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Background: Females, people with young-onset PD and older individuals, and non-white populations are historically underrepresented in clinical Parkinson’s disease (PD) research. Furthermore, research traditionally focused predominantly on motor symptoms of PD. Including a representative and diverse group of people with PD and also studying non-motor symptoms is warranted to better understand heterogeneity in PD and to generalize research findings. Objective: This project aimed to determine whether, within a consecutive series of PD studies performed within a single center in the Netherlands: (1) the proportion of included females, mean age and proportion of native Dutch people changed over time; and 2) reports of the ethnicity of participants and the proportion of studies with non-motor outcomes changed over time. Methods: Characteristics of participants and non-motor outcomes were analyzed using a unique dataset of summary statistics of studies with a large number of participants conducted at a single center during a 19-year period (2003–2021). Results: Results indicate no relationship between calendar time and proportion of females (mean 39 %), mean age (66 years), proportion of studies that reported ethnicity, and proportion of native Dutch people in studies (range 97–100 %). The proportion of participants in whom non-motor symptoms were assessed increased, but this difference was consistent with chance. Conclusion: Study participants in this center reflect the PD population in the Netherlands in terms of sex, but older individuals and non-native Dutch individuals are under-represented. We have still a lot to do in ensuring adequate representation and diversity in PD patients within our research.

Abstract Background Although deep neural networks (DNNs) are showing state of the art performance in clinical gait analysis, they are considered to be black-box algorithms. In other words, there is a lack of direct understanding of a DNN’s ability to identify relevant features, hindering clinical acceptance. Interpretability methods have been developed to ameliorate this concern by providing a way to explain DNN predictions. Methods This paper proposes the use of an interpretability method to explain DNN decisions for classifying the movement that precedes freezing of gait (FOG), one of the most debilitating symptoms of Parkinson’s disease (PD). The proposed two-stage pipeline consists of (1) a convolutional neural network (CNN) to model the reduction of movement present before a FOG episode, and (2) layer-wise relevance propagation (LRP) to visualize the underlying features that the CNN perceives as important to model the pathology. The CNN was trained with the sagittal plane kinematics from a motion capture dataset of fourteen PD patients with FOG. The robustness of the model predictions and learned features was further assessed on fourteen PD patients without FOG and fourteen age-matched healthy controls. Results The CNN proved highly accurate in modelling the movement that precedes FOG, with 86.8% of the strides being correctly identified. However, the CNN model was unable to model the movement for one of the seven patients that froze during the protocol. The LRP interpretability case study shows that (1) the kinematic features perceived as most relevant by the CNN are the reduced peak knee flexion and the fixed ankle dorsiflexion during the swing phase, (2) very little relevance for FOG is observed in the PD patients without FOG and the healthy control subjects, and (3) the poor predictive performance of one subject is attributed to the patient’s unique and severely flexed gait signature. Conclusions The proposed pipeline can aid clinicians in explaining DNN decisions in clinical gait analysis and aid machine learning practitioners in assessing the generalization of their models by ensuring that the predictions are based on meaningful kinematic features.

Abstract Freezing of gait (FOG) in Parkinson’s disease (PD) causes severe patient burden despite pharmacological management. Exercise and training are therefore advocated as important adjunct therapies. In this meta-analysis, we assess the existing evidence for such interventions to reduce FOG, and further examine which type of training helps the restoration of gait function in particular. The primary meta-analysis across 41 studies and 1838 patients revealed a favorable moderate effect size (ES = −0.37) of various training modalities for reducing subjective FOG-severity (p

Maintaining physical activity is an important clinical goal for people with Parkinson’s disease (PwPD). We investigated the validity of two commercial activity trackers (ATs) to measure daily step counts. We compared a wrist- and a hip-worn commercial AT against the research-grade Dynaport Movemonitor (DAM) during 14 days of daily use. Criterion validity was assessed in 28 PwPD and 30 healthy controls (HCs) by a 2 × 3 ANOVA and intraclass correlation coefficients (ICC2,1). The ability to measure daily step fluctuations compared to the DAM was studied by a 2 × 3 ANOVA and Kendall correlations. We also explored compliance and user-friendliness. Both the ATs and the DAM measured significantly fewer steps/day in PwPD compared to HCs (p < 0.01). Step counts derived from the ATs showed good to excellent agreement with the DAM in both groups (ICC2,1 > 0.83). Daily fluctuations were detected adequately by the ATs, showing moderate associations with DAM-rankings. While compliance was high overall, 22% of PwPD were disinclined to use the ATs after the study. Overall, we conclude that the ATs had sufficient agreement with the DAM for the purpose of promoting physical activity in mildly affected PwPD. However, further validation is needed before clinical use can be widely recommended.

Background: Measurement of freezing of gait (FOG) relies on the sensitivity and reliability of tasks to provoke FOG. It is currently unclear which tasks provide the best outcomes and how medication state plays into this. Objective: To establish the sensitivity and test-retest reliability of various FOG-provoking tasks for presence and severity of FOG, with (ON) and without (OFF) dopaminergic medication. Methods: FOG-presence and percentage time frozen (% TF) were derived from video annotations of a home-based FOG-provoking protocol performed in OFF and ON. This included: the four meter walk (4MW), Timed Up and Go (TUG) single (ST) and dual task (DT), 360° turns in ST and DT, a doorway condition, and a personalized condition. Sensitivity was tested at baseline in 63 definite freezers. Test-retest reliability was evaluated over 5 weeks in 26 freezers. Results: Sensitivity and test-retest reliability were highest for 360° turns and higher in OFF than ON. Test-retest intra-class correlation coefficients of % TF varied between 0.63–0.90 in OFF and 0.18–0.87 in ON, and minimal detectable changes (MDCs) were high. The optimal protocol included TUG ST, 360° turns ST, 360° turns DT and a doorway condition, provoking FOG in all freezers in OFF and 91.9% in ON and this could be done reliably in 95.8% (OFF) and 84.0% (ON) of the sample. Combining OFF and ON further improved outcomes. Conclusions: The highest sensitivity and reliability was achieved with a multi-trigger protocol performed in OFF + ON. However, the high MDCs for % TF underscore the need for further optimization of FOG measurement. Plain Language Summary: Freezing of gait is a very burdensome and episodic symptom in Parkinson's disease that is difficult to measure. Measurement of freezing is needed to determine whether someone has freezing and how severe this is, and relies on observation during a freezing-triggering protocol. However, it is unclear what protocol is sufficiently sensitive to trigger freezing in many freezers, and whether freezing can be triggered reliably at different timepoints. Here, we investigated 1) which tasks can trigger freezing-presence and freezing-severity sensitively and reliably, 2) how medication state influences this, and 3) what task combination was most reliable. Sixty-three patients with daily freezing performed several freezing-triggering tasks in their homes, both with (ON) and without (OFF) anti-Parkinsonian medication. In twenty-six patients, the measurement was repeated 5 weeks later to determine test-retest reliability. First, we found that performing 360° turns in place with a cognitive dual task was the most sensitive and reliable task to trigger FOG. Second, sensitivity and reliability were better in OFF than in ON. Third, the most reliable protocol included: the Timed-Up and Go, 360° turns in place with and without the dual task, and a doorway condition. This protocol triggered freezing in all patients in OFF and 91.9% in ON and did so reliably in 95.8% (OFF) and 84.0% (ON) of the sample. We recommend to measure freezing with this protocol in OFF + ON, which further improved reliability. However, the measurement error for freezing-severity was high, even for this optimal protocol, underscoring the need for further optimization of freezing measurement. [ABSTRACT FROM AUTHOR]

Abstract The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

Background Community nurses and general practitioners evaluate their patient-related communication to be poor. However, their actual communication has hardly been investigated and specific strategies for improvement are unclear. Objectives To explore actual community nurse-general practitioner communication in primary care and gain insights into communication style, and conversation structure and their determinants. Methods A mixed-methods design was applied. Telephone conversations between community nurses and general practitioners in the Netherlands were recorded and transcribed verbatim. We measured structure and the duration of their conversations, and community nurses’ self-confidence towards general practitioners and their trust in and familiarity with the conversation partner. A thematic analysis was applied to the transcripts of the conversations. Correlations between these determinants were calculated using Spearman’s correlation coefficient. Results The 18 community nurses recorded 23 conversations with general practitioners. Qualitative analysis revealed that many conversations lacked structure and conciseness, i.e. the nurses started conversations without a clearly articulated question and did not provide adequate background information. The mean duration of their conversations with doctors was 8.8 min. Community nurses with higher self-confidence towards doctors communicated in a more structured way (p = 0.01) and general practitioners were more satisfied about the conversations (p = 0.01). Conclusion This exploratory study of actual community nurse-doctor telephone conversations in primary care identified communication structure and nurse self-confidence towards general practitioners as key targets for the improvement of interprofessional communication, which may increase the effectiveness of community nurse-general practitioner collaboration.

Background The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration ISRCTN12051706.

Treadmill training with virtual reality (TT + VR) has been shown to improve gait performance and to reduce fall risk in Parkinson’s disease (PD). However, there is no consensus on the optimal training duration. This study is a sub-study of the V-TIME randomized clinical trial (NCT01732653). In this study, we explored the effect of the duration of training based on the motor–cognitive interaction on motor and cognitive performance and on fall risk in subjects with PD. Patients in Hoehn and Yahr stages II–III, aged between 40 and 70 years, were included. In total, 96 patients with PD were assigned to 6 or 12 weeks of TT + VR intervention, and 77 patients completed the full protocol. Outcome measures for gait and cognitive performance were assessed at baseline, immediately after training, and at 1- and 6-month follow-up. The incident rate of falls in the 6-month pre-intervention was compared with that in the 6-month post-intervention. Dual-task gait performance (gait speed, gait speed variability and stride length under cognitive dual task and obstacle negotiation, and the leading foot clearance in obstacle negotiation) improved similarly in both groups with gains sustained at 6-month follow-up. A higher decrease in fall rate and fear of falling were observed in participants assigned to the 12-week intervention than the 6-week intervention. Improvements in cognitive functions (i.e., executive functions, visuospatial ability, and attention) were seen only in participants enrolled in 12-week training up to 1-month follow-up but vanished at the 6-month evaluation. Our results suggest that a longer TT + VR training leads to greater improvements in cognitive functions especially those directly addressed by the virtual environment.

Introduction: Care integration in primary elderly care is suboptimal. Validated instruments are needed to enable the implementation of integrated primary care. We aimed to assess construct validity of the Rainbow Model of Integrated Care measurement tool (RMIC-MT) for healthcare professionals working in an integrated primary elderly care setting in the Netherlands. Methods: In a cross-sectional study, the RMIC-MT, a 36-item questionnaire covering all domains of the Rainbow Model of Integrated Care (RMIC), was sent out to local networks of primary elderly care professionals. Confirmatory factor analysis with maximum likelihood estimation was used for the validation of the factor structure of the RMIC-MT. Model fit was assessed by the chi-square test and fit indices. Results: The RMIC-MT was completed by 323 professionals, primarily general practitioners, community nurses, practice nurses, and case managers. Confirmatory factor analysis and corresponding fit indices showed moderate to good fit, thereby confirming a nine factor model with a total of 36 items. Conclusions: The RMIC-MT is promising for the primary elderly care setting in the Netherlands. It can be used for evaluating integrated care initiatives in a primary care setting, thereby contributing to implementation of integrated primary elderly care.

Background: Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG. Methods: Sixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., “percentage time frozen” during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology. Discussion: The DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives. Trial registration: Clinicaltrials.gov NCT03978507.

Introduction: Currently, care integration for community-dwelling persons with dementia is poor and knowledge on how to effectively facilitate development of integrated dementia care is lacking. The DementiaNet program aims to overcome this with a focus on interprofessional collaboration. The objective of this study is to investigate how care integration in interprofessional primary dementia care networks matures and to identify factors associated with (un)successfully maturation. Theory and methods: A longitudinal mixed-methods study, including 17 primary care networks participating in the DementiaNet study, was performed. Semi-structured interviews based on the Rainbow Model of Integrated Care were conducted at start, at 12- and 24 months. Network maturity scores (range 1–4) were derived from the interviews and qualitative data was used to explain the observed patterns. Results: Networks consisted on average of 9 professionals (range 4–22) covering medical, care and social disciplines. Network maturity yearly increased with 0.29 (95%-CI: 0.20–0.38). Important factors for improvement included getting to know each other’s expertise, having a capable network leader(s), stable network composition and participation of a general practitioner. Conclusions: The DementiaNet approach enables a transition towards more mature networks. Identified success factors provide better understanding of how network maturity can be achieved and gives guidance to future care integration strategies.

