Exercise knowledge, barriers and motivators among LRRK2 G2019S mutation carriers.

INTRODUCTION: People with a Gly2019Ser mutation in the leucine-rich repeat kinase 2 (LRRK2 G2019S) are at increased risk of developing Parkinson's disease (PD). Recent evidence suggests that exercise may delay or prevent the development of clinically overt symptoms of PD in people at risk of PD. We determined whether LRRK2 G2019S mutation carriers with and without manifest PD are aware of the relationship between exercise and PD and how they differ in awareness, barriers and motivators to exercise. METHODS: We deployed a survey among 4422 LRRK2 G2019S mutation carriers. In total, 505 (11.4%) of them completed the survey, of whom 105 had self-reported manifest PD. RESULTS: Ninety-two percent of the LRRK2 G2019S mutation carriers with manifest PD and 63% of those with non-manifest PD were aware of the relationship between exercise and PD. Lack of motivation was the top barrier for those without manifest PD, while having an injury/disability was the most common barrier for those with manifest PD. Improvement of body functioning was the top motivator for both. CONCLUSION: The fact that many at-risk individuals are not aware of the importance of exercise and would exercise more with fewer barriers creates opportunities for trials using exercise as a possible prevention strategy for PD.

Good vibrations: tactile cueing for freezing of gait in Parkinson's disease.

BACKGROUND: Cueing strategies can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD). We evaluated tactile cueing delivered via vibrating socks, which has the benefit of not being noticeable to bystanders. OBJECTIVE: To evaluate the effect of tactile cueing compared to auditory cueing on FOG. METHODS: Thirty-one persons with PD with FOG performed gait tasks during both ON and OFF state. The effect of open loop and closed loop tactile cueing, as delivered by vibrating socks, was compared to an active control group (auditory cueing) and to a baseline condition (uncued gait). These four conditions were balanced between subjects. Gait tasks were videotaped and annotated for FOG by two experienced raters. Motion data were collected to analyze spatiotemporal gait parameters. Responders were defined as manifesting a relative reduction of > 10% in the percent time frozen compared to uncued gait. RESULTS: The average percent time frozen during uncued gait was 11.2% in ON and 21.5% in OFF state. None of the three tested cueing modalities affected the percentage of time frozen in either the ON (p = 0.20) or OFF state (p = 0.12). The number of FOG episodes and spatiotemporal gait parameters were also not affected. We found that 22 out of 31 subjects responded to cueing, the response to the three types of cueing was highly individual. CONCLUSIONS: Cueing did not improve FOG at the group level; however, tactile as well as auditory cueing improved FOG in many individuals. This highlights the need for a personalized approach when using cueing to treat FOG.

Design of the PERSPECTIVE study: PERsonalized SPEeCh Therapy for actIVE conversation in Parkinson's disease (randomized controlled trial).

OBJECTIVE: To evaluate the effectiveness of personalized and home-based speech therapy on quality of life, intelligibility, and social participation for people with Parkinson's disease (PD) who have a reduced intelligibility of speech. BACKGROUND: Speech problems in PD have a profound negative impact on social interaction and quality of life. Evidence for speech therapy in PD is growing, but more work remains needed to explore its full potential. Efficacy exists for highly intensive standardized speech treatment programs, but not all patients can comply with this rather intense intervention, especially the more severely affected ones. Here, we aim to study the effectiveness of personalized and home-based (remote) speech therapy in PD on quality of life and speech. The intervention will be supported by a dedicated speech training app. We expect that this approach will improve speech intelligibility and quality of life in patients irrespective of disease stage. METHODS: We will perform a single blind, randomized controlled trial, comparing 8 weeks of speech therapy to no intervention using a waiting list design. A total of 215 PD patients with problems in intelligibility will be recruited by 12 highly experienced speech therapists. All patients will be measured at baseline and after 8 weeks (primary endpoint). Additionally, the experimental group will be re-assessed one more time, after a wash-out period of 24 weeks. The control group will receive deferred treatment after 8 weeks, but without additional follow-up assessments. Our primary outcome is quality of life (as measured with PDQ-39). Secondary outcomes include speech and voice quality, intelligibility, severity of voice and speech complaints, and caregiver burden. RESULTS: The inclusion of participants has started on March 1, 2019, and is expected to be finalized on April 1, 2021. We expect to have the first results in January 2022. CONCLUSIONS: We will investigate the effectiveness of speech therapy in PD. Particular strengths of our study include a randomized and single-blinded design, the personalized treatment approach, the inclusion of PD patients irrespective of disease stage or severity of the speech complaint, the long-term follow-up, the adequate power, and the use of a patient-relevant primary endpoint. This will allow us to draw firm conclusions about the effectiveness of personalized and remote speech therapy for PD patients in all disease stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT03963388 . Registered on May 24, 2019.

