Factors Predictive of the Need for Levodopa Therapy in Early, Untreated Parkinson's Disease

To identify characteristics of patients with early, untreated Parkinson's disease that are the most important predictors of rapid functional decline. Prospective observational study of a cohort of 800 patients with early, untreated Parkinson's disease who were involved in a multicenter, randomized, double-blind, controlled clinical trial of selegiline hydrochloride (l-deprenyl) and vitamin E (α-tocopherol). Time from randomization to the onset of disability that necessitated levodopa therapy (end point), as judged by the enrolling investigator. Stepwise Cox regression was used in combination with clinical judgment to identify the most important independent baseline predictors of the primary end point among a host of variables, including treatment with selegiline and vitamin E, global and specific clinical measures of disease severity, demographic variables, and neuropsychological test results. In addition to selegiline treatment and global disease severity measures, such as the stage according to the criteria of Hoehn and Yahr, impaired domestic capacity, and the activities of daily living score, the complex of postural instability/gait difficulty and bradykinesia were found to be the factors that were most highly associated with the risk of reaching the end point. The findings suggest that patients with Parkinson's disease whose early clinical presentation includes either postural instability/gait difficulty or bradykinesia are at high risk for rapid functional decline.