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Abstract

The dopamine depletion that is characteristic of Parkinson's disease has been hypothesized to result from the combination of environmentally induced subclinical damage to the substantia nigra and the age-related loss of additional nigral neurons. Essential to this hypothesis is the existence of deteriorating function in the nigrostriatal pathway with advancing age. The present study was undertaken with [18F]6-fluoro-L-dopa and positron emission tomography to determine in vivo the effects of age on the nigrostriatal pathway in a series of 10 asymptomatic subjects (age range, 22–80 years; mean, 49.8 years). A graphical approach was used in the analysis of multiple-time tracer-uptake data to establish the presence of a compartment with unidirectional uptake and to calculate the rate constant, K, for uptake of [18F]6-fluoro-L-dopa from blood to striatum during steady-state, an index of the functional integrity of nigrostriatal nerve endings. There was a significant linear relationship between K and age (r = 0.80, p < 0.005) with a decrease of 53.3% over the age range studied. These results demonstrate the application of a unidirectional transfer model to the analysis of [18F]6-fluoro-L-dopa and positron emission tomography data and provide in vivo confirmation of an age-related impairment of nigrostriatal function.