Mental health in people with Parkinson's disease during the COVID-19 pandemic: potential for targeted interventions?

The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson's disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson's Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.

Visual cues added to a virtual environment paradigm do not improve motor arrests in Parkinson's disease.

Objective. Elucidating how cueing alleviates freezing of gait (FOG) in Parkinson's disease (PD) would enable the development of more effective, personalized cueing strategies. Here, we aimed to validate a visual cueing virtual environment (VE) paradigm for future use in e.g. neuroimaging studies and behavioral studies on motor timing and scaling in PD patients with FOG.Approach. We included 20 PD patients with FOG and 16 age-matched healthy control subjects. Supine participants were confronted with a VE displaying either no cues, bars or staircases. They navigated forward using alternate suppression of foot pedals. Motor arrests (as proxy for FOG), and measures of motor timing and scaling were compared across the three VE conditions for both groups.Main results. VE cues (bars and staircases) did not reduce motor arrests in PD patients and healthy control subjects. The VE cues did reduce pedal amplitude in healthy control subjects, without effects on other motor parameters.Conclusion. We could not validate a visual cueing VE paradigm to study FOG. The VE cues possibly failed to convey the necessary spatial and temporal information to support motor timing and scaling. We discuss avenues for future research.

The late stage of Parkinson's -results of a large multinational study on motor and non-motor complications.

INTRODUCTION: There is little information on the late stages of parkinsonism. METHODS: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. RESULTS: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. CONCLUSION: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.

Validation of the Auditory Stroop Task to increase cognitive load in walking tasks in healthy elderly and persons with Parkinson's disease.

BACKGROUND: The development of treatments for freezing of gait (FOG) in Parkinson's disease (PD) requires experimental study set-ups in which FOG is likely to occur, and is amenable to therapeutic interventions. We explore whether the 'Auditory Stroop Task' (AST) can be used to increase cognitive load (and thereby elicit FOG), simultaneously with visual cues (as a therapeutic intervention for FOG). We additionally examined how these two contrasting effects might interact in affecting gait and FOG parameters. OBJECTIVES: We investigated whether: (1) the 'Auditory Stroop Task' (AST) influences gait in healthy elderly and persons with PD who experience FOG, and increases the frequency of FOG events among PD patients; (2) the AST and visual cues interact; and (3) different versions of the AST exert different cognitive loads. METHODS: In 'Experiment 1', 19 healthy elderly subjects performed a walking task while performing a high and low load version of the AST. Walking with a random numbers task, and walking without cognitive load served as control conditions. In 'Experiment 2', 20 PD patients with FOG and 18 healthy controls performed a walking task with the AST, and no additional cognitive load as control condition. Both experiments were performed with and without visual cues. Velocity, cadence, stride length, and stride time were measured in all subjects. FOG severity was measured in patients. RESULTS: Compared to the control conditions, the AST negatively affected all gait parameters in both patients and controls. The AST did not increase the occurrence of FOG in patients. Visual cues reduced the decline in stride length induced by cognitive load in both groups. Both versions of the AST exerted similar effects on gait parameters in controls. CONCLUSIONS: The AST is well-suited to simulate the effects of cognitive load on gait parameters, but not FOG severity, in gait experiments in persons with PD and FOG.

