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.

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.

Multidomain cognitive training increases physical activity in people with Parkinson's disease with mild cognitive impairment.

INTRODUCTION: Cognitive impairment in Parkinson's disease (PD), especially in patients with mild cognitive impairment (PD-MCI), coincides with less physical activity. Cognitive trainings (CT) have been found to promote laboratory environment-based movement. Knowledge about their effect in natural home-based environment, reflecting everyday function, is sparse. This explorative study investigated short-term effects of CT on physical activity assessed by home-based accelerometry, and its relation to change of cognitive function over time and non-cognitive outcomes in patients with PD-MCI. Cognitive and non-cognitive correlates of movement parameters at pretest were evaluated as well. METHODS: Eighteen patients with PD-MCI of the TrainParC study were analyzed. Those patients received either a 6-week multidomain group CT or physical training (PT). Physical activity and sedentary behavior were assessed with wearable accelerometers worn up to seven days pre- and post-training. RESULTS: Patients in the CT group displayed significantly greater increases in active periods after training than patients assigned to PT. In the CT group, increases in executive functioning were associated with increases in active periods and decreases in active mean bout length after training. At pretest, reduced working memory correlated with longer sedentary mean bout length, and impairment in activities of daily living (ADL) correlated with a higher number of sedentary periods. CONCLUSION: Study data revealed that CT can increase physical activity in patients with PD-MCI, possibly due to effects on executive functions, which needs further investigation in larger sample sizes. Lower working memory performance and ADL impairment might be associated with a more inactive lifestyle in patients with PD-MCI.

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.

Walking parameters of older adults from a lower back inertial measurement unit, a 6-year longitudinal observational study.

Gait changes during aging and differs between sexes. Inertial measurement units (IMUs) enable accurate quantitative evaluations of gait in ambulatory environments and in large populations. This study aims to provide IMU-based gait parameters' values derived from a large longitudinal cohort study in older adults. We measured gait parameters, such as velocity, step length, time, variability, and asymmetry, from straight, self-paced 20-m walks in older adults (four visits: 715/1102/1017/957 participants) every second year over 6 years using an IMU at the lower back. Moreover, we calculated the associations of gait parameters with sex and age. Women showed lower gait speed, step length, step time, stride time, swing time, and stance time, compared to men. Longitudinal analyses suggest that these parameters are at least partly deteriorating within the assessment period of 2 years, especially in men and at an older age. Variability and asymmetry parameters show a less clear sex- and age-associated pattern. Altogether, our large longitudinal dataset provides the first sex-specific information on which parameters are particularly promising for the detection of age-related gait changes that can be extracted from an IMU on the lower back. This information may be helpful for future observational and treatment studies investigating sex and age-related effects on gait, as well as for studies investigating age-related diseases.

Dual Task Turning in Place: A Reliable, Valid, and Responsive Outcome Measure of Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) is a complex symptom in Parkinson's disease (PD) that is both elusive to elicit and varied in its presentation. These complexities present a challenge to measuring FOG in a sensitive and reliable way, precluding therapeutic advancement. OBJECTIVE: We investigated the reliability, validity, and responsiveness of manual video annotations of the turning-in-place task and compared it to the sensor-based FOG ratio. METHODS: Forty-five optimally medicated people with PD and FOG performed rapid alternating 360° turns without and with an auditory stroop dual task, thrice over two consecutive days. The tasks were video recorded, and inertial sensors were placed on the lower back and shins. Interrater reliability between three raters, criterion validity with self-reported FOG, and responsiveness to single-session split-belt treadmill (SBT) training were investigated and contrasted with the sensor-based FOG ratio. RESULTS: Visual ratings showed excellent agreement between raters for the percentage time frozen (%TF) (ICC [intra-class correlation coefficient] = 0.99), the median duration of a FOG episode (ICC = 0.90), and the number of FOG episodes (ICC = 0.86). Dual tasking improved the sensitivity and validity of visual FOG ratings resulting in increased FOG detection, criterion validity with self-reported FOG ratings, and responsiveness to a short SBT intervention. The sensor-based FOG ratio, on the contrary, showed complex FOG presentation-contingent relationships with visual and self-reported FOG ratings and limited responsiveness to SBT training. CONCLUSIONS: Manual video annotations of FOG during dual task turning in place generate reliable, valid, and sensitive outcomes for investigating therapeutic effects on FOG. © 2021 International Parkinson and Movement Disorder Society.

