Functional Mobility Measures Research Articles

Backwards walking speed reserve in persons with multiple sclerosis

BackgroundDecreased gait speed is common in persons with Multiple Sclerosis (PwMS) and has been associated with elevated fall risk. The walking speed reserve (WSR) indicates the ability to increase gait speed on demand and has previously been examined in PwMS. Backward walking is a sensitive measure of fall risk in PwMS; however, no studies have reported on the utility of backward walking speed reserve (BW-WSR) as a clinical assessment tool of functional mobility or fall risk in PwMS, nor have they associated this measure with cognition. Methods23 PwMS completed walking trials at their preferred walking speed (PWS) and maximal walking speed (MWS). Participants performed these walking trials in both the forward (FW) and backward direction (BW). The forward walking speed reserve (FW-WSR) was calculated as the difference between MWS and PWS in the forward direction, while the backward walking speed reserve (BW-WSR) was calculated as the difference between MWS and PWS in the back backward direction. Correlation analyses examined the relationship between the FW- and BW-WSR with clinical assessments of functional mobility (the timed up-and-go) as well as cognitive functioning (the Symbol Digit Modalities Test, the Brief Visuospatial Memory Test-Revised, the California Verbal Learning Test, and the Trail Making Test A and B). Correlations also examined the relationship between FW- and BW-WSR with prospective falls. ResultsA lower BW-WSR was associated with disease severity and poorer performance on clinical walking and balance assessment, as well as with decreased information processing speed and attentional performance. Interestingly, FW-WSR showed similar relations. Neither FW- or BW-WSR were associated with prospective risk in this small sample of PwMS. ConclusionThe BW-WSR did not offer a distinct advantage over other measures, such as the FW-WSR, PWS, or MWS, in the forward or backward direction. The selection of the most sensitive clinical measures of functional mobility and fall risk is crucial; our study holds valuable clinical implications for PwMS by providing novel insights into functional mobility assessments in PwMS.

Blood Flow Restriction and Veterans With Multiple Sclerosis and Advanced Disability: Protocol for a Randomized Controlled Trial.

The purpose of this study will be to determine the efficacy of low intensity lower extremity resistance training with and without blood flow restriction (BFR) on quadriceps muscle strength and thickness in veterans with advanced multiple sclerosis (MS). This will be an assessor-blinded, 2-group (1 to 1 allocation) randomized controlled trial targeting an enrollment of 58 participants with advanced MS as defined by Patient-Determined Disease Steps scale levels 4 to 7. Both groups will complete 10weeks of twice weekly low-load resistance training (20%-30% of 1-repetition max) targeting knee and hip extension, knee flexion, and ankle plantarflexion. The intervention group will perform all training using BFR, with limb occlusion pressures between 60% and 80% of maximal limb occlusion pressure. Primary outcomes will be quadriceps muscle strength and thickness. Secondary outcomes will include knee flexion and ankle plantarflexion strength, functional mobility, physical activity, and patient-reported measures. All outcomes will be assessed at baseline before the intervention, immediately after the intervention, and at a 2-month follow-up assessment. The change between groups postintervention and after the 2-month follow-up will be reported for all outcomes. All analyses will assume a 2-sided test of hypothesis (α = .05). There is very little evidence for the efficacy of exercise interventions in people with MS who have advanced mobility disability. Resistance training with BFR may be an important approach for people with advanced MS who may not tolerate more conventional, moderate-to-high intensity resistance training. The results of this study will inform clinicians regarding exercise decisions for people with advanced MS and future investigations on the role of BFR in people with MS.

Novel Blood Flow Restriction Therapy Protocol for the Treatment of Postamputation Weakness and Pain due to Osteosarcoma: A Case Study

