Objective: To investigate dietary and environmental determinants of Parkinson’s disease (PD) and related mortality by integrating large-scale clinical phenotyping with network pharmacology and molecular docking analyses.

Background: PD is a common neurodegenerative disorder with limited disease-modifying therapies, and accumulating evidence implicates long-term dietary habits and environmental exposures in modulating disease susceptibility and progression. Epidemiologic data from India on these modulators, particularly in comparison to other neurodegenerative conditions, remain scarce.

Method: In a case-control study, individuals with PD (n = 200), Alzheimer’s disease (AD; n = 150), and age-matched healthy controls (n = 200) underwent detailed assessment using a validated Food-Frequency and Environmental Hazard Questionnaire. Cox regression models were used to estimate associations between specific food groups, environmental factors, and mortality risk, followed by protein–protein interaction network construction, enrichment analyses, and molecular docking to identify putative molecular targets and pathways linking these exposures to PD.

Results: PD participants showed significantly higher carbohydrate and fat intake and lower dietary fiber and fruit consumption compared with both AD and control groups. Higher meat and milk intake were independently associated with increased mortality risk in PD and AD (p < 0.01), while rural residence and regular exercise were associated with reduced mortality risk in PD (p < 0.001). Network pharmacology and docking prioritized key neurodegeneration-related targets and pathways potentially mediating the effects of these dietary and environmental exposures.

Conclusion: This integrated clinical and systems-level analysis highlights specific dietary patterns and environmental factors that correlate with PD and AD mortality and converge on shared molecular networks relevant to neurodegeneration.

These findings support the development of preventive strategies that modify diet and environment as accessible levers to mitigate PD risk and progression in resource-limited settings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dietary-and-environmental-risk-factors-of-parkinsons-disease-an-integrated-network-pharmacology-approach/