Consistency and Stability of Motor Subtype Classifications in Patients With de novo Parkinson’s Disease DOI Creative Commons
Jingru Ren, Chenxi Pan,

Yuqian Li

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: March 1, 2021

Objective Patients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine consistency between PD subtypes, assess stability over time, and explore variables influencing subtype stability. Methods This was part a longitudinal de novo patients at single center. Based three different classification systems proposed by Jankovic, Schiess, Kang, respectively categorized as tremor-dominant/indeterminate/postural instability gait difficulty (TD/indeterminate/PIGD), TD S /mixed /akinetic-rigid (ARS), or K /AR baseline evaluation then re-assessed 1 month later. Demographic clinical characteristics recorded each evaluation. assessed using Cohen’s kappa coefficient (κ). Additional compared groups two-sample t -test, Mann–Whitney U -test Chi-squared test. Results Of 283 newly diagnosed, untreated patients, 79 followed up month. There fair agreement Kang (κ = 0.383 ± 0.044, κ 0.360 0.042, SK 0.368 0.038). Among systems, Schiess most stable Jankovic unstable. non-motor symptoms questionnaire (NMSQuest) scores differed significantly unstable ( p 0.008), consistent had more severe NMSQuest than an inconsistent subtype. Conclusion Fair observed systems. For first (NMSs) found influence TD/indeterminate/PIGD classification. Our findings support combining NMSs increase effectiveness subtypes.

Language: Английский

A proteogenomic view of Parkinson’s disease causality and heterogeneity DOI Creative Commons
Sérgio Kaiser, Luqing Zhang, Brit Mollenhauer

et al.

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 11, 2023

The pathogenesis and clinical heterogeneity of Parkinson's disease (PD) have been evaluated from molecular, pathophysiological, perspectives. High-throughput proteomic analysis cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers 154 LRRK2 carriers), 534 controls, 4135 proteins analyzed. Combining CSF aptamer-based genetics we determined protein quantitative trait loci (pQTLs). Analyses pQTLs together summary statistics largest genome wide association (GWAS) identified 68 potential causal by Mendelian randomization. top protein, GPNMB, was previously reported to be upregulated substantia nigra patients. We also compared proteomes controls. Proteome differences between unaffected controls suggest degeneration dopaminergic neurons, altered dopamine metabolism increased brain inflammation. In subcohort found dysregulated lysosomal degradation, alpha-synuclein processing, neurotransmission. neuroinflammation, mitochondrial dysfunction/oxidative stress, iron neuroprotection mediated vasoactive substances. Finally, used data stratify into "endotypes". endotypes show cognitive motor progression based on protein-based risk scores.Our findings not only contribute identification therapeutic targets but shape personalized medicine CNS neurodegeneration.

Language: Английский

Citations

32
Progressive brain atrophy and clinical evolution in Parkinson’s disease DOI Creative Commons
Massimo Filippi, Elisabetta Sarasso, Noemi Piramide

et al.

NeuroImage Clinical, Journal Year: 2020, Volume and Issue: 28, P. 102374 - 102374

Published: Jan. 1, 2020

Clinical manifestations and evolution are very heterogeneous among individuals with Parkinson's disease (PD). The aims of this study were to investigate the pattern progressive brain atrophy in PD according stage elucidate what extent cortical thinning subcortical related clinical motor non-motor evolution. 154 patients at different stages assessed over time using motor, structural MRI evaluations for a maximum 4 years. Cluster analysis defined subtypes. Cortical baseline relative 60 healthy controls. Longitudinal trends progression compared between clusters. contribution predicting non-motor, cognitive mood deterioration was explored. Two main clusters defined: mild (N = 87) moderate-to-severe 67). subtypes further identified: motor-predominant 43) mild-diffuse 44), latter group being older having more severe symptoms. initial PD. Over time, had greatest accumulation cortex left hippocampus, while less distributed observed patients. Baseline 1-year associated long-term cognitive, is accelerated early after onset becomes prominent later development dysfunctions. Structural may be useful monitoring

Language: Английский

Citations

59
Parkinson’s Disease Subtypes: Critical Appraisal and Recommendations DOI
Tiago Mestre, Seyed‐Mohammad Fereshtehnejad, Daniela Berg

et al.

