Parkinson s Disease

The goal of this clinical trial is to learn whether mental imagery combined with self-regulation can improve daily activities in people with Parkinson's disease. The main questions it aims to answer are: * Does mental imagery with self-regulation improve performance in daily activities? * Does it improve overall, cognitive, and motor function? Researchers will compare mental imagery with self-regulation with exercise and health education to assess their effects. Participants will: * Complete a six-week mental imagery and self-regulation programme, conventional learning, or exercise. * Complete assessments of daily activities and overall, cognitive, and motor function.

This study aims to evaluate the efficacy of tTIS treatment in improving motor function in patients with Parkinson's disease (PD), as well as its effects on mood, activities of daily living, sleep, cognition, and other functional domains. It also seeks to assess differences in treatment response among PD subtypes (tremor-dominant, rigidity-dominant, and mixed) and across disease stages (early stage, Hoehn and Yahr \[H\&Y\] stages 1-2, and mid-to-late stage, H\&Y stages 2.5-3). The study will enroll eligible PD patients and evaluate their condition using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the 39-item Parkinson's Disease Questionnaire (PDQ-39), the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Anxiety Rating Scale (HAMA), the Hamilton Depression Rating Scale (HAMD), and a visual analog scale (VAS) for fatigue. Assessments will be performed before routine tTIS treatment, immediately after treatment, and at two and four weeks post-treatment, in order to analyze the therapeutic effect of tTIS in PD. This is an observational study without any intervention; all enrolled participants will receive standard medical care and health education.

Gut problems, such as constipation, can have an important impact on quality of life of people who have them, and have been associated with higher risk of developing neurological diseases such as Parkinson's or Alzheimer's disease. Recent studies suggest that gut problems may also have implications for the progression of these diseases, as constipation is a risk factor for faster Parkinson's and Alzheimer's progression. However, how constipation and brain diseases are linked is unknown. Previous research has suggested that gut changes may lead to inflammation, which could play a role in accelerating the progression of both movement and memory problems in Parkinson's and memory and thinking problems in people with cognitive impairment. Methane is a gas that is naturally produced by microorganisms in the gut. Levels of methane can be measured using a simple breath test. Higher methane levels in the breath are thought to be more common in people with Parkinson's disease (PwP) when compared to people without Parkinson's (healthy controls) and have been associated with gut symptoms, particularly constipation, as well as worse movement problems in PwP, although they are less understood in conditions that affect memory and thinking (like dementia or mild cognitive impairment). The investigators want to better understand the changes in the gut of PwP and people with cognitive impairment (e.g. mild cognitive impairment or dementia). They will compare breath methane levels in PwP, people with cognitive impairment, people with REM Sleep Behaviour Disorder (a sleep condition linked to a higher risk of developing Parkinson's) and healthy participants. Participants will be followed-up over time to assess how methane levels are linked to changes in the blood and the stools, gut function, and clinical symptoms. This study has 2 components: Component 1: observational study, where the study investigators will follow 200 participants over 2 visits, 18 months apart. The study will recruit 4 groups of people: 50 people with Parkinson's disease, 50 people at high risk of developing Parkinson's disease (people with REM Sleep behaviour disorder), 50 people with other conditions affecting cognition (e.g. dementia, mild cognitive impairment), and 50 healthy controls. Component 2: study with 15 people with Parkinson's, who produce high methane levels, to test whether a probiotic (Lactobacillus reuteri) affects how much methane is produced.