BACKGROUND: Pain and weakness are 2 commonly reported postamputation symptoms. The purpose of this case report is to propose a novel blood flow restriction (BFR) protocol to address pain and weakness in a patient with transtibial limb loss. CASE PRESENTATION: A 36-year-old male 2 months after transtibial amputation presented for evaluation and treatment of his postamputation pain, weakness, and poor functional mobility. The patient completed a novel BFR strength protocol twice per week for 12 weeks. OUTCOME AND FOLLOW-UP: Amputee Mobility Predictor, L Test Measure of Functional Mobility, 2-minute walk test, 30-second sit to stand, hamstring force, single-limb leg press repetition maximum, hip abduction endurance test, and numeric pain scale preintervention and postintervention were measured. The patient achieved the minimal detectable change for the L-Test and 2MWT, resulting in meaningful improvement in the patient’s strength and function following the blood flow restriction protocol. DISCUSSION: This case supports the use of blood flow restriction to address postamputation weakness and pain in a physical therapy setting. JOSPT Cases 2024;4(1):1-7. Epub 30 November 2023. doi:10.2519/josptcases.2023.11327

Adapted Home-Based Exercises in Dementia: An Exploratory Pre-post Pilot and Feasibility Study.

The goals of this exploratory pre-post pilot and feasibility study (NCT04916964) were to assess the feasibility and effectiveness of an adapted Test-and-Exercise home-based exercise program on basic functional mobility and executive functions in persons with prodromal or mild Alzheimer's disease. Participants followed an 8week exercise program at home, once per week with a physiotherapist and twice per week with their usual caregiver or independently. Functional mobility and executive functions were assessed before and after the intervention. Feasibility criteria were recruitment opportunity, participation agreement rate, cost adequacy, and drop-out rate. Twelve participants aged 80.83 ± 4.65years took part in the study. All the basic functional mobility measures showed small effect sizes. Concerning executive functions, 5 measures showed small to moderate effect sizes. The 4 feasibility criteria were met. A larger scale study would, however, need adaptations and prior research on the ability of this population to use touch-screen technology.

Multidisciplinary prehabilitation to improve frailty and functional capacity in high-risk elective surgical patients: a retrospective pilot study

BackgroundFrailty is associated with worse outcomes and higher healthcare costs. The long waiting time for surgery is a potential ‘teachable’ moment. We examined the feasibility and safety of a pilot prehabilitation programme on high-risk frail patients undergoing major elective surgery.MethodsA single-centre, retrospective pilot study (Dec 2020–Nov 2021) on a one-stop prehabilitation programme (structured exercise training, nutritional counselling/therapy, and psychological support) in collaboration with geriatricians and allied health professionals. At least 4 weeks before surgery, patients at high risk of frailty or malnutrition, or undergoing major hepatectomy, esophagectomy, pancreaticoduodenectomy, or radical cystectomy, were referred for prehabilitation (2–3 sessions/week). The primary outcomes were the feasibility and safety of prehabilitation. The secondary outcomes were changes in functional, emotional, and nutritional status and days alive and at home within 30 days after surgery (DAH30) associated with prehabilitation.ResultsOver a 12-month period, 72 out of 111 patients (64.9%) from the Perioperative Medicine Clinic were eligible for prehabilitation, of which 54 (75%) were recruited. The mean (standard deviation) age was 71.9 (6.9) years. The adherence rate to 3 weeks of prehabilitation was high in 52 (96.3%) participants. Prehabilitation improved exercise capacity (P = 0.08), enhanced some functional mobility measures (P = 0.02), and increased nutritional energy (P = 0.04) and protein intakes (P < 0.01). However, prehabilitation-related changes in muscle strength, cognitive function, and emotional resilience were minimal. The median (interquatile range) DAH30 was 19 (14–23) days. No adverse events were reported.ConclusionsThis outpatient-based, one-stop multidisciplinary prehabilitation programme was feasible, safe, and improved several measures of patient’s physiological reserve and functional capacity.Clinical trial registrationNCT05668221.

Digital gait markers to potentially distinguish fragile X-associated tremor/ataxia syndrome, Parkinson's disease, and essential tremor.

Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease that affects carriers of a 55-200 CGG repeat expansion in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, may be given an incorrect initial diagnosis of Parkinson's disease (PD) or essential tremor (ET) due to overlapping motor symptoms. It is critical to characterize distinct phenotypes in FXTAS compared to PD and ET to improve diagnostic accuracy. Fast as possible (FP) speed and dual-task (DT) paradigms have the potential to distinguish differences in gait performance between the three movement disorders. Therefore, we sought to compare FXTAS, PD, and ET patients using quantitative measures of functional mobility and gait under self-selected (SS) speed, FP, and DT conditions. Participants with FXTAS (n = 22), PD (n = 23), ET (n = 20), and controls (n = 20) underwent gait testing with an inertial sensor system (APDM™). An instrumented Timed Up and Go test (i-TUG) was used to measure movement transitions, and a 2-min walk test (2MWT) was used to measure gait and turn variables under SS, FP, and DT conditions, and dual-task costs (DTC) were calculated. ANOVA and multinomial logistic regression analyses were performed. PD participants had reduced stride lengths compared to FXTAS and ET participants under SS and DT conditions, longer turn duration than ET participants during the FP task, and less arm symmetry than ET participants in SS gait. They also had greater DTC for stride length and velocity compared to FXTAS participants. On the i-TUG, PD participants had reduced sit-to-stand peak velocity compared to FXTAS and ET participants. Stride length and arm symmetry index during the DT 2MWT was able to distinguish FXTAS and ET from PD, such that participants with shorter stride lengths were more likely to have a diagnosis of PD and those with greater arm asymmetry were more likely to be diagnosed with PD. No gait or i-TUG parameters distinguished FXTAS from ET participants in the regression model. This is the first quantitative study demonstrating distinct gait and functional mobility profiles in FXTAS, PD, and ET which may assist in more accurate and timely diagnosis.

Evaluation of a carepartner-integrated telehealth gait rehabilitation program for persons with stroke: study protocol for a feasibility study

BackgroundDespite family carepartners of individuals post-stroke experiencing high levels of strain and reduced quality of life, stroke rehabilitation interventions rarely address carepartner well-being or offer training to support their engagement in therapeutic activities. Our group has developed creative intervention approaches to support families during stroke recovery, thereby improving physical and psychosocial outcomes for both carepartners and stroke survivors. The purpose of this study is to test the feasibility of an adapted, home-based intervention (Carepartner Collaborative Integrative Therapy for Gait-CARE-CITE-Gait) designed to facilitate positive carepartner involvement during home-based training targeting gait and mobility.MethodsThis two-phased design will determine the feasibility of CARE-CITE-Gait, a novel intervention that leverages principles from our previous carepartner-focused upper extremity intervention. During the 4-week CARE-CITE-Gait intervention, carepartners review online video-based modules designed to illustrate strategies for an autonomy-supportive environment during functional mobility task practice, and the study team completes two 2-h home visits for dyad collaborative goal setting. In phase I, content validity, usability, and acceptability of the CARE-CITE-Gait modules will be evaluated by stroke rehabilitation content experts and carepartners. In phase II, feasibility (based on measures of recruitment, retention, intervention adherence, and safety) will be measured. Preliminary effects of the CARE-CITE-Gait will be gathered using a single-group, quasi-experimental design with repeated measures (two baseline visits 1 week apart, posttest, and 1-month follow-up) with 15 carepartner and stroke survivor dyads. Outcome data collectors will be blinded. Outcomes include psychosocial variables (family conflict surrounding stroke recovery, strain, autonomy support, and quality of life) collected from carepartners and measures of functional mobility, gait speed, stepping activity, and health-related quality of life collected from stroke survivors.DiscussionThe findings of the feasibility testing and preliminary data on the effects of CARE-CITE-Gait will provide justification and information to guide a future definitive randomized clinical trial. The knowledge gained from this study will enhance our understanding of and aid the development of rehabilitation approaches that address both carepartner and stroke survivor needs during the stroke recovery process.Trial registrationClinicalTrials.gov, NCT 05257928. Registered 25 February 2022.Trial statusThis trial was registered on ClinicalTrials.gov (NCT 05257928) on March 25, 2022. Recruitment of participants was initiated on May 18, 2022.

