Journal of Parkinson's Disease - Volume 10, issue 1

Authors: Suzuki, Keisuke | Okuma, Yasuyuki | Uchiyama, Tomoyuki | Miyamoto, Masayuki | Haruyama, Yasuo | Kobashi, Gen | Sakakibara, Ryuji | Shimo, Yasushi | Hatano, Taku | Hattori, Nobutaka | Yamamoto, Toshimasa | Hirano, Shigeki | Yamamoto, Tatsuya | Kuwabara, Satoshi | Kaji, Yoshiaki | Fujita, Hiroaki | Kadowaki, Taro | Hirata, Koichi

Article Type: Research Article

Abstract: Background: In Parkinson’s disease (PD) patients, the factors related to weight loss remain unclear. Objective: To investigate determinants of low body mass index (BMI) in PD patients. Methods: We identified factors associated with low BMI in PD patients in a multicenter case-control study. A total of 435 PD patients and 401 controls were included. Results: The mean BMI was significantly lower in PD patients than in controls (22.0±3.4 kg/m2 vs. 25.4±4.3 kg/m2 ), with an adjusted odds ratio (AOR) of 3.072 (95% CI, 2.103–4.488; p  < 0.001) for low BMI (<22 kg/m2 ) in PD. Compared to …the high-BMI PD group (>22 kg/m2 ), the low-BMI PD group (<22 kg/m2 ) had more women; a longer disease duration; higher revised Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II and IV scores; an increased levodopa equivalent dose (LED); and increased constipation, visual hallucination, dysphagia, dyskinesia and wearing off rates. There were no between-group differences in depression, anhedonia, apathy, sleep problems and daytime sleepiness. Multivariable analysis showed that visual hallucination (AOR, 2.408; 95% CI, 1.074–5.399; p  = 0.033) and the MDS-UPDRS IV (AOR, 1.155; 95% CI, 1.058–1.260; p  = 0.001) contributed to low BMI after controlling for clinical factors. In a second model, visual hallucination (AOR, 2.481; 95% CI, 1.104–5.576; p  = 0.028) and dyskinesia (sum of the MDS-UPDRS 4.3–4.6) (AOR, 1.319; 95% CI, 1.043–1.668; p  = 0.021) significantly contributed to low BMI. Conclusion: PD patients were 3 times more likely than healthy controls to have a low BMI. Motor complications, particularly dyskinesia, and visual hallucination were significantly associated with low BMI in PD patients. Show more

Keywords: Parkinson’s disease, body mass index, visual hallucination, dyskinesia, motor complication

DOI: 10.3233/JPD-191741

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 213-221, 2020

Authors: van den Heuvel, Lieneke | Dorsey, Ray R. | Prainsack, Barbara | Post, Bart | Stiggelbout, Anne M. | Meinders, Marjan J. | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Clinical decision making for Parkinson’s disease patients is supported by a combination of three distinct information resources: best available scientific evidence, professional expertise, and the personal needs and preferences of patients. All three sources have clear value but also share several important limitations, mainly regarding subjectivity, generalizability and variability. For example, current scientific evidence, especially from controlled clinical trials, is often based on selected study populations, making it difficult to translate the outcome to the care for individual patients in everyday clinical practice. Big data, including data from real-life unselected Parkinson populations, can help to bridge this information gap. Fine-grained …patient profiles created from big data have the potential to aid in identifying therapeutic approaches that will be most effective given each patient’s individual characteristics, which is particularly important for a disorder characterized by such tremendous interindividual variability as Parkinson’s disease. In this viewpoint, we argue that big data approaches should be acknowledged and harnessed, not to replace existing information resources, but rather as a fourth and complimentary source of information in clinical decision making, helping to represent the full complexity of individual patients. We introduce the ‘quadruple decision making’ model and illustrate its mode of action by showing how this can be used to pursue precision medicine for persons living with Parkinson’s disease. Show more

Keywords: Big data, data-driven science, evidence-based medicine, Parkinson’s disease, machine learning, personalized medicine, precision medicine, shared decision making

DOI: 10.3233/JPD-191712

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 223-231, 2020

Authors: Amundsen Huffmaster, Sommer L. | Lu, Chiahao | Tuite, Paul J. | MacKinnon, Colum D.

