LEVODOPA THERAPY AND SURVIVAL IN IDIOPATHIC PARKINSONS-DISEASE - OLMSTED COUNTY PROJECT

We studied survival in all Olmsted County Parkinson's disease (PD) pat ients seen at the Mayo Clinic from 1964 to 1978, attempting to answer two questions: (1) What effect does levodopa have on survival in PD? a nd (2) Does the timing of levodopa administration influence survival? We chose this period because it allowed us to study patient records wi th a spectrum of disease durations before levodopa treatment; in many patients, the treatment delay was exclusively due to levodopa being un available prior to 1969. Mortality of the entire PD cohort (N = 179; 6 1% levodopa-treated) was greater than that of the general population ( matched chronologically, geographically, and by age and gender). Lower age at onset of motor symptoms, lower Hoehn and Yahr stage at first n eurologic visit for parkinsonism, and treatment with levodopa were all independent predictors of improved survival. Using a time-dependent C ox regression model, we assessed the impact of the timing of levodopa administration during the course of illness on mortality, while statis tically controlling for other factors (ie, patient selection for levod opa treatment, and independent predictors of survival). Risk of death following initiation of levodopa was significantly reduced (p < 0.001) , regardless of pre-levodopa duration of illness. This reduction gradu ally diminished over a period of 4 years on levodopa, but continued to be significantly reduced. After 4 years, increasing survival benefit again progressively accrued over time to at least 17 years of levodopa treatment (p < 0.001). At no point in time was levodopa treatment ass ociated with increased mortality, arguing against substantial levodopa toxicity. However, despite levodopa-improved survival, mortality cont inues to be increased in PD relative to the general population.