Journal of Parkinson's Disease - Volume 14, issue 4

Authors: Holtz, Anna-Victoria | Fink, Anne | Tamgüney, Gültekin | Doblhammer, Gabriele

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is caused by the misfolding and aggregation of α-synuclein in neurons into toxic oligomers and fibrils that have prion-like properties allowing them to infect healthy neurons and to be transmitted to animal models of PD by injection or oral exposure. Given α-synuclein fibrils’ potential transmission on the gut-brain axis, α-synuclein may be transmitted through colonoscopy procedures. Objective: This study examines a possible association between colonoscopy and PD. Methods: Longitudinal health insurance data of 250,000 individuals aged 50+ from 2004–2019 was analyzed. Cox proportional hazard and competing risk models with death as a …competing event were estimated to calculate the risk of PD. Colonoscopy was categorized as never receiving colonoscopy, colorectal cancer (CRC) screening without or with biopsy, destruction or excision (BDE), and diagnostic colonoscopy without or with BDE. Results: We identified 6,422 new cases of PD among 221,582 individuals. The Cox model revealed a significantly increased risk of PD for patients who ever had a diagnostic colonoscopy without or with BDE (HR = 1.31; 95% CI: [1.23–1.40 ]; HR = 1.32 [1.22–1.42 ]) after adjustment for age and sex. After controlling for covariates and death, persons who ever underwent CRC screening had a 40% reduced risk of PD (CRHR = 0.60 [0.54–0.67]), while persons who underwent diagnostic colonoscopy had a 20% reduced risk of PD (CRHR = 0.81 [0.75–0.88]). Conclusions: Colonoscopy does not increase the risk of PD, after adjusting for death and covariates. Individuals who underwent only CRC screening had the lowest risk of PD, which may be a result of a more health-conscious lifestyle. Show more

Keywords: Parkinson’s disease, colonoscopy, prion disease, brain-gut axis, event history analysis, competing risks, competing risk analysis

DOI: 10.3233/JPD-240017

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 747-760, 2024

Authors: Bane, Annie | Wilson, Lorraine | Jumper, Jill | Spindler, Lindsay | Wyatt, Pricilla | Willoughby, Darryn

Article Type: Research Article

Abstract: Background: Autonomic dysfunction precedes endothelial dysfunction in Parkinson’s disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one’s quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD). Objective: To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during …LIRT-BFR and HIRT in PwPD using a novel exercise protocol. Methods: Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines. Results: LIRT-BFR significantly improved orthostatic hypotension (p  = 0.026), homocysteine levels (p  < 0.001), peripheral circulation (p  = 0.003), supine blood pressure (p  = 0.028) and heart rate variability (p  = 0.041); LIRT-BFR improved homocysteine levels (p  < 0.018), peripheral circulation (p  = 0.005), supine blood pressure (p  = 0.007) and heart rate variability (p  = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar. Conclusions: LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable. Show more

Keywords: Parkinson’s disease, exercise, blood flow restriction, endothelial function, homocysteine5

DOI: 10.3233/JPD-230259

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 761-775, 2024

Authors: Li, Xiaobing | Bai, Jing | Guo, Xin | Mu, Yaqian | Di, Zhengli | Zhang, Gejuan | Wang, Bo | Zhang, Yun | Liu, Xinyao | Shi, Yan | Lin, Shinuan | Wu, Linyu | Bai, Ya | Liu, Xuedong

Article Type: Research Article

Abstract: Background: Multiple system atrophy (MSA) is a disease with diverse symptoms and the commonly used classifications, MSA-P and MSA-C, do not cover all the different symptoms seen in MSA patients. Additionally, these classifications do not provide information about how the disease progresses over time or the expected outcome for patients. Objective: To explore clinical subtypes of MSA with a natural disease course through a data-driven approach to assist in the diagnosis and treatment of MSA. Methods: We followed 122 cases of MSA collected from 3 hospitals for 3 years. Demographic characteristics, age of onset, clinical signs, …scale assessment scores, and auxiliary examination were collected. Age at onset; time from onset to assisted ambulation; and UMSARS I, II, and IV, COMPASS-31, ICARS, and UPDRS III scores were selected as clustering elements. K-means, partitioning around medoids, and self-organizing maps were used to analyze the clusters. Results: The results of all three clustering methods supported the classification of three MSA subtypes: The aggressive progression subtype (MSA-AP), characterized by mid-to-late onset, rapid progression and severe clinical symptoms; the typical subtype (MSA-T), characterized by mid-to-late onset, moderate progression and moderate severity of clinical symptoms; and the early-onset slow progression subtype (MSA-ESP), characterized by early-to-mid onset, slow progression and mild clinical symptoms. Conclusions: We divided MSA into three subtypes and summarized the characteristics of each subtype. According to the clustering results, MSA patients were divided into three completely different types according to the severity of symptoms, the speed of disease progression, and the age of onset. Show more

