title: Progression of nonmotor symptoms in subgroups of patients with non-dopamine-deficient Parkinsonism.
abstract: BACKGROUND
  Ten to fifteen percent of Parkinson's disease (PD) patients recruited to clinical trials have scans without evidence of dopaminergic deficit, whose presence represents a heterogeneous patient population.
  
  
  METHODS
  A cohort of 41 patients with parkinsonism and scans without evidence of dopaminergic deficit at baseline, were subdivided into groups according to their final clinical diagnoses and nigrostriatal dopamine function assessed after 2 years of study. At follow up, 23 patients had clinically probable PD or unclassified parkinsonism with normal nigrostriatal dopamine imaging ("true" scans without evidence of dopaminergic deficit), nine were diagnosed with another tremulous condition, five had psychogenic parkinsonism, and four had phenoconverted to PD with reduced nigrostriatal dopamine function. We analyzed nonmotor symptoms at baseline and follow-up in subgroups of patients with scans without evidence of dopaminergic deficit in comparison with a random sample of 62 PD patients and 195 healthy controls (HCs). All patients were enrolled in the Parkinson's Progressive Marker's Initiative.
  
  
  RESULTS
  Patients who had true scans without evidence of dopaminergic deficit had more severe rapid eye movement sleep disorder, depression, anxiety, and autonomic dysfunction than HCs in addition to more frequent depressive symptoms and worse cardiovascular dysfunction than patients with PD (P = 0.038, P = 0.047, respectively). Patients with true scans without evidence of dopaminergic deficit had normal olfaction that was significantly better than that of patients with PD (P < 0.001). Subgroup analysis of the cohort with scans without evidence of dopaminergic deficit revealed that all patients shared similar nonmotor features irrespective of their final clinical diagnoses. Follow-up of subject groups showed stable nonmotor symptoms over 2 years of study.
  
  
  CONCLUSIONS
  At an early symptomatic stage, patients with scans without evidence of dopaminergic deficit and long-standing parkinsonism exhibit nonmotor features that differ from those of patients with PD on mood and cardiovascular and olfactory function, but remain similar to patients with scans without evidence of dopaminergic deficit with alternative final diagnoses.
authors: Division of Brain Sciences, Imperial College London, UK.
authors: Stuart
authors: S
authors: Taylor
authors: Division of Brain Sciences, Imperial College London, UK.
authors: Joseph
authors: J
authors: Gafton
authors: Division of Brain Sciences, Imperial College London, UK.
authors: Bina
authors: B
authors: Shah
authors: Division of Brain Sciences, Imperial College London, UK.|Department of Medicine and Health Sciences, School of Medicine, University of Molise, Campobasso, Italy.
authors: Gennaro
authors: G
authors: Pagano
authors: Kings' College London and Parkinson's Centre of Excellence, Kings College Hospital, London, UK.
authors: K Ray
authors: KR
authors: Chaudhuri
authors: Division of Brain Sciences, Imperial College London, UK.|Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience University of Aarhus, Denmark.
authors: David J
authors: DJ
authors: Brooks
authors: Division of Brain Sciences, Imperial College London, UK.|Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience University of Aarhus, Denmark.
authors: Nicola
authors: N
authors: Pavese
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003863:Depression / Q000175:diagnosis / Q000378:metabolism; D003866:Depressive Disorder / Q000175:diagnosis* / Q000209:etiology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D014202:Tremor / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine
keywords: REM sleep behavior disorder; SWEDDs; autonomic; nonmotor; olfaction