Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early Parkinson's disease.

Patients with Parkinson's disease (PD) have already at the early stages of the disease impaired performance especially in tests measuring frontal lobe functions such as attention. The pathophysiological basis of these deficits is unclear. In the present study, 21 non-demented, non-medicated patients at the early stage of PD and 24 healthy controls underwent a positron emission tomography (PET) scan with 6-[18F]fluoro-L-dopa (Fdopa) as the tracer. In addition, the PD patients performed a neuropsychological test battery, including a test measuring sustained attention (VIG) and a test requiring suppressed attention (Stroop). Both voxel-based Statistical Parametric Mapping (SPM) and automated region of interest (ROI) analysis were employed. Compared to controls, the PD patients had decreased Fdopa uptake in the striatum and a large cortical area of increased Fdopa uptake. The reaction time in the VIG test correlated positively with the Fdopa uptake of the dorsolateral prefrontal cortex and the performance in the Stroop test correlated negatively with the Fdopa uptake in an area including the medial frontal cortex and the anterior cingulate. The results show that cortical Fdopa uptake is increased in early non-medicated PD and suggest that the changes in frontal Fdopa uptake are related to cognitive impairments found in early PD.

Personality traits and striatal 6-[18F]fluoro-L-dopa uptake in healthy elderly subjects.

Positron emission tomography (PET) studies have been carried out to examine dopaminergic correlates of human personality traits. In patients with Parkinson's disease, right caudate 6-[(18)F]fluoro-L-dopa ((18)F-dopa) uptake has recently been reported to correlate with a depression/anxiety related-personality trait of harm avoidance. The present study aimed to further study personality and striatal dopaminergic function, now with (18)F-dopa in healthy individuals, and to determine specifically whether the link between harm avoidance and (18)F-dopa uptake is a general phenomenon, seen also in healthy subjects. Twenty-five Caucasian neurologically healthy elderly subjects (mean age=60 years; 13 men, 12 women) were scanned with 3D (18)F-dopa PET, coregistered with magnetic resonance imaging, and each subject filled out the Temperament and Character Inventory (TCI) and the Karolinska Scales of Personality (KSP). The TCI harm avoidance did not correlate with right caudate (18)F-dopa uptake (r=-0.08, P=0.71, uncorrected, effects of age and sex partialled out), or with the (18)F-dopa uptake in any other striatal region (r=-0.07-0.16, P>0.47). Correlations with other personality scales, including the TCI novelty-seeking and the KSP detachment, were also non-significant. The results indicate that the previous positive findings concerning harm avoidance and (18)F-dopa uptake in Parkinson's disease are disease-related, and that they can not be generalized to healthy individuals.

Striatal subregional 6-[18F]fluoro-L-dopa uptake in early Parkinson's disease: a two-year follow-up study.

Thirty-one drug-naive patients with Parkinson's disease (PD) underwent 6-[18F]fluoro-L-dopa (F-dopa) positron emission tomography (PET) scan at the time of the diagnosis (baseline) and 2 years later in order to investigate F-dopa uptake in striatal and extrastriatal regions during the first years of early PD. Twenty-four healthy controls underwent one F-dopa PET scan. The regional differences in the striatal and extrastriatal regions were analyzed with statistical parametric mapping and automated region of interest analyses. Our study shows that the F-dopa uptake in unmedicated early PD is most severely decreased in the dorsal part of caudal putamen but significant decrease can be seen throughout the striatum compared with controls. During the first years of PD, there is a progressive regional decline in striatal F-dopa uptake, the dorsal part of caudal putamen being still the most severely affected region. The absolute decline is equal between the striatal subregions. This suggests that the decline of dopamine function starts from the dorsocaudal putamen, but once started, the rate of progression is equal between the subregions of the striatum. In contrast to the striatal decline, the increased cortical F-dopa uptake prevails at least during the first years of PD.

Progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease using [18F]CFT PET.

The aim of this study was to investigate the progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease (PD). We studied 12 patients with early PD and 11 healthy controls with a dopamine transporter ligand 2beta-carbomethoxy-3beta-(4-[(18)F]-fluorophenyl)tropane ([(18)F]CFT) positron emission tomography (PET). The PET scan was carried out twice with an average interval of 2.2 years. The regions of interest (anterior and posterior putamen, caudate nucleus, and cerebellum) were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images, and copied onto the PET images. At the first PET scan in PD patients, the [(18)F]CFT uptake in the anterior putamen was 1.92 +/- 0.67, which was 45% of the control mean, and in the posterior putamen 1.02 +/- 0.55, being only 27% of the control mean. For the caudate nucleus the corresponding figure was 2.55 +/- 0.58 (71% of the control mean). The uptake ratios had declined significantly by the time of the second PET scan and the absolute annual rate of decline of the tracer uptake was 0.23 +/- 0.14 (P < 0.001) in the anterior putamen, 0.13 +/- 0.13 (P = 0.005) in the posterior putamen, and 0.20 +/- 0.15 (P < 0.001) in the caudate nucleus. There was a statistically significant difference of the decline in the tracer uptake between the anterior and posterior putamen (P = 0.033). When the rate of progression was calculated compared to the normal control mean, the rate of annual decline was 5.3% in the anterior putamen, 3.3% in the posterior putamen, and 5.6% in the caudate nucleus, without significant changes among striatal subregions (P = 0.10). When ipsi- and contralateral sides were analyzed separately, the absolute decline of [(18)F]CFT uptake in the putamen was higher in the side ipsilateral to the predominant symptoms than in the contralateral side (P = 0.035 for anterior putamen and P = 0.026 for posterior putamen). In the caudate nucleus the absolute decline was not different between ipsi- and contralateral sides (P = 0.76). In healthy controls, no significant decline of [(18)F]CFT uptake was detected. The results are suggestive of slower progression in the posterior putamen, where the disease is more advanced, but studies to follow up the same patient at several time points are needed to resolve this question. Synapse 48:109-115, 2003.