Prefrontal Cortex Activity During Gait in People With Persistent Symptoms After Concussion.

BACKGROUND: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics. METHODS: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO2]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group. RESULTS: Average NSI total score was 26.4 (13.2). HbO2 was significantly higher (P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion (r = .79; P = .001), and stride time variability (r = -.54; P = .046). CONCLUSION: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms.

Assessing the validity of the zero-velocity update method for sprinting speeds.

The zero-velocity update (ZUPT) method has become a popular approach to estimate foot kinematics from foot worn inertial measurement units (IMUs) during walking and running. However, the accuracy of the ZUPT method for stride parameters at sprinting speeds remains unknown, specifically when using sensors with characteristics well suited for sprinting (i.e., high accelerometer and gyroscope ranges and sampling rates). Seventeen participants performed 80-meter track sprints while wearing a Blue Trident IMeasureU IMU. Two cameras, at 20 and 70 meters from the start, were used to validate the ZUPT method on a stride-by-stride and on a cumulative distance basis. In particular, the validity of the ZUPT method was assessed for: (1) estimating a single stride length attained near the end of an 80m sprint (i.e., stride at 70m); (2) estimating cumulative distance from ∼20 to ∼70 m; and (3) estimating total distance traveled for an 80-meter track sprint. Individual stride length errors at the 70-meter mark were within -6% to 3%, with a bias of -0.27%. Cumulative distance errors were within -4 to 2%, with biases ranging from -0.85 to -1.22%. The results of this study demonstrate the ZUPT method provides accurate estimates of stride length and cumulative distance traveled for sprinting speeds.

Assessing the Effects of Mild Traumatic Brain Injury on Vestibular Home Exercise Performance with Wearable Sensors.

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Gait and balance in apolipoprotein Ɛ4 allele carriers in older adults and Parkinson's disease.

Background: Gait and balance impairments are among the most troublesome and heterogeneous in Parkinson's disease (PD). This heterogeneity may, in part, reflect genetic variation. The apolipoprotein E (APOE) gene has three major allelic variants (ε2, ε3 and ε4). Previous work has demonstrated that older adult (OA) APOE ε4 carriers demonstrate gait deficits. This study compared gait and balance measures between APOE ε4 carriers and non-carriers in both OA and PD. Methods: 334 people with PD (81 APOE ε4 carriers and 253 non-carriers) and 144 OA (41 carriers and 103 non-carriers) were recruited. Gait and balance were assessed using body-worn inertial sensors. Two-way analyses of covariance (ANCOVA) compared gait and balance characteristics between APOE ε4 carriers and non-carriers in people with PD and OA, controlling for age, gender, and testing site. Results: Gait and balance were worse in people with PD compared to OA. However, there were no differences between APOE ε4 carriers and non-carriers in either the OA or PD group. In addition, there were no significant group (OA/PD) by APOE ε4 status (carrier/non-carrier) interaction effects for any measures of gait or balance. Conclusions: Although we found expected impairments in gait and balance in PD compared to OA, gait and balance characteristics did not differ between APOE ε4 carriers and non-carriers in either group. While APOE status did not impact gait and balance in this cross-sectional study, future work is needed to determine whether progression of gait and balance deficits is faster in PD APOE Ɛ4 carriers.

Exploring the effects of dopamine on sensorimotor inhibition and mobility in older adults.

