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Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them.

Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Because of the significant ramifications of falls, many interventions have been proposed, but few have aimed to prevent falls via an integrated approach targeting both motor and cognitive function. We aimed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality (VR) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone. We carried out this randomised controlled trial at five clinical centres across five countries (Belgium, Israel, Italy, the Netherlands, and the UK). Adults aged 60–90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were randomly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone. Randomisation was stratified by subgroups of patients (those with a history of idiopathic falls, those with mild cognitive impairment, and those with Parkinson's disease) and sex, with stratification per clinical site. Group allocation was done by a third party not involved in onsite study procedures. Both groups aimed to train three times per week for 6 weeks, with each session lasting about 45 min and structured training progression individualised to the participant's level of performance. The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen, which was specifically designed to reduce fall risk in older adults by including real-life challenges such as obstacles, multiple pathways, and distracters that required continual adjustment of steps. The primary outcome was the incident rate of falls during the 6 months after the end of training, which was assessed in a modified intention-to-treat population. Safety was assessed in all patients who were assigned a treatment. This study is registered with ClinicalTrials.gov, NCT01732653. Between Jan 6, 2013, and April 3, 2015, 302 adults were randomly assigned to either the treadmill training plus VR group (n=154) or treadmill training alone group (n=148). Data from 282 (93%) participants were included in the prespecified, modified intention-to-treat analysis. Before training, the incident rate of falls was similar in both groups (10·7 [SD 35·6] falls per 6 months for treadmill training alone vs 11·9 [39·5] falls per 6 months for treadmill training plus VR). In the 6 months after training, the incident rate was significantly lower in the treadmill training plus VR group than it had been before training (6·00 [95% CI 4·36–8·25] falls per 6 months; p<0·0001 vs before training), whereas the incident rate did not decrease significantly in the treadmill training alone group (8·27 [5·55–12·31] falls per 6 months; p=0·49). 6 months after the end of training, the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group (incident rate ratio 0·58, 95% CI 0·36–0·96; p=0·033). No serious training-related adverse events occurred. In a diverse group of older adults at high risk for falls, treadmill training plus VR led to reduced fall rates compared with treadmill training alone. European Commission.

The cortical control of gait and mobility involves multiple brain regions. Therefore, one could speculate that the association between specific spatial patterns of cortical thickness may be differentially associated with different mobility domains. To test this possibility, 115 healthy participants aged 27–82 (mean 60.5 ± 13.8) underwent a mobility assessment (usual-walk, dual-task walk, Timed Up and Go) and MRI scan. Ten mobility domains of relatively simple (e.g., usual-walking) and complex tasks (i.e., dual task walking, turns, transitions) and cortical thickness of 68 ROIs were extracted. All associations between mobility and cortical thickness were controlled for age and gender. Scaled Subprofile Modelling (SSM), a PCA-regression, identified thickness patterns that were correlated with the individual mobility domains, controlling for multiple comparisons. We found that lower mean global cortical thickness was correlated with worse general mobility (r = − 0.296, p  = 0.003), as measured by the time to complete the Timed Up and Go test. Three distinct patterns of cortical thickness were associated with three different gait domains during simple, usual-walking: pace, rhythm, and symmetry. In contrast, cortical thickness patterns were not related to the more complex mobility domains. These findings demonstrate that robust and topographically distinct cortical thickness patterns are linked to select mobility domains during relatively simple walking, but not to more complex aspects of mobility. Functional connectivity may play a larger role in the more complex aspects of mobility.

Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74-.98, p = .021), the attention index (RR: .84; CI: .75-.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01-1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.

Background The step-by-step determination of the spatio-temporal parameters of gait is clinically relevant since it provides an estimation of the variability of specific gait patterns associated with frequent geriatric syndromes. In recent years, several methods, based on the use of magneto-inertial units (MIMUs), have been developed for the step-by-step estimation of the gait temporal parameters. However, most of them were applied to the gait of healthy subjects and/or of a single pathologic population. Moreover, spatial parameters in pathologic populations have been rarely estimated step-by-step using MIMUs. The validity of clinically suitable MIMU-based methods for the estimation of spatio-temporal parameters is therefore still an open issue. The aim of this study was to propose and validate a method for the determination of both temporal and spatial parameters that could be applied to normal and heavily compromised gait patterns. Methods Two MIMUs were attached above each subject’s ankles. An instrumented gait mat was used as gold standard. Gait data were acquired from ten hemiparetic subjects, ten choreic subjects, ten subjects with Parkinson’s disease and ten healthy older adults walking at two different gait speeds. The method detects gait events (GEs) taking advantage of the cyclic nature of gait and exploiting some lower limb invariant kinematic characteristics. A combination of a MIMU axes realignment along the direction of progression and of an optimally filtered direct and reverse integration is used to determine the stride length. Results Over the 4,514 gait cycles analyzed, neither missed nor extra GEs were generated. The errors in identifying both initial and final contact at comfortable speed ranged between 0 and 11 ms for the different groups analyzed. The stride length was estimated for all subjects with less than 3% error. Conclusions The proposed method is apparently extremely robust since gait speed did not substantially affect its performance and both missed and extra GEs were avoided. The spatio-temporal parameters estimates showed smaller errors than those reported in previous studies and a similar level of precision and accuracy for both healthy and pathologic gait patterns. The combination of robustness, precision and accuracy suggests that the proposed method is suitable for routine clinical use.

Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson’s disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators. Nine patients with advanced PD participated in a randomized, cross-over exploratory study. We applied drTMS over the medial PFC for 16 weeks, with real and sham conditions; each condition included an intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase. Scores on a FOG-provoking test, the motor part of the Unified Parkinson’s Disease Rating Scale, and gait variability significantly improved after real drTMS, but not after the sham condition. Self-report of FOG severity and cognitive scores did not improve. Due to discomfort and pain during treatment, two patients dropped out and the study was halted. These initial findings support the cause-and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to the small sample size, findings should be interpreted cautiously. Further studies are needed to more fully assess the role of the medial PFC in the underlying mechanism of FOG and the possibility of using non-invasive brain stimulation to modify FOG.

People with multiple sclerosis (pwMS) often suffer from gait impairments. These changes in gait have been well studied in laboratory and clinical settings. A thorough investigation of gait alterations during community ambulation and their contributing factors, however, is lacking. The aim of the present study was to evaluate community ambulation and physical activity in pwMS and healthy controls and to compare in-lab gait to community ambulation. To this end, 104 subjects were studied: 44 pwMS and 60 healthy controls (whose age was similar to the controls). The subjects wore a tri-axial, lower back accelerometer during usual-walking and dual-task walking in the lab and during community ambulation (1 week) to evaluate the amount, type, and quality of activity. The results showed that during community ambulation, pwMS took fewer steps and walked more slowly, with greater asymmetry, and larger stride-to-stride variability, compared to the healthy controls ( p  < 0.001). Gait speed during most of community ambulation was significantly lower than the in-lab usual-walking value and similar to the in-lab dual-tasking value. Significant group (pwMS /controls)-by-walking condition (in-lab/community ambulation) interactions were observed (e.g., gait speed). Greater disability was associated with fewer steps and reduced gait speed during community ambulation. In contrast, physical fatigue was correlated with sedentary activity, but was not related to any of the measures of community ambulation gait quality including gait speed. This disparity suggests that more than one mechanism contributes to community ambulation and physical activity in pwMS. Together, these findings demonstrate that during community ambulation, pwMS have marked gait alterations in multiple gait features, reminiscent of dual-task walking measured in the laboratory. Disease-related factors associated with these changes might be targets of rehabilitation.

Background Accumulating evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms. Recently, several studies used functional near infrared spectroscopy (fNIRS) to examine brain activity during walking, demonstrating increased oxygenated hemoglobin (HbO 2 ) levels in the frontal cortex during walking while subjects completed a verbal cognitive task. It is, however, still unclear whether this increase in activation was related to verbalization, if the response was specific to gait, or if it would also be observed during standing, a different motor control task. The aim of this study was to investigate whether an increase in frontal activation is specific to dual tasking during walking. Methods Twenty-three healthy young adults (mean 30.9 ± 3.7 yrs, 13 females) were assessed using an electronic walkway. Frontal brain activation was assessed using an fNIRS system consisting of two probes placed on the forehead of the subjects. Assessments included: walking in a self-selected speed; walking while counting forward; walking while serially subtracting 7s (Walking+S7); and standing while serially subtracting 7s (Standing+S7). Data was collected from 5 walks of 30 meters in each condition. Twenty seconds of quiet standing before each walk served as baseline frontal lobe activity. Repeated Measures Analysis of Variance (RM ANOVA) tested for differences between the conditions. Results Significant differences were observed in HbO 2 levels between all conditions (p = 0.007). HbO 2 levels appeared to be graded; walking alone demonstrated the lowest levels of HbO2 followed by walking+counting condition (p = 0.03) followed by Walking+S7 condition significantly increased compared to the two other walking conditions (p < 0.01). No significant differences in HbO 2 levels were observed between usual walking and the standing condition (p = 0.38) or between standing with or without serial subtraction (p = 0.76). Conclusions This study provides direct evidence that dual tasking during walking is associated with frontal brain activation in healthy young adults. The observed changes are apparently not a response to the verbalization of words and are related to the cognitive load during gait.

Background Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrP sc ), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion. Methods The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an “in-depth” visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a “brief” visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one “in-depth” visit, similar to the baseline visit of healthy relatives. Discussion This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions. Trial registration The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

BackgroundThe ability to maintain adequate motor-cognitive performance under increasing task demands depends on the regulation and coordination of neural resources. Studies have shown that such resources diminish with aging and disease. EEG spectral analysis is a method that has the potential to provide insight into neural alterations affecting motor-cognitive performance. The aim of this study was to assess changes in spectral analysis during dual-task walking in aging and diseaseMethods10 young adults, ten older adults, and ten patients with Parkinson’s disease (PD) completed an auditory oddball task while standing and while walking on a treadmill. Spectral power within four frequency bandwidths, delta (< 4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz), was calculated using Event-Related Spectral Perturbation (ERSP) analyses and compared between single task and dual task and between groups.ResultsDifferences in ERSP were found in all groups between the single and dual-task conditions. In response to dual-task walking, beta increased in all groups (p < 0.026), delta decreased in young adults (p = 0.03) and patients with PD (0.015) while theta increased in young adults (p = 0.028) but decreased in older adults (p = 0.02) and patients with PD (p = 0.015). Differences were seen between the young, the older adults, and the patients with PD.ConclusionsThese findings are the first to show changes in the power of different frequency bands during dual-task walking with aging and disease. These specific brain modulations may reflect deficits in readiness and allocation of attention that may be responsible for the deficits in dual-task performance.