In this prospective study of 34 patients with Parkinson's disease, measurements of the short duration levodopa motor response have been performed in defined off states at 3 yearly intervals over a mean period of 11.4 years from the point of commencement of levodopa treatment. Twenty-two patients were still available for study; 10 had died and 2 were lost to follow-up. The levodopa motor response amplitude increases over the first 5 years of treatment, and thereafter, on and off scores worsen in parallel with conservation of the response. Patients who developed motor fluctuations within the first 5 years of treatment had, on average, a stronger response to levodopa with significantly better on phase motor function (P = 0.003). Although the proportion of "midline" motor disability (affecting gait, balance, and cranial motor function) increases with time, these deficits do not actually become unresponsive to levodopa. Patients who developed dementia had a significantly more rapid decline in motor function. The latest graph of serial scores for the whole cohort shows an upward curving or exponential increase in motor disability after the first decade of treatment. Applying a notional untreated disability line to this graph--an estimate of the disability that would have accrued if drugs had never been given--we suggest that the long-duration response to levodopa eventually runs down with disease progression.

Thirty-four patients with Parkinson's disease were followed for a mean period of 8 years from the time of initiation of levodopa medication. Levodopa response was charted from the starting point of pharmacological treatment to give a longitudinal point of view of the changes that evolve as the disease progresses. Objective measurements of the motor response to levodopa test-doses were made at approximately three yearly intervals. Motor fluctuations developed in 58% of the patient group after a mean treatment period of 35 months. Dyskinesia developed in parallel with fluctuations but appeared on average 7 months before symptomatic wearing-off effects of levodopa doses. The patients with motor fluctuations had significantly better responses to levodopa. By contrast, nonfluctuators were more prone to develop increasing midline motor disability affecting speech, gait and balance. Comparison of test-dose and pretreatment scores suggested that a substantial long-duration response to levodopa remains after many years of treatment, and that lateralized motor deficits show a stronger long duration response than midline ones. Motor fluctuations are a consequence of disease progression but their early development is, on balance, associated with better long-term functional ability because these patients have the greater capacity to respond to pharmacological treatment.

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In this prospective study of 34 patients with Parkinson's disease (PD), measurements of the short duration levodopa motor response have been performed every 3 years in defined off states. The mean time from initiation of levodopa treatment was 14.8 years, and 17 patients survived to the latest assessment stage. Off phase motor function worsened at a yearly rate of 2.2% of the maximum disability score. The magnitude of the levodopa response is well preserved as the disease progresses, and patients who developed motor fluctuations maintained better on phase motor function than nonfluctuators (P = 0.01). Ten patients, of whom 5 survive, developed dementia. There was no difference in pretreatment disability or initial levodopa response between demented and nondemented subjects. However, dementia was associated with worse on and off motor disability scores after 11 and 14 years (P < 0.001), and a smaller levodopa response magnitude after 14 years (P = 0.008). The plot of sequential scores shows the association between cognitive decline and accelerating increase in motor disability. This suggests that the advanced phase of PD, when Lewy body pathology involves the cerebral cortex, progresses in an exponential rather than linear fashion.