Journal of Parkinson's Disease - Volume 13, issue 1

Authors: Bloem, Bastiaan R. | Kalia, Lorraine V.

Article Type: Editorial

Keywords: Parkinson’s disease, open access, open science, editorial, editors

DOI: 10.3233/JPD-229011

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 1-2, 2023

Authors: Leroy, Tim | Baggen, Remco J. | Lefeber, Nina | Herssens, Nolan | Santens, Patrick | De Letter, Miet | Maes, Leen | Bouche, Katie | Van Bladel, Anke

Article Type: Systematic Review

Abstract: Background: Balance impairment is a frequent cause of morbidity and mortality in people with Parkinson’s disease (PD). As opposed to the effects of appendicular motor symptoms, the effects of Levodopa on balance impairment in idiopathic PD are less clear. Objective: To review the literature on the effects of oral Levodopa on clinical balance test performance, posturography, step initiation, and responses to perturbation in people with idiopathic PD (PwPD). Methods: A systematic search of three scientific databases (Pubmed, Embase, and Web of Science) was conducted in accordance with PRISMA guidelines. For the pilot meta-analysis, standardized mean differences …with 95% confidence intervals were calculated using an inverse variance random effects model. Data not suitable for implementation in the meta-analysis (missing means or standard deviations, and non-independent outcomes) were analyzed narratively. Results: A total of 2772 unique studies were retrieved, of which 18 met the eligibility criteria and were analyzed, including data of 710 idiopathic PwPD. Levodopa had a significant positive effect on the Berg Balance Scale, the Push and Release test, and jerk and frequency parameters during posturography. In contrast, some significant negative effects on velocity-based sway parameters were found during posturography and step initiation. However, Levodopa had no significant effect on most step initiation- and all perturbation parameters. Conclusion: The effects of Levodopa on balance in PwPD vary depending on the outcome parameters and patient inclusion criteria. A systematic approach with well-defined outcome parameters, and prespecified, sensitive and reliable tests is needed in future studies to unravel the effects of oral Levodopa on balance. Show more

Keywords: Balance, medication, meta-analysis, Parkinson’s disease, postural control

DOI: 10.3233/JPD-223536

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 3-23, 2023

Authors: Li, Weimin | Shen, Jiaqi | Wu, Hao | Lin, Lishan | Liu, Yanmei | Pei, Zhong | Liu, Ganqiang

Article Type: Research Article

Abstract: Background: The motor impairment in Parkinson’s disease (PD) can be managed but effective treatments for stopping or slowing the disease process are lacking. The advent of transcriptomics studies in PD shed light on the development of promising measures to predict disease progression and discover novel therapeutic strategies. Objective: To reveal the potential role of transcripts in the motor impairment progression of patients with PD via transcriptome analysis. Methods: We separately analyzed the differentially expressed genes (DEGs) between PD cases and healthy controls in two cohorts using whole blood bulk transcriptome data. Based on the intersection of …DEGs, we established a prognostic signature by regularized regression and Cox proportional hazards analysis. We further performed immune cell analysis and single-cell RNA sequencing analysis to study the biological features of this signature. Results: We identified a two-gene-based prognostic signature that links to PD motor progression and the two-gene signature-derived risk score was associated with several types of immune cells in blood. Notably, the fraction of neutrophils increased 5% and CD4+ T cells decreased 7% in patients with high-risk scores compared to that in patients with low-risk scores, suggesting these two types of immune cells might play key roles in the prognosis of PD. We also observed the downregulated genes in PD patients with high-risk scores that enriched in PD-associated pathways from iPSC-derived dopaminergic neurons single-cell RNA sequencing analysis. Conclusion: We identified a two-gene signature linked to the motor progression in PD, which provides new insights into the motor prognosis of PD. Show more

Keywords: Parkinson’s disease, gene signature, risk score, motor progression, immune cells, dopaminergic neurons

DOI: 10.3233/JPD-223454

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 25-38, 2023

Authors: Youn, Jinyoung | Won, Ji Hye | Kim, Mansu | Kwon, Junmo | Moon, Seung Hwan | Kim, Minkyeong | Ahn, Jong Hyun | Mun, Jun Kyu | Park, Hyunjin | Cho, Jin Whan