Article Type: Research Article

Abstract: Background: It has been hypothesized that freezing of gait (FOG) in people with Parkinson’s disease (PD) is due to abnormal coupling between posture and gait. Objective: In this study, we examined the relationship between anticipatory postural adjustments (APAs) preceding gait initiation and the kinematics of the first two steps between people with FOG and without FOG. Methods: The kinetics and kinematics of self-initiated gait were recorded in 25 people with PD (11 with FOG, 14 without FOG). Outcome variables included the amplitude and timing of the ground reaction forces (GRFs), center of pressure (CoP) shifts and …the spatial and temporal characteristics of the first and second steps. Results: The magnitude and timing of the APA phase of gait initiation were not significantly different between participants with and without FOG, yet the first step in the FOG group was distinguished by a significantly wider and less variable first step width, followed by a subsequent wider and shortened second step with reduced toe clearance. Multiple linear regression showed that the relationship between the initial conditions (stance width), APAs (posterior shift of the CoP) and the kinematics of the first step were different between groups with a significantly increased slope in the FOG group. Conclusion: These findings demonstrate that the transition from standing to walking is different between those with and without FOG and that alterations in the initial conditions or APAs are more likely to impact the execution of the two steps in people with FOG. Show more

Keywords: Gait initiation, Parkinson’s disease, anticipatory postural adjustments, stepping

DOI: 10.3233/JPD-191649

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 233-243, 2020

Authors: Peterson, Daniel S. | Mancini, Martina | Fino, Peter C. | Horak, Fay | Smulders, Katrijn

Article Type: Research Article

Abstract: Background: Gait speed is an important outcome that relates to mobility, function, and mortality, and is altered in people with Parkinson’s disease (PwPD). However, changes in gait speed may not reflect changes in other important aspects of gait. Objective: To characterize which outcomes change concomitantly with walking speed in PwPD. This information can inform the choice of outcome variables for characterizing and tracking gait performance in this population. Methods: 67 PwPD and 40 neurotypical adults completed 2-minute overground walking bouts at comfortable and fast self-selected speeds. Eight inertial sensors were used to characterize gait and turning. …We identified a subset of participants (38 per group) where the PD participant’s “fast” walk was similar speed to neurotypical participants “comfortable” walk, facilitating an across-group gait comparison controlling for gait speed. Results: Walking at fast gait speed compared to comfortable lead to significant changes in stride length, cadence, and stride time variability, but not in steps to turn, trunk ROM, and trunk and lumbar stability in PwPD. Sub-group analyses showed that despite walking at a similar speed as neurotypical adults, PwPD exhibit altered turning outcomes, lumbar stability, and stride length/cadence. Conclusions: Gait speed is a critical outcome for characterizing mobility. However, in PwPD, several important outcomes do not exhibit a uniform relationship with gait speed, and remain altered compared to neurotypical adults despite “normalizing” walking speed. Given the complex relationship between gait speed and other gait quality measures, care should be taken when choosing outcome measures to characterize the breadth of gait abnormality in PwPD. Show more

Keywords: Gait, kinematics, Parkinson’s disease, speed

DOI: 10.3233/JPD-191682

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 245-253, 2020

Authors: Hermann, Wiebke | Flemming, Theresa | Brandt, Moritz D. | Langner, Simona | Reichmann, Heinz | Storch, Alexander

Article Type: Research Article

Abstract: Background: Periodic limb movements in sleep (PLMS) are repetitive movements usually of the legs strongly associated with Restless-legs syndrome (RLS), which appear more frequently in males, older age and other sleep disturbances, such as sleep-disordered breathing (SDB). Patients with Parkinson’s disease (PD) suffer from various sleep disturbances including REM sleep behavior disorder, RLS and PLMS. Although a dopaminergic pathophysiology of PLMS is discussed, no systematic data on PLMS side-to-side distribution in PD and its correlation with asymmetry of motor symptoms are available. Objective: This study aimed at elucidating PLMS asymmetry in correlation to that of motor symptoms in …PD compared to SDB and RLS. Methods: Cross-sectional, retrospective analysis of two polysomnography (PSG) recordings per patient scoring PLMS separately for both legs. Results: Of 105 patients (44 PD, 44 age- and sex-matched SDB and 17 RLS patients) PLMS measures (number of PLM, PLM-Index, PLM-arousal index) showed significant side-to-side differences in all disease entities in both PSGs (P  < 0.001; Wilcoxon rank test). PLM-Index asymmetry (PLM-I difference of >5/h between both sides) was observed less frequently in PD (34% of patients) compared to RLS (77% , P  < 0.05) and SDB (59% , P  < 0.05; χ 2 test). In asymmetric PD patients, predominant side of PLMS was more stable than in SDB and RLS comparing the two PSGs, but we did not detect an agreement between PLMS predominant side with that of motor symptoms in PD patients. Conclusions: Only the minority of PD patients shows asymmetric PLMS distribution with relatively high night-to-night stability but no correlation with motor symptom asymmetry. Show more

