Distributional data analysis via quantile functions and its application to modeling digital biomarkers of gait in Alzheimer's Disease.

With the advent of continuous health monitoring with wearable devices, users now generate their unique streams of continuous data such as minute-level step counts or heartbeats. Summarizing these streams via scalar summaries often ignores the distributional nature of wearable data and almost unavoidably leads to the loss of critical information. We propose to capture the distributional nature of wearable data via user-specific quantile functions (QF) and use these QFs as predictors in scalar-on-quantile-function-regression (SOQFR). As an alternative approach, we also propose to represent QFs via user-specific L-moments, robust rank-based analogs of traditional moments, and use L-moments as predictors in SOQFR (SOQFR-L). These two approaches provide two mutually consistent interpretations: in terms of quantile levels by SOQFR and in terms of L-moments by SOQFR-L. We also demonstrate how to deal with multi-modal distributional data via Joint and Individual Variation Explained using L-moments. The proposed methods are illustrated in a study of association of digital gait biomarkers with cognitive function in Alzheimers disease. Our analysis shows that the proposed methods demonstrate higher predictive performance and attain much stronger associations with clinical cognitive scales compared to simple distributional summaries.

Associations of pain sensitivity and conditioned pain modulation with physical activity: findings from the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. DESIGN: We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. RESULTS: Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. CONCLUSIONS: In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA.

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.

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.

Effects of a 6-Week Treadmill Training With and Without Virtual Reality on Frailty in People With Multiple Sclerosis.

OBJECTIVE: To examine the effects of a cognitive-motor rehabilitation program consisting of treadmill training (TT) augmented by virtual reality (TT+VR) on frailty in people with multiple sclerosis (pwMS). DESIGN: Secondary analysis from a multicenter randomized controlled trial investigating the effects of TT+VR, compared with TT only, on measures of mobility and cognitive function in pwMS. SETTING: Four university research laboratories in 3 countries. PARTICIPANTS: A total of 124 pwMS were randomized into the parent trial. Here, we studied a subset of n = 83 participants (mean age, 49.4±9.3y; 73.5% female; expanded disability status scale range, 2.0-6.0), who completed the intervention and had complete preintervention and postintervention frailty data. INTERVENTIONS: Participants were randomly allocated to TT+VR (n=44) or TT (n=39). Both groups trained 3 times a week for 6 weeks. MAIN OUTCOME MEASURES: Frailty was assessed using a 40-item frailty index (FI) through standard validated procedures and represented the primary study outcome. Two exploratory frailty indices were also computed by isolating health-related deficits involving the cognitive (FI-physical) or physical (FI-cognitive) domains from the main FI. The assessments were performed at baseline and after 6 weeks, upon intervention completion. RESULTS: The mean FI of study participants at baseline was 0.33±0.13, indicating a moderate average level of frailty. FI scores improved in both TT+VR and TT groups participants (pooled mean ΔFI, 0.024; 95% CI, 0.010-0.038; F=10.49; P=.002; ηp2=0.115), without any group-by-time interaction (F=0.82; P=.367; ηp2=0.010). However, a significant group-by-time interaction was found for pretraining and posttraining changes in FI-cognitive (F=5.74; P=.019; ηp2=0.066), suggesting a greater improvement for TT+VR group participants than for TT group participants. CONCLUSIONS: TT with or without virtual reality can reduce frailty levels in pwMS. While both TT and TT+VR had a positive effect on overall frailty, only TT+VR improved cognitive aspects of frailty and may represent an appropriate strategy for counteracting frailty in pwMS.

Simplification of Mobility Tests and Data Processing to Increase Applicability of Wearable Sensors as Diagnostic Tools for Parkinson's Disease.

Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on their lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed that Timed Up and Go (TUG) tasks to contribute the highest-yield predictive features, with only minor decreases in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.

CCR5-Δ32 polymorphism-a possible protective factor from gait impairment amongst post-stroke patients.

