Risk factors for early-onset Parkinson’s disease

Background Prospective evidence on factors associated with early-onset Parkinson’s disease (EOPD) remains limited. We aimed to identify factors associated with incident EOPD and compare their associations with late-onset Parkinson’s disease (LOPD). Methods This prospective cohort study included 283,934 participants aged <60 years and free of Parkinson’s disease at baseline. Thirty-eight prespecified factors were evaluated using Cox regression with Benjamini–Hochberg false discovery rate correction, followed by an exploratory mutually adjusted analysis. Sex-stratified and EOPD–LOPD comparative analyses were conducted, and sensitivity analyses excluded EOPD events occurring within the first 2 or 5 years of follow-up. Results During 2,298,992 person-years of follow-up, 168 participants developed EOPD. After mutual adjustment, EOPD was associated with older age [hazard ratio (HR) per year, 1.15; 95% confidence interval (CI), 1.10–1.20], male sex (HR, 1.93; 95% CI, 1.41–2.64), a higher polygenic risk score (HR per unit, 1.53; 95% CI, 1.31–1.78), family history of Parkinson’s disease (HR, 4.03; 95% CI, 2.49–6.50), anxiety (HR, 2.48; 95% CI, 1.60–3.86), constipation (HR, 4.90; 95% CI, 3.31–7.25), and autoimmune disease burden (HR per category, 1.98; 95% CI, 1.32–2.96). Associations with handgrip strength, hypertension, and migraine were attenuated after mutual adjustment. The principal associations were broadly consistent after excluding EOPD events occurring within the first 2 and 5 years of follow-up. Interaction tests suggested stronger associations of family history, constipation, and autoimmune disease burden with EOPD than with LOPD. Conclusion EOPD showed a distinct profile of associated risk factors, particularly greater autoimmune disease burden and familial susceptibility. These findings support heterogeneity in Parkinson’s disease according to age at onset.