Repeated Gait Perturbation Training in Parkinson's Disease and Healthy Older Adults: A Systematic Review and Meta-Analysis.

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

How many gait initiation trials are necessary to reliably detect anticipatory postural adjustments and first step characteristics in healthy elderly and people with Parkinson's disease?

BACKGROUND: The gait initiation (GI) process can be characterized by anticipatory postural adjustments (APAs) and first step characteristics. However, even within a constrained environment, it is unclear how many trials are necessary to obtain a reliable measurement of the GI process within one assessment. RESEARCH QUESTION: How many gait initiation trials are necessary to reliably detect APAs and first step characteristics in healthy elderly (HC) and people with Parkinson's disease with Freezing of Gait (PD + FOG) under single (ST) and dual task (DT) conditions and are there any potential systematic errors? METHODS: Thirty-eight PD + FOG (ON-medication) and 30 HC performed 5 trials of GI under ST and DT (auditory stroop test). APAs and first-step-outcomes were captured with IMUs placed on the lower back and on each foot. Intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM) were computed to investigate reliability and mixed model analysis to find potential systematic errors. Additionally, we computed an estimation for the number of necessary trials to reach acceptable reliability (ICC = 0.75) for each outcome. RESULTS: ICCs varied from low reliability to excellent reliability across outcomes in PD + FOG and HC. ICCs were comparable under ST and DT for most outcomes. SEM results confirmed the ICC results. A systematic error was found for the first trial in first step ROM. Number of necessary trials varied largely across outcomes. SIGNIFICANCE: Within-session reliability varied across outcomes but was similar for PD + FOG and HC, and ST and DT. ML size of APA and first step ROM were most reliable, whereas APA duration and latency were least reliable. Depending on the outcome of interest, future studies should conduct multiple trials of GI to increase reliability.

Prediction of the effect of deep brain stimulation on gait freezing of Parkinson's disease.

OBJECTIVE: The response of freezing of gait (FOG) to deep brain stimulation of the subthalamic nucleus (STN-DBS) is controversial and depends on many poorly controlled factors. On the other hand, a clinical predictor for the individual patient is needed to counsel the patient regarding this symptom. METHODS: A cohort of 124 patients undergoing STN-DBS was evaluated based on the video-documented Levodopa test at baseline in the OFF- and ON-drug condition and postoperatively in the best condition (ON-drug/ON-stim) and the worst condition (OFF-drug/ON-stim). We compared the freezing item of the Unified Parkinson's disease rating scale (#14), the UPDRS III total score, and FOG severity rated during four provoking situations with regard to its predictive value. RESULTS: We found 'FOG during the turning task' to be the best predictor with an ROC-value of 0.857 compared to 0.603 for the UPDRS Item 14 and 0.583 for the total UPDRS III. An improvement of 1 or 2 grades of the turning item during the preoperative levodopa test predicts an improvement during the worst condition postoperatively of 1 grade or more with an 80% probability. CONCLUSION: This FOG prediction test is simple and clinically useful. The test needs to be studied in a prospective study.

Exploring Interrater Disagreement on Essential Tremor Using a Standardized Tremor Elements Assessment.

