Journal of Parkinson's Disease - Volume 13, issue 6

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

Article Type: Editorial

Keywords: Metascience, replication, reproducibility, rigor, Parkinson’s disease

DOI: 10.3233/JPD-239002

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 849-850, 2023

Authors: Capriglia, Francesco | Burgess, Toby | Bandmann, Oliver | Mortiboys, Heather

Article Type: Other

DOI: 10.3233/JPD-239003

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 851-864, 2023

Authors: Cristini, Jacopo | Parwanta, Zohra | De las Heras, Bernat | Medina-Rincon, Almudena | Paquette, Caroline | Doyon, Julien | Dagher, Alain | Steib, Simon | Roig, Marc

Article Type: Systematic Review

Abstract: Background: The ability to encode and consolidate motor memories is essential for persons with Parkinson’s disease (PD), who usually experience a progressive loss of motor function. Deficits in memory encoding, usually expressed as poorer rates of skill improvement during motor practice, have been reported in these patients. Whether motor memory consolidation (i.e., motor skill retention) is also impaired is unknown. Objective: To determine whether motor memory consolidation is impaired in PD compared to neurologically intact individuals. Methods: We conducted a pre-registered systematic review (PROSPERO: CRD42020222433) following PRISMA guidelines that included 46 studies. Results: Meta-analyses …revealed that persons with PD have deficits in retaining motor skills (SMD = –0.17; 95% CI = –0.32, –0.02; p  = 0.0225). However, these deficits are task-specific, affecting sensory motor (SMD = –0.31; 95% CI –0.47, –0.15; p  = 0.0002) and visuomotor adaptation (SMD = –1.55; 95% CI = –2.32, –0.79; p  = 0.0001) tasks, but not sequential fine motor (SMD = 0.17; 95% CI = –0.05, 0.39; p  = 0.1292) and gross motor tasks (SMD = 0.04; 95% CI = –0.25, 0.33; p  = 0.7771). Importantly, deficits became non-significant when augmented feedback during practice was provided, and additional motor practice sessions reduced deficits in sensory motor tasks. Meta-regression analyses confirmed that deficits were independent of performance during encoding, as well as disease duration and severity. Conclusion: Our results align with the neurodegenerative models of PD progression and motor learning frameworks and emphasize the importance of developing targeted interventions to enhance motor memory consolidation in PD. Show more

Keywords: Parkinson’s disease, memory consolidation, motor skills, rehabilitation

DOI: 10.3233/JPD-230038

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 865-892, 2023

Authors: Camerucci, Emanuele | Mullan, Aidan F. | Turcano, Pierpaolo | Bower, James | Piat, Capucine | Ahlskog, J.E. | Savica, Rodolfo

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) most commonly surfaces at middle age. An earlier onset is named early-onset Parkinson’s disease (EOPD), but the exact definition is a matter of ongoing scientific debate. Objective: To investigate 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) to identify all incident EOPD cases in Olmsted County, 1976–2015. A movement-disorder specialist reviewed all cases to confirm the EOPD diagnosis. For EOPD definition, we used two age cut-offs: motor-symptom onset at or before 50 and 55 years. Results: …EOPD incidence was 1.43/100,000 person-years for ≤55 and 0.55/100,000 for ≤50 years. Men had a higher incidence in both groups [1.84 vs. 1.03 (p  = 0.04); and 0.70 vs. 0.40 (p  = 0.24), respectively]. EOPD incidence of patients with motor-symptom onset before age 55 increased from 1.02/100.000 person-year 1976–1985, to 1.32/100.000 person-year 2006–2015. A similar trend was observed when ≤50 years cut-off was used (0.28/100,000 person-years 1976–1985, to 0.59/100,000 person-year 2006–2015). However, negative binomial regression found no significant change in incidence per 10 years (RR = 1.04 and 1.24 in the two groups). Incidence was consistently higher in men than women. Median time from EOPD-symptom onset to death was shorter in the EOPD ≤55 group (21.9 years) compared to the EOPD ≤50 group (25.6 years). Conclusion: We observed an increased trend in the incidence of EOPD with both cut-off ages. Overall, incidence of EOPD was 1.43 (≤55) and 0.55 (≤50) cases per 100,000 person-years, higher in men. Show more

