Regional Analysis of Age-Related Decline in Dopamine Transporters and Dopamine D2-Like Receptors in Human Striatum

The purpose of this study was to evaluate the mechanisms of age-related decline of dopamine transporter (DAT) and dopamine D-2-like receptor (D2R) densities in the human striatum by focusing on regional difference. Methods: Positron emission tomography (PET) with [C-11]CFT and [C-11]raclopride for measuring DATs and D(2)Rs, respectively, was performed on 16 healthy volunteers ranging from 21 to 74 years in age. To evaluate in detail the regional difference within the striatum, in addition to the conventional region-of-interest-based analysis, we created a parametric image that enabled us to visualize the regional decline rate on a voxel-by-voxel basis, mapping the slope of the regression line between the age and uptake index of each tracer. Results: The decreasing rates corresponded to 6.1, 5.5, and 5.6% per decade for DATs and 5.8, 4.9, and 4.8% per decade for D(2)Rs in the caudate nucleus, anterior putamen, and posterior putamen, respectively. The caudate nucleus for both DATs and D(2)Rs were the fastest among the striatum, and the regional difference of the decreasing rate for DATs was consistently associated with that for D(2)Rs. Meanwhile, previous histological studies have shown that age-related cell loss in the substantia nigra is likely to preferentially affect its dorsomedial part, which projects to the caudate nucleus. Conclusions: These results suggested that neuronal cell loss in the substantia nigra may be associated with the age-related DAT decline, and DAT decline may be associated functionally with age-related D2R decline. Synapse 63:282-290, 2009. (c) 2008 Wiley-Liss, Inc.