BACKGROUND: Patients with upper limb action tremor frequently exhibit additional neurological signs of uncertain significance. Clinicians vary in their interpretation, and interrater agreement on the final diagnosis is poor. OBJECTIVES: A new clinical tool for assessing the presence or absence of clinical signs that are important in axis-1 classification of tremor patients is introduced: the Standardized Tremor Elements Assessment (STEA). Interrater agreement is determined, and signs leading to disagreement in the final diagnosis are identified. METHODS: Three tremor-focussed and one dystonia-focussed movement disorder specialists rated 59 videos of patients with upper limb action tremor syndromes using STEA. Interrater agreements for final diagnosis and STEA items were calculated. RESULTS: Interrater agreement regarding the final diagnosis was higher within the group of tremor specialists and poor between dystonia and tremor specialists. Greater agreement was found for items characterizing tremor than for signs of dystonia. CONCLUSIONS: Clinical signs leading to diagnostic disagreement were identified with STEA, and STEA should therefore be useful in future studies of diagnostic disagreement. The thresholds for considering neurological signs as soft versus significant for ataxia, parkinsonism, dystonia, etc. are critically important in tremor classification and must be studied across movement disorder subspecialties, not simply within a pool of tremor specialists.

Memory enhancement by multidomain group cognitive training in patients with Parkinson's disease and mild cognitive impairment: long-term effects of a multicenter randomized controlled trial.

BACKGROUND: Meta-analyses indicate positive effects of cognitive training (CT) in patients with Parkinson's disease (PD), however, most previous studies had small sample sizes and did not evaluate long-term follow-up. Therefore, a multicenter randomized controlled, single-blinded trial (Train-ParC study) was conducted to examine CT effects in PD patients with mild cognitive impairment (PD-MCI). Immediately after CT, an enhancement of executive functions was demonstrated. Here, we present the long-term results 6 and 12 months after CT. METHODS: At baseline, 64 PD-MCI patients were randomized to a multidomain CT group (n = 33) or to a low-intensity physical activity training control group (PT) (n = 31). Both interventions included 90 min training sessions twice a week for 6 weeks. 54 patients completed the 6 months (CT: n = 28, PT: n = 26) and 49 patients the 12 months follow-up assessment (CT: n = 25, PT: n = 24). Primary study outcomes were memory and executive functioning composite scores. Mixed repeated measures ANOVAs, post-hoc t tests and multiple regression analyses were conducted. RESULTS: We found a significant time x group interaction effect for the memory composite score (p = 0.006, η2 = 0.214), but not for the executive composite score (p = 0.967, η2 = 0.002). Post-hoc t tests revealed significant verbal and nonverbal memory improvements from pre-intervention to 6 months, but not to 12 months follow-up assessment in the CT group. No significant predictors were found for predicting memory improvement after CT. CONCLUSIONS: This study provides Class 1 evidence that multidomain CT enhances memory functioning in PD-MCI after 6 months but not after 12 months, whereas executive functioning did not change in the long-term. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00010186), 21.3.2016 (The study registration is outlined as retrospective due to an administrative delay. The first patient was enrolled three months after the registration process was started. A formal confirmation of this process from the German Clinical Trials Register can be obtained from the authors.).

YouTube Videos on Parkinson's Disease are a Relevant Source of Patient Information.

BACKGROUND: Parkinson's disease (PD) is the most frequent movement disorder. Patients access YouTube, one of the largest video databases in the world, to retrieve health-related information increasingly often. OBJECTIVE: We aimed to identify high-quality publishers, so-called "channels" that can be recommended to patients. We hypothesized that the number of views and the number of uploaded videos were indicators for the quality of the information given by a video on PD. METHODS: YouTube was searched for 8 combinations of search terms that included "Parkinson" in German. For each term, the first 100 search results were analyzed for source, date of upload, number of views, numbers of likes and dislikes, and comments. The view ratio (views / day) and the likes ratio (likes * 100 / [likes + dislikes]) were determined to calculate the video popularity index (VPI). The global quality score (GQS) and title - content consistency index (TCCI) were assessed in a subset of videos. RESULTS: Of 800 search results, 251 videos met the inclusion criteria. The number of views or the publisher category were not indicative of higher quality video content. The number of videos uploaded by a channel was the best indicator for the quality of video content. CONCLUSION: The quality of YouTube videos relevant for PD patients is increased in channels with a high number of videos on the topic. We identified three German channels that can be recommended to PD patients who prefer video over written content.

