Neuroticism and Risk of Parkinson's Disease: A Meta-Analysis

background neuroticism is linked to mood disorders and alzheimer's disease, but fewer studies have tested the prospective association with parkinson's disease (PD). objectives to examine the association between neuroticism and risk of PD in a large cohort and a meta-analysis of prospective cohort studies. methods 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. results durind 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. conclusion 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 PD.