Introduction One of the known risk factors for fall incidents is the use of specific medications, fall-risk-increasing drugs (FRIDs). However, to date, there is uncertainty related to the effectiveness of deprescribing as a single intervention in falls prevention. Thus, a comprehensive update of the literature focusing on all settings in which older people receive healthcare and all deprescribing interventions is warranted to enhance the current knowledge.Methods and analysis This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search was performed in Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO (2 November 2020). We will also search in trial registers. We will include randomised controlled trials, in which any deprescribing intervention is compared with usual care and reports falls as an outcome. Both title and abstract screening and full-text screening will be done by two reviewers. The Cochrane Collaboration revised tool of Risk of Bias will be applied to perform risk of bias assessment. We will categorise the results separately for every setting. If a group of sufficiently comparable studies will be identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the forest plot along with consideration of the χ2 test and the I2 statistic results. We have prespecified several subgroup and sensitivity analyses.Ethics and dissemination Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations. Furthermore, this systematic review will inform the recommendations of working group of polypharmacy and FRIDs of the anticipated World’s Falls Guidelines.PROSPERO registration number CRD42020218231.

Exercise has become increasingly relevant in the treatment of people with Parkinsons Disease (PD), especially for gait and balance impairments where pharmacological and surgical therapy does not fully alleviate symptoms. Split-belt treadmill (SBT) is a tool which can introduce artificial asymmetry and motor switches through belts running at different velocities and has been used to study motor control or as exercise intervention. This narrative review summarizes the current literature of SBT as a therapeutic tool for people with PD. Studies have shown that walking on an SBT is safe and feasible for people with PD and results suggest that training should best be carried out under antiparkinsonian medication. Compared to healthy adults, people with PD adapt their gait in a similar manner during and after SBT walking, but effects are smaller. One session of SBT training improved gait adaptation as well as gait during dual tasking, with results being partially retained for 24 hours. With regard to endurance, tendencies are visible that SBT training has generic health benefits similiar to aerobic exercise.Further studies are ongoing investigating long term training interventions of SBT in people with PD, including the study of retention effects. However, the clinical relevance of the above-mentioned benefits remains unclear. Finally, the aerobic benefit of the training and the potential for alleviation of fall risk in the PD population need to be investigated.Key Words: Rehabilitation, Gait Disorder, Neurological Disease, Exercise Therapy

Background: Gait impairments are common in healthy older adults (HOA) and people with Parkinson's disease (PwPD), especially when adaptations to the environment are required. Traditional rehabilitation programs do not typically address these adaptive gait demands in contrast to repeated gait perturbation training (RGPT). RGPT is a novel reactive form of gait training with potential for both short and long-term consolidation in HOA and PwPD. The aim of this systematic review with meta-analysis is to determine whether RGPT is more effective than non-RGPT gait training in improving gait and balance in HOA and PwPD in the short and longer term.Methods: This review was conducted according to the PRISMA-guidelines and pre-registered in the PROSPERO database (CRD42020183273). Included studies tested the effects of any form of repeated perturbations during gait in HOA and PwPD on gait speed, step or stride length. Studies using balance scales or sway measures as outcomes were included in a secondary analysis. Effects of randomized controlled trials (RCT) on RGPT were pooled using a meta-analysis of final measures.Results: Of the 4421 studies, eight studies were deemed eligible for review, of which six could be included in the meta-analysis, totaling 209 participants (159 PwPD and 50 HOA). The studies were all of moderate quality. The meta-analysis revealed no significant effects of RGPT over non-RGPT training on gait performance (SMD = 0.16; 95% CI = −0.18, 0.49; Z = 0.92; P = 0.36). Yet, in some individual studies, favorable effects on gait speed, step length and stride length were observed immediately after the intervention as well as after a retention period. Gait variability and asymmetry, signifying more direct outcomes of gait adaptation, also indicated favorable RGPT effects in some individual studies.Conclusion: Despite some promising results, the pooled effects of RGPT on gait and balance were not significantly greater as compared to non-RGPT gait training in PwPD and HOA. However, these findings could have been driven by low statistical power. Therefore, the present review points to the imperative to conduct sufficiently powered RCT's to verify the true effects of RGPT on gait and balance in HOA and PwPD.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php? Identifier: CRD42020183273.