Gait asymmetry and symptom laterality in Parkinson's disease: two of a kind?

BACKGROUND: The laterality of motor symptoms is considered a key feature of Parkinson's disease (PD). Here, we investigated whether gait and turning asymmetry coincided with symptom laterality as determined by the MDS-UPRDS part III and whether it was increased compared to healthy controls (HC). METHODS: We analyzed the asymmetry of gait and turning with and without a cognitive dual task (DT) using motion capture systems and wearable sensors in 97 PD patients mostly from Hoehn & Yahr stage II and III and 36 age-matched HC. We also assessed motor symptom asymmetry using the bilateral sub-items of the MDS-UPDRS-III. Finally, we examined the strength of the association between gait asymmetry and symptom laterality. RESULTS: Participants with PD had increased gait but not more turning asymmetry compared to HC (p < 0.05). Only 53.7% of patients had a shorter step length on the more affected body side as determined by the MDS-UPDRS-III. Also, 54% took more time and 29% more steps during turns toward the more affected side. The degree of asymmetry in the different domains did not correlate with each other and was not influenced by DT-load. CONCLUSIONS: We found a striking mismatch between the side and the degree of asymmetry in different motor domains, i.e., in gait, turning, and distal symptom severity in individuals with PD. We speculate that motor execution in different body parts relies on different neural control mechanisms. Our findings warrant further investigation to understand the complexity of gait asymmetry in PD.

Sensorimotor Network Segregation Predicts Long-Term Learning of Writing Skills in Parkinson's Disease.

The prediction of motor learning in Parkinson's disease (PD) is vastly understudied. Here, we investigated which clinical and neural factors predict better long-term gains after an intensive 6-week motor learning program to ameliorate micrographia. We computed a composite score of learning through principal component analysis, reflecting better writing accuracy on a tablet in single and dual task conditions. Three endpoints were studied-acquisition (pre- to post-training), retention (post-training to 6-week follow-up), and overall learning (acquisition plus retention). Baseline writing, clinical characteristics, as well as resting-state network segregation were used as predictors. We included 28 patients with PD (13 freezers and 15 non-freezers), with an average disease duration of 7 (±3.9) years. We found that worse baseline writing accuracy predicted larger gains for acquisition and overall learning. After correcting for baseline writing accuracy, we found female sex to predict better acquisition, and shorter disease duration to help retention. Additionally, absence of FOG, less severe motor symptoms, female sex, better unimanual dexterity, and better sensorimotor network segregation impacted overall learning positively. Importantly, three factors were retained in a multivariable model predicting overall learning, namely baseline accuracy, female sex, and sensorimotor network segregation. Besides the room to improve and female sex, sensorimotor network segregation seems to be a valuable measure to predict long-term motor learning potential in PD.

On-Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Cueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode. OBJECTIVES: We aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states. METHOD: In this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG. RESULTS: DeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67. CONCLUSIONS: DeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. © 2024 International Parkinson and Movement Disorder Society.

Towards a better understanding of anticipatory postural adjustments in people with Parkinson's disease.

INTRODUCTION: Previous studies have shown that anticipatory postural adjustments (APAs) are altered in people with Parkinson's disease but its meaning for locomotion is less understood. This study aims to investigate the association between APAs and gait initiation, gait and freezing of gait and how a dynamic postural control challenging training may induce changes in these features. METHODS: Gait initiation was quantified using wearable sensors and subsequent straight walking was assessed via marker-based motion capture. Additionally, turning and FOG-related outcomes were measured with wearable sensors. Assessments were conducted one week before (Pre), one week after (Post) and 4 weeks after (Follow-up) completion of a training intervention (split-belt treadmill training or regular treadmill training), under single task and dual task (DT) conditions. Statistical analysis included a linear mixed model for training effects and correlation analysis between APAs and the other outcomes for Pre and Post-Pre delta. RESULTS: 52 participants with Parkinson's disease (22 freezers) were assessed. We found that APA size in the medio-lateral direction during DT was positively associated with gait speed (p<0.001) and stride length (p<0.001) under DT conditions at Pre. The training effect was largest for first step range of motion and was similar for both training modes. For the associations between changes after the training (pooled sample) medio-lateral APA size showed a significant positive correlation with first step range of motion (p = 0.033) only in the DT condition and for the non-freezers only. CONCLUSIONS: The findings of this work revealed new insights into how APAs were not associated with first step characteristics and freezing and only baseline APAs during DT were related with DT gait characteristics. Training-induced changes in the size of APAs were related to training benefits in the first step ROM only in non-freezers. Based on the presented results increasing APA size through interventions might not be the ideal target for overall improvement of locomotion.

