Aerobic Exercise and Brain Health in Parkinson's

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.