Roberto Erro1, Marina Picillo2, Carmine Vitale3, Raffaele Palladino4, Marianna Amboni5, Marcello Moccia6, Maria Teresa Pellecchia2, Paolo Barone7. 1. 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. 2. Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy. 3. University Parthenope, Naples, Italy; IDC-Hermitage-Capodimonte, Naples, Italy. 4. Department of Primary Care and Public Health, Imperial College London, United Kingdom. 5. IDC-Hermitage-Capodimonte, Naples, Italy. 6. Department of Neuroscience, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy. 7. Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, Neuroscience Section, University of Salerno, Italy. Electronic address: pbarone@unisa.it.
Abstract
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 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. 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.
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 PDpatients 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. 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.
Authors: Fahd Baig; Michael A Lawton; Michal Rolinski; Claudio Ruffmann; Johannes C Klein; Kannan Nithi; David Okai; Yoav Ben-Shlomo; Michele T M Hu Journal: Parkinsonism Relat Disord Date: 2017-02-01 Impact factor: 4.891
Authors: Daniel Weintraub; Chelsea Caspell-Garcia; Tanya Simuni; Hyunkeun R Cho; Christopher S Coffey; Dag Aarsland; Roy N Alcalay; Matthew J Barrett; Lana M Chahine; Jamie Eberling; Alberto J Espay; Jamie Hamilton; Keith A Hawkins; James Leverenz; Irene Litvan; Irene Richard; Liana S Rosenthal; Andrew Siderowf; Michele York Journal: Ann Clin Transl Neurol Date: 2020-04-13 Impact factor: 4.511