Journal of Parkinson s Disease, Journal Year: 2021, Volume and Issue: 11(2), P. 395 - 404

Published: March 5, 2021

Background: In Parkinson’s disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this with potential contribution for knowledge of pathophysiology, natural history therapeutic development. There have been many studies but their impact remains unclear limited application research or practice. Objective: To critically evaluate subtyping systems. Methods: We conducted a systematic review subtypes, assessing characteristics reporting system first time. completed critical appraisal methodologic quality applicability using standardized checklists. Results: included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used data-driven approach 25, 65.8%), non-clinical biomarkers rarely 5, 13.1%). Motor domain most commonly reported differentiate subtypes. Most did not achieve top rating across items Methodologic Quality checklist. Clinical Applicability Checklist, importance differences between treatment implications general population rated poorly, subtype stability over time prognostic value largely unknown. Conclusion: Subtyping undertaken date significant shortcomings questionable unknown biological relevance. signature may be unique individual, rendering resistant meaningful cluster solutions. New approaches that acknowledge individual-level are more aligned personalized medicine needed.

Language: Английский

Citations

55
New therapeutic approaches to Parkinson's disease targeting GBA, LRRK2 and Parkin DOI
Konstantin Senkevich, Uladzislau Rudakou, Ziv Gan‐Or

et al.

Neuropharmacology, Journal Year: 2021, Volume and Issue: 202, P. 108822 - 108822

Published: Oct. 7, 2021

Language: Английский

Citations

53
Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity DOI Creative Commons
Wanlin Yang,

Zihan Chang,

Rongfang Que

et al.

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: March 6, 2020

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol high-sensitivity C-reactive protein (hsCRP) respectively PD patients, explore their correlation disease severity. Methods: performed a cross-sectional study that included 204 patients age-matched healthy controls (HCs). Plasma levels SOD, hsCRP, total cholesterol, high-density (HDL-C) low-density (LDL-C) were measured. A series neuropsychological assessments rate severity Results: The plasma SOD (135.7 ± 20.14 vs. 147.2 24.34, P < 0.0001), HDL-C LDL-C significantly lower than those HCs; hsCRP level was remarkably increased compared HC (2.766 3.242 1.637 1.597, 0.0001). negatively correlated while positively HDL-C, patients. H&Y, UPDRS, UPDRS (I), (II), (III) scores, but MoCA MMSE scores. Besides, MoCA; MoCA, respectively. Conclusion: Our findings suggest along LDL-C, higher might be important markers assess better understanding may yield insights into pathogenesis

Language: Английский

Citations

50
Blood-based biomarker in Parkinson’s disease: potential for future applications in clinical research and practice DOI Creative Commons
Lars Tönges, Carsten Buhmann, Stephan Klebe

et al.

Journal of Neural Transmission, Journal Year: 2022, Volume and Issue: 129(9), P. 1201 - 1217

Published: April 15, 2022

Abstract The clinical presentation of Parkinson’s disease (PD) is both complex and heterogeneous, its precise classification often requires an intensive work-up. differential diagnosis, assessment progression, evaluation therapeutic responses, or identification PD subtypes frequently remains uncertain from a point view. Various tissue- fluid-based biomarkers are currently being investigated to improve the description PD. From clinician's perspective, signatures blood that relatively easy obtain would have great potential for use in practice if they fulfill necessary requirements as biomarker. In this review article, we summarize knowledge on blood-based present researcher’s clinician’s perspective recent developments future applications.

Language: Английский

Citations

37
Abnormal cerebellum connectivity patterns related to motor subtypes of Parkinson’s disease DOI Creative Commons

Zhenzhen Chen,

Chentao He,

Piao Zhang

et al.

