Physical Activities and Parkinson's Disease Progression: A Two-Sample Mendelian Randomization Study.

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Parkinson's disease (PD) is a progressive neurodegenerative disorder.
• The role of physical activity (PA) in modulating PD progression remains incompletely understood.
• Mendelian randomization (MR) offers a powerful approach to investigate causal relationships between exposures and diseases.

Purpose of the Study:

• To investigate the potential causal effect of physical activity on Parkinson's disease progression using a two-sample Mendelian randomization analysis.
• To explore the relationship between genetically predicted physical activity levels and key PD progression markers.

Main Methods:

• Utilized genome-wide association study (GWAS) summary statistics for physical activity (N=377,000), age at onset (N=28,568), and PD progression (N=4093).
• Employed the inverse variance weighted (IVW) method for causal effect estimation.
• Assessed the robustness of findings using MR-Egger and weighted median analyses.

Main Results:

• Genetically predicted overall acceleration average (OAA) was associated with reduced constipation risk in PD (OR: 0.60, P=5.50x10⁻³).
• Moderate-to-vigorous physical activity (MVPA) showed a stronger protective effect on constipation risk (OR: 0.03, P=0.043).
• OAA also demonstrated a protective association with motor experiences of daily living (OR: 0.84, P=0.046).
• No significant causal effects were found for vigorous physical activity (VPA) or fraction of accelerations exceeding 425 milligravities (FAA) on PD progression.

Conclusions:

• Findings suggest a potential causal, protective role of physical activity in Parkinson's disease progression.
• Specific measures of physical activity, like OAA and MVPA, may influence non-motor and motor symptoms.
• These results support the consideration of physical activity interventions in PD management strategies.