Keywords: Multiple system atrophy, cluster analysis, gait ataxia, autonomic nervous system diseases, parkinsonian disorders

DOI: 10.3233/JPD-230344

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 777-795, 2024

Authors: Lage, Carmen | Sánchez-Rodríguez, Antonio | Rivera-Sánchez, María | Sierra, María | González-Aramburu, Isabel | Madera, Jorge | Delgado-Alvarado, Manuel | López-García, Sara | Martínez-Dubarbie, Francisco | Fernández-Matarrubia, Marta | Martínez-Amador, Néstor | Martínez-Rodríguez, Isabel | Calvo-Córdoba, Alberto | Rodríguez-Rodríguez, Eloy | García-Cena, Cecilia | Sánchez-Juan, Pascual | Infante, Jon

Article Type: Research Article

Abstract: Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson’s disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, …and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2 -G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers. Show more

Keywords: Parkinson’s disease, LRRK2 , oculomotor, early diagnosis, premotor, microsaccade, antisaccade, eye-tracking

DOI: 10.3233/JPD-230416

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 797-808, 2024

Authors: Zeissler, Marie-Louise | Bakshi, Nikul | Bartlett, Michèle | Batla, Amit | Byrom, David | Chapman, Rebecca | Collins, Sally | Cowd, Elaine | Deeson, Eric | Ellis-Doyle, Romy | Forbes, Jodie | Gonzalez-Robles, Cristina | Jewell, Anna | Lane, Emma L. | LaPelle, Nancy R. | Martin, Keith | Matthews, Helen | Miller, Laurel | Mills, Georgia | Morgan, Antony | Parry, Miriam | Pushparatnam, Kuhan | Ratcliffe, Natasha | Salathiel, Dorothy | Scurfield, Paula | Siu, Carroll | Whipps, Sue | Wonnacott, Sheila | Foltynie, Thomas | Carroll, Camille B. | McFarthing, Kevin

Article Type: Research Article

Abstract: Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson’s charities, investigator patient groups and participants of a Delphi study on trial design. They are supported …by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium’s five other WGs and steering group. The group’s terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review – identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research. Show more

Keywords: Evaluation study, patient and public involvement, Parkinson’s disease, clinical trial protocol

DOI: 10.3233/JPD-230444

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 809-821, 2024

Authors: Woo, Kyung Ah | Kim, Han-Joon | Shin, Jung Hwan | Cho, Kangyoung | Choi, Hongyoon | Jeon, Beomseok

Article Type: Research Article

Abstract: Background: Rapid eye movement sleep behavior disorder (RBD) may precede or follow motor symptoms in Parkinson’s disease (PD). While over 70% of idiopathic RBD cases phenoconvert within a decade, a small subset develops PD after a more extended period or remains nonconverted. These heterogeneous manifestations of RBD in PD prompt subtype investigations. Premotor RBD may signify “body-first” PD with bottom-up, symmetric synucleinopathy propagation. Objective: Explore brainstem and nigrostriatal monoaminergic degeneration pattern differences based on premotor RBD presence and duration in de novo PD patients. Methods: In a cross-sectional analysis of de novo PD patients …(n  = 150) undergoing FP-CIT PET and RBD Single-Question Screen, the cohort was categorized into groups with and without premotor RBD (PDRBD +/– ), with further classification of PDRBD + based on a 10-year duration of premotor RBD. Analysis of FP-CIT binding in the striatum and pons, striatal asymmetry, and striatum-to-pons ratios compared patterns of nigrostriatal and brainstem monoaminergic degeneration. Results: PDRBD + exhibited more severe and symmetrical striatal dopaminergic denervation compared to PDRBD– , with the difference in severity accentuated in the least-affected hemisphere. The PDRBD +<10Y subgroup displayed the most prominent striatal symmetry, supporting a more homogeneous “body-first” subtype. Pontine uptakes remained lower in PDRBD + even after adjusting for striatal uptake, suggesting early degeneration of pontine monoaminergic nuclei. Conclusions: Premotor RBD in PD is associated with severe, symmetrical nigrostriatal and brainstem monoaminergic degeneration, especially in cases with PD onset within 10 years of RBD. This supports the concept of a “widespread, bottom-up” pathophysiological mechanism associated with premotor RBD in PD. Show more