Freezing of gait assessment with inertial measurement units and deep learning: effect of tasks, medication states, and stops.

BACKGROUND: Freezing of gait (FOG) is an episodic and highly disabling symptom of Parkinson's Disease (PD). Traditionally, FOG assessment relies on time-consuming visual inspection of camera footage. Therefore, previous studies have proposed portable and automated solutions to annotate FOG. However, automated FOG assessment is challenging due to gait variability caused by medication effects and varying FOG-provoking tasks. Moreover, whether automated approaches can differentiate FOG from typical everyday movements, such as volitional stops, remains to be determined. To address these questions, we evaluated an automated FOG assessment model with deep learning (DL) based on inertial measurement units (IMUs). We assessed its performance trained on all standardized FOG-provoking tasks and medication states, as well as on specific tasks and medication states. Furthermore, we examined the effect of adding stopping periods on FOG detection performance. METHODS: Twelve PD patients with self-reported FOG (mean age 69.33 ± 6.02 years) completed a FOG-provoking protocol, including timed-up-and-go and 360-degree turning-in-place tasks in On/Off dopaminergic medication states with/without volitional stopping. IMUs were attached to the pelvis and both sides of the tibia and talus. A temporal convolutional network (TCN) was used to detect FOG episodes. FOG severity was quantified by the percentage of time frozen (%TF) and the number of freezing episodes (#FOG). The agreement between the model-generated outcomes and the gold standard experts' video annotation was assessed by the intra-class correlation coefficient (ICC). RESULTS: For FOG assessment in trials without stopping, the agreement of our model was strong (ICC (%TF) = 0.92 [0.68, 0.98]; ICC(#FOG) = 0.95 [0.72, 0.99]). Models trained on a specific FOG-provoking task could not generalize to unseen tasks, while models trained on a specific medication state could generalize to unseen states. For assessment in trials with stopping, the agreement of our model was moderately strong (ICC (%TF) = 0.95 [0.73, 0.99]; ICC (#FOG) = 0.79 [0.46, 0.94]), but only when stopping was included in the training data. CONCLUSION: A TCN trained on IMU signals allows valid FOG assessment in trials with/without stops containing different medication states and FOG-provoking tasks. These results are encouraging and enable future work investigating automated FOG assessment during everyday life.

Active and Passive Cycling Decrease Subthalamic ß Oscillations in Parkinson's Disease.

BACKGROUND: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of ß oscillations compared to walking, which facilitates motor continuation. METHODS: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated ß (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise. RESULTS: We found similarly strong suppression of pathological ß activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, ß suppression was stronger for patients with freezing of gait, especially during passive cycling. CONCLUSIONS: Our results provide evidence for a link between proprioceptive input during cycling and ß suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society.

Digital Mobility Measures: A Window into Real-World Severity and Progression of Parkinson's Disease.

