scholarly journals Comprehensively modeling heterogeneous symptom progression for Parkinson's disease subtyping

2021 ◽  
Author(s):  
Chang Su ◽  
Yu Hou ◽  
Matthew Brendel ◽  
Claire Henchcliffe ◽  
Fei Wang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Manifestations ◽  
Demographic Factors ◽  
Csf Biomarkers ◽  
Baseline Severity ◽  
Genetic Components ◽  
Unsupervised Deep Learning ◽  
Symptom Progression ◽  
Progression Patterns

The Parkinson's disease (PD) is a heterogeneous neurodegenerative disease, of which the etiological and pathological mechanisms remain unclear to date. PD has been associated with diverse movement dysfunctions and non-motor symptoms (i.e., symptom heterogeneity) and progression patterns of these symptoms differ from patient to patient (i.e., progression heterogeneity). To address these, the present investigation aims at comprehensively considering full progression course of early PDs to identify subtypes, each of which can reflect unique PD progression pattern. We retrospectively analyzed the Parkinson's Progression Markers Initiative (PPMI) and the Parkinson Disease Biomarkers Program (PDBP) as the development and validation cohorts, respectively. An unsupervised deep learning model was built to model progression trajectories in diverse clinical manifestations and cerebrospinal fluid (CSF) biomarkers to produce a representation vector for each patient, encoding his/her symptom progression profile. Then by performing clustering analysis on the patients' representation vectors, we identified three subtypes with distinct PD progression patterns in the PPMI cohort: Subtype I, mild baseline severity and mild symptom progression; mild baseline severity and moderate progression; and Subtype III, rapid symptom progression. Replication in the PDBP validation cohort demonstrated reproducibility of the subtypes. After that, we explored demographic factors, CSF biomarkers, neuroimaging biomarkers in brain regional atrophy, and genetic factors of the subtypes. Last, to enhance usability of the subtypes, predictive model of subtypes that relies on data at baseline and 1-year follow-up was trained. In conclusion, the identified subtypes revealed significant symptom progression patterns of PDs. Patients with similar baseline severities can even suffer from different progression pattern, leading to distinct prognosis. Demographic factors, biomarkers, and genetic components of the subtypes suggested distinct biological mechanisms and pathways potentially leading to those progression patterns. Our findings may benefit pathophysiological study, clinical practice, and clinical trials to advance PD.

scholarly journals Parkinson’s Disease Motor Symptom Progression Slowed with Multisensory Dance Learning over 3-Years: A Preliminary Longitudinal Investigation

2021 ◽  
Vol 11 (7) ◽  
pp. 895
Author(s):  
Karolina A. Bearss ◽  
Joseph F. X. DeSouza
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Daily Living ◽  
Rating Scale ◽  
Motor Impairment ◽  
Motor Dysfunction ◽  
Motor Symptom ◽  
Significant Group ◽  
Rate Of Decline ◽  
Symptom Progression

Parkinson’s disease (PD) is a neurodegenerative disease that has a fast progression of motor dysfunction within the first 5 years of diagnosis, showing an annual motor rate of decline of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between 5.2 and 8.9 points. We aimed to determine both motor and non-motor PD symptom progression while participating in dance classes once per week over a period of three years. Longitudinal data was assessed for a total of 32 people with PD using MDS-UPDRS scores. Daily motor rate of decline was zero (slope = 0.000146) in PD-Dancers, indicating no motor impairment, whereas the PD-Reference group showed the expected motor decline across three years (p < 0.01). Similarly, non-motor aspects of daily living, motor experiences of daily living, and motor complications showed no significant decline. A significant group (PD-Dancers and PD-Reference) by days interaction showed that PD who train once per week have less motor impairment (M = 18.75) than PD-References who do not train (M = 24.61) over time (p < 0.05). Training is effective at slowing both motor and non-motor PD symptoms over three years as shown in decreased scores of the MDS-UPDRS.

scholarly journals An Innovative Personalised Management Program for Older Adults with Parkinson’s Disease: New Concepts and Future Directions

2021 ◽  
Vol 11 (1) ◽  
pp. 43
Author(s):  
Piyush Varma ◽  
Lakshanaa Narayan ◽  
Jane Alty ◽  
Virginia Painter ◽  
Chandrasekhara Padmakumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older Persons ◽  
Clinical Manifestations ◽  
Clinical Syndrome ◽  
Management Program ◽  
Older Person ◽  
Care Needs ◽  
Future Directions ◽  
New Concepts

