title: Progression of motor and nonmotor features of Parkinson's disease and their response to treatment.
abstract: OBJECTIVE
  (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments.
  
  
  METHODS
  Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters.
  
  
  RESULTS
  Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2-3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED₅₀ of 1237 mg day⁻¹ compared with 7-24 mg day⁻¹ for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression.
  
  
  CONCLUSIONS
  This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Thuy C
authors.initials: TC
authors.lastname: Vu
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Nicholas H G
authors.initials: NH
authors.lastname: Holford
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D004185:Disability Evaluation; D018450:Disease Progression; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D018476:Hypokinesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D016014:Linear Models; D009043:Motor Activity / Q000187:drug effects*; D017711:Nonlinear Dynamics; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010352:Patient Dropouts; D004856:Postural Balance / Q000187:drug effects; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012642:Selegiline / Q000627:therapeutic use; D012678:Sensation Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D024505:Tocopherols / Q000627:therapeutic use; D016896:Treatment Outcome; D014202:Tremor / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D012642:Selegiline; D024505:Tocopherols