BACKGROUND: Real-world monitoring using wearable sensors has enormous potential for assessing disease severity and symptoms among persons with Parkinson's disease (PD). Many distinct features can be extracted, reflecting multiple mobility domains. However, it is unclear which digital measures are related to PD severity and are sensitive to disease progression. OBJECTIVES: The aim was to identify real-world mobility measures that reflect PD severity and show discriminant ability and sensitivity to disease progression, compared to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scale. METHODS: Multicenter real-world continuous (24/7) digital mobility data from 587 persons with PD and 68 matched healthy controls were collected using an accelerometer adhered to the lower back. Machine learning feature selection and regression algorithms evaluated associations of the digital measures using the MDS-UPDRS (I-III). Binary logistic regression assessed discriminatory value using controls, and longitudinal observational data from a subgroup (n = 33) evaluated sensitivity to change over time. RESULTS: Digital measures were only moderately correlated with the MDS-UPDRS (part II-r = 0.60 and parts I and III-r = 0.50). Most associated measures reflected activity quantity and distribution patterns. A model with 14 digital measures accurately distinguished recently diagnosed persons with PD from healthy controls (81.1%, area under the curve: 0.87); digital measures showed larger effect sizes (Cohen's d: [0.19-0.66]), for change over time than any of the MDS-UPDRS parts (Cohen's d: [0.04-0.12]). CONCLUSIONS: Real-world mobility measures are moderately associated with clinical assessments, suggesting that they capture different aspects of motor capacity and function. Digital mobility measures are sensitive to early-stage disease and to disease progression, to a larger degree than conventional clinical assessments, demonstrating their utility, primarily for clinical trials but ultimately also for clinical care. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neural correlates of weight-shift training in older adults: a randomized controlled study.

Mediolateral weight-shifting is an important aspect of postural control. As it is currently unknown whether a short training session of mediolateral weight-shifting in a virtual reality (VR) environment can improve weight-shifting, we investigated this question and also probed the impact of practice on brain activity. Forty healthy older adults were randomly allocated to a training (EXP, n = 20, age = 70.80 (65-77), 9 females) or a control group (CTR, n = 20, age = 71.65 (65-82), 10 females). The EXP performed a 25-min weight-shift training in a VR-game, whereas the CTR rested for the same period. Weight-shifting speed in both single- (ST) and dual-task (DT) conditions was determined before, directly after, and 24 h after intervention. Functional Near-Infrared Spectroscopy (fNIRS) assessed the oxygenated hemoglobin (HbO2) levels in five cortical regions of interest. Weight-shifting in both ST and DT conditions improved in EXP but not in CTR, and these gains were retained after 24 h. Effects transferred to wider limits of stability post-training in EXP versus CTR. HbO2 levels in the left supplementary motor area were significantly increased directly after training in EXP during ST (change < SEM), and in the left somatosensory cortex during DT (change > SEM). We interpret these changes in the motor coordination and sensorimotor integration areas of the cortex as possibly learning-related.

Prevention of Falls in Parkinson's Disease: Guidelines and Gaps.

Background: People living with Parkinson's disease (PD) have a high risk for falls. Objective: To examine gaps in falls prevention targeting people with PD as part of the Task Force on Global Guidelines for Falls in Older Adults. Methods: A Delphi consensus process was used to identify specific recommendations for falls in PD. The current narrative review was conducted as educational background with a view to identifying gaps in fall prevention. Results: A recent Cochrane review recommended exercises and structured physical activities for PD; however, the types of exercises and activities to recommend and PD subgroups likely to benefit require further consideration. Freezing of gait, reduced gait speed, and a prior history of falls are risk factors for falls in PD and should be incorporated in assessments to identify fall risk and target interventions. Multimodal and multi-domain fall prevention interventions may be beneficial. With advanced or complex PD, balance and strength training should be administered under supervision. Medications, particularly cholinesterase inhibitors, show promise for falls prevention. Identifying how to engage people with PD, their families, and health professionals in falls education and implementation remains a challenge. Barriers to the prevention of falls occur at individual, environmental, policy, and health system levels. Conclusion: Effective mitigation of fall risk requires specific targeting and strategies to reduce this debilitating and common problem in PD. While exercise is recommended, the types and modalities of exercise and how to combine them as interventions for different PD subgroups (cognitive impairment, freezing, advanced disease) need further study.

Accuracy of consumer-based activity trackers as measuring tool and coaching device in breast and colorectal cancer survivors.