Introduction: Parkinson’s disease is a heterogeneous clinical syndrome. Parkinson’s disease in older persons presents with a diverse array of clinical manifestations leading to unique care needs. This raises the need for the healthcare community to proactively address the care needs of older persons with Parkinson’s disease. Though it is tempting to categorise different phenotypes of Parkinson’s disease, a strong evidence based for the same is lacking. There is considerable literature describing the varying clinical manifestations in old age. This article aims to review the literature looking for strategies in personalising the management of an older person with Parkinson’s disease.

scholarly journals Unraveling Pathophysiological Mechanisms of Parkinson’s Disease: Contribution of CSF Biomarkers

2020 ◽  
Vol 15 ◽  
pp. 117727192096407
Author(s):  
Lucia Farotti ◽  
Federico Paolini Paoletti ◽  
Simone Simoni ◽  
Lucilla Parnetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical History ◽  
Substantial Contribution ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Disease Modifying Drugs ◽  
Precise Diagnosis ◽  
And Oxidative Stress

Diagnosis of Parkinson’s disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer’s disease (AD) biomarkers, low CSF Aβ42 levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognostic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs.

Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

2018 ◽  
Vol 18 (5-6) ◽  
pp. 233-238
Author(s):  
Frederic Sampedro ◽  
Juan Marín-Lahoz ◽  
Saul Martínez-Horta ◽  
Javier Pagonabarraga ◽  
Jaime Kulisevsky
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
De Novo ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Csf Biomarkers ◽  
Gene Encoding ◽  
Cortical Thinning ◽  
Age Related

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

scholarly journals Allelic variant in SLC6A3 rs393795 affects cerebral regional homogeneity and gait dysfunction in patients with Parkinson’s disease

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7957
Author(s):  
Lina Wang ◽  
Yongsheng Yuan ◽  
Jianwei Wang ◽  
Yuting Shen ◽  
Yan Zhi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Allelic Variation ◽  
Inferior Frontal Gyrus ◽  
Freezing Of Gait ◽  
Clinical Manifestations ◽  
Regional Homogeneity ◽  
Allelic Variant ◽  
Analysis Of Covariance ◽  
Link Type

Aims We sought to explore the role of the SLC6A3 rs393795 allelic variant in cerebral spontaneous activity and clinical features in Parkinson’s disease (PD) via imaging genetic approach. Methods Our study recruited 50 PD and 45 healthy control (HC) participants to provide clinical, genetic, and resting state functional magnetic resonance imaging (rs-fMRI) data. All subjects were separated into 16 PD-AA, 34 PD-CA/CC, 14 HC-AA, and 31 HC-CA/CC four subgroups according to SLC6A3 rs393795 genotyping. Afterwards, main effects and interactions of groups (PD versus HC) and genotypes (AA versus CA/CC) on cerebral function reflected by regional homogeneity (ReHo) were explored using two-way analysis of covariance (ANCOVA) after controlling age and gender. Finally, Spearman’ s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in PD subgroups. Results Compared with HC subjects, PD patients exhibited increased ReHo signals in left middle temporal gyrus and decreased ReHo signals in left pallidum. Compared with CA/CC carriers, AA genotype individuals showed abnormal increased ReHo signals in right inferior frontal gyrus (IFG) and supplementary motor area (SMA). Moreover, significant interactions (affected by both disease factor and allelic variation) were detected in right inferior temporal gyrus (ITG). Furthermore, aberrant increased ReHo signals in right ITG were observed in PD-AA in comparison with PD-CA/CC. Notably, ReHo values in right ITG were negatively associated with Tinetti Mobility Test (TMT) gait subscale scores and positively related to Freezing of Gait Questionnaire (FOG-Q) scores in PD-AA subgroup. Conclusions Our findings suggested that SLC6A3 rs393795 allelic variation might have a trend to aggravate the severity of gait disorders in PD patients by altering right SMA and IFG function, and ultimately result in compensatory activation of right ITG. It could provide us with a new perspective for exploring deeply genetic mechanisms of gait disturbances in PD.

scholarly journals Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Epaminondas Doxakis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Circular Rnas ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractParkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

Brain Neuroimaging of Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease: A Systematic Review