Among the different types of pain observed in Parkinson's disease, primary parkinsonian pain (PPP) is the most severe, the most difficult to treat, but also the least well characterized and the hardest to describe, not only by patients but also by neurologists. Consequently, PPP remains difficult to identify, even for clinicians with expertise in Parkinson's disease. Nevertheless, patients with Parkinson's disease who experience PPP appear to exhibit certain demographic and clinical characteristics that may help distinguish them from other patients, including a poorer motor response to levodopa, a stronger association with sleep disturbances, and cognitive and behavioral features such as impulse control disorders (ICDs). PPP may therefore be associated with a specific disease phenotype supported by distinct pathophysiological mechanisms. Recently, a disease progression model proposed the existence of a "Brain-First" subtype (characterized by disease onset in the brainstem) and a "Body-First" subtype (characterized by disease onset in the gastrointestinal system). Several clinical markers appear to distinguish these subtypes, notably the presence of REM sleep behavior disorder (RBD), which has been associated with the Body-First phenotype. The association between PPP and RBD, as well as between PPP and the Body-First subtype, has never been investigated. We hypothesize that PPP may be associated with several clinical markers of the Body-First phenotype. Identifying such associations could facilitate the routine clinical diagnosis of PPP and, consequently, improve its management, which remains inadequate at present. The primary objective is to assess the proportion of patients with primary parkinsonian pain according to the presence of probable RBD in Parkinson's disease. This prospective, cross-sectional, non-interventional category 3 study (RIPH 3) will be conducted in 300 patients. Patients contacted through the France Parkinson Association and interested in participating in the study will be able to access the online questionnaire via a QR code or a web link. Completion of the questionnaire is expected to take no more than 15 minutes. This self-administered questionnaire will include collection of general data (age, sex, disease duration, initial motor symptoms, side of symptom onset predominance, and comorbidities), assessments of pain, migraine, sleep, constipation, olfaction, anxiety and depression and impulse control disorders.

This prospective, randomized, single-blind, controlled clinical trial aims to evaluate and compare the efficacy of cognitive-based balance rehabilitation delivered via immersive Virtual Reality (VR) versus traditional Dual-Task Training (DTT) on balance, gait, cognitive functions, and quality of life in patients with Parkinson's Disease (PD). Postural instability and cognitive decline are hallmark features of progressive PD that significantly elevate fall risks and compromise daily independence, yet conventional pharmacological therapies offer limited effectiveness in restoring complex postural control. Given that motor and cognitive processes are intrinsically linked, this study addresses a critical gap in neurorehabilitation by investigating two contemporary modalities designed to challenge these systems simultaneously. A total of 34 participants diagnosed with PD (aged 40-80 years, Hoehn and Yahr stages I-III) will be randomly allocated to either the Dual-Task Group (DTG), receiving structured therapeutic exercises integrated with sequential cognitive tasks, or the Virtual Reality Group (VRG), engaging in an immersive balance program utilizing the Oculus Quest 2® headset with the FIT-XR application. Both groups will undergo an identical intervention protocol consisting of 45-minute supervised sessions, conducted twice weekly for 8 consecutive weeks during their pharmacological "on" phase. Standardized assessments will be performed by a blinded clinician at baseline and post-intervention (Week 8). The primary outcome measures will be dynamic balance and gait assessed through the Mini-Balance Evaluations Systems Test (Mini-BESTest) alongside global cognitive performance measured via the Montreal Cognitive Assessment (MoCA). Secondary outcomes will encompass objective posturographic indices using the Biodex Balance System, motor severity via the Unified Parkinson's Disease Rating Scale (UPDRS-III), freezing of gait, health-related quality of life, global perceived improvement, and potential cyber-sickness symptoms monitored through the Virtual Reality Sickness Questionnaire (VRSQ) to comprehensively determine the safety and comparative therapeutic value of these interventions.

