Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson’s disease

Blum, Daniela; Fougère, Christian la; Padovani, Alessandro; Maetzler, Walter; Berg, Daniela; Reimold, Matthias; Liepelt‐Scarfone, Inga

doi:10.1007/s00259-018-4085-1

Cited by 23 publications

(17 citation statements)

References 40 publications

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“…It seemed counterintuitive, however, that hyper-metabolism could also occur in AD due to neurodegeneration, especially in the cerebellum which has largely been viewed as preserved of AD pathology. Relative hyper-metabolism has been reported in a handful of neurodegenerative diseases including Parkinson's disease [36], Amyotrophic Lateral Sclerosis [37], and MCI [38]. There is report of increased activation in anterior cerebellar regions in MCI patients compared to controls [15].…”

Section: Discussionmentioning

confidence: 99%

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¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

Meadowcroft

Purnell

Wang

et al. 2020

Preprint

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Cerebellar involvement in Alzheimer's disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical -cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear. 18 F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN)controls. In contrast to known parietal and temporal lobe FDG hypo-metabolism within the default mode network in AD, a significant FDG hyper-metabolism was found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late-verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology. Abbreviations:18

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Section: Discussionmentioning

confidence: 99%

“…Hyper-metabolism due to disinhibition has been noted in the cerebellum in the context of motor control [40]. Cerebellar hypermetabolism has been observed in Parkinson's disease in relation to cognitive impairment [36]. Hyper-metabolism in neurodegenerative disease remains a subject of further investigation.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

Meadowcroft

Purnell

Wang

et al. 2020

Preprint

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“…1 , bottom left ). Notably, changes in cerebellar function have been associated with cognitive decline in PD patients ( Blum et al, 2018 ; Mattis et al, 2016 ; Schindlbeck and Eidelberg, 2018 ), which occur at a much slower pace than motor-related abnormalities, and changes in caudate–frontal pathways have also been implicated in this process ( Carbon et al, 2003 ). The separate PD cognitive pattern (PDCP) identified by Huang et al (2008 , 2007 ) was further shown by Mattis et al (2016) to be spatially and functionally distinct from that seen in relation to AD.…”

Section: Discussionmentioning

confidence: 99%

Spectral guided sparse inverse covariance estimation of metabolic networks in Parkinson's disease

Spetsieris

Eidelberg

2021

NeuroImage

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In neurodegenerative disorders, a clearer understanding of the underlying aberrant networks facilitates the search for effective therapeutic targets and potential cures. [ 18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging data of brain metabolism reflects the distribution of glucose consumption known to be directly related to neural activity. In FDG PET resting-state metabolic data, characteristic disease-related patterns have been identified in group analysis of various neurodegenerative conditions using principal component analysis of multivariate spatial covariance. Notably, among several parkinsonian syndromes, the identified Parkinson’s disease-related pattern (PDRP) has been repeatedly validated as an imaging biomarker of PD in independent groups worldwide. Although the primary nodal associations of this network are known, its connectivity is not fully understood. Here, we describe a novel approach to elucidate functional principal component (PC) network connections by performing graph theoretical sparse network derivation directly within the disease relevant PC partition layer of the whole brain data rather than by searching for associations retrospectively in whole brain sparse representations. Using sparse inverse covariance estimation of each overlapping PC partition layer separately, a single coherent network is detected for each layer in contrast to more spatially modular segmentation in whole brain data analysis. Using this approach, the major nodal hubs of the PD disease network are identified and their characteristic functional pathways are clearly distinguished within the basal ganglia, midbrain and parietal areas. Network associations are further clarified using Laplacian spectral analysis of the adjacency matrices. In addition, the innate discriminative capacity of the eigenvector centrality of the graph derived networks in differentiating PD versus healthy external data provides evidence of their validity.

