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ORIGINAL RESEARCH article

Front. Hum. Neurosci.
Sec. Brain Health and Clinical Neuroscience
Volume 19 - 2025 | doi: 10.3389/fnhum.2025.1525248

Joint effect of modifiable risk factors on Parkinson's Disease：A large-scale longitudinal study

Provisionally accepted
Panlong Li Panlong Li 1Xirui Zhu Xirui Zhu 1Min Liu Min Liu 2Yanfeng Wang Yanfeng Wang 1Chun Huang Chun Huang 1Junwei Sun Junwei Sun 1Shan Tian Shan Tian 3Yuna Li Yuna Li 3Yuan Qiao Yuan Qiao 3Junting Yang Junting Yang 3Shan-Shan Cao Shan-Shan Cao 3Chaohua Cong Chaohua Cong 3Lei Zhao Lei Zhao 3Jingjing Su Jingjing Su 3*Dandan Tian Dandan Tian 2*
  • 1 Zhengzhou University of Light Industry, Zhengzhou, China
  • 2 Henan Provincial People's Hospital, Zhengzhou, Henan Province, China
  • 3 Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Shanghai, China

The final, formatted version of the article will be published soon.

    Previous researches have often underestimated the diversity and combined effects of risk factors for Parkinson's disease (PD). This study aimed to identify how multiple modifiable risk factors collectively impact PD. The study included 452,492 participants from the UK Biobank, utilizing genetic data and 255 phenotypic variables. A broad exposure association study was conducted across seven domains: socioeconomic status, medical history, psychosocial factors, physical measures, early life, local environment, and lifestyle. Risk scores of each domain for each participant were generated. The joint effects of modifiable and genetic risks assessed using Cox proportional hazards model. Population attributable fraction (PAF) was estimated to quantify contribution ratio of risk factors in different domains to the occurrence of PD. Multiple risk factors significantly (p<1.96×10−4) associated with PD was observed. The top 5 factors were hand grip strength (hazard ratio (HR)=0.98, P=1.59×10−24), long-standing illness (HR=1.38, P=3.63×10−20), self-reported nervousness (HR=1.56, P=5.9×10−20), ever suffered from mental health concerns (HR=1.42, P=5.48×10−18) and chest pain (HR=1.42, P=1.43×10−18). Individuals with unfavourable medical history, psychosocial factors, physical measures, and lifestyle had an increased risk of PD by 33% to 51% compared to those with favourable factors (P<0.001). Results indicated that addressing modifiable risk factors, especially in physical measures and psychological factors, could potentially prevent up to 33.87% of PD cases. In formulating prevention strategies, it is recommended to prioritize domains such as physical measures, psychosocial factors, lifestyle, and medical history.

    Keywords: Parkinson's disease, modifiable risk factors, population attributable fraction (PAF), Physical measurement, lifestyle, medical history

    Received: 09 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Li, Zhu, Liu, Wang, Huang, Sun, Tian, Li, Qiao, Yang, Cao, Cong, Zhao, Su and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jingjing Su, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, Shanghai, China
    Dandan Tian, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China

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