Dopaminergic activity decreases in older adults (OAs) with normal aging and is further reduced in Parkinson's disease (PD), affecting cortical motor and sensorimotor pathways. Levodopa is the prevailing therapy to counter dopamine loss in PD, though not all PD motor signs improve with levodopa. The purpose of this preliminary study was to explore the effects of levodopa on sensorimotor inhibition, gait and quiet standing in OAs and to investigate the relationships between sensorimotor inhibition and both gait and standing balance both OFF- and ON-levodopa. Fifteen OA males completed a gait, balance and sensorimotor assessments before and 1 h after they were given a 100 mg dose of levodopa. Short-latency afferent inhibition quantified sensorimotor inhibition. Wearable sensors characterized gait (two-minute walk) and standing balance (1-min stance). No sensorimotor inhibition, gait, or standing balance measures changed from OFF- to ON-levodopa. When OFF-levodopa, worse inhibition significantly related to increased double stance (r = 0.62; p = 0.01), increased jerkiness of sway (r = 0.57; p = 0.03) and sway area (r = 0.58; p = 0.02). While ON-levodopa, worse inhibition related to increased arm swing range of motion (r = 0.63; p = 0.01) and jerkiness of sway (r = 0.53; p = 0.04). The relationship between SAI and arm swing excursion significantly changed from OFF- to ON-levodopa (z = - 3.05; p = 0.002; 95% confidence interval = - 0.95, - 0.21). Sensorimotor inhibition relationships to both gait and balance may be affected by dopamine in OAs. Cortical restructuring due to the loss of dopamine may be responsible for the heterogeneity of levodopa effect in people with PD and OAs.

Symptoms and Central Sensory Integration in People With Chronic mTBI: Clinical Implications.

INTRODUCTION: Balance deficits in people with chronic mild traumatic brain injury (mTBI; ≥3 months post-mTBI), thought to relate to central sensory integration deficits, are subtle and often difficult to detect. The purpose of this study was to determine the sensitivity of the instrumented modified clinical test of sensory integration for balance (mCTSIB) in identifying such balance deficits in people with symptomatic, chronic mTBI and to establish the associations between balance and mTBI symptom scores in the chronic mTBI group. METHODS: The Institutional Review Board approved these study methods. Forty-one people with chronic mTBI and balance complaints and 53 healthy controls performed the mCTSIB (eyes open/closed on firm/foam surfaces; EoFi, EcFi, EoFo, and EcFo) with a wearable sensor on their waist to quantify sway area (m2/s4). Sensory reweighting variables were calculated for the firm and foam stance conditions. A stopwatch provided the clinical outcome for the mCTSIB (time). Each participant completed the Neurobehavioral Symptom Inventory (NSI), which quantifies mTBI-related symptoms and provides a total score, as well as sub-scores on affective, cognitive, somatic, and vestibular domains. RESULTS: The mTBI group reported significantly higher symptom scores across each NSI sub-score (all Ps < .001). The mTBI group had a significantly larger sway area than the control group across all mCTSIB conditions and the mTBI group had significantly higher sensory reweighting scores compared to the control group on both the firm (P = .01) and foam (P = .04) surfaces. Within the mTBI group, the NSI vestibular score significantly related to the mCTSIB sway area EcFi (r = 0.38; P = .02), sway area EcFo (r = 0.43; P = .006), sensory reweighting firm (r = 0.33; P = .04), and sensory reweighting foam (r = 0.38; P = .02). The average sway area across the 4 mCTSIB conditions was significantly (area under the curve: 0.77; P < .001) better at differentiating groups than the mCTSIB clinical total score. The average sway area across the 4 mCTSIB conditions had a sensitivity of 73% and a specificity of 71%. The clinical mCTSIB outcome scores were not different between groups. CONCLUSION: People with chronic mTBI appear to have central sensory integration deficits detectable by instrumented measures of postural assessment. These findings suggest that central sensory integration should be targeted in rehabilitation for people with chronic mTBI.

Exploring Age and Sex Patterns for Rehabilitation Referrals After a Concussion: A Retrospective Analysis.

Objective: To explore patterns of postconcussion care at a level 1 trauma center. Design: Retrospective cohort study. Setting: U.S. level 1 trauma center and local satellite units. Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417). Intervention: Not applicable. Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis. Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR]unadjusted=75.05, P<.001), primary care providers (ORunadjusted=7.98, P<.001), and specialty care departments (ORunadjusted=7.62, P<.001) than from the emergency department. Women were more likely to receive a referral (ORunadjusted=1.92, P<.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (ORadjusted=2.12, P<.001) to get a rehabilitation referral than patients without a comorbidity. Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion.

Cognition as a mediator for gait and balance impairments in GBA-related Parkinson's disease.

