The Metabolic Topography of Parkinsonism

Eidelberg, David; Moeller, James R.; Dhawan, Vijay; Spetsieris, Phoebe; Takikawa, Shugo; Ishikawa, Tatsuya; Chaly, Thomas; Robeson, William; Margouleff, Donald; Przedborski, Serge; Fahn, Stanley

doi:10.1038/jcbfm.1994.99

Cited by 420 publications

(326 citation statements)

References 58 publications

(23 reference statements)

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“…We have found that this disease is associated with a specific spatial covariance pattern involving metabolic abnormalities in basal ganglia thalamocortical functional/anatomic pathways (Eidelberg et al, 1994(Eidelberg et al, , 1997. Indeed, this PD-related covariance pattern (PDRP) has been detected in multiple independent patient populations scanned in the resting condition (Moeller et al, 1999;Feigin et al, 2002;Lozza et al, 2004;Asanuma et al, 2005).…”

Section: Introductionmentioning

confidence: 97%

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Tang

Spetsieris

et al. 2007

J Cereb Blood Flow Metab

281

385

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Parkinson's disease (PD) is associated with an abnormal pattern of regional brain function. The expression of this PD-related covariance pattern (PDRP) has been used to assess disease progression and the response to treatment. In this study, we validated the PDRP network as a measure of parkinsonism by prospectively computing its expression (PDRP scores) in 15 O-water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans from PD patients and healthy volunteers. The reliability of this measure was also assessed within subjects using a test-retest design in mildly affected and advanced PD patients scanned at baseline and during treatment with levodopa or deep brain stimulation (DBS). We found that PDRP expression was significantly elevated in PD patients (P < 0.001) relative to controls in a prospective analysis of brain scans obtained with either H 2 15 O or FDG PET. A significant correlation (R 2 = 0.61; P < 0.001) was evident between PDRP scores computed from H 2 15 O and FDG images in PD subjects scanned with both tracers. Test-retest reproducibility was very high (intraclass correlation coefficient (ICC) > 0.92) for PDRP scores measured both within PET session and between sessions separated by up to 2 months. This high reproducibility was observed in both early stage and advanced PD patients scanned at baseline and during treatment. The within-subject variability of this measure was less than 10% for both unmedicated and treated conditions. These findings suggest that the PDRP network is a reproducible and stable descriptor of regional functional abnormalities in parkinsonism. The quantification of PDRP expression in PD patients can serve as a potential biomarker in PET intervention studies for this disorder.

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Section: Introductionmentioning

confidence: 97%

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Tang

Spetsieris

et al. 2007

J Cereb Blood Flow Metab

281

385

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“…Studies combining neuroimaging and CSF in PD are scarce, but CSF A β correlate with reduced gray matter volume and associated neuropsychological function 22, 23. FDG‐PET studies have identified a widespread, specific pattern of reduced glucose metabolism in PD,24 most prominent in the frontoparietal and occipital cortices, even in the early stages of the disease 25. Cerebral glucose metabolism reflects cortical activation and synaptic density 26.…”

Section: Introductionmentioning

confidence: 99%

Impaired synaptic function is linked to cognition in Parkinson's disease

Selnes

Stav

Johansen

et al. 2017

Ann Clin Transl Neurol

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ObjectiveCognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein.MethodsThirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years).ResultsAll subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group.Interpretation CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.

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“…In particular, network analyses of regional PET data have consistently revealed the presence of a reproducible abnormal spatial covariance pattern associated with parkinsonism (Eidelberg et al, 1994;Moeller et al, 1999;Lozza et al, 2004;Asanuma et al, 2005a). This PD-related pattern (PDRP) is characterized by pallido-thalamic and pontine hypermetabolism associated with relative metabolic decrements in premotor, prefrontal, and posterior parietal cortical regions (Carbon and Eidelberg, 2002;Asanuma et al, 2005a).…”

Section: Introductionmentioning

confidence: 99%

“…This PD-related pattern (PDRP) is characterized by pallido-thalamic and pontine hypermetabolism associated with relative metabolic decrements in premotor, prefrontal, and posterior parietal cortical regions (Carbon and Eidelberg, 2002;Asanuma et al, 2005a). We have attributed this abnormal metabolic topography to overactivity of internal pallidal (GPi) afferents from STN and consequent increases in inhibitory pallidal outflow to the ventral thalamus and pons (Eidelberg et al, 1994(Eidelberg et al, , 1997. To test this hypothesis, we quantified PDRP expression in patients with advanced disease undergoing stereotaxic subthalamotomy (Su et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

et al. 2006

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Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning.We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation.These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

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The Metabolic Topography of Parkinsonism

Cited by 420 publications

References 58 publications

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Impaired synaptic function is linked to cognition in Parkinson's disease

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

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