Impact of an INtervention to increase MOBility in older hospitalized medical patients (INTOMOB): Study protocol for a cluster randomized controlled trial

BackgroundLow mobility during an acute hospitalization is frequent and associated with adverse effects, including persistent functional decline, institutionalization and death. However, we lack effective interventions to improve mobility that are scalable in everyday practice. The INTOMOB trial – INtervention to increase MOBility in older hospitalized medical patients – will test the effect of a multilevel intervention to improve mobility of older hospitalized patients on functional mobility.MethodsThe INTOMOB multicenter superiority parallel cluster randomized controlled trial will enroll in total 274 patients in Swiss hospitals. Community-dwelling adults aged ≥ 60 years, admitted to a general internal medicine ward with an anticipated length of hospital stay of ≥ 3 days, will be eligible for participation. Unit of randomization will be the wards. A multilevel mobility intervention will be compared to standard of care and target the patients (information and exercise booklets, mobility diary, iPad with exercise videos), healthcare professionals (e-learning, oral presentation, mobility checklist), and environment (posters and pictures on the wards). The primary outcome will be life-space level, measured by the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), at 30 days after enrollment. The LSA is a measure of functional mobility, i.e., how far participants move from bedroom to outside town. Secondary outcomes include, among others, LSA at 180 days, mobility and falls during hospitalization, muscle strength at discharge, and falls, emergency room visits, readmissions, and death within 180 days.DiscussionThis study has the potential to improve outcomes of older hospitalized patients through an intervention that should be scalable in clinical practice because it fosters patient empowerment and does not require additional resources. The tools provided to the patients can help them implement better mobility practices after discharge, which can contribute to better functional outcomes. The choice of a functional patient-reported outcome measure as primary outcome (rather than a “simple” objective mobility measure) reinforces the patient-centeredness of the study.Trial registrationclinicaltrials.gov (NCT05639231, released on December 19 2022); Swiss National Clinical Trial Portal (SNCTP000005259, released on November 28 2022).

Translation and cross-cultural adaptation of the functional mobility scale in children with cerebral palsy into Arabic.

Cerebral palsy (CP) is a lifelong disorder of posture and movement which often leads to a myriad of limitations in functional mobility. The Functional Mobility Scale (FMS) is a parent-report measure of functional mobility for children with CP at three different distances (5 m, 50 m, and 500 m). This is a cross-sectional study which sought to translate and culturally adapt the FMS into Arabic and to validate the translated version. Functional mobility for children and adolescents with CP in Saudi Arabia was examined. The translation methodology complied with the World Health Organization Disability Assessment Schedule 2.0 translation package. A total of 154 children with CP were recruited (mean age 8.16 ± 3.32 years). Parents were interviewed to rate the usual walking ability of their children on the Arabic FMS. The re-test assessment was done with 34 families. The mean time interval between the first and second sessions was 14.3 days (SD = 8.5), with a range of 6-37 days. Concurrent validity was explored using Spearman's rank correlation coefficient between scores of the Arabic FMS with their corresponding score on the Gross Motor Function Classification System (GMFCS). Spearman's r values ranged between (-0.895 and -0.779), indicating strong to very strong correlations. The Test-retest reliability was examined using Cohen's weighted kappa, which showed almost perfect agreements. There was greater limitation for functional mobility at longer distances as 55.2% of children could not complete 500 meters (FMS score N). Overall, there was limited use of wheelchairs for all distances (ranging from 9.1% to 14.3%). Levels IV and V on the GMFCS had less variation in FMS scores and most of the children in these levels either did not complete the distances (no functional mobility at all distances) or used a wheelchair for mobility. The Arabic FMS was shown to be a reliable and valid measure of functional mobility for children with CP in their environment based on the parental reports. Functional mobility varied at different distances and within each GMFCS level. The use of both the GMFCS and FMS when assessing children with CP is recommended.

Precipitating Mechanisms of Falls in Preclinical Alzheimer's Disease.

Individuals with Alzheimer's disease (AD) are more than twice as likely to incur a serious fall as the general population of older adults. Although AD is commonly associated with cognitive changes, impairments in other clinical measures such as strength or functional mobility (i.e., gait and balance) may precede symptomatic cognitive impairment in preclinical AD and lead to increased fall risk. To examine mechanisms (i.e., functional mobility, cognition, AD biomarkers) associated with increased falls in cognitively normal older adults. This 1-year study was part of an ongoing longitudinal cohort study. We examined the relationships among falls, clinical measures of functional mobility and cognition, and neuroimaging AD biomarkers in cognitively normal older adults. We also investigated which domain(s) best predicted fall propensity and severity through multiple regression models. A total of 182 older adults were included (mean age 75 years, 53% female). A total of 227 falls were reported over the year; falls per person ranged from 0-16 with a median of 1. Measures of functional mobility were the best predictors of fall propensity and severity. Cognition and AD biomarkers were associated with each other but not with the fall outcome measures. These results suggest that, although subtle changes in cognition may be more closely associated with AD neuropathology, functional mobility indicators better predict falls in cognitively normal older adults. This study adds to our understanding of the mechanisms underlying falls in older adults and could lead to the development of targeted fall prevention strategies.