The Personalized Parkinson Project: examining disease progression through broad biomarkers in early Parkinson's disease.

BACKGROUND: Our understanding of the etiology, pathophysiology, phenotypic diversity, and progression of Parkinson's disease has stagnated. Consequently, patients do not receive the best care, leading to unnecessary disability, and to mounting costs for society. The Personalized Parkinson Project (PPP) proposes an unbiased approach to biomarker development with multiple biomarkers measured longitudinally. Our main aims are: (a) to perform a set of hypothesis-driven analyses on the comprehensive dataset, correlating established and novel biomarkers to the rate of disease progression and to treatment response; and (b) to create a widely accessible dataset for discovery of novel biomarkers and new targets for therapeutic interventions in Parkinson's disease. METHODS/DESIGN: This is a prospective, longitudinal, single-center cohort study. The cohort will comprise 650 persons with Parkinson's disease. The inclusion criteria are purposely broad: age ≥ 18 years; and disease duration ≤5 years. Participants are followed for 2 years, with three annual assessments at the study center. Outcomes include a clinical assessment (including motor and neuro-psychological tests), collection of biospecimens (stool, whole blood, and cerebrospinal fluid), magnetic resonance imaging (both structural and functional), and ECG recordings (both 12-lead and Holter). Additionally, collection of physiological and environmental data in daily life over 2 years will be enabled through the Verily Study Watch. All data are stored with polymorphic encryptions and pseudonyms, to guarantee the participants' privacy on the one hand, and to enable data sharing on the other. The data and biospecimens will become available for scientists to address Parkinson's disease-related research questions. DISCUSSION: The PPP has several distinguishing elements: all assessments are done in a single center; inclusion of "real life" subjects; deep and repeated multi-dimensional phenotyping; and continuous monitoring with a wearable device for 2 years. Also, the PPP is powered by privacy and security by design, allowing for data sharing with scientists worldwide respecting participants' privacy. The data are expected to open the way for important new insights, including identification of biomarkers to predict differences in prognosis and treatment response between patients. Our long-term aim is to improve existing treatments, develop new therapeutic approaches, and offer Parkinson's disease patients a more personalized disease management approach. TRIAL REGISTRATION: Clinical Trials NCT03364894 . Registered December 6, 2017 (retrospectively registered).

Exploring the Parkinson patients' perspective on home-based video recording for movement analysis: a qualitative study.

BACKGROUND: Parkinson's disease is a complex neurological disorder characterized by a variety of motor- as well as non-motor symptoms. Video-based technology (using continuous home monitoring) may bridge the gap between the fragmented in-clinic observations and the need for a comprehensive understanding of the progression and fluctuation of disease symptoms. However, continuous monitoring can be intrusive, raising questions about feasibility as well as potential privacy violation. METHODS: We used a grounded theory approach in which we performed semi-structured interviews to explore the opinion of Parkinson's patients on home-based video recording used for vision-based movement analysis. RESULTS: Saturation was reached after sixteen interviews. Three first-level themes were identified that specify the conditions required to perform continuous video monitoring: Camera recording (e.g. being able to turn off the camera), privacy protection (e.g. patient's behaviour, patient's consent, camera location) and perceived motivation (e.g. contributing to science or clinical practice). CONCLUSION: Our findings show that Parkinson patients' perception of continuous, home-based video recording is positive, when a number of requirements are taken into account. This knowledge will enable us to start using this technology in future research and clinical practice in order to better understand the disease and to objectify outcomes in the patients' own homes.

Design and effects of outcome-based payment models in healthcare: a systematic review.

