Clinical clusters and dopaminergic dysfunction in de-novo Parkinson disease

Background: The heterogeneity of PD suggests the existence of different subtypes. While some motor clusters have been consistently identified, little is known about non-motor PD subtypes and motor-non motor interplay. Research in this regard has produced somewhat contradictory results, which might be biased by the inclusion of treated patients. Patients and methods: We performed a non-hierarchical cluster analysis using both motor and non motor data on 398 newly diagnosed untreated PD patients enrolled in the Parldnson's Progressive Marker Initiative (PPMI) study. We further evaluated whether dopaminergic dysfunction, as measured by (123)[I]-FP-CIT SPECT scan, could explain, at least partially, the observed difference between the clusters. Results: Three clusters were identified. Group 1 was characterized by the lowest motor and non-motor burden, whereas group 2 and 3 had similar motor disability, but different non-motor involvement, especially with regards to apathy and hallucinations. (123)[I]-FP-CIT binding values paralleled motor disability burden among the 3 clusters, but further multivariate analyses also revealed a negative correlation with depression. Discussion: Our results confirm the motor as well as non-motor heterogeneity of PD, suggesting the existence of 3 different subtypes. Dopaminergic dysfunction only marginally explains the non-motor variability of PD. Identification of such clusters can have important implications for generating novel pathophysiological hypotheses and therapeutic strategies. (C) 2016 Elsevier Ltd. All rights reserved.