BACKGROUND AND PURPOSE: Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke. METHOD: Participants were 575 survivors of first-ever, mild-moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients. RESULTS: CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity. CONCLUSIONS: Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.

Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis.

BACKGROUND: In amyotrophic lateral sclerosis (ALS), gait abnormalities contribute to poor mobility and represent a relevant risk for falls. To date, gait studies in ALS patients have focused on the motor dimension of the disease, underestimating the cognitive aspects. METHODS: Using a wearable gait analysis device, we compared gait patterns in ambulatory ALS patients with mild cognitive impairment (ALS MCI+; n = 18), and without MCI (ALS MCI-; n = 24), and healthy subjects (HS; n = 16) under two conditions: (1) normal gait (single task) and (2) walking while counting backward (dual task). Finally, we examined if the occurrence and number of falls in the 3 months following the baseline test were related to cognition. RESULTS: In the single task condition, ALS patients, regardless of cognition, displayed higher gait variability than HS, especially for stance and swing time (p < 0.001). The dual task condition revealed additional differences in gait variability parameters between ALS MCI+ and ALS MCI- for cadence (p = 0.005), stance time (p = 0.04), swing time (p = 0.04) and stability index (p = 0.02). Moreover, ALS MCI+ showed a higher occurrence (p = 0.001) and number of falls (p < 0.001) at the follow-up. Regression analyses demonstrated that MCI condition predicted the occurrence of future falls (ß = 3.649; p = 0.01) and, together with executive dysfunction, was associated with the number of falls (cognitive impairment: ß = 0.63; p < 0.001; executive dysfunction: ß = 0.39; p = 0.03), regardless of motor impairment at clinical examination. CONCLUSION: In ALS, MCI is associated with exaggerated gait variability and predicts the occurrence and number of short-term falls.

The Potential of Transcranial Alternating Current Stimulation to Alleviate Dual-Task Gait Costs in Older Adults: Insights from a Double-Blinded Pilot Study.

BACKGROUND: The performance of an attention-demanding task while walking, i.e., dual-tasking, leads to dual-task costs (e.g., reduced gait speed) in older adults. Previous studies have shown that dual-task costs in gait are associated with future falls and cognitive decline. According to the communication through coherence hypothesis, transcranial alternating current stimulation (tACS) might help alleviate this problem. OBJECTIVE: The aim of this study was to examine the effects of a single session of theta-tACS targeting the left fronto-parietal network (L-FPN) on dual-task walking and cognitive function compared to sham stimulation and transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex, a node within the L-FPN. METHODS: Twenty older adults completed a four-visit, double-blinded, within-subject, cross-over study in which usual-walking, dual-task walking, and cognitive function were evaluated before and immediately after 20 min of tACS, tDCS, or sham (order randomized) stimulation. Dual-task costs to gait speed (primary outcome) and other measures were analyzed. RESULTS: The dual-task cost to gait speed tended to be lower (i.e., better) after tACS (p = 0.067, Cohen's d = 0.433∼small); tDCS significantly reduced this dual-task cost (p = 0.012, Cohen's d = 0.618∼medium), and sham stimulation had no effect (p = 0.467). tACS significantly reduced the dual-task cost to step length (p = 0.037, Cohen's d = 0.502∼medium); a trend was seen after tDCS (p = 0.069, Cohen's d = 0.443∼small). No statistical differences were found for other measures of gait or cognitive function. CONCLUSIONS: The positive effects of tACS on dual-task gait speed and step length were roughly similar to those seen with tDCS. These results suggest that tACS affects the fronto-parietal network and, similar to tDCS, tACS may improve dual-tasking. Nonetheless, to achieve larger benefits and differentiate the effects of tACS and tDCS on brain function and dual-task walking in older adults, other stimulation montages and protocols should be tested.

The impact of neck pain on gait health: a systematic review and meta-analysis.

