Dataset Information

Parkinson's disease subtypes show a specific link between dopaminergic and glucose metabolism in the striatum.

ABSTRACT:

Background

Previous studies have shown different clinical and imaging pattern in tremordominant and akinetic-rigid Parkinson's disease (PD) subtypes. The association between dopaminergic and glucose metabolism has in contrast not been investigated yet. Therefore, this study compared PD subtypes with respect to clinical and imaging findings with the aim of establishing a relationship between clinical subtypes, dopamine and glucose metabolism.

Methods

Two groups of a total of 64 idiopathic PD patients (42 male, 22 female, mean age 56 ± 10.9 years) were analysed: akinetic-rigid (AR, n?=?32) and tremor-dominant (TD, n?=?32) patients. Both were compared with respect to differential involvement of local striatal dopamine and glucose metabolism using [18F]-fluoro-L-dopa (F-dopa) and [18F]-fluorodeoxyglucose (FDG)-PET.

Results

The analysis of PD subgroups showed significant differences in the F-dopa uptake in the anterior putamen. Using the results of the local striatal dopamine difference as a volume of interest for the FDG-analysis, analysis of AR patients revealed a significantly lower normalised cerebral metabolic rate of glucose (nCMRGlc) within the ventral striatum.

Conclusions

The dual tracer study illlustrates clear differences between TD and AR subtypes in the ventral striatum. In accordance with previous FP-CIT-SPECT studies, it discloses congruent results for the presynaptic dopaminergic system and extends the knowledge about an additional involvement of local metabolic activity in the caudate and anterior putamen. The findings corroborate the specific role of distinct PD subtypes within the cerebello-thalamo-cortical-circuits. Multitracer PET imaging may thus enhance the knowledge about the clinical segregation into subtypes.

SUBMITTER: Eggers C

PROVIDER: S-EPMC4029550 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Parkinson's disease subtypes show a specific link between dopaminergic and glucose metabolism in the striatum.

Eggers Carsten C Schwartz Frank F Pedrosa David J DJ Kracht Lutz L Timmermann Lars L

PloS one 20140521 5

<h4>Background</h4>Previous studies have shown different clinical and imaging pattern in tremordominant and akinetic-rigid Parkinson's disease (PD) subtypes. The association between dopaminergic and glucose metabolism has in contrast not been investigated yet. Therefore, this study compared PD subtypes with respect to clinical and imaging findings with the aim of establishing a relationship between clinical subtypes, dopamine and glucose metabolism.<h4>Methods</h4>Two groups of a total of 64 idi ...[more]

PMID: 24848641

Similar Datasets

Project description:While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene (PRKN) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both 11C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose PET were enrolled. The 11C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in patients with GU-EOPD only. Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, PRKN-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD.Supplementary informationThe online version contains supplementary material available at 10.1007/s43657-022-00077-8.

Project description:The pathological hallmark of Parkinson's disease is the degeneration of dopaminergic nigrostriatal neurons, leading to depletion of striatal dopamine. Recent neuroanatomical work has identified pathways for communication across striatal subdivisions, suggesting that the striatum provides a platform for integration of information across parallel corticostriatal circuits. The aim of this study was to investigate whether dopaminergic dysfunction in Parkinson's disease was associated with impairments in functional connectivity across striatal subdivisions, which could potentially reflect reduced integration across corticostriatal circuits. Utilizing resting-state functional magnetic resonance imaging (fMRI), we analyzed functional connectivity in 39 patients with Parkinson's disease, both "on" and "off" their regular dopaminergic medications, along with 40 age-matched healthy controls. Our results demonstrate widespread impairments in connectivity across subdivisions of the striatum in patients with Parkinson's disease in the "off" state. The administration of dopaminergic medication significantly improved connectivity across striatal subdivisions in Parkinson's disease, implicating dopaminergic deficits in the pathogenesis of impaired striatal interconnectivity. In addition, impaired striatal interconnectivity in the Parkinson's disease "off" state was associated with pathological decoupling of the striatum from the thalamic and sensorimotor (SM) networks. Specifically, we found that although the strength of striatal interconnectivity was positively correlated with both (i) the strength of internal thalamic connectivity, and (ii) the strength of internal SM connectivity, in both healthy controls and the Parkinson's disease "on" state, these relationships were absent in Parkinson's disease when in the "off" state. Taken together our findings emphasize the central role of dopamine in integrated striatal function and the pathological consequences of striatal dopamine denervation in Parkinson's disease.

Project description:SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B-positive cognitively normal older subjects (T = 10.62, P < 0.001), but, only the Pittsburgh compound B-positive cognitively normal older subjects group showed significantly higher Pittsburgh compound B retention in the highest compared to the lowest glucose metabolism regions defined in young adults (T = 2.05, P < 0.05). Regional differences in age and amyloid-β-dependent changes in glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose metabolism in the precuneus was maintained across the lifespan (right hemisphere: F = 7.69, P < 0.001; left hemisphere: F = 8.69, P < 0.001). Greater Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-β-related increases in glucose metabolism. Our results indicate that although early and life-long regional variation in glucose metabolism relates to the regional vulnerability to amyloid-β accumulation, Alzheimer's disease-related hypometabolism is more specific to brain regions showing age-invariant glucose metabolism and amyloid-β-related hypermetabolism.

Dataset Information

Parkinson's disease subtypes show a specific link between dopaminergic and glucose metabolism in the striatum.

Background

Methods

Results

Conclusions

Publications

Parkinson's disease subtypes show a specific link between dopaminergic and glucose metabolism in the striatum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets