Search

Objective. The purpose of this study was to examine the association between frailty and the quantity and quality of freeliving walking and the mediating effect of frailty on the relationship between disability and walking performance in people with multiple sclerosis (MS). Methods. Ninety-nine people with relapsing-remitting MS (mean age = 49.3 [SD = 9.8] years; 73.7% women; Expanded Disability Status Scale [EDSS] score range = 2.0-6.0) wore a triaxial accelerometer for 7 days. Recorded measures reflected the quantity (daily step counts, number of 30-second walking bouts, and signal vector magnitude [SVM]) and quality (gait speed, step cadence, step and stride regularity, and sample entropy) of walking. For each walking quality measure, the typical (median), best (90th percentile), and worst (10th percentile) values were calculated. Frailty was evaluated through a 38-item frailty index. Results. Participants were classified as not frail (n = 31), moderately frail (n = 34), and severely frail (n = 34) on the basis of established procedures. Patients who were moderately and severely frail exhibited poorer performance in all measures of walking quantity and quality, except for sample entropy, than individuals who were not frail. No differences in freeliving walking performance were observed between the moderately and severely frail groups. Frailty did not mediate the relationship between disability (EDSS) and measures of walking quality. Conversely, frailty had a significant mediating effect on the relationship between disability and measures of walking quantity, such as daily step counts (indirect effect: b =-220.42, 95% CI = -452.03 to -19.65) and SVM (indirect effect: b =-1.00, 95% CI = -1.86 to -0.30). Conclusion. Frailty is associated with poorer free-living walking performance in people with MS. The study findings suggest that frailty, rather than disability, may be primarily responsible for the lower amount of physical activity performed by people with MS in the real world. Impact. The observation that frailty and disability are differently related to measures of walking quality and quantity underscores the importance of a targeted approach to rehabilitation in people with MS. Keywords: Disability, Frailty, Gait, Multiple Sclerosis, Physical Activity, Walking, Introduction Frailty is a biological syndrome that reflects decreased reserve and resistance to stressors arising from cumulative declines across multiple physiologic systems. (1) Although aging plays a central role in [...]

Objective. Freezing of gait (FOG) is an episodic, debilitating phenomenon that is common among people with Parkinson disease. Multiple approaches have been used to quantify FOG, but the relationships among them have not been well studied. In this cross-sectional study, we evaluated the associations among FOG measured during unsupervised daily-living monitoring, structured in-home FOG-provoking tests, and self-report. Methods. Twenty-eight people with Parkinson disease and FOG were assessed using self-report questionnaires, percentage of time spent frozen (%TF) during supervised FOG-provoking tasks in the home while off and on dopaminergic medication, and %TF evaluated using wearable sensors during 1 week of unsupervised daily-living monitoring. Correlations between those 3 assessment approaches were analyzed to quantify associations. Further, based on the %TF difference between in-home off-medication testing and in-home on-medication testing, the participants were divided into those responding to Parkinson disease medication (responders) and those not responding to Parkinson disease medication (nonresponders) in order to evaluate the differences in the other FOG measures. Results. The %TF during unsupervised daily living was mild to moderately correlated with the %TF during a subset of the tasks of the in-home off-medication testing but not the on-medication testing or self-report. Responders and nonresponders differed in the %TF during the personal "hot spot" task of the provoking protocol while off medication (but not while on medication) but not in the total scores of the self-report questionnaires or the measures of FOG evaluated during unsupervised daily living. Conclusion. The %TF during daily living was moderately related to FOG during certain in-home FOG-provoking tests in the off-medication state. However, this measure of FOG was not associated with self-report or FOG provoked in the on-medication state. These findings suggest that to fully capture FOG severity, it is best to assess FOG using a combination of all 3 approaches. Impact. These findings suggest that several complementary approaches are needed to provide a complete assessment of FOG severity. Keywords: Daily-Living Monitoring, FOG Assessment, FOG Severity, Freezing of Gait, Introduction Freezing of gait (FOG) is an episodic, unpredictable phenomenon that commonly impacts people with Parkinson disease. Up to 70% to 80% of people with Parkinson disease experience FOG, especially [...]

Background: Measurement of freezing of gait (FOG) relies on the sensitivity and reliability of tasks to provoke FOG. It is currently unclear which tasks provide the best outcomes and how medication state plays into this.Objective: To establish the sensitivity and test-retest reliability of various FOG-provoking tasks for presence and severity of FOG, with (ON) and without (OFF) dopaminergic medication.Methods: FOG-presence and percentage time frozen (% TF) were derived from video annotations of a home-based FOG-provoking protocol performed in OFF and ON. This included: the four meter walk (4MW), Timed Up and Go (TUG) single (ST) and dual task (DT), 360° turns in ST and DT, a doorway condition, and a personalized condition. Sensitivity was tested at baseline in 63 definite freezers. Test-retest reliability was evaluated over 5 weeks in 26 freezers.Results: Sensitivity and test-retest reliability were highest for 360° turns and higher in OFF than ON. Test-retest intra-class correlation coefficients of % TF varied between 0.63–0.90 in OFF and 0.18–0.87 in ON, and minimal detectable changes (MDCs) were high. The optimal protocol included TUG ST, 360° turns ST, 360° turns DT and a doorway condition, provoking FOG in all freezers in OFF and 91.9% in ON and this could be done reliably in 95.8% (OFF) and 84.0% (ON) of the sample. Combining OFF and ON further improved outcomes.Conclusions: The highest sensitivity and reliability was achieved with a multi-trigger protocol performed in OFF?+?ON. However, the high MDCs for % TF underscore the need for further optimization of FOG measurement.

The objective of this study was to identify gait alterations related to worsening knee pain and worsening physical function, using machine learning approaches applied to wearable sensor–derived data from a large observational cohort. Participants in the Multicenter Osteoarthritis Study (MOST) completed a 20‐m walk test wearing inertial sensors on their lower back and ankles. Parameters describing spatiotemporal features of gait were extracted from these data. We used an ensemble machine learning technique (“super learning”) to optimally discriminate between those with and without worsening physical function and, separately, those with and without worsening pain over two years. We then used log‐binomial regression to evaluate associations of the top 10 influential variables selected with super learning with each outcome. We also assessed whether the relation of altered gait with worsening function was mediated by changes in pain. Of 2,324 participants, 29% and 24% had worsening knee pain and function over two years, respectively. From the super learner, several gait parameters were found to be influential for worsening pain and for worsening function. After adjusting for confounders, greater gait asymmetry, longer average step length, and lower dominant frequency were associated with worsening pain, and lower cadence was associated with worsening function. Worsening pain partially mediated the association of cadence with function. We identified gait alterations associated with worsening knee pain and those associated with worsening physical function. These alterations could be assessed with wearable sensors in clinical settings. Further research should determine whether they might be therapeutic targets to prevent worsening pain and worsening function.

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.

Background. Current literature views safe gait as a complex task, relying on motor and cognitive resources. The use of virtual reality (VR) in gait training offers a multifactorial approach, showing positive effects on mobility, balance, and fall risk in elderly people and individuals with neurological disorders. This form of training has been described as a viable research tool; however, it has not been applied routinely in clinical practice. Recently, VR was used to develop an adjunct training method for use by physical therapists in an ambulatory clinical setting. Objective. The aim of this article is to describe the initial clinical experience of applying a 5-week VR clinical service to improve gait and mobility in people with a history of falls, poor mobility, or postural instability. Design. A retrospective data analysis was conducted. Methods. The clinical records of the first 60 patients who completed the VR gait training program were examined. Training was provided 3 times per week for 5 weeks, with each session lasting approximately 1 hour and consisting of walking on a treadmill while negotiating virtual obstacles. Main outcome measures were compared across time and included the Timed 'Up & Go' Test (TUG), the Two-Minute Walk Test (2MWT), and the Four Square Step Test (FSST). Results. After 5 weeks of training, time to complete the TUG decreased by 10.3%, the distance walked during the 2MWT increased by 9.5%, and performance on the FSST improved by 13%. Limitations. Limitations of the study include the use of a retrospective analysis with no control group and the lack of objective cognitive assessment. Conclusions. Treadmill training with VR appears to be an effective and practical tool that can be applied in an outpatient physical therapy clinic. This training apparently leads to improvements in gait, mobility, and postural control. It, perhaps, also may augment cognitive and functional aspects., Gait disturbances are prevalent in aging and contribute to an increased risk of falls, reduced mobility, and poor quality of life. (1) The result is a major health problem. Impaired [...]

Background. Previous studies have demonstrated that the performance of a secondary task during walking alters gait. Objective. This study investigated the effects of task prioritization on walking in young and older adults to evaluate the 'default' prioritization scheme used, the flexibility to alter prioritization and cortical resources allocated to gait and a secondary cognitive task, and any age-associated changes in these abilities. Design, A cross-sectional study that explicitly altered the focus of attention was used to investigate the effects of prioritization in young and older adults who were healthy. Methods. Gait speed and gait variability were evaluated in young adults (n=40) and older adults (n=17) who were healthy, both during usual walking and under 3 dual-task conditions: (1) no specific prioritization instructions, (2) prioritization of gait, and (3) prioritization of the cognitive task. Results. Young adults significantly increased gait speed in the gait prioritization condition compared with gait speed in the no-instruction condition; a similar tendency was seen in the older adults. Gait speed was reduced when priority was given to the cognitive task in both age groups; however, this effect was less dramatic in the older adults. In the young adults, prioritization of gait tended to have different effects on gait speed among both men and women. In the older adults, but not in the young adults, all dual-task conditions produced increased gait variability, whereas prioritization did not alter this gait feature. Limitations. The sample size and the relative homogeneity of the older adults could be considered as possible limitations of the study. Conclusions, Even among young adults, the effects of secondary, cognitive tasks on gait speed are strongly influenced by prioritization. This finding was less significant in the older adults, suggesting that there is an age-associated decline in the ability to flexibly allocate attention to gait. Somewhat surprisingly, when prioritization was not explicitly instructed, gait speed in both young and older adults most closely resembled that of the condition when they were instructed to focus attention on the cognitive task., In the classic publications on gait, (1,2) cognitive function is hardly mentioned. It is only in the last decade or so that we have come to realize the impact of [...]

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2007.01623.x Byline: Ron Ben-Itzhak (*[dagger]), Nir Giladi (*[double dagger]), Leor Gruendlinger (*), Jeffrey M. Hausdorff (*s.[parallel]) Keywords: methylphenidate; gait variability; falls; cognitive function; aging Abstract: OBJECTIVES: To test the hypothesis that methylphenidate modifies markers of fall risk in older adults. DESIGN: Randomized, double-blind, placebo-controlled, single-dose cross-over study. SETTING: Outpatient movement disorders clinic. PARTICIPANTS: Twenty-six community-living older adults without dementia (mean age 73.8) with subjective complaints of 'memory problems.' INTERVENTIONS: The study examined the effects of a single dose of 20 mg of methylphenidate (MPH) on cognitive function and gait. Participants were evaluated before and 2 hours after taking MPH or a placebo in sessions 1 to 2 weeks apart. MEASUREMENTS: The Timed Up and Go and gait variability quantified mobility and fall risk. A computerized neuropsychology battery quantified memory and executive function (EF). RESULTS: Timed Up and Go times, stride time variability, and measures of EF significantly improved in response to MPH but not in response to the placebo. In contrast, MPH did not significantly affect memory or finger tapping abilities. CONCLUSION: In older adults, MPH appears to improve certain aspects of EF, mobility, and gait stability. Although additional studies are required to assess clinical utility and efficacy, the present findings suggest that methylphenidate and other drugs that are designed to enhance attention may have a role as a therapeutic option for reducing fall risk in older adults. Author Affiliation: (*)Movement Disorders Unit, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel ([dagger])Department of Geriatrics, Reuth Medical Center, Tel Aviv, Israel ([double dagger])Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (s.)Department of Physical Therapy, Harvard Medical School, Boston, Massachusetts ([parallel])Division on Aging, Harvard Medical School, Boston, Massachusetts Article note: Address correspondence to Jeffrey M. Hausdorff, PhD, Laboratory for Gait Analysis & Neurodynamics, Movement Disorders Unit, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. E-mail: jhausdor@tasmc.health.gov.il

The power of ageism on physical function of the elderly has been investigated in a randomized intervention study with 47 community-dwelling men and women aged 63-82 who walked independently and thought of themselves as healthy. The hypothesis was that age-associated physical function changes, walking especially, are influenced by ageism and that putting positive stereotypes into place might partially reverse the changes. Findings indicate stereotypes of aging have powerful impacts on gaits of the elderly and that interventions may prove beneficial.

The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson’s disease (PD) patients for whom such changes may be even more enhanced. In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults. 30 PD patients, 30 older adults, and 11 young adults performed a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity. The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F = 5.619, p = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p = 0.013). In addition, P300 latency was significantly longer in PD patients (p < 0.001) and older adults (p = 0.032) during walking compared to sitting and during ‘NoGo’ trials compared with ‘Go’ trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated. The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels.

Background: Given the evidence of the links between cognition and mobility, participation in cognitive activities may benefit neuromotor performance and mobility in older adults. Aims: To examine the association between participation in cognitive activities and foot reaction time (RT) and gait speed in community-dwelling older adults. Methods: The MOBILIZE Boston Study II (MBSII) re-enrolled 354 community-dwelling older adults aged ≥ 70 years from the original MBS cohort. Of these, 310 completed the performance testing and we excluded three participants who had Parkinson’s disease. Cognitive Activities Scale (CAS) assessed participation in 17 cognitive activities. Simple and Choice foot RT (SRT, CRT, msec) and gait speed (m/s) were measured using a sensored GAITRite® gait mat. Results: The average age of the 307 participants was 84 years; 79% were white and 65% were women. The average CAS score was 25.5 ± 11.7, indicating participation in approximately 26 activities per week on average. The average foot SRT was 245 ± 57msec and average CRT was 323 ± 85msec. Usual-paced gait speed was 0.9 ± 0.3 m/s on average. More frequent participation in cognitive activities was associated with shorter SRT (β= − 0.759, p= 0.015) and CRT (β= − 1.125, p= 0.013), and faster gait speed (β= 0.003, p= 0.026), after adjusting for potential confounders. Discussion: Participation in cognitively stimulating activities may be beneficial for neuromotor performance and mobility in older adults. Conclusions: Prospective and intervention studies are needed to determine whether participation in cognitive activities may prevent mobility decline over time, and thus reduce fall risk.

•Chronic pain is associated with slower foot reaction time in older adults.•Education may play a protective role in the impacts of pain on mobility.•Chronic pain may contribute to falls through a cognitive and neuromotor pathway.

The increasing prevalence of neurodegenerative conditions such as Parkinson’s disease (PD) and related mobility issues places a serious burden on healthcare systems. The COVID-19 pandemic has reinforced the urgent need for better tools to manage chronic conditions remotely, as regular access to clinics may be problematic. Digital health technology in the form of remote monitoring with body-worn sensors offers significant opportunities for transforming research and revolutionizing the clinical management of PD. Significant efforts are being invested in the development and validation of digital outcomes to support diagnosis and track motor and mobility impairments “off-line”. Imagine being able to remotely assess your patient, understand how well they are functioning, evaluate the impact of any recent medication/intervention, and identify the need for urgent follow-up because things are changing? This could offer new pragmatic solutions for personalized care and clinical research. So the question remains: how close are we to achieving this? Here, we describe the state-of-the-art based on representative papers published between 2017 and 2020. We focus on remote (i.e., real-world, daily-living) monitoring of PD using body-worn sensors (e.g., accelerometers, inertial measurement units) for assessing motor symptoms and their complications. Despite the tremendous potential, existing challenges exist (e.g., validity, regulatory) that are preventing the widespread clinical adoption of body-worn sensors as a digital outcome. We propose a roadmap with clear recommendations for addressing these challenges and future directions to bring us closer to the implementation and widespread adoption of this important way of improving the clinical care, evaluation, and monitoring of PD.

Supplemental Digital Content is available in the text.

The effect of cognitive function and divided attention on gait in Alzheimer's disease (AD) is evaluated. The results support the concept that persons with AD have significant impairments in the cognitive domain of attention and that locomotor function relies upon cognitive and executive function.

Up to two thirds of people with multiple sclerosis (pwMS) are frail. Frailty within MS is associated with adverse clinical outcomes such as falls, independently of age, gender, and disability levels. Consequently, there is a critical need to identify strategies to counteract frailty in pwMS. Since MS affects both motor and cognitive function, cognitive-motor rehabilitation is a potentially viable strategy to reduce frailty in pwMS. Therefore, the purpose of this study was to examine the effects of a cognitive-motor rehabilitation intervention consisting of virtual reality treadmill training (VRTT) compared to treadmill training (TT) alone, on frailty in pwMS.

Physical activity is lower in people with multiple sclerosis (pwMS) compared to healthy controls. Previous work focused on studying activity levels or activity volume, but studies of daily-living rest-activity fragmentation patterns, circadian rhythms, and fractal regulation in pwMS are limited. Based on findings in other cohorts, one could suggest that these aspects of daily-living physical activity will provide additional information about the health and well-being of pwMS. Therefore, here, we aimed to (1) identify which fragmentation, fractal, and circadian amplitude measures differ between pwMS and healthy controls, (2) evaluate the relationship between fragmentation, fractal, and circadian amplitude measures and disease severity, and (3) begin to evaluate the added value of those measures, as compared to more conventional measures of physical activity (e.g., mean signal vector magnitude (SVM). A global measure of the overall volume of physical activity).

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.

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis.

Patients with stroke are at risk for developing cognitive impairment. We tested whether the assessment of balance and gait can enhance the prediction of long-term cognitive outcome in stroke survivors.

Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.

To assess differences in gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype.

Freezing of gait (FOG) is a disabling phenomenon common in patients with advanced Parkinson's disease (PD). The cause of FOG is unclear. The objective of this study was to explore a novel hypothesis stating that FOG is related to asymmetric motor performance. We compared PD patients that experience FOG episodes (PD+FOG) with PD patients that do not (PD−FOG) and studied the relationship of FOG to asymmetry in gait and in rhythmic hand movement performance to determine whether potential FOG‐related gait asymmetry is unique to walking or whether it is systemic. Subjects were tested in an “off” (unmedicated) and again in an “on” (medicated) state. Gait was more asymmetric in PD+FOG than in PD−FOG during “off” state (p= 0.005) and during “on” (p= 0.016). Rhythmicity of foot swing in one leg was correlated with the other leg in PD−FOG but not in PD+FOG. There was no difference in asymmetry in performance of rhythmic hand movements between the two groups. No correlation was found between asymmetry of clinical symptoms and gait asymmetry. Taken together, the results of this study suggest that bilateral uncoordinated gait and marked gait asymmetry, but not asymmetry in motor performance in general, are associated with FOG. Ann Neurol 2005;57:656–663

Gait disturbances are among the primary symptoms of Parkinson's disease (PD) and contribute significantly to a patient's loss of function and independence. Standard treatment includes antiparkinsonian drugs, primarily levodopa. In addition to the standard drug regime, physical therapy is often prescribed to help manage the disease. In recent years, there have been promising reports of physical therapy programs combined with various types of sensory cueing for PD. In this brief review of the literature, we summarize the evidence regarding the clinical efficacy of different physical therapy programs for PD, specifically with respect to improving gait. We also discuss the potential therapeutic mechanisms of sensory cueing and review the studies that have used cueing in the treatment of gait in PD. This review of the literature shows two key findings: (1) despite its relatively long history, the evidence supporting the efficacy of conventional physical therapy for treatment of gait in PD is not strong; and (2) although further investigation is needed, sensory cueing appears to be a powerful means of improving gait in PD. © 2002 Movement Disorder Society

Increased gait instability is common in older adults, even in the absence of overt disease. The goal of the present study was to quantitatively investigate the factors that contribute to gait instability and its potential reversibility in functionally impaired older adults. We studied 67 older men and women with functional impairment before and after they participated in a randomized placebo-controlled, 6-mo multimodal exercise trial. We found that 1) gait instability is multifactorial; 2) stride time variability is strongly associated with functional status and performance-based measures of function that have previously been shown to predict significant clinical outcomes such as morbidity and nursing home admission;3) neuropsychological status and health-related quality of life play important, independent roles in gait instability; and4) improvement in physiological capacity is associated with reduced gait instability. Although the etiology of gait instability in older persons with mild-moderate functional impairment is multifactorial, interventions designed to reduce gait instability may be effective in bringing about a more consistent and more stable walking pattern.

Chronic heart failure (CHF) is characterized by a skeletal muscle myopathy not optimally addressed by current treatment paradigms or aerobic exercise. Sixteen older women with CHF were compared with 80 age-matched peers without CHF and randomized to progressive resistance training or control stretching exercises for 10 wk. Women with CHF had significantly lower muscle strength (P< 0.0001) but comparable aerobic capacity to women without CHF. Exercise training was well tolerated and resulted in no changes in resting cardiac indexes in CHF patients. Strength improved by an average of 43.4 ± 8.8% in resistance trainers vs. −1.7 ± 2.8% in controls (P= 0.001), muscle endurance by 299 ± 66% vs. 1 ± 3% (P= 0.001), and 6-min walk distance by 49 ± 14 m (13%) vs. −3 ± 19 m (−3%) (P= 0.03). Increases in type I fiber area (9.5 ± 16%) and citrate synthase activity (35 ± 21%) in skeletal muscle were independently predictive of improved 6-min walk distance (r2= 0.78;P= 0.0024). High-intensity progressive resistance training improves impaired skeletal muscle characteristics and overall exercise performance in older women with CHF. These gains are largely explained by skeletal muscle and not resting cardiac adaptations.