BACKGROUND: Evidence exists demonstrating the negative impacts of chronic musculoskeletal pain on key measures of gait. Despite neck pain being the second most common musculoskeletal pain condition, there is a paucity of evidence exploring the impacts of neck pain specifically on these outcomes. The aims of this work were to systematically review the current evidence of the associations between chronic neck pain and measures of gait health and to conduct meta-analysis for quantitative assessment of the effect sizes under different walking conditions. METHODS: Systematic review was conducted following PRISMA guidelines. Databases searched included MEDLINE, Embase, Web of Science, CINAHL, and PEDro. Eligible study designs included observational studies consisting of an exposure group with chronic neck pain and control group without chronic neck pain and primary outcomes relating to gait health. For outcomes amenable to meta-analysis, a random-effects model was used to derive summary estimates of Hedge's g depicted graphically with forest plots. Other gait outcomes were narratively summarized. Risk of bias was also assessed. RESULTS: The original search yielded 1918 articles; 12 met final eligibility criteria including 10 cross-sectional studies. Outcomes were grouped first by the five domains of gait: pace, rhythm, asymmetry, variability, and postural control; and second by the tested walking conditions. Meta-analyses for gait speed revealed large effect-sizes indicating that individuals with chronic neck pain had slower measures of gait and lower measures of cadence. Gait outcomes that were narratively summarized supported these findings. CONCLUSION: The quantitative and qualitative findings of this systematic review and meta-analysis suggest a negative impact of CNNP on measures of gait health, particularly gait speed, under various walking conditions. However, broad interpretation of these results should be cautious. Testing gait under dual task conditions may be particularly sensitive to the impact of CNNP, and future work is needed to better understand how pain disrupts this important functionality of the locomotor system. Additionally, consideration should be made to assess measures of variability and investigate these relationships in the older adult population.

Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium.

BACKGROUND: Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates. METHODS: Twenty healthy older adults, 20 people with Parkinson's disease, 20 with multiple sclerosis, 19 with proximal femoral fracture, 17 with chronic obstructive pulmonary disease and 12 with congestive heart failure were monitored for 2.5 h in the real-world, using a single wearable device worn on the lower back. A reference system combining inertial modules with distance sensors and pressure insoles was used for comparison of DMOs from the single wearable device. We assessed and validated three algorithms for gait sequence detection, four for ICD, three for CAD and four for SL by concurrently comparing their performances (e.g., accuracy, specificity, sensitivity, absolute and relative errors). Additionally, the effects of walking bout (WB) speed and duration on algorithm performance were investigated. RESULTS: We identified two cohort-specific top performing algorithms for gait sequence detection and CAD, and a single best for ICD and SL. Best gait sequence detection algorithms showed good performances (sensitivity > 0.73, positive predictive values > 0.75, specificity > 0.95, accuracy > 0.94). ICD and CAD algorithms presented excellent results, with sensitivity > 0.79, positive predictive values > 0.89 and relative errors < 11% for ICD and < 8.5% for CAD. The best identified SL algorithm showed lower performances than other DMOs (absolute error < 0.21 m). Lower performances across all DMOs were found for the cohort with most severe gait impairments (proximal femoral fracture). Algorithms' performances were lower for short walking bouts; slower gait speeds (< 0.5 m/s) resulted in reduced performance of the CAD and SL algorithms. CONCLUSIONS: Overall, the identified algorithms enabled a robust estimation of key DMOs. Our findings showed that the choice of algorithm for estimation of gait sequence detection and CAD should be cohort-specific (e.g., slow walkers and with gait impairments). Short walking bout length and slow walking speed worsened algorithms' performances. Trial registration ISRCTN - 12246987.

Correlates of Person-Specific Rates of Change in Sensor-Derived Physical Activity Metrics of Daily Living in the Rush Memory and Aging Project.

