title: Clinical clusters and dopaminergic dysfunction in de-novo Parkinson disease.
abstract: 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.
  
  
  
  We performed a non-hierarchical cluster analysis using both motor and non-motor data on 398 newly diagnosed untreated PD patients enrolled in the Parkinson'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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom; Dipartimento di Scienze Neurologiche e del Movimento, Università di Verona, Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Erro
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Picillo
authors.affiliation: University Parthenope, Naples, Italy; IDC-Hermitage-Capodimonte, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Department of Primary Care and Public Health, Imperial College London, United Kingdom.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palladino
authors.affiliation: IDC-Hermitage-Capodimonte, Naples, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Amboni
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Moccia
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pellecchia
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy. Electronic address: pbarone@unisa.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
mesh_terms: D000368:Aged; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000145:classification* / Q000378:metabolism* / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon
keywords: Clusters; Heterogeneity; Non-motor; Parkinson; Subtypes