Dopaminergic correlates of metabolic network activity in Parkinson's disease

Abstract

Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss.

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder

“…Although a trend was observed, PDRP and striatal DAT binding were not significantly correlated. Previous studies in PD have shown that PDRP expression shows only modest correlation to DAT binding 10, 28, 29. This may indicate a partly nondopaminergic genesis of the PDRP.…”

Metabolic Imaging in Parkinson Disease

“…After anatomic registration and ratio-normalization, a common and straightforward approach to the analysis of 18 F-FDG PET images is the application of univariate models in the software package statistical parametric mapping (SPM; http://www.fil.ion.ucl.ac.uk/spm/). In such studies, regions of altered relative 18 F-FDG uptake in patients compared with controls are identified or correlations between 18 F-FDG uptake in certain regions and clinical metrics are determined.…”

“…The components that best discriminate between controls and patients are identified as the relevant disease-related pattern. An important advantage of this approach is that once a pattern has been identified, the degree of its expression can be quantified in any 18 F-FDG PET scan. This expression score is reflected by a single numeric value that can be used to investigate relationships with clinical or physiologic metrics or to make predictions.…”

“…18 F-FDG uptake increases with synaptic activity and decreases with neural dysfunction in a patternlike manner, following the neuronal systems that are affected. 18 F-FDG PET studies are especially relevant in PD and other neurodegenerative diseases, in which neuronal dysfunction precedes structural changes not detected by anatomic brain imaging. The current review focuses on recent human 18 F-FDG PET studies in PD.…”

“…18 F-FDG PET studies are especially relevant in PD and other neurodegenerative diseases, in which neuronal dysfunction precedes structural changes not detected by anatomic brain imaging. The current review focuses on recent human 18 F-FDG PET studies in PD. Both glucose metabolism and cerebral blood flow are coupled to regional neuronal activity.…”