This study characterized person-specific rates of change of total daily physical activity (TDPA) and identified correlates of this change. TDPA metrics were extracted from multiday wrist-sensor recordings from 1083 older adults (average age 81 years; 76% female). Thirty-two covariates were collected at baseline. A series of linear mixed-effect models were used to identify covariates independently associated with the level and annual rate of change of TDPA. Though, person-specific rates of change varied during a mean follow-up of 5 years, 1079 of 1083 showed declining TDPA. The average decline was 16%/year, with a 4% increased rate of decline for every 10 years of age older at baseline. Following variable selection using multivariate modeling with forward and then backward elimination, age, sex, education, and 3 of 27 non-demographic covariates including motor abilities, a fractal metric, and IADL disability remained significantly associated with declining TDPA accounting for 21% of its variance (9% non-demographic and 12% demographics covariates). These results show that declining TDPA occurs in many very old adults. Few covariates remained correlated with this decline and the majority of its variance remained unexplained. Further work is needed to elucidate the biology underlying TDPA and to identify other factors that account for its decline.

An Educational Program for Remote Training and Supervision of Home-Based Transcranial Electrical Stimulation: Feasibility and Preliminary Effectiveness.

OBJECTIVES: There has been recent interest in the administration of transcranial electrical stimulation (tES) by a caregiver, family member, or patient themselves while in their own homes (HB-tES). The need to properly train individuals in the administration of HB-tES is essential, and the lack of a uniform training approach across studies has come to light. The primary aim of this paper is to present the HB-tES training and supervision program, a tele-supervised, instructional, and evaluation program to teach laypersons how to administer HB-tES to a participant and to provide a standardized framework for remote monitoring of participants by teaching staff. The secondary aim is to present early pilot data on the feasibility and effectiveness of the training portion of the program based on its implementation in 379 sessions between two pilot clinical trials. MATERIALS AND METHODS: The program includes instructional materials, standardized tele-supervised hands-on practice sessions, and a system for remote supervision of participants by teaching staff. Nine laypersons completed the training program. Data on the feasibility and effectiveness of the program were collected. RESULTS: No adverse events were reported during the training or any of the HB-tES sessions after the training. All laypersons successfully completed the training. The nine laypersons reported being satisfied with the training program and confident in their tES administration capabilities. This was consistent with laypersons requiring technical assistance from teaching staff very infrequently during the 379 completed sessions. The average adherence rate between all administrators was >98%, with seven of nine administrators having 100% adherence to the scheduled sessions. CONCLUSIONS: These findings indicate that the HB-tES program is effective and is associated with participant satisfaction. SIGNIFICANCE: We hope that the remote nature of this training program will facilitate increased accessibility to HB-tES research for participants of different demographics and locations. This program, designed for easy adaptation to different HB-tES research applications and devices, also is accessible online. The adoption of this program is expected to facilitate uniformity of study methods among future HB-tES studies and thereby accelerate the pace of tES intervention discovery.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Frailty and Falls in People Living With Multiple Sclerosis.

OBJECTIVE: To explore the association between frailty and history of falls in people living with multiple sclerosis (MS). DESIGN: Secondary analysis. SETTING: University research laboratories in the United States and Israel. PARTICIPANTS: A total of 118 people (N=118) with relapsing-remitting MS (mean age, 48.9±10.0 years; 74.6% female; Expanded Disability Status Scale [EDSS] range, 1.0-6.0) were studied in this cross-sectional analysis. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A frailty index was calculated from 40 health deficits by following standard validated procedures. The number of falls (12-month history) was recorded. RESULTS: Overall, 33.9%, 29.7%, and 36.4% of participants were classified as nonfrail, moderately frail, and severely frail, respectively. The frailty index was significantly correlated (ρ=0.37, P<.001) with higher scores on the EDSS. In univariable negative binomial regression analysis, the frailty index was associated with a higher number of falls (incidence rate ratio [IRR]=3.33; 95% CI, 1.85-5.99; P<.001). After adjustment for age, sex, and EDSS, frailty remained strongly associated with history of falls (IRR=2.78; 95% CI, 1.51-5.10; P=.001). CONCLUSIONS: The current study identifies a significant relationship between frailty and history of falls in MS, independent of age, sex, and disease severity. These findings support the notion that frailty is a syndrome related to but independent of disability in MS.

