Study of levodopa response in Parkinson's disease: observations on rates of motor progression

<strong>Introduction:</strong> It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment.<p></p> <p><strong>Methods:</strong> The methods for this study comprised prospective defined <i>off</i> state measurements of the levodopa response at 3-year intervals over a mean 13.3-year period in 34 patients enrolled before treatment initiation.</p> <p><strong>Results:</strong> Despite worsening of <i>on</i> and <i>off</i> 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 (<i>P</i> = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died.</p> <p><strong>Conclusions:</strong> These observations should inform clinical trial design for drugs with possible neuroprotective properties.</p>