Article Type: Research Article

Abstract: Background: The “motor reserve” is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. Objective: We investigated brain structures relevant to the motor reserve in Parkinson’s disease (PD) in this study. Methods: Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson’s Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT …uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. Results: We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. Conclusion: Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures. Show more

Keywords: Parkinson’s disease, motor reserve, compensation, basal ganglia, diffusion tensor

DOI: 10.3233/JPD-223542

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 39-48, 2023

Authors: Valent, Dora | Krismer, Florian | Grossauer, Anna | Peball, Marina | Heim, Beatrice | Mahlknecht, Philipp | Djamshidian, Atbin | Poewe, Werner | Seppi, Klaus

Article Type: Research Article

Abstract: Background: Early identification of Parkinson’s disease (PD) patients at risk for becoming functionally dependent is important for patient counseling. Several models describing the relationship between predictors and outcome have been reported, however, most of these require computer software for practical use. Objective: Here we report the development of a risk nomogram allowing an approximate graphical computation of the risk of becoming functionally dependent in early PD. Methods: We analyzed data form the Parkinson’s Progression Markers Initiative cohort of newly diagnosed PD patients from baseline through the first 5 years of follow-up. Functional dependence was defined as …a score < 80 on the Schwab & England Activities of Daily Living scale. A binary logistic model was developed to estimate the risk of functional dependence and based on the results, a nomogram for the prediction of functional dependence was drawn in order to provide an easy-to-use tool in clinical and academic settings as a part of personalized medicine approach to PD treatment. Results: At baseline, three patients and over the five-year follow-up, 85 (22%) out of 395 patients were functionally dependent as scored by the Schwab & England Activities of Daily Living rating scale. The binary logistic model showed that clinical parameters such as MDS-UPDRS I (rater part), MDS-UPDRS II, and MDS-UPDRS axial motor score were significant predictors for functional dependence within 5 years. Conclusion: We here provide an easy-to-use tool to estimate the risk of functional dependence in PD patients based on the MDS-UPDRS part I, II and axial motor score. Show more

Keywords: Parkinson’s disease, nomograms, functional status, prognosis, risk, early diagnosis

DOI: 10.3233/JPD-223501

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 49-55, 2023

Authors: Opova, Karolina | Limousin, Patricia | Akram, Harith

Article Type: Systematic Review

Abstract: Background: Spinal cord stimulation (SCS) is a therapeutic procedure widely used in the management of refractory chronic pain. Evidence from case reports and small descriptive studies has emerged suggesting a role for SCS in patients with gait dysfunction, such as freezing of gait (FoG) and postural imbalance. These are severely debilitating symptoms of advanced Parkinson’s disease (PD). Objective: To establish the current evidence base for the potential application of SCS on gait and balance dysfunction in PD patients. Methods: Three online databases were screened for relevant manuscripts. Two separate searches and four different search strategies were …applied to yield relevant results. The main parameters of interest were postural and gait symptoms; secondary outcomes were Quality of Life (QoL) and adverse effects. Results: Nineteen studies fulfilled the inclusion criteria. Motor improvements using section III of the Unified Parkinson’s Disease Rating Score (UPDRS-III) were available in 13 studies. Measurements to assess FoG reported the following improvements: FoG questionnaires (in 1/19 studies); generalized freezing parameters (2); and walkway/wireless accelerometer measurements (2). Parameters of postural imbalance and falling improved as follows: BBS (1); posture sagittal vertical axis (1); and generalized data on postural instability (8). Two studies reported on adverse effects. QoL was shown to improve as follows: EQ-5D (2); ADL (1); SF-36 (1); BDI-II (1); PDQ-8 (1); HDRS (1); and VAS (5). Conclusion: SCS may have a therapeutic potential in advanced PD patients suffering from postural and gait-related symptoms. The existing evidence suggests that SCS positively affects patients’ QoL with an acceptable safety profile in this patient population. Show more

Keywords: Parkinson’s disease, spinal cord stimulation, gait, freezing, balance, review, falls, posture

