Nigrostriatal function in humans studied with positron emission tomography

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 [18 F]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 [18 F]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 [18 F]6‐fluoro‐L‐dopa and positron emission tomography data and provide in vivo confirmation of an age‐related impairment of nigrostriatal function.