopaminergic agonists. Confirming a particular pattern of denervation in Parkinson's patients with RBD that may favor the emergence of ICDs constitutes a personalized medicine approach with a readily identifiable risk marker in routine clinical practice and offers the possibility of adapting the management of these patients. The main objective of this study is to investigate the availability of D2 dopaminergic receptors in subcortical structures (particularly the mesocorticolimbic system) in patients with idiopathic Parkinson's disease, depending on the presence or absence of RBD

Clozapine is a second generation antipsychotic drug used in psychiatry to treat schizophrenia, affective disorders or certain symptoms of dementia. In neurology, clozapine is frequently used and recommended to manage symptoms of psychosis associated with Parkinson's disease (PD). The risk of neutropenia or agranulocytosis associated with clozapine estimated at 1.3% is well known to doctors around the world with a peak at one month and a decrease in risk after more than a year of treatment. This risk has led to the policy of "no blood, no drugs" and monitoring of the complete blood count (CBC) weekly for 18 weeks and then monthly for the duration of treatment. Some studies suggest an increased risk of infections related to immunodeficiency induced by clozapine itself. This clozapine-induced immunodeficiency would be comparable to that encountered in patients with common variable immunodeficiency or under immunosuppressive treatment. In addition, this immunosuppressive effect linked to clozapine would not be dose dependent but time dependent. However, the only studies currently performed have been in psychiatric patients treated for schizophrenia. It seems important to specifically explore clozapine-related immunodeficiency in PD patients treated with clozapine for PD-related psychosis. In this study, the investigators propose to evaluate the variations in serum immunoglobulin levels and lymphocyte subpopulations (B, T, NK) in parkinsonian patients treated with Clozapine at 6 months and 1 year after initiation of treatment.

This multi-center pilot study compares conventional DBS (cDBS) and adaptive DBS (aDBS) in Parkinson's disease patients using the Medtronic Percept™ system. The aim of the study is to identify which patients benefit most from aDBS, and to explore patient and LFP signal characteristics as well as stimulation parameters as potential predictors of treatment preference and efficacy. The study utilizes a blinded, randomized N-of-1 trial design, where each patient tests the following: * Original cDBS settings (cDBS); * Optimized cDBS settings (O-cDBS); * Optimized aDBS settings (O-aDBS) Each setting is evaluated for a minimum of 2 and maximum of 7 days at home in a randomized order (patient blinded). The main study outcome consists of the patient's final preference among the three DBS programs: original cDBS, O-cDBS, or O-aDBS. Secondary outcomes focus on differences between cDBS, O-cDBS and O-aDBS regarding the following parameters (among others): * Quality of life (PDQ-39); * Patient satisfaction (5-point Likert Scale); * (Non)-motor fluctuations (MDS-UPDRS-III + MDS-NMS-Q); * Time spent in "ON"/"OFF" motor phases (symptom diary + MDS-UPDRS IV); * Time spent experiencing dyskinesia (symptom diary + MDS-UPDRS IV); * Time spent with the most bothersome symptom (symptom diary + MDSUPDRS IV); * Stimulation parameters; * Local field potentials. The study also incorporates real-world home-based assessments using the Experience Sampling Method (ESM) to capture motor and non-motor symptom fluctuations in daily life and identify differences among the three settings.

Gait changes in Parkinson's disease are complex, variable, and difficult to detect during short clinic assessments. The aim of this study is to collect gait measurements in Parkinson's patients through sensors in a novel shoe device, NUSHU by Magnes AG. The shoe additionally provides vibrational feedback that can potentially help gait difficulties experienced by Parkinson's patients.

The goal of this clinical trial is to learn if the oral drug candidate EC5026 is safe and targets the correct pathways to treat Parkinson's Disease in adults. It will also learn about the levels of drug that are achieved in blood and in the fluid surrounding the brain (spinal fluid). The main questions it aims to answer are: * Is EC5026 safe in adults with Parkinson's Disease? * What are the levels of EC5026 achieved after oral administration for 28 days? * What molecules or pathways does EC5026 target, and to what extent? In addition, although it is not one of the primary aims of the study, this clinical trial will also explore if oral administration of EC5026 improves the symptoms of Parkinson's Disease. Researchers will compare EC5026 to a placebo (a look-alike substance that contains no drug). Participants will: * Take EC5026 or a placebo every day for 28 consecutive days * Visit the clinic for frequent checkups, blood tests, spinal fluid tests, and questionnaires

This 2x2 factorial, randomized, controlled pilot study aims to identify a specific microbiota pattern, which could constitute a biomarker of Parkinson's disease, and to evaluate whether specific pathotypes can be associated with different stages of the disease; furthermore, the investigators are committed to evaluating how and to what extent the changes induced by a personalized nutritional intervention combined with physical exercise affect the symptoms and quality of life of patients.