Psychometric properties of the Brazilian-Portuguese version of the Falls Behavioral Scale in people with Parkinson’s disease

Purpose To verify the psychometric properties of the Brazilian-Portuguese version of the Falls Behavioral (FaB-Brazil) Scale in Parkinson’s disease (PD). Material and Methods Participants (n = 96) were assessed by disease-specific, self-report and functional mobility measures. Internal consistency of the FaB-Brazil scale was evaluated using Cronbach’s alpha and inter-rater and test–retest reliability using intraclass correlation coefficients (ICC). The standard error of measurement (SEM), minimal detectable change (MDC), ceiling and floor effects, and convergent and discriminative validity were evaluated. Results Internal consistency was moderate (α = 0.77). Excellent inter-rater (ICC = 0.90; p < 0.001) and test–retest (ICC = 0.91; p < 0.001) reliability were found. The SEM was 0.20 and MDC was 0.38. Ceiling and floor effects were not found. Convergent validity was established by the positive correlations between the FaB-Brazil scale and age, modified Hoehn and Yahr, PD duration, Movement Disorders Society-Unified Parkinson’s Disease Rating Scale, Motor Aspects of Experiences of Daily Living, Timed Up & Go and 8-item Parkinson’s Disease Questionnaire, and negative correlations between the FaB-Brazil scale and community mobility, Schwab & England, and Activities-specific Balance Confidence scale. Females showed greater protective behaviors than males; recurrent fallers showed greater protective behaviors than non-recurrent fallers (p < 0.05). Conclusions The FaB-Brazil scale is reliable and valid for assessing people with PD.

Examining Patient Outcomes at a Faculty-Led Clinic for Uninsured and Underserved Clients.

Routine measurements used in clinical settings can foster evidence-based interventions and show the treatment effectiveness. To examine the efficacy of occupational therapy services for health outcomes, as determined by modified self-care and mobility items of the Continuity Assessment Record and Evaluation Tool, also known as Section GG. Retrospective and longitudinal. Data were obtained from medical records at four time points over 1 yr. The study took place at a pro bono, faculty-led clinic. Ninety-one client charts were reviewed; 64 (70%) clients met the inclusion criteria and were enrolled. Interventions were provided by registered occupational therapists and entry-level occupational therapy students under supervision. Self-care and mobility function were measured using modified GG0130 and GG0170 items from the Centers for Medicare & Medicaid Services Quality Reporting Program; three additional functional items were added. The 36-Item Short Form Health Survey, Version 2® (SF-36v2) was used to evaluate clients' quality of life at intake. Self-care and mobility composites significantly improved throughout the 1-yr intervention period. The additional functional composite significantly improved during the first 6 mo. Clients' scores on the physical function subdomain of the SF-36v2 were significantly related to their self-care, mobility, and additional functional items. Faculty-led clinics can improve the occupational performance of clients in need of occupational therapy services, particularly in the areas of self-care and mobility, which have previously been identified as top priorities for clients. What This Article Adds: This study addressed health disparities in unique and effective ways. By using objective measures of functional mobility and self-care, the study provides robust evidence of the faculty-led clinic's impact in providing underserved and uninsured communities with effective client-centered occupational therapy services.

Effects of Dual Task Training and Transcranial Direct Current Stimulation in Children with Spastic Cerebral Palsy: A Pilot Randomized Control Trial

ABSTRACT Objective Compare the effectiveness of active and sham transcranial direct current stimulation (tDCS) during the training of a dual task in children with spastic cerebral palsy (CP). Methods Thirty children with CP were submitted to ten sessions of either active (n = 15) or sham (n = 15) tDCS over the motor cortex for 20 minutes during the training of a dual task. Pre-intervention, post-intervention and follow-up evaluations involved measures of functional performance, intellectual performance, functional mobility and cortical excitability. Results The combination of active tDCS and dual task training led to improvements in functional mobility as well as functional and intellectual performances one month after the end of the intervention. Conclusion The combination of active tDCS and dual task training demonstrated promising effects for children with spastic CP.