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(4), P. 549 - 560

Published: March 1, 2023

Abstract Cerebellar dysfunction may substantially contribute to the clinical symptoms of Parkinson’s disease (PD). The role cerebellar subregions in tremors and gait disturbances PD remains unknown. To investigate alterations subregion volumes functional connectivity (FC), as well FC between dentate nucleus (DN) ventral lateral posterior (VLp) thalamus, which are potentially involved different motor subtypes. We conducted morphometric resting-state analyses various 22 tremor-dominant (TD)-PD 35 postural instability difficulty dominant (PIGD)-PD patients 38 sex- age-matched healthy controls (HCs). volume neural correlates these changes with severity scores were investigated. PIGD-PD group showed greater right cerebellum (CBMm) left postcentral gyrus than HC group, a higher was associated less severe PIGD symptoms. In contrast, TD-PD had decreased DN VLp compared groups, lower worse TD Furthermore, inferior temporal group. Morphometric analysis revealed that significantly CBMm Our findings point differential alteration patterns offer new perspective on pathophysiology subtypes PD.

Language: Английский

Citations

17
Lee Silverman Voice Treatment for dysarthria in patients with Parkinson’s disease: a systematic review and meta‐analysis DOI
Fang Yuan, Xiaoling Guo, Xin Wei

et al.

European Journal of Neurology, Journal Year: 2020, Volume and Issue: 27(10), P. 1957 - 1970

Published: June 15, 2020

Approximately 89% of patients with Parkinson's disease (PD) suffer from dysarthria. Lee Silverman Voice Treatment (LSVT), a behavioral therapy, aims to improve speech and voice functions. The objective was assess the effectiveness LSVT compared other/no interventions for dysarthria in PD. Electronic databases, including PubMed, Embase Cochrane Library, were searched. publication date all included studies before 6 March 2020. Only randomized controlled trials (RCTs) that evaluated intervention considered. data obtained described mean differences calculated. Eight RCTs this meta-analysis comparing interventions. In comparison versus no intervention, vocal intensity sustained 'Ah' phonation, reading 'Rainbow passage', monologue describing picture increased by 8.87, 4.34, 3.25 3.31 dB, respectively, after 1 month therapy. Compared respiratory therapy group, group also showed significant improvement passage' immediately treatment (13.39, 6.66 3.19 dB). Positive still existed 24 months. There difference therapeutic effect between face-to-face online LSVT. PD verified these trials. However, future sufficient participants are essential evaluate

Language: Английский

Citations

47
Robust identification of Parkinson's disease subtypes using radiomics and hybrid machine learning DOI
Mohammad R. Salmanpour,

Mojtaba Shamsaei,

Abdollah Saberi

et al.

Computers in Biology and Medicine, Journal Year: 2020, Volume and Issue: 129, P. 104142 - 104142

Published: Nov. 26, 2020

Language: Английский

Citations

42
Functional Connectomics and Disease Progression in Drug‐Naïve Parkinson's Disease Patients DOI
Rosa De Micco, Federica Agosta, Silvia Basaia

et al.

Movement Disorders, Journal Year: 2021, Volume and Issue: 36(7), P. 1603 - 1616

Published: Feb. 27, 2021

ABSTRACT Background Functional brain connectivity alterations may be detectable even before the occurrence of atrophy, indicating their potential as early markers pathological processes. Objective We aimed to determine whole‐brain network topologic organization functional connectome in a large cohort drug‐naïve Parkinson's disease (PD) patients using resting‐state magnetic resonance imaging and explore whether baseline changes predict clinical progression. Methods One hundred forty‐seven drug‐naïve, cognitively unimpaired PD were enrolled study at compared 38 age‐ gender‐matched controls. Non‐hierarchical cluster analysis motor non‐motor data was applied stratify into two subtypes: 77 early/mild 70 early/severe. Graph theory connectomics used assess global local topological properties regional baseline. Stepwise multivariate regression investigated predictors progression over 2 years. Results At baseline, widespread abnormalities detected basal ganglia, sensorimotor, frontal, occipital networks Decreased involving mostly striato‐frontal, temporal, occipital, limbic connections differentiated from early/severe patients. Connectivity found independent cognitive 2‐year follow‐up. Conclusions Our findings revealed that reorganization occurs underlies crucial involvement striatal projections. Connectomic measures helpful identify specific patient subtype, characterized by severe burden well abnormalities. © 2021 International Parkinson Movement Disorder Society

Language: Английский

Citations

38