Predictors for early‐onset psychotic symptoms in patients newly diagnosed with Parkinson's disease without psychosis at baseline: A 5‐year cohort study

Abstract Aims To investigate the risk factors for early‐onset psychosis in Parkinson's disease (PD) in a cohort of patients from the Parkinson's Progression Markers Initiative. Methods Longitudinal data on motor and non‐motor features, dopamine transporter (DAT) imaging, and cerebrospinal fluid (CSF) measurements were collected. The survival probability of psychotic symptoms, potential risk factors for psychosis development over a 5‐year follow‐up period, and the performance of the prediction model were evaluated. Results Among the 338 newly diagnosed patients with PD, 83 developed psychotic symptoms. Gastrointestinal autonomic dysfunction, presence of probable rapid‐eye‐movement sleep behavior disorder, and the ratio Aβ42: total‐tau could independently predict onset of psychosis in PD (hazard ratio ( HR ) = 1.157, 95% confidence interval ( CI ) 1.022–1.309, p = 0.021, HR = 2.596, 95% CI 1.287–5.237, p = 0.008, and HR = 0.842, 95% CI 0.723–0.980, p = 0.027, respectively). The combined model integrating baseline clinical predictors, DAT imaging, and CSF measurements achieved better sensitivity than the clinical predictors alone (area under the curve = 0.770 95% CI 0.672–0.868 vs. 0.714 95% CI 0.625–0.802, p = 0.098). Conclusion We identified clinical and CSF predictors of early‐onset psychosis in patients with PD. Our study provides evidence and implications for prognostic stratification and therapeutic approaches for PD psychosis.