PURPOSE: Consumer-based activity trackers are used to measure and promote PA. We studied the accuracy of a wrist- and waist-worn activity tracker in cancer survivors and compared these results to a healthy age-matched control group. METHODS: Twenty-two cancer survivors and 35 healthy subjects wore an activity tracker at the waist and at the wrist combined with a reference activity monitor at the waist (Dynaport Movemonitor). The devices were worn for 14 consecutive days. The mean daily step count from both activity trackers was compared with the reference activity monitor to investigate accuracy and agreement (paired t-test, intraclass correlation, Bland-Altman plots). To evaluate the accuracy as a coaching tool, day-by-day differences within patients were calculated. The Kendall correlation coefficient was used to test the consistency of ranking daily steps between the activity trackers and the reference activity monitor. RESULTS: The wrist-worn wearable significantly overestimated the daily step count in the cancer group (mean ± SDΔ: + 1305 (2685) steps per day; p = 0.033) and in the healthy control group (mean ± SDΔ: + 1598 (2927) steps per day; p = 0.003). The waist-worn wearable underestimated the step count in both groups, although this was not statistically significant. As a coaching device, moderate (r = 0.642-0.670) and strong (r = 0.733-0.738) accuracy was found for the wrist- and waist-worn tracker, respectively, for detecting day-by-day variability in both populations. CONCLUSION: Our results show that wrist-worn activity trackers significantly overestimate daily step count in both cancer survivors and healthy control subjects. Based on the accuracy, in particular, the waist-worn activity tracker could possibly be used as a coaching tool.

Effect of transcranial direct current stimulation on learning in older adults with and without Parkinson's disease: A systematic review with meta-analysis.

Older adults with and without Parkinson's disease show impaired retention after training of motor or cognitive skills. This systematic review with meta-analysis aims to investigate whether adding transcranial direct current stimulation (tDCS) to motor or cognitive training versus placebo boosts motor sequence and working memory training. The effects of interest were estimated between three time points, i.e. pre-training, post-training and follow-up. This review was conducted according to the PRISMA guidelines (PROSPERO: CRD42022348885). Electronic databases were searched from conception to March 2023. Following initial screening, 24 studies were eligible for inclusion in the qualitative synthesis and 20 could be included in the meta-analysis, of which 5 studies concerned motor sequence learning (total n = 186) and 15 working memory training (total n = 650). Results were pooled using an inverse variance random effects meta-analysis. The findings showed no statistically significant additional effects of tDCS over placebo on motor sequence learning outcomes. However, there was a strong trend showing that tDCS boosted working memory training, although methodological limitations and some heterogeneity were also apparent. In conclusion, the present findings do not support wide implementation of tDCS as an add-on to motor sequence training at the moment, but the promising results on cognitive training warrant further investigations.

Lower back muscle activity during weight-shifting is affected by ageing and dual-tasking.

PURPOSE: Postural control deteriorates with age, especially under dual-task conditions. It is currently unknown how a challenging virtual reality weight-shifting task affects lower back muscle activity. Hence, this study investigated erector spinae neuromuscular control during mediolateral weight-shifting as part of an exergame during single- (ST) and dual-task (DT) conditions in young and older adults. METHODS: Seventeen young and 17 older adults performed mediolateral weight-shifts while hitting virtual wasps in a virtual environment with and without a serial subtraction task (DT). Center of mass position was recorded in real-time using 3D motion capturing. Electromyography recorded bilateral activation of the lumbar longissimus and iliocostalis muscles. RESULTS: Weight-shifting (p < 0.03) and targeting the wasps (p < 0.005) deteriorated with age and DT. Relative muscle activation during both quiet stance and weight-shifting increased with age, while the DT-effect did not differ consistently between age-groups. However, bilateral muscle co-contraction decreased with DT in young adults only. When switching direction and targeting the wasps, variability of muscle activation increased with age and DT and proved related to worse targeting performance. These effects were mainly visible at the non-dominant body side. CONCLUSION: Older adults showed a higher erector spinae muscle contribution to perform weight-shifts with increased variability at the end of a shift, whereby muscle activity was modulated less well in older than in young adults in response to DT. Hence, the current findings point to the potential for developing postural training in which older adults learn to fine-tune trunk muscle activity to improve weight-shifting and reduce fall risk.