INTRODUCTION: Outcome-based payment models (OBPMs) might solve the shortcomings of fee-for-service or diagnostic-related group (DRG) models using financial incentives based on outcome indicators of the provided care. This review provides an analysis of the characteristics and effectiveness of OBPMs, to determine which models lead to favourable effects. METHODS: We first developed a definition for OBPMs. Next, we searched four data sources to identify the models: (1) scientific literature databases; (2) websites of relevant governmental and scientific agencies; (3) the reference lists of included articles; (4) experts in the field. We only selected studies that examined the impact of the payment model on quality and/or costs. A narrative evidence synthesis was used to link specific design features to effects on quality of care or healthcare costs. RESULTS: We included 88 articles, describing 12 OBPMs. We identified two groups of models based on differences in design features: narrow OBPMs (financial incentives based on quality indicators) and broad OBPMs (combination of global budgets, risk sharing, and financial incentives based on quality indicators). Most (5 out of 9) of the narrow OBPMs showed positive effects on quality; the others had mixed (2) or negative (2) effects. The effects of narrow OBPMs on healthcare utilization or costs, however, were unfavourable (3) or unknown (6). All broad OBPMs (3) showed positive effects on quality of care, while reducing healthcare cost growth. DISCUSSION: Although strong empirical evidence on the effects of OBPMs on healthcare quality, utilization, and costs is limited, our findings suggest that broad OBPMs may be preferred over narrow OBPMs.

Balancing between the two: Are freezing of gait and postural instability in Parkinson's disease connected?

Postural instability and freezing of gait (FoG) are key features of Parkinson's disease (PD) closely related to falls. Growing evidence suggests that co-existing postural deficits could influence the occurrence and severity of FoG. To date, the exact nature of this interrelationship remains largely unknown. We analyzed the complex interaction between postural instability and gait disturbance by comparing the findings available in the posturographic literature between patients with and without FoG. Results showed that FoG and postural instability are intertwined, can influence each other behaviorally and may coincide neurologically. The most common FoG-related postural deficits included weight-shifting impairments, and inadequate scaling and timing of postural responses most apparent at forthcoming postural changes under time constraints. Most likely, a negative cycle of combined and more severe postural deficits in people with FoG will enhance postural stability breakdown. As such, the wide brain network deficiencies involved in FoG may also concurrently influence postural stability. Future work needs to examine whether training interventions targeting both symptoms will have extra clinical benefits on fall frequency.

Professional occupation and the risk of Parkinson's disease.

BACKGROUND AND PURPOSE: Creativity in Parkinson's disease (PD) is strongly related to dopaminergic activity and medication. We hypothesized that patients with PD, including those who are in the pre-diagnostic phase of PD, are prone to choose highly structured 'conventional' professional occupations and avoid highly creative 'artistic' occupations. METHODS: At baseline of the population-based Rotterdam Study, we asked 12 147 individuals aged ≥45 years about their latest occupation and categorized occupations according to the RIASEC model. Participants underwent baseline and follow-up (median 11 years) examinations for PD. We determined associations of artistic (versus any other occupation) and conventional (versus any other occupation) occupations with PD. Additionally, we pooled our results with a recently published case-control study (Radboud Study). RESULTS: At baseline, conventional occupations were common [n = 4356 (36%)], whereas artistic occupations were rare [n = 137 (1%)]. There were 217 patients with PD, including 91 with prevalent PD and 126 with incident PD. The risk of PD varied substantially across occupational categories (chi-square, 14.61; P = 0.01). The penalized odds ratio (OR) of artistic occupations for PD was 0.19 [95% confidence interval (CI), 0.00-1.31; P = 0.11], whereas the OR of conventional occupations for PD was 1.23 (95% CI, 0.95-1.66; P = 0.10). The direction and magnitude of ORs were similar in cross-sectional and longitudinal subsamples. Pooled ORs across the Rotterdam and Radboud Studies were 0.20 (95% CI, 0.08-0.52; P < 0.001) for artistic and 1.23 (95% CI, 0.92-1.67; P = 0.08) for conventional occupations. CONCLUSIONS: The risk of PD varies substantially by choice of professional occupation. Our findings suggest that dopaminergic degeneration affects choice of occupation, which may start in the pre-diagnostic phase of PD.

