title: Variation in Recent Onset Parkinson's Disease: Implications for Prodromal Detection.
abstract: The detection of prodromal Parkinson's disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations.
  
  
  
  To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort.
  
  
  
  Hyposmia (University of Pennsylvania smell identification test ≤15th centile or Sniffin' Sticks at or ≤10th centile corrected for age and sex), rapid-eye movement sleep behaviour disorder (RBD questionnaire >4), constipation (<1 daily spontaneous bowel motion) and depression (Leeds >6) were recorded in recent onset PD cases, and proposed non-motor screening criteria applied.
  
  
  
  In 1,719 PD cases, mean age 68.6 years (SD 8.1), 65.5% male, mean disease duration 1.3 years (SD 0.9), 72.2% were hyposmic, 43.3% had RBD, 22.1% depression, and 21.5% constipation. 11.6% of cases had no key non-motor features, 38.8% one, 32.1% two, 15.5% three, and 2.0% all four. Increasing numbers of non-motor features were associated with younger age (p = 0.019), higher motor scores (p < 0.001), more postural instability gait difficulty (PIGD) (p < 0.001), greater cognitive impairment (p < 0.001) and higher total non-motor burden (p < 0.001). Cases with hyposmia alone were younger (p < 0.001), had less severe cognitive (p = 0.006) and other non-motor features (p < 0.001). All screening criteria selected younger patients (p = 0.001, p < 0.001), three of four greater overall non-motor burden (p = 0.005, p < 0.001), and inclusion of RBD more cognitive impairment (p = 0.003, p = 0.001) and PIGD (p = 0.004, p = 0.001).
  
  
  
  Varying sensitivity levels, and age and phenotype selectivity, are found when different non-motor screening methods to detect prodromal PD are applied to an early clinical PD cohort.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Glasgow, UK.
authors.forename: Diane M A
authors.initials: DM
authors.lastname: Swallow
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lawton
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Glasgow, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Grosset
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Glasgow, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Malek
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Glasgow, UK.
authors.forename: Callum R
authors.initials: CR
authors.lastname: Smith
authors.affiliation: Department of Neurology, Queen's Medical Centre, Nottingham, UK.
authors.forename: Nin P
authors.initials: NP
authors.lastname: Bajaj
authors.affiliation: Clinical Neurosciences, John van Geest Centre for Brain Repair, Cambridge, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: Institute of Neuroscience, University of Newcastle, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.affiliation: Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Foltynie
authors.affiliation: Reta Lila Weston Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
authors.affiliation: Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Williams
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Glasgow, UK.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Grosset
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003248:Constipation / Q000175:diagnosis / Q000209:etiology; D003863:Depression / Q000175:diagnosis / Q000209:etiology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D000857:Olfaction Disorders / Q000175:diagnosis / Q000209:etiology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis*; D020187:REM Sleep Behavior Disorder / Q000175:diagnosis / Q000209:etiology; D012680:Sensitivity and Specificity
keywords: Parkinson disease; anosmia; constipation; depression; rapid eye movement sleep behavior disorder