scholarly journals Hybrid PET-MRI for early detection of dopaminergic dysfunction and microstructural degradation involved in Parkinson’s disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Song’an Shang ◽  
Daixin Li ◽  
Youyong Tian ◽  
Rushuai Li ◽  
Hongdong Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Standardized Uptake Value ◽  
Motor Dysfunction ◽  
Nigrostriatal Pathway ◽  
Early Stages ◽  
Microstructural Degradation ◽  
Dopaminergic Dysfunction

AbstractDopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD.

scholarly journals Characterizing white matter alterations in drug-naïve de novo Parkinson’s disease with diffusion MRI

2021 ◽  
Author(s):  
Yiming Xiao ◽  
Terry M. Peters ◽  
Ali R. Khan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
De Novo ◽  
Neurodegenerative Disorder ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Motor Dysfunction ◽  
White Matter Integrity ◽  
Drug Naïve

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and non-motor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease-related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel-based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel-based analysis (FBA) is a recent framework that offers tract-specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug-naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to both functional degeneration and the creation of compensatory networks in the early stage.

scholarly journals Slow Motion Analysis of Repetitive Tapping (SMART) Test: Measuring Bradykinesia in Recently Diagnosed Parkinson’s Disease and Idiopathic Anosmia

2021 ◽  
pp. 1-15
Author(s):  
Cristina Simonet ◽  
Miquel A. Galmes ◽  
Christian Lambert ◽  
Richard N. Rees ◽  
Tahrina Haque ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Early Stage ◽  
Slow Motion ◽  
Motor Dysfunction ◽  
Prodromal Phase ◽  
Floor Effect ◽  
Cross Sectional ◽  
Early Stages

Background: Bradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. Methods: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. Results: People in the early stage of PD performed the task with slower velocity (p <  0.001) and with greater frequency slope than controls (p = 0.003). The combination of reduced velocity and greater frequency slope obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p = 0.001) and smaller amplitude (p <  0.001) compared with controls. Conclusion: We present a simple, proof-of-concept method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may suggest that some are in the prodromal phase of PD.

scholarly journals Slow Motion Analysis of Repetitive Tapping (SMART) test: measuring bradykinesia in recently diagnosed Parkinson’s disease and idiopathic anosmia

2021 ◽  
Author(s):  
C. Simonet ◽  
MA. Galmes ◽  
C. Lambert ◽  
RN. Rees ◽  
T. Haque ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Early Stage ◽  
Motor Dysfunction ◽  
Finger Tapping ◽  
Prodromal Phase ◽  
Floor Effect ◽  
Simple Method ◽  
Early Stages

ABSTRACTBackgroundBradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed.ObjectivesTo develop a quantitative method to track repetitive finger tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia.MethodsThis was a cross-sectional study of 99 participants (early-stage PD=26, controls=64, idiopathic anosmia=9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. Three parameters were extracted from videos: amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second). Clinical assessment was based on the motor section of MDS-UPDRS.ResultsPeople in the early stage of PD performed the task with slower velocity (p<0.001) and with greater decrement in frequency than controls (p=0.003). The combination of slower velocity and greater decrement in frequency obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p=0.001) and smaller amplitude (p<0.001) compared with controls.ConclusionsWe present a new simple method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may be important indication of the prodromal phase of PD.

scholarly journals KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease

2021 ◽  
Author(s):  
Min-Ho Nam ◽  
Jong-Hyun Park ◽  
Hyo Jung Song ◽  
Ji Won Choi ◽  
Siwon Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Potential ◽  
Motor Dysfunction ◽  
Monoamine Oxidase B ◽  
Nigrostriatal Pathway ◽  
Neuroprotective Effects ◽  
Mao B ◽  
6 Hydroxydopamine ◽  
Mptp Model

AbstractMonoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.

scholarly journals Alteration of Diffusion-Tensor Magnetic Resonance Imaging Measures in Brain Regions Involved in Early Stages of Parkinson's Disease

2018 ◽  
Vol 8 (6) ◽  
pp. 343-349 ◽  
Author(s):  
Nan-Kuei Chen ◽  
Ying-Hui Chou ◽  
Mark Sundman ◽  
Patrick Hickey ◽  
Willard S. Kasoff ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Resonance Imaging ◽  
Early Stages

scholarly journals White Matter Microstructural Integrity and Executive Function in Parkinson's Disease

2013 ◽  
Vol 19 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Catherine Gallagher ◽  
Brian Bell ◽  
Barbara Bendlin ◽  
Matthew Palotti ◽  
Ozioma Okonkwo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Executive Function ◽  
White Matter ◽  
Diffusion Tensor ◽  
A Priori ◽  
Mean Diffusivity ◽  
Pathological Process ◽  
Intracranial Volume ◽  
Mean Values

AbstractRecent studies suggest that white matter abnormalities contribute to both motor and non-motor symptoms of Parkinson's disease. The present study was designed to investigate the degree to which diffusion tensor magnetic resonance imaging (DTI) indices are related to executive function in Parkinson's patients. We used tract-based spatial statistics to compare DTI data from 15 patients to 15 healthy, age- and education-matched controls. We then extracted mean values of fractional anisotropy (FA) and mean diffusivity (MD) within an a priori frontal mask. Executive function composite Z scores were regressed against these DTI indices, age, and total intracranial volume. In Parkinson's patients, FA was related to executive composite scores, and both indices were related to Stroop interference scores. We conclude that white matter microstructural abnormalities contribute to cognitive deficits in Parkinson's disease. Further work is needed to determine whether these white matter changes reflect the pathological process or a clinically important comorbidity. (JINS, 2013, 19, 1–6)

scholarly journals Corpus Callosum and Cingulum Tractography in Parkinson's Disease

2010 ◽  
Vol 37 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Katie Wiltshire ◽  
Luis Concha ◽  
Myrlene Gee ◽  
Thomas Bouchard ◽  
Christian Beaulieu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Method ◽  
Motor Symptoms ◽  
Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

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