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. Objectives: To examine the association between neuroticism and risk of Parkinson's disease in a large cohort and a meta-analysis of prospective cohort studies. Method: Participants from the UK Biobank (N = 490.755) completed a neuroticism scale in 2006-2010. Incident Parkinson's disease was ascertained using electronic health records or death records up to 2018. The systematic search and meta-analysis followed the MOOSE guidelines. Results: During 11.91 years of follow-up (mean = 8.88 years; 4.360.105 person-years) 1,142 incident Parkinson's disease cases were identified. Neuroticism was associated with higher risk of incident Parkinson's disease, 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 five 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 Parkinson's disease (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. Conclusions: 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 Parkinson's disease.