The extent to which the heterogeneity of gait and balance problems in PD may be explained by genetic variation is unknown. Variants in the glucocerebrosidase (GBA) gene are the strongest known genetic risk factor for PD and are associated with greater motor and cognitive severity. However, the impact of GBA variants on comprehensive measures of gait and balance and their relationship to cognition remains unknown. We aimed to determine differences in gait and balance impairments in those with and without GBA variants (mutation carriers and E326K polymorphism) and explore direct and indirect effects of GBA status on gait, balance, and cognition. 332 participants, 43 of whom had GBA variants, were recruited. Participants completed a comprehensive, objective assessment of gait and standing balance using body-worn inertial sensors. Group differences in gait and balance between PD with and without GBA variants were assessed with linear regression, adjusting for age, gender, clinical testing site, disease duration, and apolipoprotein E (APOE) ɛ4 status. Structural equation modeling (SEM) explored direct relationships between GBA status and gait and balance and indirect relationships between GBA status and gait and balance via cognition. The GBA variant group had more impaired gait (pace and variability) and balance (sway area/jerk and sway velocity), than the non-GBA variant group. SEM demonstrated cognition as a mediator of GBA status on gait and balance. The close relationships among GBA, gait/balance, and cognition suggest potential for novel therapeutics to target the GBA pathway and/or cognition to improve mobility in PD GBA variants.

Exploring persistent complaints of imbalance after mTBI: Oculomotor, peripheral vestibular and central sensory integration function.

BACKGROUND: Little is known on the peripheral and central sensory contributions to persistent dizziness and imbalance following mild traumatic brain injury (mTBI). OBJECTIVE: To identify peripheral vestibular, central integrative, and oculomotor causes for chronic symptoms following mTBI. METHODS: Individuals with chronic mTBI symptoms and healthy controls (HC) completed a battery of oculomotor, peripheral vestibular and instrumented posturography evaluations and rated subjective symptoms on validated questionnaires. We defined abnormal oculomotor, peripheral vestibular, and central sensory integration for balance measures among mTBI participants as falling outside a 10-percentile cutoff determined from HC data. A X-squared test associated the proportion of normal and abnormal responses in each group. Partial Spearman's rank correlations evaluated the relationships between chronic symptoms and measures of oculomotor, peripheral vestibular, and central function for balance control. RESULTS: The mTBI group (n = 58) had more abnormal measures of central sensory integration for balance than the HC (n = 61) group (mTBI: 41% -61%; HC: 10%, p's < 0.001), but no differences on oculomotor and peripheral vestibular function (p > 0.113). Symptom severities were negatively correlated with central sensory integration for balance scores (p's < 0.048). CONCLUSIONS: Ongoing balance complaints in people with chronic mTBI are explained more by central sensory integration dysfunction rather than peripheral vestibular or oculomotor dysfunction.

The Adapted Resistance Training with Instability Randomized Controlled Trial for Gait Automaticity.

BACKGROUND: Deficits in the cerebellar locomotor region (CLR) have been associated with loss of gait automaticity in individuals with freezing of gait in Parkinson's disease (freezers); however, exercise interventions that restore gait automaticity in freezers are lacking. We evaluated the effects of the adapted resistance training with instability ([ARTI] complex exercises) compared with traditional motor rehabilitation (without complex exercises) on gait automaticity and attentional set-shifting. We also verified associations between gait automaticity change and CLR activation change previously published. METHODS: Freezers were randomized either to the experimental group (ARTI, n = 17) or to the active control group (traditional motor rehabilitation, n = 15). Both training groups performed exercises 3 times a week for 12 weeks. Gait automaticity (dual-task and dual-task cost [DTC] on gait speed and stride length), single-task gait speed and stride length, attentional set-shifting (time between Trail Making Test parts B and A), and CLR activation during a functional magnetic resonance imaging protocol of simulated step initiation task were evaluated before and after interventions. RESULTS: Both training groups improved gait parameters in single task (P < 0.05), but ARTI was more effective than traditional motor rehabilitation in improving DTC on gait speed, DTC on stride length, dual-task stride length, and CLR activation (P < 0.05). Changes in CLR activation were associated with changes in DTC on stride length (r = 0.68, P = 0.002) following ARTI. Only ARTI improved attentional set-shifting at posttraining (P < 0.05). CONCLUSIONS: ARTI restores gait automaticity and improves attentional set-shifting in freezers attributed to the usage of exercises with high motor complexity. © 2020 International Parkinson and Movement Disorder Society.