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“…The hypermetabolic changes however previously rose some controversy regarding their meaning (77–80). Recent results (81–83) show that relative hypermetabolism is a true (compensatory) feature of cognitive changes in neurodegenerative diseases and not just a side-effect of normalization. Furthermore, heterogeneity of PD-MCI sample (84), different image reconstruction algorithms (85) or the selection of a comparison group could also be a source of confounding results.…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Furthermore, it was shown that PDCP expression is in correlation with the worsening of cognitive impairment (107) and with the loss of dopaminergic input in the anterior striatum, particularly in the caudate nucleus, as shown with dopamine transporter imaging ([ 18 F]-fluoropropyl-β-CIT PET and [ 18 F]-fluorodihydroxyphenylalanine (FDOPA) PET) (108, 109). Hypermetabolic cerebellar changes, once argued to be an artifact (77), have recently been proven a true feature of cognitive decline representing a compensatory activation of cognitive networks including the cerebropontocerebellar tract (81). Since original PDCP was identified in non-demented patients, further studies explored its relationship to other dementia syndromes.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Correlations of Neuropsychological and Metabolic Brain Changes in Parkinson's Disease and Other α-Synucleinopathies

2019

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Cognitive impairment is a common feature in Parkinson's disease (PD) and other α-synucleinopathies as 80% of PD patients develop dementia within 20 years. Early cognitive changes in PD patients present as a dysexecutive syndrome, broadly characterized as a disruption of the fronto-striatal dopamine network. Cognitive deficits in other domains (recognition memory, attention processes and visuospatial abilities) become apparent with the progression of PD and development of dementia. In dementia with Lewy bodies (DLB) the cognitive impairment develops early or even precedes parkinsonism and it is more pronounced in visuospatial skills and memory. Cognitive impairment in the rarer α-synucleinopathies (multiple system atrophy and pure autonomic failure) is less well studied. Metabolic brain imaging with positron emission tomography and [18F]-fluorodeoxyglucose (FDG-PET) is a well-established diagnostic method in neurodegenerative diseases, including dementias. Changes in glucose metabolism precede those seen on structural magnetic resonance imaging (MRI). Reduction in glucose metabolism and atrophy have been suggested to represent consecutive changes of neurodegeneration and are linked to specific cognitive disorders (e.g., dysexecutive syndrome, memory impairment, visuospatial deficits etc.). Advances in the statistical analysis of FDG-PET images enabling a network analysis broadened our understanding of neurodegenerative brain processes. A specific cognitive pattern related to PD was identified by applying voxel-based network modeling approach. The magnitude of this pattern correlated significantly with patients' cognitive skills. Specific metabolic brain changes were observed also in patients with DLB as well as in a prodromal phase of α-synucleinopathy: REM sleep behavior disorder. Metabolic brain imaging with FDG-PET is a reliable biomarker of neurodegenerative brain diseases throughout their course, precisely reflecting their topographic distribution, stage and functional impact.

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Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson’s disease

Abstract: We found CI-related hypermetabolism in cerebellar regions that are known to be involved in several cognitive functions and in the pons. These alterations may represent compensatory activation of cognitive networks including cerebropontocerebellar tracts.

Cited by 23 publications

References 40 publications

¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

Spectral guided sparse inverse covariance estimation of metabolic networks in Parkinson's disease

Correlations of Neuropsychological and Metabolic Brain Changes in Parkinson's Disease and Other α-Synucleinopathies

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Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson’s disease

Abstract: We found CI-related hypermetabolism in cerebellar regions that are known to be involved in several cognitive functions and in the pons. These alterations may represent compensatory activation of cognitive networks including cerebropontocerebellar tracts.

Cited by 23 publications

References 40 publications

18F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

18F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

Spectral guided sparse inverse covariance estimation of metabolic networks in Parkinson's disease

Correlations of Neuropsychological and Metabolic Brain Changes in Parkinson's Disease and Other α-Synucleinopathies

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Product

Resources

About

¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex

¹⁸F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex