scholarly journals Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2757-2770 ◽  
Author(s):  
Emma Biondetti ◽  
Rahul Gaurav ◽  
Lydia Yahia-Cherif ◽  
Graziella Mangone ◽  
Nadya Pyatigorskaya ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Severity ◽  
Disease Diagnosis ◽  
Signal To Noise ◽  
Control Subjects ◽  
Clinical Scores ◽  
Spatiotemporal Changes ◽  
Healthy Control

Abstract This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson’s disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson’s disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson’s disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson’s disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra’s morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson’s disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

Stereopsis Deficits in Parkinson’s Disease and Their Clinical Implications

2020 ◽  
Author(s):  
Fang Ba ◽  
Tina T. Sang ◽  
Jaleh Fatehi ◽  
Wenjing He ◽  
Emanuel Mostofi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Severity ◽  
Rating Scale ◽  
Disease Status ◽  
Cognitive Status ◽  
Control Group ◽  
Motor Disorder ◽  
Healthy Control ◽  
Stereo Acuity

Abstract Background: Parkinson's disease (PD) is not exclusively a motor disorder. Among non-motor features, PD patients possess sensory visual dysfunctions. Stereopsis deficit can significantly impact patients' motor performance. However, it is not routinely tested, and its significance is under-investigated. Studying stereopsis using reliable 3D stimuli may help determine its implications in disease status in PD.The objective of the study is to investigate stereopsis abnormalities in PD with reliable and more physiological tools, and their correlation with indicators of PD severity. Methods: Twenty-four healthy control and 20 PD participants were first evaluated for visual acuity, visual field, contrast acuity, and stereoperception with 2D and Titmus stereotests, followed by the assessment with the 3D active shutter system. The correlation between stereopsis and disease severity, Unified Parkinson’s disease rating scale motor scores (UPDRS-III), levodopa equivalent daily dose (LEDD), course of disease and cognitive status were evaluated using univariate regression models. Results: Screening visual tests did not reveal any differences between PD and control group. With the 3D active shutter system, PD patients demonstrated significantly worse stereopsis (i.e p=0.002, 26 seconds of arc). There was a trend that UPDRS-III and LEDD negatively correlate with the stereo acuity, suggesting poorer stereoperception is related to disease severity. Preserved cognitive function correlated with more intact stereo acuity. Conclusion: With more reliable and physiological tools, PD patients exhibit poorer stereopsis. These deficits reflected PD motor and cognitive status. How stereopsis relates to gait, fall risks and navigation warrants more investigations in the future.

scholarly journals Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2580
Author(s):  
Sarah Plum ◽  
Britta Eggers ◽  
Stefan Helling ◽  
Markus Stepath ◽  
Carsten Theiss ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Gradient Centrifugation ◽  
Synaptic Function ◽  
Substantia Nigra Pars Compacta ◽  
Differential Analysis ◽  
Mitochondrial Translation ◽  
Control Subjects ◽  
Core Proteome

The pathological hallmark of Parkinson’s disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.

scholarly journals Dynamic functional connectivity changes associated with dementia in Parkinson’s disease

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2860-2872 ◽  
Author(s):  
Eleonora Fiorenzato ◽  
Antonio P Strafella ◽  
Jinhee Kim ◽  
Roberta Schifano ◽  
Luca Weis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Parkinson’S Disease Dementia ◽  
Dynamic Functional Connectivity ◽  
Control Subjects ◽  
Healthy Control ◽  
Normal Cognition

AbstractDynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson’s disease. In this study, we evaluated 118 patients with Parkinson’s disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson’s disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity ‘States’ across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson’s disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson’s disease subgroups analyses showed the segregated state occurred more frequently in Parkinson’s disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson’s disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson’s disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson’s disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson’s disease cognitive states.

scholarly journals Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2474-2489 ◽  
Author(s):  
Yiwei Qian ◽  
Xiaodong Yang ◽  
Shaoqing Xu ◽  
Pei Huang ◽  
Binyin Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Confidence Interval ◽  
Multiple System Atrophy ◽  
Gut Microbiome ◽  
Disease Index ◽  
Gene Markers ◽  
Control Subjects ◽  
Healthy Control

Abstract Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.

scholarly journals Sentence Comprehension and Its Association with Executive Functions in Patients with Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Katrien S. F. Colman ◽  
Janneke Koerts ◽  
Laurie A. Stowe ◽  
Klaus L. Leenders ◽  
Roelien Bastiaanse
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Executive Functions ◽  
Sentence Comprehension ◽  
Sentence Length ◽  
Control Subjects ◽  
Set Switching ◽  
Moderate Disease ◽  
Healthy Control ◽  
Structure Complexity

Coexistent impairments in executive functions and language comprehension in patients with Parkinson's disease (PD) have been repeatedly observed. In this study, the aim was to provide insights into the interaction between linguistic representation and processing and executive functioning. Therefore, sentence comprehension and executive functions were assessed in 28 Dutch-speaking PD patients and 28 healthy control subjects. Three aspects of the sentence materials were varied: (1) phrase structure complexity, (2) sentence length, and (3) picture congruence. PD patients with mild-to-moderate disease severity showed decreased sentence comprehension compared to healthy control subjects. The difficulties encountered by PD patients were not limited to one aspect of the sentence materials. The same pattern of results was present in healthy control subjects. Deficits in set-switching were specifically associated with the comprehension of passive sentences. Generally, our study confirms that there does not appear to be a language faculty encapsulated from the influence of executive functions.

Speech Breathing in Parkinson’s Disease

1993 ◽  
Vol 36 (2) ◽  
pp. 294-310 ◽  
Author(s):  
Nancy Pearl Solomon ◽  
Thomas J. Hixon
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Minute Ventilation ◽  
Indirect Evidence ◽  
Tidal Breathing ◽  
Rib Cage ◽  
Control Subjects ◽  
Tracheal Pressure ◽  
Speech Breathing ◽  
Healthy Control

Breathing was investigated in 14 male subjects with Parkinson’s disease and 14 healthy male control subjects. Kinematic, spirometric, acoustic, and pressure data were used to assess function during resting tidal breathing, reading aloud, and monologue production. Data were collected at two times during the drug cycle for subjects with Parkinson’s disease. During resting tidal breathing, subjects with Parkinson’s disease, on average, had a faster breathing rate, greater minute ventilation, and smaller relative contribution of the rib cage to lung volume change than did healthy control subjects. During speech breathing, rib cage volume was smaller and abdominal volume was larger at initiation of the breath groups for subjects with Parkinson’s disease than for healthy control subjects. Subjects with Parkinson’s disease produced fewer words and spent less time producing speech per breath group and tended to have a faster interpause speech rate than did healthy control subjects. There was no difference between groups for duration of inspirations between speech breath groups. Oral pressure was lower for subjects with Parkinson’s disease but estimated tracheal pressure did not differ between the two subject groups. Few differences were found between the two times in the drug cycle for resting and speech breathing. Results provide indirect evidence for reduced relative compliance of the rib cage to the abdomen for subjects with Parkinson’s disease as compared to healthy control subjects. In addition, the results support the possibility of inadequate valving of the air stream for subjects with Parkinson’s disease.

scholarly journals Parkinson’s disease progression in the substantia nigra: location, location, location

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2628-2630
Author(s):  
David E Vaillancourt ◽  
Trina Mitchell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Progression ◽  
Spatiotemporal Changes

This scientific commentary refers to ‘Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease’, by Biondetti et al. (doi:10.1093/brain/awaa216

scholarly journals Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder

Brain ◽  
2021 ◽  
Author(s):  
Liche Zhou ◽  
Guanglu Li ◽  
Yuyao Zhang ◽  
Miao Zhang ◽  
Zhichun Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Substantia Nigra ◽  
Rem Sleep ◽  
Free Water ◽  
Behaviour Disorder ◽  
Control Subjects ◽  
Sleep Behaviour ◽  
Rem Sleep Behaviour Disorder ◽  
Healthy Control ◽  
Water Values

Abstract Imaging markers sensitive to neurodegeneration in the substantia nigra are critically needed for future disease-modifying trials. Previous studies have demonstrated the utility of posterior substantia nigra free water as a marker of progression in Parkinson’s disease. In this study, we tested the hypothesis that free water is elevated in the posterior substantia nigra of idiopathic REM sleep behaviour disorder, which is considered a prodromal stage of synucleinopathy. We applied free-water imaging to 32 healthy control subjects, 34 patients with idiopathic REM sleep behaviour disorder and 38 patients with Parkinson’s disease. Eighteen healthy control subjects and 22 patients with idiopathic REM sleep behaviour disorder were followed up and completed longitudinal free-water imaging. Free-water values in the substantia nigra were calculated for each individual and compared among groups. We tested the associations between posterior substantia nigra free water and uptake of striatal dopamine transporter in idiopathic REM sleep behaviour disorder. Free-water values in the posterior substantia nigra were significantly higher in the patients with idiopathic REM sleep behaviour disorder patients than in the healthy control subjects, but were significantly lower in patients with idiopathic REM sleep behaviour disorder than in patients with Parkinson’s disease. In addition, we observed significantly negative associations between posterior substantia nigra free-water values and dopamine transporter striatal binding ratios in the idiopathic REM sleep behaviour disorder patients. Longitudinal free-water imaging analyses were conducted with a linear mixed-effects model, and showed a significant Group × Time interaction in posterior substantia nigra, identifying increased mean free-water values in posterior substantia nigra of idiopathic REM sleep behaviour disorder over time. These results demonstrate that free water in the posterior substantia nigra is a valid imaging marker of neurodegeneration in idiopathic REM sleep behaviour disorder, which has the potential to be used as an indicator in disease-modifying trials.

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