Gait Performance in People with Symptomatic, Chronic Mild Traumatic Brain Injury.

There is a dearth of knowledge about how symptom severity affects gait in the chronic (>3 months) mild traumatic brain injury (mTBI) population despite up to 53% of people reporting persisting symptoms after mTBI. The aim of this investigation was to determine whether gait is affected in a symptomatic, chronic mTBI group and to assess the relationship between gait performance and symptom severity on the Neurobehavioral Symptom Inventory (NSI). Gait was assessed under single- and dual-task conditions using five inertial sensors in 57 control subjects and 65 persons with chronic mTBI (1.0 year from mTBI). The single- and dual-task gait domains of Pace, Rhythm, Variability, and Turning were calculated from individual gait characteristics. Dual-task cost (DTC) was calculated for each domain. The mTBI group walked (domain z-score mean difference, single-task = 0.70; dual-task = 0.71) and turned (z-score mean difference, single-task = 0.69; dual-task = 0.70) slower (p < 0.001) under both gait conditions, with less rhythm under dual-task gait (z-score difference = 0.21; p = 0.001). DTC was not different between groups. Higher NSI somatic subscore was related to higher single- and dual-task gait variability as well as slower dual-task pace and turning (p < 0.01). Persons with chronic mTBI and persistent symptoms exhibited altered gait, particularly under dual-task, and worse gait performance related to greater symptom severity. Future gait research in chronic mTBI should assess the possible underlying physiological mechanisms for persistent symptoms and gait deficits.

Relationships Between Sensorimotor Inhibition and Mobility in Older Adults With and Without Parkinson's Disease.

BACKGROUND: Reduced cortical sensorimotor inhibition is associated with mobility and cognitive impairments in people with Parkinson's disease (PD) and older adults (OAs). However, there is a lack of clarity regarding the relationships among sensorimotor, cognitive, and mobility impairments. The purpose of this study was to determine how cortical sensorimotor inhibition relates to impairments in mobility and cognition in people with PD and OAs. METHOD: Cortical sensorimotor inhibition was characterized with short-latency afferent inhibition (SAI) in 81 people with PD and 69 OAs. Six inertial sensors recorded single- and dual-task gait and postural sway characteristics during a 2-minute walk and a 1-minute quiet stance. Cognition was assessed across the memory, visuospatial, executive function, attention, and language domains. RESULTS: SAI was significantly impaired in the PD compared to the OA group. The PD group preformed significantly worse across all gait and postural sway tasks. In PD, SAI significantly correlated with single-task foot strike angle and stride length variability, sway area, and jerkiness of sway in the coronal and sagittal planes. In OAs, SAI significantly related to single-task gait speed and stride length, dual-task stride length, and immediate recall (memory domain). No relationship among mobility, cognition, and SAI was observed. CONCLUSIONS: Impaired SAI related to slower gait in OA and to increased gait variability and postural sway in people with PD, all of which have been shown to be related to increased fall risk.

Sensorimotor Inhibition and Mobility in Genetic Subgroups of Parkinson's Disease.