Promoting independence in Lewy body dementia through exercise: the PRIDE study.

BACKGROUND: Lewy body dementia (LBD) is an aggressive type of dementia of rapid, fluctuating disease trajectory, higher incidence of adverse events, and poorer functional independence than observed in Alzheimer's disease dementia. Non-pharmacological treatments such as progressive, high-intensity exercise are effective in other neurological cohorts but have been scarcely evaluated in LBD. METHODS: The Promoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial was a non-randomised, non-blinded, crossover pilot trial involving older adults with LBD consisting of a baseline assessment, an 8-week wait-list, and an 8-week exercise intervention. The aims of this study were to evaluate the determinants of the primary outcome functional independence, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, and the feasibility and preliminary efficacy of an exercise intervention on this outcome. Additionally, important clinical characteristics were evaluated to explore associations and treatment targets. The exercise intervention was supervised, clinic-based, high-intensity progressive resistance training (PRT), challenging balance, and functional exercises, 3 days/week. RESULTS: Nine participants completed the baseline cross-sectional study, of which five had a diagnosis of Parkinson's disease dementia (PDD), and four dementia with Lewy Bodies (DLB). Six completed the exercise intervention (three PDD, three DLB). The cohort was diverse, ranging from mild to severe dementia and living in various residential settings. Greater functional independence at baseline was significantly associated with better physical function, balance, cognition, quality of life, muscle mass ratio, walking endurance, faster walking speed and cadence, and lower dementia severity (p < 0.05). Participants declined by clinically meaningful amounts in functional independence, cognition, physical function, muscle mass, and weight over the wait-list period (p < 0.05). Following exercise, participants improved by clinically meaningful amounts in functional independence, cognition, physical function, and strength (p < 0.05). Progressive, high intensity exercise was well-tolerated (> 80% adherence), and only one minor exercise-related adverse event occurred. CONCLUSIONS: PRIDE is the first exercise trial conducted specifically within individuals diagnosed with LBD, and provides important insight for the design of larger, randomized trials for further evaluation of progressive, high-intensity exercise as a valuable treatment in LBD. TRIAL REGISTRATION: The PRIDE trial protocol has previously been prospectively registered (08/04/2016, ANZCTR: ACTRN12616000466448).

A systematic review of chiropractic care for fall prevention: rationale, state of the evidence, and recommendations for future research.

BACKGROUND: Falls in older adults are a significant and growing public health concern. There are multiple risk factors associated with falls that may be addressed within the scope of chiropractic training and licensure. Few attempts have been made to summarize existing evidence on multimodal chiropractic care and fall risk mitigation. Therefore, the broad purpose of this review was to summarize this research to date. BODY: Systematic review was conducted following PRISMA guidelines. Databases searched included PubMed, Embase, Cochrane Library, PEDro, and Index of Chiropractic Literature. Eligible study designs included randomized controlled trials (RCT), prospective non-randomized controlled, observational, and cross-over studies in which multimodal chiropractic care was the primary intervention and changes in gait, balance and/or falls were outcomes. Risk of bias was also assessed using the 8-item Cochrane Collaboration Tool. The original search yielded 889 articles; 21 met final eligibility including 10 RCTs. One study directly measured the frequency of falls (underpowered secondary outcome) while most studies assessed short-term measurements of gait and balance. The overall methodological quality of identified studies and findings were mixed, limiting interpretation regarding the potential impact of chiropractic care on fall risk to qualitative synthesis. CONCLUSION: Little high-quality research has been published to inform how multimodal chiropractic care can best address and positively influence fall prevention. We propose strategies for building an evidence base to inform the role of multimodal chiropractic care in fall prevention and outline recommendations for future research to fill current evidence gaps.