Parkinson's disease (PD) is a brain disorder that causes progressive problems with movement, such as slowness, stiffness, tremor, and difficulty walking. Many people with PD also develop problems with thinking and memory. Current medications can help control movement symptoms but often become less effective over time and may cause side effects. There is a need for additional treatment options that can address both movement and thinking difficulties in PD. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that uses magnetic pulses delivered to the scalp to stimulate specific areas of the brain. Previous research has shown that rTMS targeting the motor cortex (the part of the brain that controls movement) can improve motor symptoms in people with PD. The purpose of this pilot study is to evaluate whether an accelerated course of rTMS targeting the motor cortex can improve movement and thinking abilities in people with mild to moderate Parkinson's disease. The study will enroll 40 participants aged 50 to 90 years at the San Francisco Neurology and Sleep Center. Participants will receive 6 sessions of rTMS using the EXOMIND™ device, administered twice per week over approximately 3 weeks. Each session delivers high-frequency magnetic stimulation to the motor cortex on both sides of the brain. Participants will be assessed before treatment, at the last treatment session, and at 1-month and 3-month follow-up visits. The primary outcome measure is the change in motor symptoms as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) at 1 month after treatment. Secondary outcomes include additional measures of walking and gait, domain-specific cognitive testing using the Creyos cognitive battery (assessing memory, attention, reasoning, and other thinking skills), the Montreal Cognitive Assessment (MoCA), depression symptoms (PHQ-9), and quality of life (PDQ-39). This is a single-center, open-label study with no placebo or control group. Total participation duration is up to 139 days, including screening, treatment, and follow-up visits.

This clinical study, designed as a randomized, double-blind, placebo-controlled trial, aims to investigate if modulation of the N-methyl-D-aspartate receptor (NMDAR) via its co-agonist D-serine has therapeutic benefits in Parkinson's disease (PD). All patients will receive both placebo and D-serine over different time periods during the study. Preclinical studies have shown that blocking glycine transporters, which elevates endogenous glycine levels, can restore NMDAR function and improve motor deficits in PD models. A clinical trial demonstrated that oral D-serine (30 mg/kg/day for 6 weeks) significantly reduced extrapyramidal and abnormal involuntary movements in PD patients compared to placebo, with improvements observed in both motor and non-motor symptoms. D-serine supplementation has shown an acceptable safety profile with doses up to 120 mg/kg showing no significant adverse effects in clinical studies. The D-SPARK trial primarily aims to determine the efficacy of D-serine supplementation on clinical severity of PD as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary aims are to determine the efficacy of D-serine supplementation on improving dopaminergic nigrostriatal innervation as measured by single-photon emission tomography (SPECT) based imaging of the dopamine transporter (DaT-scan) and cognition as measured by the California Verbal Learning Test version 2 (CLVT-II). The study will include 100 persons with Parkinson's disease (PwPD) diagnosed no longer than 5 years before baseline. Participants will be randomly assigned to receive D-Serine 4000 mg daily or placebo for defined periods of time during a 58 week treatment period, followed by a 12 week washout period. Participants will undergo: * Clinical evaluations, including clinical rating scales and questionnaires. * Cognitive assessments. * Bio sampling of whole blood and blood plasma. * Single-photon emission tomography (SPECT) imaging of dopamine transporter levels (DaT-scan) The outcomes of this study could potentially demonstrate that D-serine reduces symptom severity in Parkinson's disease and/or has an impact on the clinical trajectory of Parkinson's disease, benefiting persons living with Parkinson's disease, their families and society as a whole.

Parkinson's disease (PD) is movement disorder of the nervous system that worsens over time. As nerve cells (neurons) in parts of the brain weaken or are damaged or die, people may begin to notice problems with movement, tremor, stiffness in the limbs or the trunk of the body, or impaired balance. As these symptoms become more obvious, people may have difficulty walking, talking, or completing other simple tasks. Not everyone with one or more of these symptoms has PD, as the symptoms appear in other diseases as well. Both non-modifiable (age, gender) and modifiable risk factors such as occupation, exposure to pesticides, and depression have an association with PD. Several studies have suggested that Parkinson disease is more common in men. The MT mechanism is based on the concept of visual illusion. The movement of the non-paretic part in front of the mirror (reflective side) is perceived as that of the paretic body part (hidden beside the mirror). MT allows an individual to have an experience of normal movement, even for the severely paralyzed limb. In addition, wherever other rehabilitation methods fail to induce normal movements without any compensation, MT may act as a foundation step for further motor therapy. The perception of movement illusion, a neuropsychological phenomenon may induce neural activation of the lesioned brain and enhance associated motor recovery. Therefore the aim of this study is to compare the effects of truck control exercise program and mirror therapy on balance and postural instability in patients with Parkinson's disease.