Background: Mobility and sensorimotor inhibition impairments are heterogeneous in Parkinson's disease (PD). Genetics may contribute to this heterogeneity since the apolipoprotein (APOE) ε4 allele and glucocerebrosidase (GBA) gene variants have been related to mobility impairments in otherwise healthy older adult (OA) and PD cohorts. The purpose of this study is to determine if APOE or GBA genetic status affects sensorimotor inhibition and whether the relationship between sensorimotor inhibition and mobility differs in genetic sub-groups of PD. Methods: Ninety-three participants with idiopathic PD (53 non-carriers; 23 ε4 carriers; 17 GBA variants) and 72 OA (45 non-carriers; 27 ε4 carriers) had sensorimotor inhibition characterized by short-latency afferent inhibition. Mobility was assessed in four gait domains (pace/turning, rhythm, trunk, variability) and two postural sway domains (area/jerkiness and velocity) using inertial sensors. Results: Sensorimotor inhibition was worse in the PD than OA group, with no effect of genetic status. Gait pace/turning was slower and variability was higher (p < 0.01) in PD compared to OA. Postural sway area/jerkiness (p < 0.01) and velocity (p < 0.01) were also worse in the PD than OA group. Genetic status was not significantly related to any gait or postural sway domain. Sensorimotor inhibition was significantly correlated with gait variability (r = 0.27; p = 0.02) and trunk movement (r = 0.23; p = 0.045) in the PD group. In PD non-carriers, sensorimotor inhibition related to variability (r = 0.35; p = 0.010) and trunk movement (r = 0.31; p = 0.025). In the PD ε4 group, sensorimotor inhibition only related to rhythm (r = 0.47; p = 0.024), while sensorimotor inhibition related to pace/turning (r = -0.49; p = 0.046) and rhythm (r = 0.59; p = 0.013) in the PD GBA group. Sensorimotor inhibition was significantly correlated with gait pace/turning (r = -0.27; p = 0.04) in the OA group. There was no relationship between sensorimotor inhibition and postural sway. Conclusion: ε4 and GBA genetic status did not affect sensorimotor inhibition or mobility impairments in this PD cohort. However, worse sensorimotor inhibition was associated with gait variability in PD non-carriers, but with gait rhythm in PD ε4 carriers and with gait rhythm and pace in PD with GBA variants. Impaired sensorimotor inhibition had a larger effect on mobility in people with PD than OA and affected different domains of mobility depending on genetic status.

Analysis of Free-Living Mobility in People with Mild Traumatic Brain Injury and Healthy Controls: Quality over Quantity.

Balance and mobility issues are common non-resolving symptoms following mild traumatic brain injury (mTBI). Current approaches for evaluating balance and mobility following an mTBI can be subjective and suboptimal as they may not be sensitive to subtle deficits, particularly in those with chronic mTBI. Wearable inertial measurement units (IMU) allow objective quantification of continuous mobility outcomes in natural free-living environments. This study aimed to explore free-living mobility (physical activity and turning) of healthy and chronic mild traumatic brain injury (mTBI) participants using a single IMU. Free-living mobility was examined in 23 healthy control (48.56 ± 23.07 years) and 29 symptomatic mTBI (40.2 ± 12.1 years) participants (average 419 days post-injury, persistent balance complaints) over 1 week, using a single IMU placed at the waist. Free-living mobility was characterized in terms of macro (physical activity volume, pattern and variability) and micro-level (discrete measures of turning) features. Macro-level outcomes showed those with chronic mTBI had similar quantities of mobility compared with controls. Micro-level outcomes within walking bouts showed that chronic mTBI participants had impaired quality of mobility. Specifically, people with chronic mTBI made larger turns, had longer turning durations, slower average and peak velocities (all p < 0.001), and greater turn variability compared with controls. Results highlighted that the quality rather than quantity of mobility differentiated chronic mTBI from controls. Our findings support the use of free-living IMU continuous monitoring to enhance understanding of specific chronic mTBI-related mobility deficits. Future work is required to develop an optimal battery of free-living measures across the mTBI spectrum to aid application within clinical practice.

Gait measurement in chronic mild traumatic brain injury: A model approach.