Brain activity during dual-task standing in older adults.

BACKGROUND: In older adults, the extent to which performing a cognitive task when standing diminishes postural control is predictive of future falls and cognitive decline. The neurophysiology of such "dual-tasking" and its effect on postural control (i.e., dual-task cost) in older adults are poorly understood. The purpose of this study was to use electroencephalography (EEG) to examine the effects of dual-tasking when standing on brain activity in older adults. We hypothesized that compared to single-task "quiet" standing, dual-task standing would decrease alpha power, which has been linked to decreased motor inhibition, as well as increase the ratio of theta to beta power, which has been linked to increased attentional control. METHODS: Thirty older adults without overt disease completed four separate visits. Postural sway together with EEG (32-channels) were recorded during trials of standing with and without a concurrent verbalized serial subtraction dual-task. Postural control was measured by average sway area, velocity, and path length. EEG metrics included absolute alpha-, theta-, and beta-band powers as well as theta/beta power ratio, within six demarcated regions-of-interest: the left and right anterior, central, and posterior regions of the brain. RESULTS: Most EEG metrics demonstrated moderate-to-high between-day test-retest reliability (intra-class correlation coefficients > 0.70). Compared with quiet standing, dual-tasking decreased alpha-band power particularly in the central regions bilaterally (p = 0.002) and increased theta/beta power ratio in the anterior regions bilaterally (p < 0.001). A greater increase in theta/beta ratio from quiet standing to dual-tasking in numerous demarcated brain regions correlated with greater dual-task cost (i.e., absolute increase, indicative of worse performance) to postural sway metrics (r = 0.45-0.56, p < 0.01). Lastly, participants who exhibited greater alpha power during dual-tasking in the anterior-right (r = 0.52, p < 0.01) and central-right (r = 0.48, p < 0.01) regions had greater postural sway velocity during dual-tasking. CONCLUSION: In healthy older adults, alpha power and theta/beta power ratio change with dual-task standing. The change in theta/beta power ratio in particular may be related to the ability to regulate standing postural control when simultaneously performing unrelated, attention-demanding cognitive tasks. Modulation of brain oscillatory activity might therefore be a novel target to minimize dual-task cost in older adults.

Design and validation of a multi-task, multi-context protocol for real-world gait simulation.

BACKGROUND: Measuring mobility in daily life entails dealing with confounding factors arising from multiple sources, including pathological characteristics, patient specific walking strategies, environment/context, and purpose of the task. The primary aim of this study is to propose and validate a protocol for simulating real-world gait accounting for all these factors within a single set of observations, while ensuring minimisation of participant burden and safety. METHODS: The protocol included eight motor tasks at varying speed, incline/steps, surface, path shape, cognitive demand, and included postures that may abruptly alter the participants' strategy of walking. It was deployed in a convenience sample of 108 participants recruited from six cohorts that included older healthy adults (HA) and participants with potentially altered mobility due to Parkinson's disease (PD), multiple sclerosis (MS), proximal femoral fracture (PFF), chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF). A novelty introduced in the protocol was the tiered approach to increase difficulty both within the same task (e.g., by allowing use of aids or armrests) and across tasks. RESULTS: The protocol proved to be safe and feasible (all participants could complete it and no adverse events were recorded) and the addition of the more complex tasks allowed a much greater spread in walking speeds to be achieved compared to standard straight walking trials. Furthermore, it allowed a representation of a variety of daily life relevant mobility aspects and can therefore be used for the validation of monitoring devices used in real life. CONCLUSIONS: The protocol allowed for measuring gait in a variety of pathological conditions suggests that it can also be used to detect changes in gait due to, for example, the onset or progression of a disease, or due to therapy. TRIAL REGISTRATION: ISRCTN-12246987.