The aim is To examine the association between neuroticism and risk of PD in a large cohort and a meta-analysis of prospective cohort studies. Participants from the UK Biobank (N = 490,755) completed a neuroticism scale in 2006–2010. Incident PD was ascertained using electronic health records or death records up to 2018. The systematic search and meta-analysis followed the MOOSE guidelines.

During 11.91 years of follow-up (mean = 8.88 years; 4,360,105 person-years) 1142 incident PD cases were identified. Neuroticism was associated with higher risk of incident PD, both as continuous (HR = 1.28; 95% CI: 1.21–1.36) and categorical variable (top vs. bottom quartiles: HR = 1.88; 95% CI: 1.60–2.22). The association remained significant after accounting for age, sex, smoking, physical activity, anxiety, and depressed mood, and after excluding cases that occurred within the first 5 years of follow-up. The associations were similar for women and men and across levels of socioeconomic status. Random-effect meta-analysis of four prospective studies (N = 548,284) found neuroticism associated with increased risk of incident PD (HR = 1.82; 95% CI: 1.59–2.08; P = 7.31−19). There was no evidence of heterogeneity across studies with follow-ups ranging from one to four decades. The results from the large UK Biobank and meta-analysis of prospective studies indicate that neuroticism is consistently associated with a higher risk of incident. 

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