This study aims to explore how young adults, older adults and people with Parkinson's disease (PwP), perceive their abilty to cross obstacles while walking, and how this perception is related to their actual performance of obstacle crossing and disease-related motor and cognitive impairments. The study will explore this percepeption and the actual performance in different walking environments(floor, synthetic grass turf). Understanding how people perceive obstacles may help improve rehabilitation methods and reduce the risk of falls. The study will take place at the Motor Performance Laboratory, University of Haifa, and will include walking tasks, eye-tracking measurements, and motor and cognitive assessments.

Parkinson's disease (PD) is a condition that affects movement and gets worse over time. It is more common in older adults. People with PD may have symptoms like shaking, stiff muscles, slow movement, and trouble with balance. They may also experience other issues like pain, depression, anxiety, and memory problems, which can make daily life harder. Physiological resilience is the body's ability to recover or stay strong despite challenges like aging or illness. People with low resilience may struggle to cope with illness, become less active, and have a higher risk of weakness or hospitalization. Since both PD and low resilience are more common in older adults, understanding how PD affects resilience can help improve care. This study will look at resilience in people with PD by measuring heart, lung, muscle, coordination, memory, and thinking abilities. It will also compare two types of single-session aerobic exercise-cycling and walking on a treadmill-regarding participants' perspectives. Participants will be randomly chosen to do one of these exercises for 40 minutes at a moderate level. Afterward, they will share their thoughts on how enjoyable and comfortable the exercise was and whether they would continue doing it. Aerobic exercise is often recommended for people with PD, but it is unclear which type is best for people with PD and which type is mostly preferred by participants with PD. The results of this study will help practitioners make better exercise recommendations for people with PD, leading to better symptom management and a higher quality of life.

This study investigates the impact of an 8-week ballet-based dance therapy on people with Parkinson's disease. It aims to assess the effect of ballet on motor and non-motor symptoms, such as balance, cognitive function, functional capacity, and quality of life. The study will provide insights into the potential of ballet therapy as an effective, non-pharmacological treatment for Parkinson's disease.

Synopsis：The brain glymphatic system is a newly discovered anatomical system for removing waste products and maintaining homeostasis in the brain, and its damage is closely related to a variety of neurological diseases. The diffusion tensor image-analysis along the perivascular space (DTI-ALPS) technique has the advantage of being non-invasive and has been shown to be useful for assessing brain glymphatic system function. The purpose of this study is to use DTI-ALPS technology to evaluate the functional changes of the brain glymphatic system in patients with primary Parkinson's disease at different stages of the disease . Impact:DTI-ALPS technology is a potential imaging indicator for early diagnosis and monitoring of Parkinson's disease progression, and has definite value for clinical application. Purpose :the functional changes of brain glymphatic system in patients with Parkinson's disease at different stages of the disease will be investigated based on DTI-ALPS technology Methods:The clinical data of 100 patients with primary Parkinson's disease will be admitted to the First People's Hospital of Yunnan Province from March 2025 to April 2026 wil be prospectively collected, and they will be divided into two groups: 50 patients with early Parkinson's disease and 50 patients with late Parkinson's disease according to the Hoehn-Yahr Scale , and 50 healthy volunteers (HC) matched with them will be collected. All subjects will be scanned with a 3.0 T MRI system（MAGNETOM Prisma,Siemens Healthcare,Erlangen,Germany）.The scanning sequences included conventional MRI noncontrast and DTI sequences, which acquired images of b=0 s/mm² and b=1000 s/mm²4. FSL and ITK-SANP software will be used to delineate circular ROIs with voxel diameters of 5 mm in the projection fiber and contact fiber regions at the bilateral ventricular body level of the anisotropy score map, and the diffusivity of each fiber on the x, y, and z axes will be measured, and the DTI-ALPS index value will be calculated, and the one-way ANOVA wii be performed by IBM SPSS statistic 25.0 software, and the differences in the mean ALPS values of the left brain, right brain, and both sides of the subjects in the three groups will be compared. The correlation between the index and clinical data such as age, course of disease, Mini-Mental State Examination Score (MMSE), Montreal Cognitive Assessment Scale, Quality of Life Questionnaire for Patients with Parkinson's Disease (PDQ-39), Parkinson's Disease Non-motor Symptom Evaluation Scale (NMSS), Hamilton Depression Rating Scale score(HAMD), and Unified Parkinson's Rating Scale score (URPDS)will be analyzed.

To compare the efficacy, programming burden, power consumption, and physicians' and patients' satisfaction between current mode and voltage mode of deep brain stimulation in each period one year after surgery.