Keywords: Parkinson’s disease, early-onset Parkinson’s disease, incidence, rochester epidemiology project (REP)

DOI: 10.3233/JPD-230049

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 893-898, 2023

Authors: Brumm, Michael C. | Siderowf, Andrew | Simuni, Tanya | Burghardt, Elliot | Choi, Seung Ho | Caspell-Garcia, Chelsea | Chahine, Lana M. | Mollenhauer, Brit | Foroud, Tatiana | Galasko, Douglas | Merchant, Kalpana | Arnedo, Vanessa | Hutten, Samantha J. | O’Grady, Alyssa N. | Poston, Kathleen L. | Tanner, Caroline M. | Weintraub, Daniel | Kieburtz, Karl | Marek, Kenneth | Coffey, Christopher S.

Article Type: Research Article

Abstract: Background: Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge. Objective: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods: Using data from the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and …conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression. Results: Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p  < 0.0001), greater MDS-UPDRS total scores (p  < 0.0001), higher GDS-15 depression scores (p  = 0.0341), lower dopamine transporter binding (p  = 0.0043), and lower CSF total α-synuclein levels (p  = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p  = 0.1639). Conclusion: Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies. Show more

Keywords: Parkinson’s disease, disease progression, outcome measures, clinical trials as topic

DOI: 10.3233/JPD-223433

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 899-916, 2023

Authors: Trevarrow, Michael P. | Munoz, Miranda J. | Rivera, Yessenia M. | Arora, Rishabh | Drane, Quentin H. | Rosenow, Joshua M. | Sani, Sepehr B. | Pal, Gian D. | Verhagen Metman, Leonard | Goelz, Lisa C. | Corcos, Daniel M. | David, Fabian J.

Article Type: Research Article

Abstract: Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves intensive aspects of movement (velocity) in people with Parkinson’s disease (PD) but impairs the more cognitively demanding coordinative aspects of movement (error). We extended these findings by evaluating STN-DBS induced changes in intensive and coordinative aspects of movement during a memory-guided reaching task with varying retention delays. Objective: We evaluated the effect of STN-DBS on motor control during a memory-guided reaching task with short and long retention delays in participants with PD and compared performance to healthy controls (HC). Methods: Eleven participants with PD completed the motor section …of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III) and performed a memory-guided reaching task under four different STN-DBS conditions (DBS-OFF, DBS-RIGHT, DBS-LEFT, and DBS-BOTH) and two retention delays (0.5 s and 5 s). An additional 13 HC completed the memory-guided reaching task. Results: Unilateral and bilateral STN-DBS improved the MDS-UPDRS III scores. In the memory-guided reaching task, both unilateral and bilateral STN-DBS increased the intensive aspects of movement (amplitude and velocity) in the direction toward HC but impaired coordinative aspects of movement (error) away from the HC. Furthermore, movement time was decreased but reaction time was unaffected by STN-DBS. Shorter retention delays increased amplitude and velocity, decreased movement times, and decreased error, but increased reaction times in the participants with PD. There were no interactions between STN-DBS condition and retention delay. Conclusion: STN-DBS may affect cognitive-motor functioning by altering activity throughout cortico-basal ganglia networks and the oscillatory activity subserving them. Show more

Keywords: Deep brain stimulation, memory-guided, Parkinson’s disease, STN-DBS, subthalamic nucleus

DOI: 10.3233/JPD-225041

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 917-935, 2023

Authors: Du, Juanjuan | Cui, Shishuang | Huang, Pei | Gao, Chao | Zhang, Pingchen | Liu, Jin | Li, Hongxia | Huang, Maoxin | Shen, Xin | Liu, Zixian | Chen, Zilu | Tan, Yuyan | Chen, Shengdi