Keywords: Parkinson’s disease, sleep-disordered breathing, periodic limb movements in sleep (PLMS), Willis-Ekbom disease, Restless-legs-syndrome

DOI: 10.3233/JPD-191667

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 255-266, 2020

Authors: Olsson, Tomas T. | Svensson, Martina | Hållmarker, Ulf | James, Stefan | Deierborg, Tomas

Article Type: Research Article

Abstract: Background: Physical activity is associated with reduced risk of Parkinson’s disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD. Objective: We aimed to investigate if physical activity is associated with long-term lower risk of PD and if this association could be explained by physically active people being able to sustain more PD neuropathology before clinical symptoms, a motor reserve. Methods: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n  = 197,685), exhibited reduced …incidence of PD compared to matched individuals from the general population (n  = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Results: Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of PD (HR: 0.71; 95 % CI 0.56–0.90) compared to non-skiers. When reducing risk for reverse causation by excluding PD cases within the first five years from race participation, there was still a trend for lower risk of PD (HR: 0.80; 95 % CI 0.62–1.03). Further, the PD prevalence converged between skiers and non-skiers after 15 years of follow-up, which is more consistent with a motor reserve in the physically active rather than neuroprotection. Conclusions: A physical active lifestyle is associated with reduced risk for PD. This association weakens with time and might be explained by a motor reserve among the physically active. Show more

Keywords: Physical activity, exercise, Parkinson’s disease, motor reserve

DOI: 10.3233/JPD-191762

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 267-274, 2020

Authors: Pintér, Dávid | Forjaz, Maria João | Martinez-Martin, Pablo | Rodriguez-Blazquez, Carmen | Ayala, Alba | Juhász, Annamária | Harmat, Márk | Janszky, József | Kovács, Norbert

Article Type: Research Article

Abstract: Background: Several scales are available for rating the severity of tremor at present. However, the sensitivity to change of these instruments has remained to be clarified. Objective: To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments. Methods: Enrolling subjects with parkinsonism associated with tremor, we analyzed two scenarios: (1) tremor changes associated with acute levodopa challenge (n  = 287) and (2) a 12-month outcome of different treatment options (n  = 512) …including deep brain stimulation (n  = 146), levodopa/carbidopa intestinal gel infusion (n  = 30), and initiating (n  = 63) or adjusting oral antiparkinsonian medication (n  = 273). Changes in tremor scales were assessed by effect size values (Cohen’s d and eta-square). Results: Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen’s d = –1.04, η 2  = 0.12). However, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen’s d = –0.33, η 2  = 0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up. Conclusions: The Fahn-Tolosa-Marin Tremor Rating Scale has a better ability to capture changes due to levodopa challenge or antiparkinsonian treatment than MDS-UPDRS Part III or MDS-UPDRS Tremor Scale. Show more

Keywords: Parkinsonism, rating scales, treatment response, tremor

DOI: 10.3233/JPD-191800

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 275-282, 2020

Authors: Del Din, Silvia | Yarnall, Alison J. | Barber, Thomas R. | Lo, Christine | Crabbe, Marie | Rolinski, Michal | Baig, Fahd | Hu, Michele T. | Rochester, Lynn