Promising non-pharmacological therapies in PD: Targeting late stage disease and the role of computer based cognitive training.

Non-pharmacological interventions are increasingly being acknowledged as valuable treatment options to overcome or reduce functional problems in patients with Parkinson's disease (PD). There is a wide range of such non-pharmacological treatments for which the supportive evidence is emerging. Physiotherapy is one good example in this domain. However, there are also several promising non-pharmacological treatment strategies that have thus far received less research attention. Here, we describe two relatively new, but encouraging approaches. First, we focus on a hitherto largely overseen subgroup of PD, namely those with late-stage disease, a population that is often excluded from clinical studies. Importantly, the aims and therapeutic strategies in late-stage PD differ considerably from those in early-stage PD, and an emphasis on non-pharmacological management is particularly important for this vulnerable subgroup. Second, we focus on computer-based cognitive training, as an example of a relatively new intervention that includes innovative elements such as personalized training, artificial intelligence, and virtual reality. We review the latest evidence, practical considerations and future research perspectives, both for non-pharmacological approaches in late-stage PD and for computer-based cognitive training.

[Shared decision-making: dilemmas in daily practice]. / Samen beslissen: dilemma's in de praktijk.

Shared decision-making is an essential - but often neglected - component of evidence-based medicine. In practice, doctors, nurses and patients encounter dilemmas which are understandable, but not insurmountable. We illustrate this by means of a complex decision concerning therapy in the advanced stage of Parkinson's disease. Evidence of effectiveness differs with each individual therapy, and, in practice, the experiences of neurologists also vary widely. In addition, the various treatment strategies all require a different sort of daily care, and have differing impacts on people's lives. It is time that we worked towards a realistic view of shared decision-making. Shared decision-making cannot be generalised to a 'one size fits all' strategy that we can choose to apply or not to apply at will. It should be a flexible instrument which, depending on the individual and the specific situation, can be put to use to deliver the best tailored care.

Prevalence and Prescribed Treatments of Orthostatic Hypotension in Institutionalized Patients with Parkinson's Disease.

BACKGROUND: Orthostatic hypotension (OH) in Parkinson's disease (PD) is a common non-motor sign that can be hard to recognize and treat. OH prevalence and treatment in institutionalized PD-patients remains unknown. OBJECTIVE: The aim of this study was to explore the prevalence and prescribed treatments of OH in institutionalized patients with PD. METHOD: A cross-sectional study of nursing homes in the south-east of the Netherlands identified 64 residents with PD (inclusion criteria: MMSE >18). Assessments included blood pressure measurement, both supine and in the upright position (after 1 minute and after 3 minutes of standing), and 2 questions on cardiovascular items including falls of the validated Non-Motor Symptom Scale (NMSS). OH was defined according to the consensus guidelines. OH was considered as 'probably symptomatic' if patients had a concomitant frequency score >1 on the selected NMSS items, and 'probably asymptomatic' for a frequency score of 0. If OH was not present, but patients had a frequency score >1, OH was considered as 'possibly symptomatic'. RESULTS: The prevalence of OH was 51.6%, almost equally divided into probably symptomatic and probably asymptomatic cases. Another 20.6% had possibly symptomatic OH. Importantly, only two patients with symptomatic OH had an OH diagnosis noted in their medical records. Five received domperidone, one received fludrocortison and none received midodrine. CONCLUSION: One half of institutionalized PD patients had OH, of whom half were probably symptomatic. OH was rarely noted in the medical records, suggesting underdiagnosis. Finally, OH was rarely treated, suggesting undertreatment.