A study of the reliability and validity of the Six-Spot Step Test Cognitive in ambulatory persons with Parkinson's disease

IntroductionAlthough dual-task walking deficits challenge ambulatory function in persons with Parkinson's disease (PwPD), ambulation measures that incorporate cognitive dual-task loads seem scarce. In its construct and instruction, the Six-Spot Step Test Cognitive (SSSTcog) ensures an equal focus on cognitive and motor tasks. The present study investigated the construct validity and test-retest reliability of the SSSTcog in PwPD. MethodsSeventy-eight PwPD were recruited from outpatient clinics. The SSSTcog was completed twice within the same day and again three to seven days later. In addition, the cognitive Timed “Up and Go” test (TUGcog) and the Mini-BESTest were also conducted on the last day. Reliability and validity were estimated using Bland-Altman statistics, the minimal difference (MD), Intraclass Correlation Coefficient (ICC), and Spearman's rank correlation coefficient (ρ). ResultsThe SSSTcog was found reliable (ICC: 0.84–0.89; MD: 23.7%–30.2%) and showed moderate construct validity to the TUGcog (ρ = 0.62, p < 0.001). Weak correlations to the Mini-BESTest (ρ = −0.33, p < 0.003) indicated low construct validity. Significantly (p < 0.001) higher dual-task costs were seen when performing the SSSTcog (77.6%) compared to the TUGcog (24.3%). ConclusionsIn PwPD, the SSSTcog showed promising construct validity, acceptable to excellent reliability, making it a valid measure of functional mobility, including cognitive dual-tasking. Higher dual-task cost for the SSSTcog indicated actual cognitive-motor interference while performing the test.

Cross-cultural adaptation, reliability and validation of the Gillette Functional Assessment Questionnaire (FAQ) into Brazilian Portuguese in patients with cerebral palsy

BackgroundThe purpose of this study was to translate, cross-culturally adapt and validate the Gillette Functional Assessment Questionnaire (FAQ) into Brazilian Portuguese.MethodsThe translation and cross-cultural adaptation was carried out in accordance with international recommendations. The FAQ was applied to a sample of 102 patients diagnosed with cerebral palsy (CP). Construct validity was assessed using Spearman’s correlation coefficient (rho), and the FAQ score was correlated with the Functional Mobility Scale (FMS) and Gross Motor Function Classification Scale (GMFCS). A subsample of 50 patients was used to assess reliability using intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimum detectable difference (MDD). Ceiling and floor effects were also evaluated.ResultsThe Brazilian version of the FAQ showed excellent test-retest reliability by the assessment of the physiotherapist (ICC = 0.99) and respondent (ICC = 0.97), as well as excellent inter-examiner reliability (ICC = 0.94). The SEM was 0.23 (physiotherapist), 0.47 (respondent) and 0.64 (inter-examiner), while the MDD was 0.64 (physiotherapist), 1.29 (respondent) and 1.76 (inter-examiner). The classification of gross motor function showed a high correlation with the FAQ applied by the physiotherapist (rho = -0.89) and by the respondent (rho = -0.87). The FMS-5 m was highly correlated with the FAQ applied by the physiotherapist and the respondent (rho = 0.88 and rho = 0.87, respectively). The FMS-50 and FMS-500 presented very high correlation with the FAQ applied by the physiotherapist (rho = 0.91 for both) and high correlation with the FAQ applied by the respondent (rho = 0.89 and rho = 0.88, respectively). The Brazilian version of the FAQ did not present the ceiling and floor effects.ConclusionThe FAQ presented adequate psychometric properties in patients with CP, indicating that it is possible to use it as a measure of functional gait mobility in Brazil.

Increased BMI and late-life mobility dysfunction; overlap of genetic effects in brain regions.