Validation of the German Version of the New Freezing of Gait Questionnaire for People with Parkinson's Disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is a highly disabling symptom which impacts quality of life. The New FOG Questionnaire (NFOG-Q) is the most commonly used tool worldwide to characterize FOG severity in PD. This study aims to provide a German translation of the NFOG-Q and to assess its validity in people with PD. The questionnaire was translated using forward-backward translation. Validity was tested in 57 PD patients with FOG via Cronbach's alpha for internal consistency and Spearman correlations with several clinical measures to quantify disease severity, mobility, fall risk, and cognitive state for convergent and divergent validity. The German version of the NFOG-Q shows good internal consistency (Cα = 0.84). Furthermore, the NFOG-Q score was significantly correlated with the MDS-UPDRS III, H&Y stage, Timed Up and Go test, and the subjective fear of falling (FES-I). The lack of correlation with cognition (MoCA) points towards good divergent validity. This study provides a German version of the NFOG-Q which proved to be valid for the assessment of FOG severity in individuals with PD.

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait.

INTRODUCTION: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG). METHODS: Twenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated. RESULTS: Contrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (ß = -0.191, p = 0.001 for velocity). CONCLUSION: In PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

BACKGROUND: Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson's disease (PD) patients. However, the patients' cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted. OBJECTIVE: To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictors. METHODS: Sixty-four PD-MCI patients (age: 67.61 ± 7.70; UPDRS-III: 26.58 ± 13.54; MoCA: 24.47 ± 2.78) were randomized to either a CT group or a low-intensity physical activity CG for six weeks (twice weekly, 90 minutes). Outcomes were assessed before and after training. MANOVAs with follow-up ANOVAs and multiple regression analyses were computed. RESULTS: Both interventions were highly feasible (participation, motivation, and evaluation); the overall dropout rate was 4.7%. Time × group interaction effects favoring CT were observed for phonemic fluency as a specific executive test (p=0.018, η p 2=0.092) and a statistical trend for overall executive functions (p=0.095, η p 2=0.132). A statistical trend for a time × group interaction effect favoring CG was shown for the digit span backward as a working memory test (p=0.098, η p 2=0.043). Regression analyses revealed cognitive baseline levels, education, levodopa equivalent daily dose, motor scores, and ApoE status as significant predictors for CT success. CONCLUSIONS: CT is a safe and feasible therapy option in PD-MCI, yielding executive functions improvement. Data indicate that vulnerable individuals may show the largest cognitive gains. Longitudinal studies are required to determine whether CT may also attenuate cognitive decline in the long term. This trial is registered with DRKS00010186.

Short-Term Effects of Single-Session Split-Belt Treadmill Training on Dual-Task Performance in Parkinson's Disease and Healthy Elderly.

Background: Dual-tasking is challenging for people with Parkinson's disease and freezing of gait (PD+FOG) and can exacerbate freezing episodes and falls. Split-belt treadmill training (SBT) is a novel tool to train complex gait and may improve dual-task (DT) walking and turning. Objective: To investigate the single-session effects of SBT on DT walking and DT turning performance in PD+FOG and older adults (OA), compared to regular treadmill training. Methods: Forty-five PD+FOG and 36 OA participated in a single training session (30 min). They were randomized into one of four training groups: (A) SB75-steady belt speed ratio 0.75:1; (B) SB50-steady belt speed ratio 0.5:1; (C) SBCR-changing belt speed ratios between 0.75:1 and 0.5:1; and (D) Tied-Belt (TBT). Over-ground straight-line gait and an alternating turning in place task combined with a cognitive dual-task (DT) (auditory Stroop) were assessed pre- and post-training, and the following day (retention). Constrained longitudinal data analysis was used to investigate the training effects for all participants and for PD+FOG alone. Results: DT gait speed improved at post-training for all groups (p < 0.001). However, SBT (SB50 and SBCR) led to larger post-training improvements compared to TBT, which were still visible at retention (SB50). For mean DT turning speed and Stroop response time while walking, only SBT groups showed significant improvements at post-training or retention. DT stride length, peak DT turning speed, and Stroop performance index while walking also showed larger gains in SBT compared to TBT. Results for PD+FOG alone showed similar effects although with smaller effect sizes. Conclusions: A single session of SBT in PD+FOG and OA showed larger short-term effects on DT walking and turning compared to TBT. Cognitive DT performance was also improved in SBT, likely due to reduced cortical control of gait. These results illustrate the potential for SBT to improve DT during complex gait and possibly reduce fall risk in clinical and healthy populations.