2021 ◽  
pp. 1-15
Author(s):  
Rafail Matzaras ◽  
Kuangyu Shi ◽  
Artemios Artemiadis ◽  
Panagiotis Zis ◽  
Georgios Hadjigeorgiou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Manifestations ◽  
Brain Regions ◽  
Primary Objective ◽  
Current Evidence ◽  
Nuclear Medicine Imaging ◽  
Sleep Behavior ◽  
Imaging Results

Background: REM-sleep behaviour disorder (RBD) is a parasomnia and a common comorbidity in Parkinson’s disease (PD). There is evidence that the presence of RBD is associated with more severe PD. The differences in the clinical manifestations and the natural history are likely to imply underlying differences in the pathophysiology among PD patients with and without RBD. The increasing number of neuroimaging studies support this notion. Objective: Our primary objective was to review the current evidence regarding the brain neuroimaging findings in PD patients with RBD (PDRBD). Methods: A systematic review of articles, published in PubMed between January 1, 2000 and September 23, 2020 was performed. We evaluate previous studies that assessed PD patients with RBD using various brain structural and functional magnetic resonance imaging (MRI) techniques and brain nuclear medicine imaging. Results: Twenty-nine studies, involving a total of 3,347 PD subjects among which 912 subjects with PDRBD, met the selection criteria and were included. The presence of RBD in PD patients is associated with structural and functional alterations in several brain regions, mainly in brainstem, limbic structures, frontotemporal cortex, and basal ganglia, raising the hypothesis of a PDRBD neuroimaging phenotype. Conclusion: The current review provides up-to-date knowledge in this field and summarizes the neurobiological/neuroimaging substrate of RBD in PD.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in Parkinson’s disease and atypical parkinsonian syndromes

2021 ◽  
Author(s):  
Michaela Kaiserova ◽  
Monika Chudackova ◽  
Hana Prikrylova Vranova ◽  
Katerina Mensikova ◽  
Anetta Kastelikova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Statistical Significance ◽  
Corticobasal Degeneration ◽  
Control Group ◽  
Csf Biomarkers ◽  
Parkinsonian Syndromes ◽  
Significant Difference ◽  
Hydroxyindoleacetic Acid

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).

scholarly journals Altered Insulin Receptor Substrate 1 Phosphorylation in Blood Neuron-Derived Extracellular Vesicles From Patients With Parkinson’s Disease

2020 ◽  
Vol 8 ◽  
Author(s):  
Szu-Yi Chou ◽  
Lung Chan ◽  
Chen-Chih Chung ◽  
Jing-Yuan Chiu ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Extracellular Vesicles ◽  
Insulin Signaling ◽  
Clinical Manifestations ◽  
Insulin Signaling Pathway ◽  
Insulin Receptor Substrate ◽  
Neuronal Markers

IntroductionDiabetes increases the risk of Parkinson’s disease (PD). The phosphorylation of type 1 insulin receptor substrate (IRS-1) determines the function of insulin signaling pathway. Extracellular vesicles (EVs) are emerging as biomarkers of human diseases. The present study investigated whether PD patients exert altered phosphorylation IRS-1 (p-IRS-1) inside the blood neuron-derived extracellular vesicles (NDEVs).Research Design and MethodsIn total, there were 94 patients with PD and 63 healthy controls recruited and their clinical manifestations were evaluated. Blood NDEVs were isolated using the immunoprecipitation method, and Western blot analysis was conducted to assess total IRS-1, p-IRS-1, and downstream substrates level in blood NDEVs. Statistical analysis was performed using SPSS 19.0, and p &lt; 0.05 was considered significant.ResultsThe isolated blood EVs were validated according to the presence of CD63 and HSP70, nanoparticle tracking analysis and transmission electron microscopy. NDEVs were positive with neuronal markers. PD patients exerted significantly higher level of p-IRS-1S312 in blood NDEVs than controls. In addition, the p-IRS-1S312 levels in blood NDEVs was positively associated with the severity of tremor in PD patients after adjusting of age, sex, hemoglobin A1c, and body mass index (BMI).ConclusionPD patients exerted altered p-IRS-1S312 in the blood NDEVs, and also correlated with the severity of tremor. These findings suggested the association between dysfunctional insulin signaling pathway with PD. The role of altered p-IRS-1S312 in blood NDEVs as a segregating biomarker of PD required further cohort study to assess the association with the progression of PD.

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