The goal of this study is to use ultra-high-resolution (UHR) PET imaging to better understand how the brain and spinal cord change in healthy aging and in neurological and psychiatric disorders such as Alzheimer's disease (AD), Parkinson's disease and related movement disorders, amyotrophic lateral sclerosis (ALS), and psychotic disorders. Researchers will use the NeuroExplorer PET/CT system, a new scanner that can show very small structures in the brain and spinal cord in much more detail than regular PET. The main questions this study aims to answer are: * How do small but important brain regions (like the locus coeruleus, substantia nigra, and thalamic nuclei) change in healthy aging? * What early brain changes occur in neurodegenerative and psychotic disorders, and can they help improve early diagnosis? Participants will: * Undergo PET and MRI brain scans using different tracers that measure brain metabolism (18F-FDG), synaptic density (¹⁸F-SynVesT-1), dopamine transporters (¹⁸F-PE2I), and tau protein buildup (¹⁸F-MK6240). * Complete cognitive and clinical assessments related to memory, mood, and motor or psychiatric symptoms, depending on their group. This study will include healthy volunteers and patients with mild cognitive impairment due to Alzheimer´s disease, ALS, Parkinson's disease and related disorders, or psychotic disorders. The results will help create detailed brain imaging maps for healthy aging and identify early biomarkers for different diseases to support better diagnosis and treatment in the future.

The goal of this observational study is to learn whether tissue samples taken from the colon during routine colonoscopy can detect signs of Parkinson's disease or REM Sleep Behavior Disorder (RBD). The main question it aims to answer is: Can doctors find a protein called alpha-synuclein in colon tissue samples from people with Parkinson's disease and RBD? Currently, Parkinson's disease is diagnosed by observing symptoms like tremors and movement problems and RBD by loss of muscle atonia during REM sleep, but by then the disease has already progressed significantly. Earlier detection could help doctors start treatment sooner.

Parkinson's disease (PD) is a progressive neurodegenerative disorder commonly associated with gait disturbances, balance impairments, and freezing of gait, which significantly increase the risk of falls and reduce functional independence. Conventional physical therapy improves mobility in individuals with PD; however, persistent gait deficits often remain. Rhythmic Auditory Stimulation (RAS) is an emerging, evidence-based intervention that uses external auditory cues to enhance gait timing, stride length, and movement initiation. This randomized controlled trial aims to evaluate the effectiveness of rhythmic auditory stimulation using personalized music therapy combined with conventional physical therapy compared to conventional physical therapy alone in individuals with Parkinson's disease. The primary outcomes include freezing of gait, gait velocity, and balance performance. Forty-two clinically diagnosed Parkinson's disease patients will be randomly allocated into two groups. Group A will receive conventional physical therapy, while Group B will receive rhythmic auditory stimulation using personalized music in addition to conventional therapy over an 8-week intervention period. The findings of this study may provide clinical evidence supporting the integration of personalized rhythmic auditory stimulation into rehabilitation programs for improving gait and balance in individuals with Parkinson's disease.

This study investigates magnetic resonance-guided focused ultrasound thalamotomy (MRgFUSth) for people with Parkinson's disease (PD) and tremor not responding to conventional standard doses of dopamine replacement therapy. The aim is to identify clinical and imaging biomarkers predictive of sustained tremor control up to 24 months after MRgFUSth treatment. Participants will undergo a suprathreshold levodopa test and ¹⁸F-DOPA PET imaging to evaluate dopaminergic and serotonergic involvement in tremor. All participants will receive MRgFUSth and be followed for 24 months with standardized clinical, cognitive, and quality-of-life assessments. The study seeks to improve understanding the possible mechanisms of tremor relapse and inform patient selection for MRgFUSth in PD.