Neuroplasticity in RBD

Study Overview
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Brief Summary
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REM sleep behavior disorder is a parasomnia that reflects the presence of alpha-synucleinopathy in the brain and is highly predictive of eventual phenoconversion to Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy over the course of years to decades. Neuroplastic adaptations in the brain during the prodromal stage of disease are thought to mask the expression of motor and non-motor signs and may substantially delay diagnosis during a potentially critical time window. This study will examine the state and progression (over 30 to 36 months) of neuroplastic changes in the excitability of the motor and prefrontal cortex (using transcranial magnetic stimulation), the structural and functional connectivity of the brain (using highfield, 7T, magnetic resonance imaging), and the relationship of these changes to the expression of motor and neuropsychological signs, in a cohort of individuals with REM sleep behavior disorder and matched controls.

Official Title
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Neuroplasticity in REM Sleep Behavior Disorder

Conditions
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Parkinson

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the iRBD Group: Diagnosis of polysomnogram-confirmed isolated iRBD. Able to ambulate independently without the use of an assistive device (e.g., cane) for 50 meters. Age: 21-75 years. Inclusion Criteria For Control Subject Group: Age: 21-75 years. Able to ambulate independently without the use of an assistive device (e.g., cane or walker for 50 meters. Exclusion criteria for iRBD group: Dementia diagnosis and/or a University of California Brief Assessment of Capacity to Consent (UBACC) score and MacCAT-CR score indicating impaired capacity to consent. History of musculoskeletal disorders that significant affect movement of lower or upper limbs as determined at the time of enrollment. Other significant neurological disorders that may affect participation or performance in the study. Anti-depressant associated RBD. Individuals will be excluded if their dream enactment emerged or clearly worsened after initiating an antidepressant medication. Meet criteria for overt Parkinson's disease, dementia with Lewy bodies, Multiple Systems Atrophy, Alzheimer's disease, or other neurodegenerative disorder, or other known cause of RBD (e.g., narcolepsy and drug induced RBD). Untreated sleep-disordered breathing History of musculoskeletal disorders that significantly affect movement of lower or upper limbs as determined at the time of enrollment. Pregnant women Additional exclusion criteria for TMS experiments (note that individuals who are excluded from the TMS experiment still have the opportunity to participate in the other data collection sessions): History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury Intracranial metallic or magnetic devices (e.g. cochlear implant, deep brain stimulator) Pacemaker or any implanted device History of surgery on blood vessels, brain, or heart Unexplained, recurring headaches or concussion within the last six months Severe hearing impairment If participant is taking one of the following medications that affects neuroplasticity testing, they will be excluded from the TMS experiment: haloperidol (dopamine antagonist), prazosin (norepinephrine antagonist), biperiden (acetylcholine antagonist), dopamine modulators, NMDA receptor and calcium channel modulators, GABAergic drugs (benzodiazepines), lithium, lovastatin, and cannabis. Exclusion Criteria for Control subject Group: Same as exclusion criteria as the iRBD group History of dream enactment from either patient report or from a bed partner witness that may suggest iRBD. History of untreated sleep-disordered breathing. Presence of parkinsonism or cognitive impairment (including dementia or mild cognitive impairment). Active central nervous system, systemic, psychiatric conditions or use of psychoactive medication that would adversely affect cognitive, neuropsychiatric, motor, or autonomic functioning

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational Group<br>Each subject will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG). | Other: No intervention<br>* Each subject will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Progression over 30 to 36 months | Yes/No whether a change was observed from baseline | 30 to 36 months from baseline | 
| Change in Beck Depression Inventory score | Higher score means more impairment | 30 to 36 months from baseline | 
| Change in Mattis Dementia Rating Scale | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Rey Complex Figure | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in WAIS-IV Matrix Reasoning | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Stroop Color | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Stroop Word | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Stroop Color Word | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Wisconsin Card Sorting Test | Higher score means more impairment for subsections # persev errors and FMS; less impairment for subsections # categories and conceptualization | 30 to 36 months from baseline | 
| Change in D-KEFS | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in BVMT-R | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in HVLT | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in WMS-3 Spatial Span | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Boston Naming Test | Higher score means less impairment | 30 to 36 months from baseline | 
| Change in Trail Making Test A | Higher score means more impairment | 30 to 36 months from baseline | 
| Change in Trail Making Test B | Higher score means more impairment | 30 to 36 months from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson