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Contains fulltext : 306765.pdf (Publisher’s version ) (Open Access), Radboud University, 19 juni 2024, Promotores : Bloem, B.R., Heskes, T.M. Co-promotores : Meinders, M.J., Krijthe, J.H., 397 p.

Contains fulltext : 307331.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 306774.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 306385.pdf (Publisher’s version ) (Closed access), 01 juni 2024

Contains fulltext : 306751.pdf (Publisher’s version ) (Open Access), Radboud University, 03 juni 2024, Promotores : Oertelt, S., Bloem, B.R. Co-promotor : Darweesh, S.K.L., 257 p.

Contains fulltext : 307329.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: People living with Parkinson's disease experience progressive motor and non-motor symptoms, which negatively impact on health-related quality of life and can lead to an increased risk of hospitalisation. It is increasingly recognised that the current care models are not suitable for the needs of people with parkinsonism whose care needs evolve and change as the disease progresses. This trial aims to evaluate whether a complex and innovative model of integrated care will increase an individual's ability to achieve their personal goals, have a positive impact on health and symptom burden and be more cost-effective when compared with usual care. METHODS: This is a single-centre, randomised controlled trial where people with parkinsonism and their informal caregivers are randomised into one of two groups: either PRIME Parkinson multi-component model of care or usual care. Adults ≥18 years with a diagnosis of parkinsonism, able to provide informed consent or the availability of a close friend or relative to act as a personal consultee if capacity to do so is absent and living in the trial geographical area are eligible. Up to three caregivers per patient can also take part, must be ≥18 years, provide informal, unpaid care and able to give informed consent. The primary outcome measure is goal attainment, as measured using the Bangor Goal Setting Interview. The duration of enrolment is 24 months. The total recruitment target is n=214, and the main analyses will be intention to treat. DISCUSSION: This trial tests whether a novel model of care improves health and disease-related metrics including goal attainment and decreases hospitalisations whilst being more cost-effective than the current usual care. Subject to successful implementation of this intervention within one centre, the PRIME Parkinson model of care could then be evaluated within a cluster-randomised trial at multiple centres.

Contains fulltext : 291078.pdf (Publisher’s version ) (Open Access), In stressful or anxiety-provoking situations, most people with Parkinson's disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, a proportion of patients actually report benefits from experiencing-or even purposely inducing-stressful or high-arousal situations. Using data from a large-scale international survey study among 4324 people with PD and gait impairments within the online Fox Insight (USA) and ParkinsonNEXT (NL) cohorts, we demonstrate that individuals with PD deploy an array of mental state alteration strategies to cope with their gait impairment. Crucially, these strategies differ along an axis of arousal-some act to heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest that arousal may act as a double-edged sword for gait control in PD. We propose a theoretical, neurobiological framework to explain why heightened arousal can have detrimental effects on the occurrence and severity of gait impairments in some individuals, while alleviating them in others. Specifically, we postulate that this seemingly contradictory phenomenon is explained by the inherent features of the ascending arousal system: namely, that arousal is related to task performance by an inverted u-shaped curve (the so-called Yerkes and Dodson relationship). We propose that the noradrenergic locus coeruleus plays an important role in modulating PD symptom severity and expression, by regulating arousal and by mediating network-level functional integration across the brain. The ability of the locus coeruleus to facilitate dynamic 'cross-talk' between distinct, otherwise largely segregated brain regions may facilitate the necessary cerebral compensation for gait impairments in PD. In the presence of suboptimal arousal, compensatory networks may be too segregated to allow for adequate compensation. Conversely, with supraoptimal arousal, increased cross-talk between competing inputs of these complementar

01 januari 2023, Item does not contain fulltext

01 februari 2023, Item does not contain fulltext, OBJECTIVES: To determine the association of palliative care for progressive neurologic diseases with patient- and caregiver-centered outcomes. DESIGN: Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies, including pilot studies. SETTING AND PARTICIPANTS: Adults with progressive neurologic diseases (dementia, multiple sclerosis, Parkinson's disease, motor neuron disease, multiple system atrophy, and progressive supranuclear palsy) and their caregivers. METHODS: MEDLINE, EMBASE, CINAHL PLUS, Cochrane CENTRAL, and PubMed were searched from inception to September 2021. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tools. Narrative synthesis was conducted. Patient quality of life (QoL), symptom burden, caregiver burden, and satisfaction with care were meta-analyzed using a random-effects model. RESULTS: Fifteen trials provided data on 3431 patients (mean age, 73.9 years). Compared with usual care, palliative care was statistically significantly associated with lower symptom burden [standardized mean difference (SMD), -0.34 (95% Cl, -0.59 to -0.09)] and higher caregiver satisfaction [SMD, 0.41 (95% Cl, 0.12 to 0.71)] and patient satisfaction [SMD, 0.43 (95% Cl, -0.01 to 0.87)]. However, the associations were not significant after excluding studies with high risk of bias. Insignificant associations of palliative care with caregiver burden [SMD, -0.09 (95% Cl, -0.21 to 0.03)] and patient QoL [SMD, 0.19 (95% Cl, -0.07 to 0.44)] were observed. CONCLUSIONS AND IMPLICATIONS: Palliative care is likely to improve symptom burden and satisfaction with care among patients with progressive neurologic diseases and their caregivers, while its effects on QoL and caregiver burden remains inconclusive. Specific intervention components including interdisciplinary team, palliative care physicians, home visits, and spiritual care appeared to be associated with increased ef

Item does not contain fulltext, BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with a fast increasing prevalence. Several pharmacological and non-pharmacological interventions are available to alleviate symptoms. Technology can be used to improve the efficiency, accessibility and feasibility of these treatments. Although many technologies are available, only few are actually implemented in daily clinical practice. AIM: Here, we study the barriers and facilitators, as experienced by patients, caregivers and/or healthcare providers, to successful implement technology for PD management. METHODS: We performed a systematic literature search in the PubMed and Embase databases until June 2022. Two independent raters screened the titles, abstracts and full texts on: 1) people with PD; 2) using technology for disease management; 3) qualitative research methods providing patients', caregivers and/or healthcare providers' perspective, and; 4) full text available in English or Dutch. Case studies, reviews and conference abstracts were excluded. RESULTS: We found 5420 unique articles of which 34 were included in this study. Five categories were made: cueing (n = 3), exergaming (n = 3), remote monitoring using wearable sensors (n = 10), telerehabilitation (n = 8) and remote consultation (n = 10). The main barriers reported across categories were unfamiliarity with technology, high costs, technical issues and (motor) symptoms hampering the use of some technologies. Facilitators included good usability, experiencing beneficial effects and feeling safe whilst using the technology. CONCLUSION: Although only few articles presented a qualitative evaluation of technologies, we found some important barriers and facilitators that may help to bridge the gap between the fast developing technological world and actual implementation in day-to-day living with PD.

01 januari 2023, Item does not contain fulltext

Item does not contain fulltext, 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.

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Item does not contain fulltext, Heterogeneity in Parkinson's disease (PD) presents a barrier to understanding disease mechanisms and developing new treatments. This challenge may be partially overcome by stratifying patients into clinically meaningful subtypes. A recent subtyping scheme classifies de novo PD patients into three subtypes: mild-motor predominant, intermediate, or diffuse-malignant, based on motor impairment, cognitive function, rapid eye movement sleep behavior disorder (RBD) symptoms, and autonomic symptoms. We aimed to validate this approach in a large longitudinal cohort of early-to-moderate PD (n = 499) by assessing the influence of subtyping on clinical characteristics at baseline and on two-year progression. Compared to mild-motor predominant patients (42%), diffuse-malignant patients (12%) showed involvement of more clinical domains, more diffuse hypokinetic-rigid motor symptoms (decreased lateralization and hand/foot focality), and faster two-year progression. These findings extend the classification of diffuse-malignant and mild-motor predominant subtypes to early-to-moderate PD and suggest that different pathophysiological mechanisms (focal versus diffuse cerebral propagation) may underlie distinct subtype classifications.

Radboud University, 27 februari 2023, Promotor : Bloem, B.R. Co-promotor : Helmich, R.C.G., Item does not contain fulltext

Radboud University, 22 februari 2023, Promotores : Bloem, B.R., Hoyng, C.B. Co-promotores : Vries, N.M. de, Theelen, T., Contains fulltext : 288679.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 292718.pdf (Publisher’s version ) (Open Access), BACKGROUND: The circadian system and its dysfunction in persons with Parkinson's disease (PwP) has a clear impact on both motor and non-motor symptoms. Examples include circadian patterns in motor disability, with worsening of symptoms throughout the day, but also the existence of similar patterns in non-motor symptoms. OBJECTIVE: In this narrative review, we discuss the role of the circadian system, we address the role of dopamine in this system, and we summarise the evidence that supports the use of circadian system treatments for motor and non-motor symptoms in PwP. METHODS: A systematic search in PubMed and Web of Science database was performed and the final search was performed in November 2021. We included articles whose primary aim was to investigate the effect of melatonin, melatonin agonists, and light therapy in PwP. RESULTS: In total 25 articles were retrieved. Of these, 12 were related to bright light therapy and 13 to melatonin or/and melatonin agonists. Most, but not all, studies showed that melatonin and melatonin agonists and light therapy induced improvements in measures of sleep, depression, motor function, and some also cognitive function and other non-motor symptoms. For some of these outcomes, including daytime sleepiness, depressive symptoms, and some motor symptoms, there is level 2 B evidence for the use of circadian treatments in PwP. CONCLUSIONS: Treatment with bright light therapy, exogenous melatonin and melatonin agonists seems to have not only positive effects on sleep quality and depression but also on motor function in PwP. Drawbacks in earlier work include the relatively small number of participants and the heterogeneity of outcome measures. Further large and well-designed trials are needed to address these shortcomings and to confirm or refute the possible merits of the circadian system as a treatment target in PwP.

Radboud University, 08 juni 2023, Promotores : Bloem, B.R., Verbeek, M.M. Co-promotor : Esselink, R.A.J., Item does not contain fulltext

Contains fulltext : 293036.pdf (Publisher’s version ) (Open Access), The discovery of levodopa in the late 60 s of twentieth century was a 'golden moment' for people with Parkinson's disease (PD). Unfortunately, clinical experience showed that some symptoms escaped from symptomatic control, and long-term complications developed. Back then, neurologists coined the term "honeymoon period" for the early phase of uncomplicated response to levodopa, and it continues to be used in scientific literature. However, medical terms are no longer restricted to professionals, and few people with PD relate to the notion of a "honeymoon". We examine the reasons why this term, once helpful, but inaccurate and inappropriate, should be abandoned.

Contains fulltext : 293125.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 293128.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Digital tools such as wearable sensors may help to monitor Parkinson's disease (PD) in daily life. To optimally achieve the expected benefits, such as personized care and improved self-management, it is essential to understand the perspective of both patients and the healthcare providers. OBJECTIVES: We identified the motivations for and barriers against monitoring PD symptoms among PD patients and healthcare providers. We also investigated which aspects of PD were considered most important to monitor in daily life, and which benefits and limitations of wearable sensors were expected. METHODS: Online questionnaires were completed by 434 PD patients and 166 healthcare providers who were specialized in PD care (86 physiotherapists, 55 nurses, and 25 neurologists). To gain further understanding in the main findings, we subsequently conducted homogeneous focus groups with patients (n = 14), physiotherapists (n = 5), and nurses (n = 6), as well as individual interviews with neurologists (n = 5). RESULTS: One third of the patients had monitored their PD symptoms in the past year, most commonly using a paper diary. Key motivations were: (1) discuss findings with healthcare providers, (2) obtain insight in the effect of medication and other treatments, and (3) follow the progression of the disease. Key barriers were: (1) not wanting to focus too much on having PD, (2) symptoms being relatively stable, and (3) lacking an easy-to-use tool. Prioritized symptoms of interest differed between patients and healthcare providers; patients gave a higher priority to fatigue, problems with fine motor movements and tremor, whereas professionals more frequently prioritized balance, freezing and hallucinations. Although both patients and healthcare providers were generally positive about the potential of wearable sensors for monitoring PD symptoms, the expected benefits and limitations varied considerably between groups and within the patient group. CONCLUSION: This study prov

Contains fulltext : 293771.pdf (Publisher’s version ) (Open Access)

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01 april 2023, Item does not contain fulltext, It is challenging to reliably assess the motor features of Parkinson's disease in real-time. This has motivated the search for new digital outcomes that can objectively and remotely measure the severity of parkinsonian motor impairments over an extended period of time. The United States Food and Drug Administration (FDA) has recently granted a 510(k) clearance to the Rune Labs Kinematics System, an ambulatory, smartwatch-based monitoring system to remotely track tremor and dyskinesias in persons with Parkinson's disease. The FDA clearance means that this new digital approach can be regarded as being safe for use in daily practice, with acceptable correlations to clinically based measures. However, the immediate implications for clinicians are limited, because it remains to be demonstrated whether the digital signals correlate well to clinically meaningful outcomes at patient level. The impact on research is also restricted for now, as more validation studies are needed before this new digital approach can be used as primary or secondary endpoint in clinical trials. ANN NEUROL 2023;93:681-685.

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Item does not contain fulltext, INTRODUCTION: Axial disability, including gait disturbances, is common in Parkinson's disease (PD), especially in advanced stages. Epidural spinal cord stimulation (SCS) has been investigated as a treatment option for gait disorders in PD. Here, we review the literature on SCS in PD and evaluate its efficacy, optimal stimulation parameters, optimal electrode locations, possible effects of concurrent deep brain stimulation, and possible working mechanisms on gait. METHODS: Databases were searched for human studies involving PD patients who received an epidural SCS intervention and who had at least one gait-related outcome measure. The included reports were reviewed with respect to design and outcomes. Additionally, the possible mechanisms of action underlying SCS were reviewed. RESULTS: Out of 433 records identified, 25 unique studies with in total 103 participants were included. Most studies included only a few participants. The gait disorders of most PD patients with concurrent pain complaints, mostly low back pain, improved with SCS in almost all cases, regardless of stimulation parameters or electrode location. Higher-frequency stimulation (>200 Hz) seemed to be more effective in pain-free PD patients, but the results were inconsistent. Heterogeneity in outcome measures and follow-up times hindered comparability. CONCLUSIONS: SCS may improve gait in PD patients with neuropathic pain, but its efficacy in pain-free patients remains uncertain due to a lack of thorough double-blind studies. Apart from a well-powered, controlled, double-blind study design, future studies could further explore the initial hints that higher-frequency stimulation (>200 Hz) might be the best approach to improve gait outcomes in pain-free patients.

Item does not contain fulltext, BACKGROUND: There is no systematic insight into the effect of case management on common complications of chronic diseases, including depressive symptoms and symptoms of anxiety. This is a significant knowledge gap, given that people with a chronic disease such as Parkinson Disease or Alzheimer's Disease have identified care coordination as one of their highest priorities. Furthermore, it remains unclear whether the putative beneficial effects of case management would vary by crucial patient characteristics, such as their age, gender, or disease characteristics. Such insights would shift from "one size fits all" healthcare resource allocation to personalized medicine. OBJECTIVE: We systematically examined the effectiveness of case management interventions on two common complications associated PD and other chronic health conditions: Depressive symptoms and symptoms of anxiety. METHODS: We identified studies published until November 2022 from PubMed and Embase databases using predefined inclusion criteria. For each study, data were extracted independently by two researchers. First, descriptive and qualitative analyses of all included studies were performed, followed by random-effects meta-analyses to assess the impact of case management interventions on anxiety and depressive symptoms. Second, meta-regression was performed to analyze potential modifying effects of demographic characteristics, disease characteristics and case management components. RESULTS: 23 randomized controlled trials and four non-randomized studies reported data on the effect of case management on symptoms of anxiety (8 studies) or depressive symptoms (26 studies). Across meta-analyses, we observed a statistically significant effect of case management on reducing symptoms of anxiety (Standardized Mean Difference [SMD] = - 0.47; 95% confidence interval [CI]: -0.69, -0.32) and depressive symptoms (SMD = - 0.48; CI: -0.71, -0.25). We found large heterogeneity in effect estimates across studies, but t

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Contains fulltext : 292335.pdf (Publisher’s version ) (Open Access), BACKGROUND: Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson's disease. Because the symptom is heterogeneous in phenotypical presentation (it can present as trembling/shuffling, or akinesia) and manifests during various circumstances (it can be triggered by e.g. turning, passing doors, and dual-tasking), it is particularly difficult to detect with motion sensors. The freezing index (FI) is one of the most frequently used accelerometer-based methods for FOG detection. However, it might not adequately distinguish FOG from voluntary stops, certainly for the akinetic type of FOG. Interestingly, a previous study showed that heart rate signals could distinguish FOG from stopping and turning movements. This study aimed to investigate for which phenotypes and evoking circumstances the FI and heart rate might provide reliable signals for FOG detection. METHODS: Sixteen people with Parkinson's disease and daily freezing completed a gait trajectory designed to provoke FOG including turns, narrow passages, starting, and stopping, with and without a cognitive or motor dual-task. We compared the FI and heart rate of 378 FOG events to baseline levels, and to stopping and normal gait events (i.e. turns and narrow passages without FOG) using mixed-effects models. We specifically evaluated the influence of different types of FOG (trembling vs akinesia) and triggering situations (turning vs narrow passages; no dual-task vs cognitive dual-task vs motor dual-task) on both outcome measures. RESULTS: The FI increased significantly during trembling and akinetic FOG, but increased similarly during stopping and was therefore not significantly different from FOG. In contrast, heart rate change during FOG was for all types and during all triggering situations statistically different from stopping, but not from normal gait events. CONCLUSION: When the power in the locomotion band (0.5-3 Hz) decreases, the FI increases and is unable to

Contains fulltext : 292371.pdf (Publisher’s version ) (Open Access), BACKGROUND: Currently available treatment options for Parkinson's disease are symptomatic and do not alter the course of the disease. Recent studies have raised the possibility that cardiovascular risk management may slow the progression of the disease. OBJECTIVES: We estimated the effect of baseline cardiovascular risk factors on the progression of Parkinson's disease, using measures for PD-specific motor signs and cognitive functions. METHODS: We used data from 424 de novo Parkinson's disease patients and 199 age-matched controls from the observational, multicenter Parkinson's Progression Markers Initiative (PPMI) study, which included follow-up of up to 9 years. The primary outcome was the severity of PD-specific motor signs, assessed with the MDS-UPDRS part III in the "OFF"-state. The secondary outcome was cognitive function, measured with the Montreal Cognitive Assessment, Symbol Digit Modalities Test, and Letter-Number Sequencing task. Exposures of interest were diabetes mellitus, hypertension, body mass index, cardiovascular event history and hypercholesterolemia, and a modified Framingham risk score, measured at baseline. The effect of each of these exposures on disease progression was modeled using linear mixed models, including adjustment for identified confounders. A secondary analysis on the Tracking Parkinson's cohort including 1,841 patients was performed to validate our findings in an independent patient cohort. RESULTS: Mean age was 61.4 years, and the average follow-up was 5.5 years. We found no statistically significant effect of any individual cardiovascular risk factor on the MDS-UPDRS part III progression (all 95% confidence intervals (CIs) included zero), with one exception: in the PD group, the estimated effect of a one-point increase in body mass index was 0.059 points on the MDS-UPDRS part III per year (95% CI: 0.017 to 0.102). We found no evidence for an effect of any of the exposures on the rate of change in cognitive functioning in the PD