Article Type: Research Article

Abstract: Background: Patients with REM sleep behavior disorder (RBD) have a high risk of developing PD, and thus can be used to study prodromal biomarkers. RBD has been associated with changes in gait; quantifying these changes using wearable technology is promising; however, most data are obtained in clinical settings precluding pragmatic application. Objective: We aimed to investigate if wearable-based, real-world gait monitoring can detect early gait changes and discriminate individuals with RBD from controls, and explore relationships between real-world gait and clinical characteristics. Methods: 63 individuals with RBD (66±10 years) and 34 controls recruited in the Oxford …Parkinson’s Disease Centre Discovery Study were assessed. Data were collected using a wearable device positioned on the lower back for 7 days. Real-world gait was quantified in terms of its Macrostructure (volume, pattern and variability (S2 )) and Microstructure (14 characteristics). The value of Macro and Micro gait in discriminating RBD from controls was explored using ANCOVA and ROC analysis, and correlation analysis was performed between gait and clinical characteristics. Results: Significant differences were found in discrete Micro characteristics in RBD with reduced gait velocity, variability and rhythm (p ≤0.023). These characteristics significantly discriminated RBD (AUC≥0.620), with swing time as the single strongest discriminator (AUC=0.652). Longer walking bouts discriminated best between the groups for Macro and Micro outcomes (p ≤0.036). Conclusions: Our results suggest that real-world gait monitoring may have utility as “risk” clinical marker in RBD participants. Real-world gait assessment is low-cost and could serve as a pragmatic screening tool to identify gait impairment in RBD. Show more

Keywords: Free-living, gait, prodromal, REM sleep behavior disorder, wearables

DOI: 10.3233/JPD-191773

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 283-299, 2020

Authors: Gan-Or, Ziv | Rao, Trisha | Leveille, Etienne | Degroot, Clotilde | Chouinard, Sylvain | Cicchetti, Francesca | Dagher, Alain | Das, Samir | Desautels, Alex | Drouin-Ouellet, Janelle | Durcan, Thomas | Gagnon, Jean-François | Genge, Angela | Karamchandani, Jason | Lafontaine, Anne-Louise | Sun, Sonia Lai Wing | Langlois, Mélanie | Levesque, Martin | Melmed, Calvin | Panisset, Michel | Parent, Martin | Poline, Jean-Baptiste | Postuma, Ronald B. | Pourcher, Emmanuelle | Rouleau, Guy A. | Sharp, Madeleine | Monchi, Oury | Dupré, Nicolas | Fon, Edward A.

Article Type: Research Article

Abstract: Background: Genetic, biologic and clinical data suggest that Parkinson’s disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository. Objective: To present the QPN and to perform preliminary analysis of the QPN data. Methods: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients …with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups. Results: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN’s creation, over 60 studies and 30 publications have included patients and data from the QPN. Conclusions: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/ ), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources. Show more

Keywords: Parkinson disease, Quebec Parkinson Network, registry, biobank

DOI: 10.3233/JPD-191775

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 301-313, 2020

Authors: Rastgardani, Tara | Armstrong, Melissa J. | Gagliardi, Anna R. | Grabovsky, Arthur | Marras, Connie

Article Type: Research Article

Abstract: Background: OFF periods impair quality of life in Parkinson’s disease but the nature and degree of this impact is largely unquantified. Optimal treatment relies on assessing the experience and impact of these periods on patients and their carepartners. Objectives: To understand the experience and impact of OFF periods on their lives. Methods: Informed by qualitative interviews we designed questionnaires and surveyed neurologists, people with Parkinson’s disease and carepartners. Results: 50 general neurologists, 50 movement disorder neurologists, 442 patients (median disease duration 5 years) and 97 carepartners were included. The most common OFF symptoms reported …by patients and carepartners were stiffness, slowness of movement and changes in gait. Non-motor symptoms were less common. A higher proportion of carepartners reported each symptom. A minority of neurologists recognized pain, sweating and anxiety as possible symptoms of OFF periods. The three OFF symptoms most frequently designated as having great impact by people with Parkinson’s disease were changes in gait, slowness and stiffness. In contrast, cognitive impairment was most frequently rated as having great impact on carepartners. OFF periods were reported to impact many aspects of the lives of both patients and carepartners. Conclusions: In people with Parkinson’s disease of under 10 years duration, motor symptoms of OFF periods predominate in impact, however cognitive impairment has great impact on carepartners. Education is needed for neurologists regarding the non-motor aspects of OFF. The importance of involving carepartners in the assessment regarding OFF periods is supported by the higher frequency of symptom reporting by carepartners, and the significant impact on their lives. Show more

Keywords: Parkinson’s disease, fluctuations, impact, ‘off’ periods

DOI: 10.3233/JPD-191785

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 315-324, 2020