APOE contributes to longitudinal impulse control disorders progression in Parkinson’s disease

Abstract

Abstract Background Impulse control disorders (ICDs) are an increasingly recognized complication in Parkinson disease (PD). The pathogenesis of ICDs is currently unclear. Few genetic studies have been conducted in this area. Objective We aimed to ascertain the correlation between APOE and ICDs, and identify clinical predictors of ICDs in PD. Methods This study included 287 PD patients from the Parkinson’s Progression Markers Initiative. They were followed up to investigate the progression of ICDs over a period of 5 years. The cumulative incidence of ICDs and potential risk factors were evaluated using Kaplan-Meier and Cox regression analyses. Results 44.3% (31/70) patients with APOE ɛ4 and 32.3% (70/217) patients without APOE ɛ4 developed ICDs during the five-year follow up period. There were significant differences between the PD with and without ICDs development group in age, MSEADLG score, ESS score, GDS score, and STAI score at baseline. In multivariable Cox regression analysis, APOE ε4 (HR = 1.450, p = 0.048) and STAI score (HR = 1.017, p = 0.001) were predictors of the development of ICDs. Patients with APOE ɛ4 group showed significantly lower CSF Aβ42 and CSF α-syn level than patients without APOE ɛ4 group at baseline. In patients with APOE ɛ4 group, the “low α-syn level” group and the “low ptau/tau ratio” group had a significantly higher incidence of ICDs, respectively. Conclusions This study provides important insights into the potential role of the APOE gene in the development of ICDs in PD. Further studies are needed to confirm our findings and to investigate the underlying mechanisms in more detail.

Keywords

• APOE
• Parkinson’s disease
• Impulse control disorders
• Cox regression
• Α-synuclein