How obesity earlier in life impacts upon mobility dysfunctions in late life is not well understood. Pernicious effects of excess weight on the musculoskeletal system and mobility dysfunctions are well-recognized. However, increasingly more data support the link of obesity to overall motor defects that are regulated in the brain. To assess the causal relationship between body mass index (BMI) at midlife and performance of the Timed Up-and-Go test (TUG) in late life among a population-based longitudinal cohort of Chinese adults living in Singapore. We evaluated genetic predispositions for BMI in 8342 participants who were followed up from measurement of BMI at average 53 years, to TUG test (as a functional mobility measure) 20 years later. A robust 75.83% of genetically determined BMI effects on late-life TUG scores were mediated through midlife BMI (Pindirect-effect = 9.24 × 10-21). Utilizing Mendelian randomization, we demonstrated a causal effect between BMI and functional mobility in late life (βIVW = 0.180, PIVW = 0.001). Secondary gene enrichment evaluations highlighted down-regulation of genes at BMI risk loci that were correlated with poorer functional mobility in the substantia nigra and amygdala regions as compared to all other tissues. These genes also exhibit differential expression patterns during human brain development. We report a causal effect of obesity on mobility dysfunction. Our findings highlight potential neuronal dysfunctions in regulating predispositions on the causal pathway from obesity to mobility dysfunction.

Associations between myelin water imaging and measures of fall risk and functional mobility in multiple sclerosis.

Myelin water fraction (MWF) deficits as measured by myelin water imaging (MWI) have been related to worse motor function in persons with multiple sclerosis (PwMS). However, it is unknown if measures from MWI metrics in motor areas relate to fall risk measures in PwMS. The objective of this study was to examine the relationship between MWI measures in motor areas to performance on clinical measures of fall risk and disability in PwMS. Sixteen individuals with relapsing-remitting MS participated (1 male, 15 female; age 47.1 years [12.3]; Expanded Disability Status Scale 4.0 [range 0-6.5]) and completed measures of walking and fall risk (Timed 25 Foot Walk [T25FW] and Timed Up and Go). MWF and the geometric mean of the intra-/extracellular water T2 (geomT2IEW ) values reflecting myelin content and contribution of large-diameter axons/density, respectively, were assessed in three motor-related regions. The geomT2IEW of the corticospinal tract (r=-.599; p=.018) and superior cerebellar peduncles (r=-.613; p=.015) demonstrated significant inverse relationships with T25FW, suggesting that decreased geomT2IEW was related to slower walking. Though not significant, MWF in the corticospinal tract and superior cerebellar peduncles also demonstrated fair relationships with the T25FW, suggesting that worse performance on the T25FW was associated with lower MWF values. MWI of key motor regions was associated with walking performance in PwMS. Further MWI studies are needed to identify relationships between pathology and clinical function in PwMS to guide targeted rehabilitation therapies aimed at preventing falls.

Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration

The endosome-associated GTPase Rab5 is a central player in the molecular mechanisms leading to degeneration of basal forebrain cholinergic neurons (BFCN), a long-standing target for drug development. As p38α is a Rab5 activator, we hypothesized that inhibition of this kinase holds potential as an approach to treat diseases associated with BFCN loss. Herein, we report that neflamapimod (oral small molecule p38α inhibitor) reduces Rab5 activity, reverses endosomal pathology, and restores the numbers and morphology of BFCNs in a mouse model that develops BFCN degeneration. We also report on the results of an exploratory (hypothesis-generating) phase 2a randomized double-blind 16-week placebo-controlled clinical trial (Clinical trial registration: NCT04001517/EudraCT #2019-001566-15) of neflamapimod in mild-to-moderate dementia with Lewy bodies (DLB), a disease in which BFCN degeneration is an important driver of disease expression. A total of 91 participants, all receiving background cholinesterase inhibitor therapy, were randomized 1:1 between neflamapimod 40 mg or matching placebo capsules (taken orally twice-daily if weight <80 kg or thrice-daily if weight >80 kg). Neflamapimod does not show an effect in the clinical study on the primary endpoint, a cognitive-test battery. On two secondary endpoints, a measure of functional mobility and a dementia rating-scale, improvements were seen that are consistent with an effect on BFCN function. Neflamapimod treatment is well-tolerated with no study drug associated treatment discontinuations. The combined preclinical and clinical observations inform on the validity of the Rab5-based pathogenic model of cholinergic degeneration and provide a foundation for confirmatory (hypothesis-testing) clinical evaluation of neflamapimod in DLB.