Item does not contain fulltext, INTRODUCTION: Advanced Parkinson's disease (aPD) patients have a high risk on definite nursing home admission. We analyzed the effectiveness of an in-and outpatient multidisciplinary rehabilitation, focusing on activities of daily living (ADL) and delaying definite nursing home admission. METHODS: This study included 24 aPD patients, who received a 6-week inpatient multidisciplinary rehabilitation program, including optimization of pharmacotherapy, which was followed by an individualized outpatient support program during 2 years (intervention group). A non-randomized matched control group (n = 19), received care as usual. Primary endpoints consisted of the Amsterdam Linear Disability Scale (ALDS) and percentage of patients being able to live independently at home after 2 years. Secondary endpoints included changes in medication (LEDD), motor performance (SCOPA-SPES), cognition (SCOPA-COG), hallucinations (NPI) and depression (BDI). RESULTS: Overall, 83% of patients were able to return home after the 6-week inpatient intervention, and 65% still lived at home at 2 years follow-up. Median ALDS scores after 2 years in the intervention group were significantly better, compared to the control group (p = 0.002). All secondary endpoints had improved significantly vs. baseline directly after the 6-week inpatient rehabilitation, which had disappeared at 2 years follow-up, with the exception of the daily dose of medication, which was significantly higher in the intervention group. CONCLUSION: This 2-year follow-up study showed that a combined multidisciplinary in/outpatient rehabilitation program for aPD patients, was able to stabilize ADL functions, and finally delayed definite nursing home admissions in 65% of treated patients. TRIAL REGISTRATION: filenumber M10.091051; ABR code NL32699.042.10.

Item does not contain fulltext, Prescribing dopamine replacement therapy remains the most common approach used by physicians who strive to support persons with Parkinson's disease. In this viewpoint, we argue that instead of merely prescribing dopamine, healthcare professionals should particularly encourage and enable persons with Parkinson's disease to draft their own personalized prescription of "hopamine". The term hopamine is a self-invented neologism representing the uniquely personal set of hopes, desires, experiences, and skills of each individual with a dopamine deficit. As such, the concept of hopamine-as a reflection of the unique personal characteristics of each person with Parkinson's disease-really supplements that of dopamine-as a reflection of each person's unique physical characteristics. Whereas a prescription of dopamine replacement medication necessitates the diagnosed individual to lay his or her fate in the hands of medical professionals, adding a personalized dose of hopamine to the therapeutic mix empowers persons to self-manage daily life with Parkinson's disease. In this viewpoint, we argue that hopamine is a prerequisite for personalized medicine and offer several practical recommendations for how medical professionals can introduce the concept of hopamine in daily clinical practice.

Contains fulltext : 296508.pdf (Publisher’s version ) (Open Access), BACKGROUND: Exercise has various health benefits for people with Parkinson's disease (PD). However, implementing exercise into daily life and long-term adherence remain challenging. To increase a sustainable engagement with physical activity of people with PD, interventions that are motivating, accessible, and scalable are needed. We primarily aim to investigate whether a smartphone app (STEPWISE app) can increase physical activity (i.e., step count) in people with PD over one year. Our second aim is to investigate the potential effects of the intervention on physical fitness, and motor- and non-motor function. Our third aim is to explore whether there is a dose-response relationship between volume of physical activity and our secondary endpoints. METHODS: STEPWISE is a double-blind, randomized controlled trial. We aim to include 452 Dutch people with PD who can walk independently (Hoehn & Yahr stages 1-3) and who do not take more than 7,000 steps per day prior to inclusion. Physical activity levels are measured as step counts on the participant's own smartphone and scaled as percentage of each participant's baseline. Participants are randomly assigned to an active control group with an increase of 5-20% (active controls) or any of the three intervention arms with increases of 25-100% (intermediate dose), 50-200% (large dose), or 100-400% (very large dose). The primary endpoint is change in step count as measured by the STEPWISE smartphone app from baseline to 52 weeks. For our primary aim, we will evaluate the between-group difference in average daily step count change from baseline to 52 weeks. For our second aim, measures of physical fitness, and motor- and non-motor function are included. For our third aim, we will associate 52-week changes in step count with 52-week changes in secondary outcomes. DISCUSSION: This trial evaluates the potential of a smartphone-based intervention to increase activity levels in people with PD. We envision that motivational apps wil