Keywords: Parkinson’s disease, REM sleep behavior disorder, Lewy body disease, positron emission tomography

DOI: 10.3233/JPD-230459

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 823-831, 2024

Authors: Liu, Sicheng | Zhou, Cheng | Fang, Yuelin | Zhu, Bingting | Wu, Haoting | Wu, Chenqing | Guo, Tao | Wu, Jingjing | Wen, Jiaqi | Qin, Jianmei | Chen, Jingwen | Duanmu, Xiaojie | Tan, Sijia | Guan, Xiaojun | Xu, Xiaojun | Zhang, Minming | Zhang, Baorong | Zhao, Guohua | Yan, Yaping

Article Type: Research Article

Abstract: Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson’s disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor …QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC ) and free-water value of LC (FWLC ) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p  = 0.047) and PD (p  = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS. Show more

Keywords: Essential tremor, Parkinson’s disease, locus coeruleus. magnetic resonance imaging, sleep disorders

DOI: 10.3233/JPD-240001

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 833-842, 2024

Authors: Imbalzano, Gabriele | Artusi, Carlo Alberto | Ledda, Claudia | Montanaro, Elisa | Romagnolo, Alberto | Rizzone, Mario Giorgio | Bozzali, Marco | Lopiano, Leonardo | Zibetti, Maurizio

Article Type: Research Article

Abstract: Background: Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson’s disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time. Objective: To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and …their correlation with changes in gait parameters and FoG severity. Methods: This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores. Results: Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p  = 0.018; T2-T0 p  < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p  = 0.002, T0-T1 p  = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation. Conclusion: Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy. Show more

Keywords: Parkinson’s disease, levodopa intestinal gel, freezing of gait, parkinsonian gait, wearable sensors

DOI: 10.3233/JPD-240003

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 843-853, 2024

Authors: Chang, Bowen | Mei, Jiaming | Ni, Chen | Chen, Peng | Jiang, Yuge | Niu, Chaoshi

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety. Objective: The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration. Methods: An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses. Results: The study included 68 non-anxiety …PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01–0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD. Conclusions: Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes. Show more

Keywords: Parkinson’s disease, anxiety, rs-fMRI, graph theory analysis, oscillation-specific nodal

DOI: 10.3233/JPD-240055

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 855-864, 2024

Authors: Mantri, Sneha | Purks, Jennifer L. | Kinel, Daniel | Arbatti, Lakshmi | Hosamath, Abhishek | Allen, Allison | Amara, Amy | Anderson, Karen | Chahine, Lana M. | Eberly, Shirley | Mathur, Soania | Standaert, David | Oakes, David | Weintraub, Daniel | Shoulson, Ira | Marras, Connie

Article Type: Short Communication

Abstract: Parkinson’s disease (PD) carries substantial psychosocial burden. Using a database of responses by people with PD reporting up to five “most bothersome problems,” we identified 225 fear-based verbatims, which were organized using the framework method into 26 categories. Commonly-reported fears included uncertainty of progression (n  = 60, 26.7%), fear of future cognitive impairment (n  = 24, 10.7%) and fear of becoming a burden on others (n  = 23, 10.2%). Fears in PD are wide-ranging and can constitute the most bothersome aspect of the condition. These data can be used to design interventions to lessen the psychosocial burden of PD.

Keywords: Parkinson’s disease, quality of life, qualitative

DOI: 10.3233/JPD-230305

Citation: Journal of Parkinson's Disease, vol. 14, no. 4, pp. 865-872, 2024