Physical Exercise for Managing Fatigue in Parkinson’s Disease: Clinical and Research Recommendations From a Systematic Review and Meta-Analysis

BACKGROUND AND PURPOSE: Fatigue is among the most disabling symptoms of Parkinson's disease (PD), and physical exercise is a promising intervention. This study aimed to evaluate the effects of physical exercise on PD-related fatigue and provide clinical and research recommendations. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent investigators conducted searches using the "Patient, Intervention, Comparison, Outcome" strategy in PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Physiotherapy Evidence Database (PEDro) until August 2024. Randomized clinical trials examining physical exercise and fatigue in PD were included. The standardized mean difference (SMD) was used for effect estimation, and a random-effects model was applied for meta-analysis. Methodological quality was assessed using the PEDro scale, and confidence in cumulative evidence was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluation framework. RESULTS: Twenty-two studies were included. Meta-analysis comparing exercise with nonexercise (usual care) interventions showed a large effect favoring exercise (SMD = -0.92, 95% CI: -1.57 to -0.28; 7 studies), with interventions including multimodal training, walking, strengthening, and dance. An overview of all the studies with available data (19 studies) suggested that interventions with greater specificity, intensity, or active engagement had larger effects. However, certain control interventions, such as sleep hygiene, relaxation/education, and stretching, may play a role comparable to some active exercises. Fatigue was primarily measured using the Parkinson's Fatigue Scale and the Fatigue Severity Scale. CONCLUSIONS: Moderate-certainty evidence supports that physical exercise, particularly active, continuous modalities such as walking, aerobic, resistance, and multimodal training at moderate intensity (at least twice weekly for 20-60 minutes), can reduce PD-related fatigue. Future research should distinguish between central and peripheral fatigue, compare high-intensity exercise interventions, and explore combinations of exercise with other promising interventions.