Regional gray matter changes and age predict individual treatment response in Parkinson's disease

Abstract

We aimed at testing the potential of biomarkers in predicting individual patient response to dopaminergic therapy for Parkinson's disease. Treatment efficacy was assessed in 30 Parkinson's disease patients as motor symptoms improvement from unmedicated to medicated state as assessed by the Unified Parkinson's Disease Rating Scale score III. Patients were stratified into weak and strong responders according to the individual treatment response. A multiple regression was implemented to test the prediction accuracy of age, disease duration and treatment dose and length. Univariate voxel-based morphometry was applied to investigate differences between the two groups on age-corrected T1-weighted magnetic resonance images. Multivariate support vector machine classification was used to predict individual treatment response based on neuroimaging data. Among clinical data, increasing age predicted a weaker treatment response. Additionally, weak responders presented greater brain atrophy in the left temporoparietal operculum. Support vector machine classification revealed that gray matter density in this brain region, including additionally the supplementary and primary motor areas and the cerebellum, was able to differentiate weak and strong responders with 74% accuracy. Remarkably, age and regional gray matter density of the left temporoparietal operculum predicted both and independently treatment response as shown in a combined regression analysis. In conclusion, both increasing age and reduced gray matter density are valid and independent predictors of dopaminergic therapy response in Parkinson's disease. Keywords: Parkinson's disease, Dopaminergic therapy, Voxel-based morphometry, Support vector machine classification, Predictive models