Article Type: Research Article

Abstract: Background: Multiple system atrophy (MSA) is an intractable neurodegenerative disorder with poorly understanding of prognostic factors. Objective: The purpose of this retrospective longitudinal study was to explore the main predictors of survival of MSA patients with new clinical subtypes based on cluster analysis. Methods: A total of 153 Chinese MSA patients were recruited in our study. The basic demographic data and motor and nonmotor symptoms were assessed. Cluster and principal component analysis (PCA) were used to eliminate collinearity and search for new clinical subtypes. The multivariable Cox regression was used to find factors associated with survival …in MSA patients. Results: The median survival time from symptom onset to death (estimated using data from all patients by Kaplan-Meier analysis) was 6.3 (95% CI = 6.1–6.7) years. The survival model showed that a shorter survival time was associated with motor principal component (PC)1 (HR = 1.71, 95% CI: 1.26–2.30, p  < 0.001) and nonmotor PC3 (HR = 1.68, 95% CI: 1.31–2.10, p  < 0.001) through PCA. Four clusters were identified: Cluster 1 (mild), Cluster 2 (mood disorder-dominant), Cluster 3 (axial symptoms and cognitive impairment-dominant), and Cluster 4 (autonomic failure-dominant). Multivariate Cox regression indicated that Cluster 3 (HR = 4.15, 95% CI: 1.73–9.90, p  = 0.001) and Cluster 4 (HR = 4.18, 95% CI: 1.73–10.1, p  = 0.002) were independently associated with shorter survival time. Conclusion: More serious motor symptoms, axial symptoms such as falls and dysphagia, orthostatic hypotension, and cognitive impairment were associated with poor survival in MSA via PCA and cluster analysis. Show more

Keywords: Cluster analysis, multiple system atrophy, principal component analysis, prognosis

DOI: 10.3233/JPD-225127

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 937-946, 2023

Authors: de Luna, João Rafael Gomes | Lima, Danielle Pessoa | Gomes, Vlademir Carneiro | de Almeida, Samuel Brito | Monteiro, Pauliana Alencar | Viana-Júnior, Antonio Brazil | Marques da Silva, Thabta Aparecida | Gradvohl, Leticia Brasil | Bruno, Luísa Bedê | Lindsay Silva Marques, Miriam | Cunha, Letícia Chaves Vieira | Feitosa, Camila Ximenes | Braga-Neto, Pedro | Roriz-Filho, Jarbas de Sá | Montenegro-Júnior, Renan Magalhaes

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) and sarcopenia share similar pathophysiological mechanisms. Objective: Estimate the prevalence of sarcopenia in PD patients and describe clinical and demographic features associated with sarcopenia. Methods: A cross-sectional study was carried out at a tertiary public hospital in Brazil. A modified HY scale of stage 1 to 3, being at least 40 years old and having the ability to stand and walk unassisted were required for eligibility. We evaluated physical performance and muscle mass using DEXA. Results: The study population comprised 124 patients, of which 53 (42.7%) were women. The mean …age and mean disease duration were 65.8±10.5 and 10.1±5.8 years, respectively. The mean handgrip strength of 20.4±6.9 in woman and 34.6±8.4 kg in men. Moreover, 50.8% patients had positive SARC-F, 20% patients had probable sarcopenia, 9.6% confirmed sarcopenia, and 16.8% patients showed low muscle mass quantity measured by DEXA. Lower Levodopa Equivalent Dosage (LED) and calf circumference (CC) were independently associated with confirmed sarcopenia. LLED, higher MDS-UPDRS Part III, and lower MMSE scores were independently associated with probable sarcopenia. The CC demonstrated accuracy to identify PD patients with confirmed sarcopenia with a cut-off of <31 cm in women and <34 cm in men. Conclusion: We found low prevalence of confirmed sarcopenia among PD patients. We propose that healthcare providers introduce measuring CC, which is a quick and inexpensive method to assess for sarcopenia in PD patients. Show more

Keywords: Sarcopenia, Parkinson’s disease, strength

DOI: 10.3233/JPD-230010

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 947-959, 2023

Authors: Virmani, Tuhin | Landes, Reid D. | Pillai, Lakshmi | Glover, Aliyah | Larson-Prior, Linda | Prior, Fred | Factor, Stewart A.

