Presynaptic striatal dopaminergic depletion predicts the later development of freezing of gait in de novo Parkinson's disease: An analysis of the PPMI cohort

The current study was designed to determine whether the degree of presynaptic striatal dopamine depletion can predict the later development of freezing of gait (FOG) in Parkinson's disease (PD).This retrospective cohort study included 390 de novo patients with PD without FOG at baseline. The participants were divided into tertiles according to the baseline dopamine transporter (DAT) uptake of each striatal subregion, and the cumulative risk of FOG was compared using the Kaplan-Meier method. Cox proportional hazard models were used to assess the predictive power of DAT uptake of striatal subregions for the development of FOG.During a median follow-up period of 4.0 years, 143 patients with PD (36.7%) developed FOG. The severe reduction group of DAT uptake in the caudate nucleus and putamen had a significantly higher incidence of FOG than that of the mild and moderate reduction groups. Multivariate Cox regression analyses showed that DAT uptakes in the caudate nucleus (hazard ratio [HR] 0.551; 95% confidence interval [CI] 0.392-0.773; p = 0.001) and putamen (HR 0.441; 95% CI 0.214-0.911; p = 0.027) predicted the development of FOG. In addition, male sex, higher postural instability and gait difficulty score, and a lower Montreal Cognitive Assessment score were also significant predictors of FOG.Our finding suggests that presynaptic striatal dopaminergic denervation predicts the later development of FOG in de novo patients with PD, which may provide reliable insight into the mechanism of FOG in terms of nigrostriatal involvement.