Amyotrophic lateral sclerosis (ALS) is a disorder marked by loss of motoneurons. We hypothesized that subjects with ALS would have an altered gait rhythm, with an increase in both the magnitude of the stride-to-stride fluctuations and perturbations in the fluctuation dynamics. To test for this locomotor instability, we quantitatively compared the gait rhythm of subjects with ALS with that of normal controls and with that of subjects with Parkinson's disease (PD) and Huntington's disease (HD), pathologies of the basal ganglia. Subjects walked for 5 min at their usual pace wearing an ankle-worn recorder that enabled determination of the duration of each stride and of stride-to-stride fluctuations. We found that the gait of patients with ALS is less steady and more temporally disorganized compared with that of healthy controls. In addition, advanced ALS, HD, and PD were associated with certain common, as well as apparently distinct, features of altered stride dynamics. Thus stride-to-stride control of gait rhythm is apparently compromised with ALS. Moreover, a matrix of markers based on gait dynamics may be useful in characterizing certain pathologies of motor control and, possibly, in quantitatively monitoring disease progression and evaluating therapeutic interventions.

OBJECTIVES:To determine the effects of congestive heart failure on a person's ability to walk at a steady pace while ambulating at a self‐determined rate.

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride‐to‐stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride‐to‐stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease‐free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

Somatic mutations have long been considered a possible cause of ageing1,2. To directly study mutational events in organs and tissues of ageing mammals, a transgenic mouse model has been generated that harbours lacZ reporter genes as part of chromosomally integrated plasmids3–5. Using this model, we determined spontaneous mutant frequencies and spectra in mouse liver and brain as a function of age. In the liver, mutant frequencies increased with age from birth to 34 months; in the brain, an increase was observed only between birth and 4–6 months. Molecular characterization of the mutations showed that a substantial portion involved genome rearrangement events, with one breakpoint in a reporter gene and the other in the mouse flanking sequence. In the liver, these genome rearrangements did not increase with age until after 27 months, when they increased rapidly. In brain, the frequency of genome rearrangements was lower than in liver and did not increase with age.

Hausdorff, Jeffrey M., Susan L. Mitchell, Renée Firtion, C. K. Peng, Merit E. Cudkowicz, Jeanne Y. Wei, and Ary L. Goldberger.Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington’s disease.J. Appl. Physiol.82(1): 262–269, 1997.—Fluctuations in the duration of the gait cycle (the stride interval) display fractal dynamics and long-range correlations in healthy young adults. We hypothesized that these stride-interval correlations would be altered by changes in neurological function associated with aging and certain disease states. To test this hypothesis, we compared the stride-interval time series of 1) healthy elderly subjects and young controls and of 2) subjects with Huntington’s disease and healthy controls. Using detrended fluctuation analysis, we computed α, a measure of the degree to which one stride interval is correlated with previous and subsequent intervals over different time scales. The scaling exponent α was significantly lower in elderly subjects compared with young subjects (elderly: 0.68 ± 0.14; young: 0.87 ± 0.15; P< 0.003). The scaling exponent α was also smaller in the subjects with Huntington’s disease compared with disease-free controls (Huntington’s disease: 0.60 ± 0.24; controls: 0.88 ± 0.17; P< 0.005). Moreover, α was linearly related to degree of functional impairment in subjects with Huntington’s disease (r= 0.78, P< 0.0005). These findings demonstrate that stride-interval fluctuations are more random (i.e., less correlated) in elderly subjects and in subjects with Huntington’s disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG.

Objectives To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson’s disease (PD) and to select outcomes most responsive to TC assessed during off-medication states.Design Two-arm, wait-list controlled RCT.Settings Tertiary care hospital.Subjects Thirty-two subjects aged 40–75 diagnosed with idiopathic PD within 10 years.Interventions Six-month TC intervention added to usual care (UC) versus UC alone.Outcome Measures Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson’s Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications.Results Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [−0.1%] group [effect size 0.49; P= .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups.Conclusions Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.