Hemispheric Network Expression in Parkinson’s Disease: Relationship to Dopaminergic Asymmetries

2020 ◽  
Vol 10 (4) ◽  
pp. 1737-1749
Author(s):  
Chris C. Tang ◽  
Florian Holtbernd ◽  
Yilong Ma ◽  
Phoebe Spetsieris ◽  
Alice Oh ◽  
...  

Background: Parkinson’s disease (PD) is characterized by brain metabolic networks, specifically associated with motor and cognitive manifestations. Few studies have investigated network changes in cerebral hemispheres ipsilateral and contralateral to the clinically more affected body side. Objective: We examined hemispheric network abnormalities and their relationship to striatal dopaminergic deficits in PD patients at different stages. Methods: 45 PD patients underwent dual-tracer positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluorodopa (FDOPA) in a high-resolution PET scanner. In all patients, we computed expression levels for the PD-related motor/cognition metabolic patterns (PDRP/PDCP) as well as putamen/caudate FDOPA uptake values in both hemispheres. Resulting hemispheric measures in the PD group were compared with corresponding healthy control values and assessed across disease stages. Results: Hemispheric PDRP and PDCP expression was significantly elevated contralateral and ipsilateral to the more affected body side in patients with unilateral symptoms (H&Y 1: p < 0.01) and in patients with bilateral limb involvement (H&Y 2-3: p < 0.001; H&Y 4: p < 0.003). Elevations in pattern expression were symmetrical at all disease stages. By contrast, FDOPA uptake in the caudate and putamen was reduced bilaterally (p < 0.002), with lower values on both sides at more advanced disease stages. Hemispheric uptake was asymmetrical in both striatal regions, with lower contralateral values at all disease stages. The magnitude of hemispheric uptake asymmetry was smaller with more advanced disease, reflecting greater change ipsilaterally. Conclusion: Symmetrical network expression in PD represents bilateral functional effects unrelated to nigrostriatal dopaminergic asymmetries.

2019 ◽  
Vol 12 ◽  
pp. 175628641985140
Author(s):  
Yu-jie Yang ◽  
Jing-jie Ge ◽  
Feng-tao Liu ◽  
Zhen-yang Liu ◽  
Jue Zhao ◽  
...  

Parkinson’s disease (PD) is a highly heterogeneous clinical entity. Patients with young-onset PD (YOPD) show some characteristic manifestations to late-onset PD (LOPD). The current study aimed to investigate the cerebral dopaminergic and metabolic characteristics in YOPD with positron emission tomography (PET) imaging. In our study, 103 subjects (42 YOPD and 61 LOPD patients) accepted both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) cerebral PET imaging. Sixty-two patients out of 103 patients in our study completed the cognition tests. In this limited subsection, YOPD patients performed better in cognitive functioning than LOPD patients of similar disease duration. In 11C-CFT imaging, dopamine transporter binding in caudate was relatively spared in YOPD compared with lesions in putamen. In 18F-FDG PET, YOPD patients showed increased metabolism in basal ganglia relative to the healthy controls. When compared with LOPD patients, YOPD patients exhibited hypermetabolism in caudate and hypometabolism in putamen. Furthermore, the regional metabolic values in caudate correlated positively and moderately with the dopaminergic binding deficiency in caudate. The findings of this imaging study might offer new perspectives in understanding the characteristic manifestations in YOPD in light of better-preserved cognition function.


SLEEP ◽  
2021 ◽  
Author(s):  
Christopher E J Doppler ◽  
Julia A M Smit ◽  
Maximilian Hommelsen ◽  
Aline Seger ◽  
Jacob Horsager ◽  
...  

Abstract Study Objectives Parkinson’s disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients. Methods We analysed 27 PD patients and 13 healthy control (HC) subjects who underwent over-night polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters as well as CAP metrics were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density. Results PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex. Conclusions Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040527
Author(s):  
Julia C Greenland ◽  
Emma Cutting ◽  
Sonakshi Kadyan ◽  
Simon Bond ◽  
Anita Chhabra ◽  
...  

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.


2021 ◽  
Author(s):  
Ecehan Abdik ◽  
Tunahan Cakir

Genome-scale metabolic networks enable systemic investigation of metabolic alterations caused by diseases by providing interpretation of omics data. Although Mus musculus (mouse) is one of the most commonly used model...


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sangwoo Kim ◽  
Youngjeon Lee ◽  
Chang-Yeop Jeon ◽  
Yeung Bae Jin ◽  
Sukhoon Oh ◽  
...  

Abstract Background Although the thalamus is known to modulate basal ganglia function related to motor control activity, the abnormal changes within the thalamus during distinct medical complications have been scarcely investigated. In order to explore the feasibility of assessing iron accumulation in the thalamus as an informative biomarker for Parkinson’s disease (PD), this study was designed to employ quantitative susceptibility mapping using a 7 T magnetic resonance imaging system in cynomolgus monkeys. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-injected cynomolgus monkey and a healthy control (HC) were examined by 7 T magnetic resonance imaging. Positron emission tomography with 18F-N-(3-fluoro propyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane was also employed to identify the relationship between iron deposits and dopamine depletion. All acquired values were averaged within the volume of interest of the nigrostriatal pathway. Findings Compared with the HC, the overall elevation of iron deposition within the thalamus in the Parkinson’s disease model (about 53.81% increase) was similar to that in the substantia nigra (54.81%) region. Substantial susceptibility changes were observed in the intralaminar part of the thalamus (about 70.78% increase). Additionally, we observed that in the Parkinson’s disease model, binding potential values obtained from positron emission tomography were considerably decreased in the thalamus (97.51%) and substantia nigra (92.48%). Conclusions The increased iron deposition in the thalamus showed negative correlation with dopaminergic activity in PD, supporting the idea that iron accumulation affects glutaminergic inputs and dopaminergic neurons. This investigation indicates that the remarkable susceptibility changes in the thalamus could be an initial major diagnostic biomarker for Parkinson’s disease-related motor symptoms.


2021 ◽  
Author(s):  
Anat Mirelman ◽  
Mor Ben Or Frank ◽  
Michal Melamed ◽  
Lena Granovsky ◽  
Alice Nieuwboer ◽  
...  

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