Functional mobility decline and incident mild cognitive impairment and early dementia in community-dwelling older adults: the Singapore Longitudinal Ageing Study.

Motor and gait disturbances are evident in early Alzheimer and non-Alzheimer dementias and may predict the likelihood of mild cognitive impairment (MCI) or progression to dementia. We investigated the Timed-Up-and-Go (TUG) measure of functional mobility in predicting cognitive decline and incident MCI or early dementia (MCI-dementia). Prospective cohort study with 4.5years follow-up. Population based. 2,544 community-dwelling older adults aged 55+ years. Participants with baseline data on TUG, fast gait speed (GS), knee extension strength (KES) and performance-oriented mobility assessment (POMA) gait and balance were followed up for cognitive decline (Mini-Mental State Exam; MMSE drop of ≥2, among 1,336 dementia-free participants) and incident MCI-dementia (among 1,208 cognitively normal participants). Odds ratio (OR) and 95% confidence intervals (95% CI) were adjusted for age, sex, education, smoking, physical, social and productive activity, multi-morbidity, metabolic syndrome and MMSE. Per standard deviation increase in TUG, POMA, GS and KES were significantly associated with incident MCI-dementia: TUG (OR = 2.84, 95% CI = 2.02-3.99), GS (OR = 2.17, 95% CI = 1.62-2.91), POMA (OR = 1.88, 95% CI = 1.22-2.92) and KES (OR = 1.52, 95% CI = 1.15-2.02). Adjusted OR remained significant only for TUG (OR = 1.52, 95% CI = 1.01-2.31) and GS (OR = 1.53, 95% CI = 1.08-2.16). Areas under the curve (AUC) for TUG (AUC = 0.729, 95% CI = 0.671-0.787) were significantly greater than GS (AUC = 0.683, 95% CI = 0.619-0.746), KES (AUC = 0.624, 95% CI = 0.558-0.689) and POMA (AUC = 0.561, 95% CI = 0.485-0.637). Similar associations with cognitive decline were significant though less pronounced, and adjusted ORs remained significant for TUG, GS and POMA. Functional mobility decline precedes incident MCI and early dementia. The TUG appears to be especially accurate in predicting the future risks of adverse cognitive outcomes. ClinicalTrials.gov NCT03405675. Registered 23 January 2018 (retrospectively registered).

The relationship between physical qualities and contact technique in academy rugby union players

This study investigated the relationship between physical qualities and contact technique proficiency in rugby union players. Thirty-eight (n = 38) male academy rugby union players participated in the study. Physical measures of anthropometry, functional mobility, strength endurance, strength, power, speed, agility, and anaerobic and aerobic endurance were assessed. Tackler, ball-carrier, and ruck technique were assessed using video analysis of a standardised two-on-two contact drill. Seven physical qualities were moderately associated with tackler technique; Push-ups (r2 = 0.2; β = 0.04; p = 0.005; ES = 0.26), Sit-ups (r2 = 0.2; β = 0.08; p = 0.004; ES = 0.27), Relative 1RM Bench Press (r2 = 0.2; β = 2.32; p = 0.003; ES = 0.29), Broad Jump (r2 = 0.2; β = 0.03; p = 0.009; ES = 0.22), Agility (r2 = 0.2; β = −0.47; p = 0.019; ES = 0.19), 40m-Speed with Ball (r2 = 0.1; β = 0.93; p = 0.027; ES = 0.16) and Functional Mobility (r2 = 0.2; β = 0.16; p = 0.007; ES = 0.25). There was a large association between ball-carrier technique and Medicine Ball Throw (r2 = 0.3; β = 1.13; p = 0.001; ES = 0.37), and a moderate association between ruck technique and agility without (r2 = 0.2; β = −0.75; p = 0.005; ES = 0.21) and with (r2 = 0.2; β = −0.55; p = 0.015; ES = 0.29) the ball. The findings demonstrate the important contribution of physical strength and conditioning to contact technique in rugby union players. Contact technique training should be accompanied with physical strength and conditioning, as improvements in physical qualities may serve as foundational components to underpin improvements in technique.