Clinical patterns of gait freezing in Parkinson's disease and their response to interventions: An observer-blinded study.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown. METHODS: Two blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation. RESULTS: Eighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS. CONCLUSION: Turning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination.

The Effect of One Session Split-Belt Treadmill Training on Gait Adaptation in People With Parkinson's Disease and Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with gait asymmetry and switching difficulty. A split-belt treadmill may potentially address those deficits. OBJECTIVE: To investigate the immediate and retention effects of one-session split-belt treadmill training (SBT) in contrast to regular tied-belt treadmill training (TBT) on gait asymmetry and adaptation in people with PD and FOG (PD + FOG) and healthy controls (HC). Additionally, to investigate differential effects of 3 SBT protocols and compare different gait adaptation outcomes. METHODS: PD + FOG (n = 45) and HC (n = 36) were randomized to 1 of 3 SBT groups (belt speeds' ratio 0.75:1; 0.5:1 or changing ratios) or TBT group. Participants were tested at Pre, Post, and Retention after one treadmill training session. Gait asymmetry was measured during a standardized adaptation test on the split-belt treadmill. RESULTS: SBT proved beneficial for gait adaptation in PD + FOG and HC (P < .0001); however, HC improved more. SBT with changing ratios demonstrated significant effects on gait adaptation from Pre to Post in PD + FOG, supported by strong effect sizes (d = 1.14) and improvements being retained for 24 hours. Mean step length asymmetry during initial exposure was lower in HC compared with PD + FOG (P = .035) and differentiated best between the groups. CONCLUSIONS: PD + FOG improved gait adaptation after a single SBT session although effects were smaller than in HC. SBT with changing ratios was the most effective to ameliorate gait adaptation in PD + FOG. These promising results warrant future study on whether long-term SBT strengthens adaptation in PD + FOG and has potential to induce a better resilience to FOG. Clinical trial ID: NCT03725215.

Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review.

INTRODUCTION: Advances in wearable sensor technology now enable frequent, objective monitoring of real-world walking. Walking-related digital mobility outcomes (DMOs), such as real-world walking speed, have the potential to be more sensitive to mobility changes than traditional clinical assessments. However, it is not yet clear which DMOs are most suitable for formal validation. In this review, we will explore the evidence on discriminant ability, construct validity, prognostic value and responsiveness of walking-related DMOs in four disease areas: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease and proximal femoral fracture. METHODS AND ANALYSIS: Arksey and O'Malley's methodological framework for scoping reviews will guide study conduct. We will search seven databases (Medline, CINAHL, Scopus, Web of Science, EMBASE, IEEE Digital Library and Cochrane Library) and grey literature for studies which (1) measure differences in DMOs between healthy and pathological walking, (2) assess relationships between DMOs and traditional clinical measures, (3) assess the prognostic value of DMOs and (4) use DMOs as endpoints in interventional clinical trials. Two reviewers will screen each abstract and full-text manuscript according to predefined eligibility criteria. We will then chart extracted data, map the literature, perform a narrative synthesis and identify gaps. ETHICS AND DISSEMINATION: As this review is limited to publicly available materials, it does not require ethical approval. This work is part of Mobilise-D, an Innovative Medicines Initiative Joint Undertaking which aims to deliver, validate and obtain regulatory approval for DMOs. Results will be shared with the scientific community and general public in cooperation with the Mobilise-D communication team. REGISTRATION: Study materials and updates will be made available through the Center for Open Science's OSFRegistry (https://osf.io/k7395).