Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

Br J Clin Pharmacol. 2012 Aug;74(2):267-83. doi: 10.1111/j.1365-2125.2012.04192.x.


Aims: (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiparkinson Agents / therapeutic use*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Cognition Disorders / psychology
  • Depression / drug therapy
  • Depression / etiology
  • Depression / psychology
  • Disability Evaluation
  • Disease Progression
  • Drug Substitution
  • Drug Therapy, Combination
  • Gait Disorders, Neurologic / drug therapy
  • Gait Disorders, Neurologic / etiology
  • Gait Disorders, Neurologic / physiopathology
  • Humans
  • Hypokinesia / drug therapy
  • Hypokinesia / etiology
  • Hypokinesia / physiopathology
  • Linear Models
  • Motor Activity / drug effects*
  • Nonlinear Dynamics
  • Parkinson Disease / complications
  • Parkinson Disease / diagnosis
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / psychology
  • Patient Dropouts
  • Postural Balance / drug effects
  • Predictive Value of Tests
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Selegiline / therapeutic use
  • Sensation Disorders / drug therapy
  • Sensation Disorders / etiology
  • Sensation Disorders / physiopathology
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Time Factors
  • Tocopherols / therapeutic use
  • Treatment Outcome
  • Tremor / drug therapy
  • Tremor / etiology
  • Tremor / physiopathology


  • Antiparkinson Agents
  • Selegiline
  • Tocopherols