title: Profiling cognitive and neuropsychiatric heterogeneity in Parkinson's disease.
abstract: Parkinson's disease (PD) is a highly heterogeneous disease, in which motor symptom subtypes are often-described. While it is recognized that motor, cognitive and affective neuropsychiatric symptoms negatively influence the patients' quality of life, it is currently unknown how these symptoms contribute to phenotypic subtypes. The objective of this study was to assess subtypes of motor, cognitive and affective symptoms in PD.
  
  
  
  A hierarchical cluster analysis was conducted on clinical data of 226 PD patients screened at the VU University Medical Center using comprehensive assessment of cognitive, affective and motor symptoms. Subsequent linear discriminant analyses were conducted to investigate discriminating constructs between clusters.
  
  
  
  The cluster analysis yielded four clusters: (1) a young-age (59.9 years), mildly affected cluster (N = 86), (2) an old-age (72.3 years) cluster with severe motor and non-motor symptoms (N = 15), (3) a cluster (age 64.7 years) with mild motor symptoms, below-average executive functioning and affective symptoms (N = 46) and (4) a cluster (age 64.8 years) with severe motor symptoms, affective symptoms and below-average verbal memory (N = 79).
  
  
  
  Cluster 1 and 2 seem to represent opposite ends of the PD disease stages. Patients in clusters 3 and 4 had similar age, educational level and disease duration but different symptom profiles - we therefore suggest that these clusters represent different pathways of disease progression, presumably with distinct underlying pathology localization. Future research on the neuropathophysiological characteristics of these two clusters and monitoring of disease progression is required.
authors.affiliation: Department of Psychiatry, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Department of Anatomy and Neurosciences, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University/VU University Medical Center, Amsterdam, The Netherlands. Electronic address: t.vanbalkom@vumc.nl.
authors.forename: Tim D
authors.initials: TD
authors.lastname: van Balkom
authors.affiliation: Department of Psychiatry, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Department of Anatomy and Neurosciences, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University/VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology, VU University Medical Center, Amsterdam, PO Box 7057, 1007 MB, The Netherlands. Electronic address: c.vriend@vumc.nl.
authors.forename: Chris
authors.initials: C
authors.lastname: Vriend
authors.affiliation: Neuroscience Campus Amsterdam, VU University/VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology, VU University Medical Center, Amsterdam, PO Box 7057, 1007 MB, The Netherlands. Electronic address: h.berendse@vumc.nl.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Berendse
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, PO Box 7057, 1007 MB, The Netherlands. Electronic address: e.foncke@vumc.nl.
authors.forename: Elisabeth M J
authors.initials: EM
authors.lastname: Foncke
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University/VU University Medical Center, Amsterdam, The Netherlands. Electronic address: yd.vanderwerf@vumc.nl.
authors.forename: Ysbrand D
authors.initials: YD
authors.lastname: van der Werf
authors.affiliation: Department of Psychiatry, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Department of Anatomy and Neurosciences, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University/VU University Medical Center, Amsterdam, The Netherlands. Electronic address: oa.vandenheuvel@vumc.nl.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Medical Psychology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: m.klein@vumc.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
mesh_terms: D000342:Affective Symptoms / Q000209:etiology / Q000503:physiopathology*; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000145:classification* / Q000150:complications / Q000503:physiopathology*; D010641:Phenotype; D012720:Severity of Illness Index
keywords: Cluster analysis; Cognition; Neuropsychiatry; Parkinson’s disease; Profiling