Abnormal pattern of brain glucose metabolism in Parkinson’s disease: replication in three European cohorts

Abstract

Rationale In Parkinson's disease (PD), spatial covariance analysis of 18 F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP). Methods The PDRP NL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRP IT was identified in 20 controls and 20 "de-novo" PD patients from an Italian cohort. A further 24 controls and 18 "de-novo" Italian patients were used for validation. The PDRP SP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy. Results A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in "de-novo" PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRP IT , PDRP NL , and PDRP SP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA.

Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease

“…Our SPM analysis also confirmed the results of the above segmentation analysis and 18 F-FDG uptake changes in patients with PD and MSA-P. PD patients were found to have a significant glucose hypermetabolism in the bilateral putamen, cerebellum, and occipital lobes, and a significant glucose hypometabolism in the bilateral putamen was detected in patients with MSA-P. SPM analysis can clearly differentiate between these two forms of parkinsonism: the glucose metabolism in the putamen is preserved or elevated in PD but significantly decreased in MSA-P, which is useful in the group analysis of FDG PET image. Our results are consistent with previous studies (Ma et al, 2007;Meles et al, 2020). However, the widespread implementation of such cerebral disease-related metabolic patterns in multicenter collaborations and clinical practice has been hindered by differences between PET scanners as well as reconstruction algorithms (Kogan et al, 2019).…”

“…However, the widespread implementation of such cerebral disease-related metabolic patterns in multicenter collaborations and clinical practice has been hindered by differences between PET scanners as well as reconstruction algorithms (Kogan et al, 2019). For example, hypermetabolism in the putamen was shown in the abnormal metabolic network in PD (Ma et al, 2007;Meles et al, 2020), but there was no significant change in metabolism of the putamen in the PD-related pattern analysis in several FDG PET studies (Holtbernd et al, 2015;Ko et al, 2017). The selection of a normal control group with differing ages, genders, and ethnicities could also cause potential bias in the SPM analysis (Kogan et al, 2019).…”

Multicenter Validation of Metabolic Abnormalities Related to PSP According to the MDS‐PSP Criteria

“…In the multivariate analysis, we used SSM/PCA to identify a PSPRP among the FDG‐PET data from PSP patients and HCs in cohorts A, B, and C. We applied an automated algorithm written in‐house, based on the method described by Spetsieris and Eidelberg 34,35 as detailed elsewhere 36 . A final pattern was identified in each cohort (PSPRP A , PSPRP B , PSPRP C ).…”

Neuroimaging evaluation of deep brain stimulation in the treatment of representative neurodegenerative and neuropsychiatric disorders

“…The last decade has witnessed the development and clinical validation of large-scale metabolic brain networks involving widely-distributed functional neuroanatomical structures. This was especially true with FDG PET in patients with PD and atypical PD such as multiple system atrophy, progressive supranuclear palsy and cortico-basal degeneration (Teune et al, 2013 , Niethammer et al, 2014 , Peng et al, 2014b , Ge et al, 2018 , Schindlbeck and Eidelberg, 2018 , Meles et al, 2020 , Shen et al, 2020 ). Novel classification algorithms based on the expression levels of these networks provided accurate differential diagnosis even in early-stage parkinsonian populations (Tang et al, 2010 , Tripathi et al, 2016 ), given that DBS was ineffective in pathologically-confirmed patients with atypical PD who were inadvertently misdiagnosed to receive the invasive treatment (Meissner et al, 2016 ).…”