A smartphone-based tapping task as a marker of medication response in Parkinson's disease: a proof of concept study.

Tapping tasks have the potential to distinguish between ON-OFF fluctuations in Parkinson's disease (PD) possibly aiding assessment of medication status in e-diaries and research. This proof of concept study aims to assess the feasibility and accuracy of a smartphone-based tapping task (developed as part of the cloudUPDRS-project) to discriminate between ON-OFF used in the home setting without supervision. 32 PD patients performed the task before their first medication intake, followed by two test sessions after 1 and 3 h. Testing was repeated for 7 days. Index finger tapping between two targets was performed as fast as possible with each hand. Self-reported ON-OFF status was also indicated. Reminders were sent for testing and medication intake. We studied task compliance, objective performance (frequency and inter-tap distance), classification accuracy and repeatability of tapping. Average compliance was 97.0% (± 3.3%), but 16 patients (50%) needed remote assistance. Self-reported ON-OFF scores and objective tapping were worse pre versus post medication intake (p < 0.0005). Repeated tests showed good to excellent test-retest reliability in ON (0.707 ≤ ICC ≤ 0.975). Although 7 days learning effects were apparent, ON-OFF differences remained. Discriminative accuracy for ON-OFF was particularly good for right-hand tapping (0.72 ≤ AUC ≤ 0.80). Medication dose was associated with ON-OFF tapping changes. Unsupervised tapping tests performed on a smartphone have the potential to classify ON-OFF fluctuations in the home setting, despite some learning and time effects. Replication of these results are needed in a wider sample of patients.

Test-retest reliability of functional near-infrared spectroscopy during a finger-tapping and postural task in healthy older adults.

Significance: Functional near-infrared spectroscopy (fNIRS) is increasingly employed in studies requiring repeated measurements, yet test-retest reliability is largely unknown. Aim: To investigate test-retest reliability during a postural and a finger-tapping task with and without cap-removal. Approach: Twenty healthy older adults performed a postural and a finger-tapping task. The tasks were repeated twice in one session and once the next day. A portable fNIRS system measured cortical hemodynamics (HbO2) in five regions of interest for the postural task and in the hand motor region for finger-tapping. Results: Test-retest reliability without cap-removal was excellent for the prefrontal cortex (PFC), the premotor cortex (PMC) and the somatosensory cortex (SSC) (intraclass correlation coefficient (ICC)≥0.78), and fair for the frontal eye fields (FEF) and the supplementary motor area (SMA) (ICC≥0.48). After cap-removal, reliability reduced for PFC and SSC (ICC≥0.50), became poor for SMA (ICC=0.01) and PMC (ICC=0.00) and remained good for FEF (ICC=0.64). Similarly, good reliability (ICC=0.66) was apparent for the hand motor region without cap-removal, which deteriorated after cap-removal (ICC=0.38). Conclusions: Test-retest reliability of fNIRS measurements during two separate motor tasks in healthy older adults was fair to excellent when the cap remained in place. However, removing the fNIRS cap between measurements compromised reliability.

Neural underpinnings of freezing-related dynamic balance control in people with Parkinson's disease.

INTRODUCTION: People with Parkinson's disease (PD) with freezing of gait (FOG; freezers) show impaired dynamic balance and experience falls more frequently compared to those without (non-freezers). Here, we explore the neural underpinnings of these freezing-related balance problems. METHODS: 12 freezers, 16 non-freezers and 14 controls performed a dynamic balance task in the lab. The next day, the same task was investigated in the MRI-scanner through motor imagery (MI). A visual imagery (VI) control task was also performed. Imagery engagement was determined by comparing the performance times between the dynamic balance task, and its MI- and VI-variants. Balance-related brain activations in regions of interest were contrasted between groups based on an MI > rest versus VI > rest contrast. RESULTS: Freezers and non-freezers were matched for age, cognition and disease severity. Similar performance times between the balance control task and the MI-conditions revealed excellent imagery engagement. Compared to non-freezers, freezers showed decreased activation in regions of interest located in the left mesencephalic locomotor region (MLR; p = 0.006), right anterior cerebellum (p = 0.017) and cerebellar vermis (p < 0.001). Intriguingly, non-freezers showed higher activations in the cerebellar vermis than controls (p = 0.010). CONCLUSION: Overall, we showed that decreased activation in the left MLR, and cerebellar regions in freezers relative to non-freezers could explain why dynamic balance is more affected in freezers. As non-freezers displayed increased cerebellar vermis activation compared to controls, it is possible that freezers show an inability to recruit sufficient compensatory cerebellar activity for effective dynamic balance control.