Article Type: Research Article

Abstract: Background: Freezing of gait (FOG) is a debilitating, variably expressed motor symptom in people with Parkinson’s disease (PwPD) with limited treatments. Objective: To determine if the rate of progression in spatiotemporal gait parameters in people converting from a noFOG to a FOG phenotype (FOGConv) was faster than non-convertors, and determine if gait parameters can help predict this conversion. Methods: PwPD were objectively monitored longitudinally, approximately every 6 months. Non-motor assessments were performed at the initial visit. Steady-state gait in the levodopa ON-state was collected using a gait mat (Protokinetics) at each visit. The rate of progression …in 8 spatiotemporal gait parameters was calculated. FOG convertors (FOGConv) were classified if they did not have FOG at initial visit and developed FOG at a subsequent visit. Results: Thirty freezers (FOG) and 30 non-freezers were monitored an average of 3.5 years, with 10 non-freezers developing FOG (FOGConv). FOGConv and FOG had faster decline in mean stride-length, swing-phase-percent, and increase in mean total-double-support percent, coefficient of variability (CV) foot-strike-length and CV swing-phase-percent than the remaining non-freezers (noFOG). On univariate modeling, progression rates of mean stride-length, stride-velocity, swing-phase-percent, total-double-support-percent and of CV swing-phase-percent had high discriminative power (AUC > 0.83) for classification of the FOGConv and noFOG groups. Conclusion: FOGConv had a faster temporal decline in objectively quantified gait than noFOG, and progression rates of spatiotemporal gait parameters were more predictive of FOG phenotype conversion than initial (static) parameters Objectively monitoring gait in disease prediction models may help define FOG prone groups for testing putative treatments. Show more

Keywords: Freezing of gait, gait, falls, Parkinson’s disease, phenotype conversion

DOI: 10.3233/JPD-230020

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 961-973, 2023

Authors: Panyakaew, Pattamon | Duangjino, Kotchakorn | Kerddonfag, Apiwoot | Ploensin, Teerit | Piromsopa, Krerk | Kongkamol, Chanon | Bhidayasiri, Roongroj

Article Type: Research Article

Abstract: Background: Impaired dexterity is an early motor symptom in Parkinson’s disease (PD) that significantly impacts the daily activity of patients; however, what constitutes complex dexterous movements remains controversial. Objective: To explore the characteristics of finger dexterity in mild-to-moderate stage PD. Methods: We quantitatively assessed finger dexterity in 48 mild-to-moderate stage PD patients and 49 age-matched controls using a simple alternating two-finger typing test for 15 seconds. Time-series analyses of various kinematic parameters with machine learning were compared between sides and groups. Results: Both the more and less affected hands of patients with PD had …significantly lower typing frequency and slower typing velocity than the non-dominant and the dominant hands of controls (p  = 0.019, p  = 0.016, p  < 0.001, p  < 0.001). The slope of the typing velocity decreased with time, indicating a sequence effect in the PD group. A typing duration of 6 seconds was determined sufficient to discriminate PD patients from controls. Typing error, repetition, and repetition rate were significantly higher in the more affected hands of patients with PD than in the non-dominant hand of controls (p  < 0.001, p  = 0.03, p  < 0.001). The error rate was constant, whereas the repetition rate was steep during the initiation of typing. A predictive model of the more affected hand demonstrated an accuracy of 70% in differentiating PD patients from controls. Conclusion: Our study demonstrated complex components of impaired finger dexterity in mild-to-moderate stage PD, namely bradykinesia with sequence effects, error, and repetition at the initiation of movement, suggesting that multiple neural networks may be involved in dexterity deficits in PD. Show more

Keywords: Finger dexterity, bradykinesia, quantitative analysis, keyboard typing test, Parkinson’s disease

DOI: 10.3233/JPD-230029

Citation: Journal of Parkinson's Disease, vol. 13, no. 6, pp. 975-988, 2023