Study of levodopa response in Parkinson's disease: Observations on rates of motor progression. 
It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment.  The methods for this study comprised prospective defined off state measurements of the levodopa response at 3-year intervals over a mean 13.3-year period in 34 patients enrolled before treatment initiation.  Despite worsening of on and off scores, the magnitude of the l-dopa short-duration response is maintained as the disease progresses.  A linear mixed-effects regression analysis of off phase motor scores showed a yearly deterioration of 2.3% of the maximum disability score.  Greater motor disability at the commencement of treatment was an independent predictor of faster progression.  Demented patients had worse motor function than those without dementia (P = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died.  These observations should inform clinical trial design for drugs with possible neuroprotective properties.