DOI: 10.3233/JPD-223284

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 57-70, 2023

Authors: Yoo, Hakje | Chung, Se Hwa | Lee, Chan-Nyoung | Joo, Hyung Joon

Article Type: Research Article

Abstract: Background: Although idiopathic Parkinson’s disease (IPD) is increasing with the aging population, there is no adequate screening test for early diagnosis of IPD. Cardiac autonomic dysfunction begins in the early stages of IPD, and an electrocardiogram (ECG) contains precise information on the heart. Objective: This study is to develop an ECG deep learning algorithm that can efficiently screen for IPD. Methods: Data were collected from 751 IPD patients (2,138 ECGs), 751 age and sex-matched non-IPD patients (2,673 ECGs) as a control group, and 297 drug-induced Parkinsonism (DPD) patients (875 ECGs) as a disease control group. ECG …data were randomly divided into training set, validation set, and test set at a ratio of 6:2:2. We developed a deep-convolutional neural network (CNN) consisting of 16 layers with Bayesian optimization that classified IPD patients by ECG data. The robustness of the deep learning model was verified through 5-fold cross-validation. Results: The AUROC of the model for detection of IPD was 0.924 (95% CI, 0.913–0.936) in the test set. That for detecting DPD was 0.473 (95% CI, 0.453–0.504). The sensitivities of the model according to Unified Parkinson’s Disease Rating Scale III and Hoehn & Yahr scale were also similar. Conclusion: In conclusion, the CNN-based deep learning model using ECG data showed quite good performance in identifying IPD patients. Standardized 12-lead ECG test could be one of the clinically feasible candidate methods for early screening of IPD in the future. Show more

Keywords: Parkinson’s disease, mass screening, electrocardiography, deep learning

DOI: 10.3233/JPD-223549

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 71-82, 2023

Authors: Li, Xin-Yi | Chen, Ming-Jia | Liang, Xiao-Niu | Yao, Rui-Xin | Shen, Bo | Wu, Bin | Li, Gen | Sun, Yi-Min | Wu, Jian-Jun | Liu, Feng-Tao | Yang, Yu-Jie | Wang, Jian

Article Type: Research Article

Abstract: Background: The self-reported quality of life (QoL) should be carefully listened to in progressive supranuclear palsy (PSP) from the patient-centered perspective. However, there was still a lack of short QoL measurement tool in atypical parkinsonism. Objective: We aimed to test whether the short Parkinson’s Disease Questionnaire-8 (PDQ-8) was effective in assessing QoL in PSP, comparing with Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) and Parkinson’s Disease Questionnaire-39 (PDQ-39). Methods: 132 patients with clinical diagnosed PSP, including PSP-Richardson syndrome (RS) subtype (n = 71) and PSP-non-RS subtype (n = 61) were recruited for clinical …evaluation including QoL assessment. The detailed QoL profiles and possibility of using PDQ-8 were systemically analyzed. The determinants to the QoL were then calculated by multivariate linear regression analysis. Results: The PSP-QoL total score summary index (SI) was 22.8 (10.1, 41.1), while the PDQ-8 and PDQ-39 total SI score were 28.1 (12.5, 46.9) and 29.5 (15.4, 49.4). Mobility, activities of daily life, cognition and communication were the main affected QoL subdomains (median SI: 40.0, 31.3, 25.0 and 25.0 respectively). PSP-RS subtype showed more severe damage physically (p <0.001) and mentally (p = 0.002) compared to other subtypes. More importantly, the strong relevance of PDQ-8 and recommended PSP QoL tools were confirmed (p <0.001). In addition, disease severity, depression and daytime sleepiness were proved to be critical determinants for QoL in PSP. Conclusions: PDQ-8 could be an easy, reliable, and valid tool to evaluate QoL in patients with PSP. Besides motor symptoms, more attention should be paid to non-motor impairment such as depression in PSP. Show more

Keywords: Health-related quality of life, PDQ-8, PSP-QoL, progressive supranuclear palsy

DOI: 10.3233/JPD-223553

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 83-91, 2023

Authors: Carey, Guillaume | Lopes, Renaud | Moonen, Anja J.H. | Mulders, Anne E.P. | de Jong, Joost J.A. | Kuchcinski, Gregory | Defebvre, Luc | Kuijf, Mark L. | Dujardin, Kathy | Leentjens, Albert F.G.

