Aerobic Exercise and Brain Health in Parkinson's

Study Overview
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Brief Summary
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The purpose of the project is to investigate how moderate to high intensity aerobic exercise affects brain health in patients with Parkinson's disease. Assessments include MRI, blood markers, cognition, functional tests, questionnaires, and cardiorespiratory fitness. The study will be a single blinded randomized controlled trial with a 6-month long intervention.

Detailed Description
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Background: No approved medical treatments preventing, delaying or stopping Parkinson's disease (PD) exist, making identification of interventions having this potential a major priority. Exercise studies have demonstrated beneficial effects of aerobic exercise (AE) on aerobic capacity, cognition, depression and the Unified Parkinson's Disease Rating Scale (UPDRS). Animal studies show that AE can reduce α-synuclein aggregation and toxin-induced lesions in the nigrostriatal pathway while improving motor and cognitive function. Consequently, AE possesses neuroprotective potentials and thus represents a potentially inexpensive and easily accessible disease modifying therapy in PD. Evolving magnetic resonance imaging (MRI) techniques offer valid and reliable biomarkers to monitor disease progression, but no longitudinal MRI study has assessed the neuroprotective potentials of AE in PD. Aim: To investigate whether 24 weeks of AE can delay PD progression markers and improve motor/non-motor symptoms in PD. Methods: 70 PD patients will be randomized 1:1 to 24 weeks of supervised AE (60 sessions, moderate to high intensity) or standard care. Neuroprotective effects will be determined by MRI scans (R2*, quantitative susceptibility mapping, diffusion kurtosis imaging, neuromelanin-weighted MRI, volumetry), blood markers and Levodopa equivalents. Clinical (MDS-UPDRS III) and subjective (MDS-UPDRS I) outcomes are also assessed. Perspectives: By combining expertise from exercise physiology, radiology, endocrinology and neuropsychology a novel approach is taken aiming to understand the possible neuroprotective effects of AE in PD. This would be of high relevance to PD patients and their relatives. From a societal perspective it may lower disability-related costs by optimizing PD rehabilitation. In case of positive findings, this would provide the first convincing human evidence of a disease modifying effect of AE in PD potentially changing clinical practice.

Official Title
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Effects of Aerobic Exercise on Brain Health in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Age ≥ 40 years Idiopathic PD diagnosis (within the previous five years) Patients in symptomatic therapy / not in therapy. Patients who are not already taking medication are not expected to need medication within 6 months of inclusion (in case of drug startup, this is noted) Hoehn & Yahr ≤ 3 Ability to transport oneself to and from exercise and testing Exclusion Criteria: Alcohol abuse, depression, pacemaker Comorbidity/competing (neurological) disorder preventing participation in the intervention Pregnancy Metallic implants that prevent MRI. Expected exercise adherence below 85% of all planned sessions. Systematic moderate-high-level AE more than twice per week prior to start-up in the project

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 100 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic exercise<br>Moderate to high intensity aerobic exercise for 24 weeks. | Other: Aerobic exercise<br>* Progressive moderate to high intensity aerobic exercise.<br>|
| No Intervention: Standard care<br>Habitual lifestyle including standard care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R2* MRI change | Effective transverse relaxation rate (R2*) | 0, 24 and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QSM MRI change |  | 0, 24 and 48 weeks | 
| DKI MRI change |  | 0, 24 and 48 weeks | 
| Neuromelanin MRI change |  | 0, 24 and 48 weeks | 
| Volumetry MRI change |  | 0, 24 and 48 weeks | 
| Change in blood markers (e.g. α-synuclein) |  | 0, 24 and 48 weeks | 
| Change in Levodopa equivalents |  | 0, 24 and 48 weeks | 
| MDS-UPDRS change |  | 0, 24 and 48 weeks | 
| Aerobic capacity (VO2max test) |  | 0, 24 and 48 weeks | 
| Timed up and go (TUG) change |  | 0, 24 and 48 weeks | 
| 6 min walk test (6MWT) change |  | 0, 24 and 48 weeks | 
| Balance (Mini BESTest) change |  | 0, 24 and 48 weeks | 
| Cognition (The Montreal Cognitive Assessment (MoCA)) change |  | 0, 24 and 48 weeks | 
| Health-related quality of life (Parkinson's Disease Questionnaire (PDQ-39)) change |  | 0, 24 and 48 weeks | 
| Depression (Beck Depression Inventory-II (BDI-II)) change |  | 0, 24 and 48 weeks | 
| Non-motor symptoms (Non-Motor Symptoms Questionnaire (NMSQ)) change |  | 0, 24 and 48 weeks |