Neuroplasticity in Parkinson´s Disease After Training

Study Overview
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Brief Summary
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This project aims to determine the effects of the HiBalance program on neuroplastic changes in people with mild to moderate Parkinson´s disease. The main hypothesis is that highly challenging exercise will lead to greater gait and balance ability, increased levels of physical activity and an improved health related quality of life. The investigators further hypothesize that neuroplasticity changes will be seen in corresponding areas of the brain, neuropsychological changes on cognitive test measures, and that exercise will inhibit the degeneration of dopaminergic neurons in the brain through the mediation of neurotrophic factors.

Detailed Description
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Parkinson's disease (PD) is a neurodegenerative disease affecting many physiological systems essential for balance control. New findings suggest that intensive, challenging and cognitively demanding exercises could induce neuroplasticity in PD. A new balance training (the HiBalance program) have therefore been developed; emphasizing critical aspects of balance control through highly challenging and progressive exercises incorporating dual/multi-tasking (Conradsson et al, 2012). In an RCT, the HiBalance-program was shown to improve balance, gait and physical activity level in favor for the training group (Conradsson et al, 2015). In this proposal the investigators will combine physiotherapy, neurology and neuroimaging to characterise and determine the effects on physical and cognitive symptoms as well as structural and functional changes and wet biomarkers in the brain after the training. Participants will be recruited through Karolinska University Hospital and via announcements in relevant forums like for instance the Swedish Parkinson Association. According to earlier power calculations for detecting effects in balance and gait measures after this particular intervention, the investigators anticipate 40 to 50 participants in each group to detect significant changes. The investigators will perform both per protocol analysis and intention to treat analysis using mixed model or repeated measurement ANOVAs if the data is normally distributed.

Official Title
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Effects of the HiBalance-program: Linking Clinical Signs and Symptoms to Changes in the Brain in People With Parkinson´s Disease

Conditions
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Parkinson Disease, Physical Activity, Gait Disorders, Neurologic, Neural Degeneration

Intervention / Treatment
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* Behavioral: HiBalance
* Behavioral: Speech and communication therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic Parkinson´s disease Hoehn & Yahr 2-3 ≥ 60 years of age Be able to ambulate indoors without mobility aid Balance impairment Exclusion Criteria: =< 21 points on MoCA Other medical conditions that could substantially influence balance performance, voice or speech performance or participation in the interventions Participating in an intensive exercise program for balance or speech during the last six months. Additional exclusion criteria for the brain imaging will include the presence of; pacemakers, deep brain stimulators or other MRI incompatible implants, claustrophobia, inability to hear instructions without hearing aid, unilateral or bilateral blindness, severe diplopia, tremor, dyskinesia or dystonia.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HiBalance<br>The HiBalance program is based on scientifically well-established principles of exercise training and postural control as well as current research on training in PD. The training will be conducted as a progressive individually adjusted group program in order to challenge the specific balance disorder of every participant and endorse progression. The intervention will be performed for an hour, 2 times/week in groups of six to eight participants for a total of 10 weeks and one home training session on their own. | Behavioral: HiBalance<br>* Intervention of highly challenging balance training for 10 weeks.<br>|
| Active Comparator: Speech therapy<br>The control group will receive a group treatment (2 times/w for 10 w + 1 home training session) consisting of speech and communication therapy performed by a speech therapist. This intervention will be performed in a sitting position. The speech and communication treatment will aim at increasing vocal loudness and improving articulatory precision. Level of difficulty is gradually increased by progressing from using loud voice and clear speech in short and automatized utterances, to using the same technique in more complex sentences and situations. The group format is used to practice techniques in communicative situations and also to introduce increasing level of multitasking by combining speech training with cognitively more challenging tasks in the group training. | Behavioral: Speech and communication therapy<br>* Intervention conducted by speech and language therapist for 10 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-BESTest |  | Change in balance performance at 10 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gait parameters |  | Change in gait parameters at 10 weeks | 
| Neuropsychological tests |  | Change in cognitive functions at 10 weeks | 
| Quality of life questionnaires |  | Change in quality of life at 10 weeks | 
| Movement Disorder Society - Unified Parkinsons disease rating scale | Disease severity in Parkinsons disease | Change in disease severity at 10 weeks | 
| Physical activity measured with accelerometers |  | Change in physical activity at 10 weeks | 
| Structural Magnetic Resonance Imaging |  | Change in structures of the brain at 10 weeks | 
| Functional Magnetic Resonance Imaging |  | Change in functional connectivity at 10 weeks. | 
| Wet biomarkers | BDNF in serum | Change in wet biomarkers at 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Balance control, Exercise, Magnetic Resonance Imaging, Functional Magnetic Resonance Imaging