Article Type: Research Article

Abstract: Background: Cognitive behavioral therapy (CBT) reduces anxiety symptoms in patients with Parkinson’s disease (PD). Objective: The objective of this study was to identify changes in functional connectivity in the brain after CBT for anxiety in patients with PD. Methods: Thirty-five patients with PD and clinically significant anxiety were randomized over two groups: CBT plus clinical monitoring (10 CBT sessions) or clinical monitoring only (CMO). Changes in severity of anxiety symptoms were assessed with the Parkinson Anxiety Scale (PAS). Resting-state functional brain MRI was performed at baseline and after the intervention. Functional networks were extracted by an …Independent Component Analysis (ICA). Functional connectivity (FC) changes between structures involved in the PD-related anxiety circuits, such as the fear circuit (involving limbic, frontal, and cingulate structures) and the cortico-striato-thalamo-cortical limbic circuit, and both within and between functional networks were compared between groups and regressed with anxiety symptoms changes. Results: Compared to CMO, CBT reduced the FC between the right thalamus and the bilateral orbitofrontal cortices and increased the striato-frontal FC. CBT also increased the fronto-parietal FC within the central executive network (CEN) and between the CEN and the salience network. After CBT, improvement of PAS-score was associated with an increased striato-cingulate and parieto-temporal FC, and a decreased FC within the default-mode network and between the dorsal attentional network and the language network. Conclusion: CBT in PD-patients improves anxiety symptoms and is associated with functional changes reversing the imbalance between PD-related anxiety circuits and reinforcing cognitive control on emotional processing. Show more

Keywords: Parkinson’s disease, anxiety, connectivity, cognitive behavioral therapy, fear circuit Trial registration: ClinicalTrials.gov Identifier: NCT02648737

DOI: 10.3233/JPD-223527

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 93-103, 2023

Authors: Santos García, Diego | de Deus Fonticoba, Teresa | Cores, Carlos | Suárez Castro, Ester | Hernández Vara, Jorge | Jesús, Silvia | Mir, Pablo | Cosgaya, Marina | José Martí, Maria | Pastor, Pau | Cabo, Iria | Seijo, Manuel | Legarda, Inés | Vives, Bárbara | Caballol, Nuria | Rúiz Martínez, Javier | Croitoru, Ioana | Cubo, Esther | Miranda, Javier | Alonso Losada, Maria Gema | Labandeira, Carmen | López Ariztegui, Nuria | Morales-Casado, Mabel | González Aramburu, Isabel | Infante, Jon | Escalante, Sonia | Bernardo, Noemí | Blázquez Estrada, Marta | Menéndez González, Manuel | García Caldentey, Juan | Borrué, Carmen | Vela, Lydia | Catalán, Maria José | Gómez Mayordomo, Víctor | Kurtis, Mónica | Prieto, Cristina | Ordás, Carlos | Nogueira, Víctor | López Manzanares, Lydia | Ávila Rivera, Maria Asunción | Puente, Victor | García Moreno, Jose Manuel | Solano Vila, Berta | Álvarez Sauco, María | Carrillo Padilla, Francisco | Martínez Castrillo, Juan Carlos | Sánchez Alonso, Pilar | Gastón, Itziar | Kulisevsky, Jaime | Valero, Caridad | de Fábregues, Oriol | González Ardura, Jessica | López Díaz, Luis Manuel | Martinez-Martin, Pablo

Article Type: Research Article

Abstract: Background: There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed …on time to hospital encounter 1-year after the baseline visit. Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065–5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319–6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757–8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080–8.322; p = 0.035) was an independent predictor of AH. Conclusion: Falls is an independent predictor of AH in PD patients. Show more

DOI: 10.3233/JPD-212539

Citation: Journal of Parkinson's Disease, vol. 13, no. 1, pp. 105-124, 2023