<p>Parkinson’s disease (PD) represents a significant neurodegenerative challenge, particularly affecting the aging population, with rising incidence and mortality rates contributing to substantial societal and healthcare burdens. Current diagnostic and therapeutic approaches primarily focus on symptomatic treatment, leaving a gap in understanding the environmental and lifestyle factors influencing PD-related mortality. This study aimed to investigate the causal relationship between outdoor activity duration, environmental temperature fluctuations, and PD mortality rates using a combination of epidemiological statistical analyses and Mendelian randomization (MR) methods. Utilizing death rate data from the United States from 1999 to 2023, alongside genetic data from the UK Biobank and the European Bioinformatics Institute, we assessed the impact of seasonal outdoor activity and temperature on PD outcomes. The results showed an overall upward trend in PD mortality in the United States, with significant regional, gender, racial, and age-related disparities. Notably, lower temperature environments, especially temperature fluctuations, significantly increased PD mortality risk. Furthermore, MR analysis revealed that increased outdoor activity duration in winter was associated with a marked reduction in PD risk, highlighting a protective effect that was not observed for summer outdoor activity. Overall, this research provides valuable insights into the temporal dynamics of PD mortality in the United States, elucidating the U-shaped impact of temperature fluctuations on mortality risk and establishing a causal link between increased winter outdoor activity duration and reduced PD risk. These findings contribute to a deeper understanding of the interplay between environmental factors and PD pathogenesis, offering theoretical foundations for public health interventions and clinical management.</p>