Validation of Commercial Activity Trackers in Everyday Life of People with Parkinson's Disease.

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.

Transcranial direct current stimulation enhances motor learning in Parkinson's disease: a randomized controlled trial.

Writing training has shown clinical benefits in Parkinson's disease (PD), albeit with limited retention and insufficient transfer effects. It is still unknown whether anodal transcranial direct current stimulation (atDCS) can boost consolidation in PD and how this interacts with medication. To investigate the effects of training + atDCS versus training + sham stimulation on consolidation of writing skills when ON and OFF medication. Second, to examine the intervention effects on cortical excitability. In this randomized sham-controlled double-blind study, patients underwent writing training (one session) with atDCS (N = 20) or sham (N = 19) over the primary motor cortex. Training was aimed at optimizing amplitude and assessed during online practice, pre- and post-training, after 24-h retention and after continued learning (second session) when ON and OFF medication (interspersed by 2 months). The primary outcome was writing amplitude at retention. Cortical excitability and inhibition were assessed pre- and post-training. Training + atDCS but not training + sham improved writing amplitudes at retention in the ON state (p = 0.017, g = 0.75). Transfer to other writing tasks was enhanced by atDCS in both medication states (g between 0.72 and 0.87). Also, training + atDCS improved continued learning. However, no online effects were found during practice and when writing with a dual task. A post-training increase in cortical inhibition was found in the training + atDCS group (p = 0.039) but not in the sham group, irrespective of medication. We showed that applying atDCS during writing training boosted most but not all consolidation outcomes in PD. We speculate that atDCS together with medication modulates motor learning consolidation via inhibitory processes ( https://osf.io/gk5q8/ , 2018-07-17).

Time trends in demographic characteristics of participants and outcome measures in Parkinson's disease research: A 19-year single-center experience.

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.

Split-Belt Treadmill Training to Improve Gait Adaptation in Parkinson's Disease.

BACKGROUND: Gait deficits in people with Parkinson's disease (PD) are triggered by circumstances requiring gait adaptation. The effects of gait adaptation training on a split-belt treadmill (SBT) are unknown in PD. OBJECTIVE: We investigated the effects of repeated SBT versus tied-belt treadmill (TBT) training on retention and automaticity of gait adaptation and its transfer to over-ground walking and turning. METHODS: We recruited 52 individuals with PD, of whom 22 were freezers, in a multi-center randomized single-blind controlled study. Training consisted of 4 weeks of supervised treadmill training delivered three times per week. Tests were conducted pre- and post-training and at 4-weeks follow-up. Turning (primary outcome) and gait were assessed over-ground and during a gait adaptation protocol on the treadmill. All tasks were performed with and without a cognitive task. RESULTS: We found that SBT-training improved gait adaptation with moderate to large effects sizes (P < 0.02) compared to TBT, effects that were sustained at follow-up and during dual tasking. However, better gait adaptation did not transfer to over-ground turning speed. In both SBT- and TBT-arms, over-ground walking and Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (MDS-UPDRS-III scores were improved, the latter of which reached clinically meaningful effects in the SBT-group only. No impact was found on freezing of gait. CONCLUSION: People with PD are able to learn and retain the ability to overcome asymmetric gait-speed perturbations on a treadmill remarkably well, but seem unable to generalize these skills to asymmetric gait off-treadmill. Future study is warranted into gait adaptation training to boost the transfer of complex walking skills. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement-the Mobilise-D study protocol.

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.