INTRODUCTION: Mild traumatic brain injury (mTBI) can impact gait, with deficits linked to underlying neural disturbances in cognitive, motor and sensory systems. Gait is complex as it is comprised of multiple characteristics that are sensitive to underlying neural deficits. However, there is currently no clear framework to guide selection of gait characteristics in mTBI. This study developed a model of gait in chronic mTBI and replicated this in a separate group of controls, to provide a comprehensive and structured methodology on which to base gait assessment and analysis. METHODS: Fifty-two people with chronic mTBI and 59 controls completed a controlled laboratory gait assessment; walking for two minutes back and forth over a 13 m distance while wearing five wirelessly synchronized inertial sensors. Thirteen gait characteristics derived from the inertial sensors were selected for entry into the principle component analysis based on previous literature, robustness and novelty. Principle component analysis was then used to derive domains (components) of gait. RESULTS: Four gait domains were derived for our chronic mTBI group (variability, rhythm, pace and turning) and this was replicated in a separate control cohort. Domains totaled 80.8% and 77.4% of variance in gait for chronic mTBI and controls, respectively. Gait characteristic loading was unambiguous for all features, with the exception of gait speed in controls that loaded on pace and rhythm domains. CONCLUSION: This study contributes a four component model of gait in chronic mTBI and controls that can be used to comprehensively assess and analyze gait and underlying mechanisms involved in impairment, or examine the influence of interventions.

Effects of augmenting cholinergic neurotransmission on balance in Parkinson's disease.

INTRODUCTION: Degeneration of cholinergic systems may contribute to impairments of balance and gait in Parkinson's disease (PD) and phase 2 clinical trials have suggested that centrally acting cholinesterase inhibitors reduce falls. Here, we examined the effects of augmenting cholinergic neurotransmission on static and dynamic balance, indices of fall risk. METHODS: A single-site, randomized, double-blind, crossover trial examined the effect of donepezil in patients with PD. Forty-nine participants with idiopathic PD were randomized and 45 completed the trial. Each treatment period was 6 weeks with a 6-week washout between treatments. Donepezil in 2.5 mg capsules, or identical appearing placebo capsules, was increased from two per day (5 mg) to four capsules (10 mg) after 3 weeks. The primary outcome measures were the range of the medio-lateral sway when standing (static balance) and the variability of the stride duration when walking (dynamic balance). A linear mixed model was used to investigate whether the change in outcomes between weeks 0 and 6 differed between phases. RESULTS: There were no significant differences in treatment effects between placebo and donepezil for medio-lateral sway range during quiet standing (p = 0.28), nor in gait variability (p = 0.31). None of the secondary outcome measures or exploratory analyses were significant although one secondary measure of static balance was increased by donepezil. CONCLUSIONS: Contrary to our hypothesis, cholinergic augmentation with donepezil at 10 mg/day for 6 weeks did not affect measures of static or dynamic balance in people with PD. These results are compared with other phase 2 trials of cholinesterase inhibitors and considerations for future trials are discussed.

Cognitive associations with comprehensive gait and static balance measures in Parkinson's disease.

INTRODUCTION: Gait and balance impairments are cardinal features of Parkinson's disease (PD) that require cognitive input. However, the extent to which specific gait and balance characteristics relate to cognition in PD is unclear. In addition, independent models of gait and balance have not been developed from the same cohort. We aimed to i) develop models of gait and balance in a large PD cohort and ii) determine which gait and balance characteristics best related to cognition. METHODS: One hundred and ninety-eight people with PD were recruited to the Pacific Udall Center. Using six inertial sensors (APDM, Inc.), comprehensive gait measurements were collected over a 2-min continuous walk and comprehensive static balance measures were collected during a 60-second standing task. Six domains of cognition were assessed: global cognition, attention, executive function, language, memory, and visuospatial function. Correlations and hierarchical linear regression determined independent associations. RESULTS: Principal components analysis identified a gait model containing four domains accounting for 80.1% of total variance: pace/turning, rhythm, variability, and trunk. The balance model contained four independent domains accounting for 84.5% of total variance: sway area/jerkiness, sway velocity, sway frequency anteroposterior, and sway frequency mediolateral. Gait domains of pace/turning and variability were strongly associated with attention and executive function. Sway area and jerkiness of balance associated with attention and visuospatial function. CONCLUSIONS: Gait and balance characteristics were associated with specific types of cognition. The specific relationships between gait or balance with cognitive functions suggests shared cerebral cortical circuitry for mobility and cognitive functions.

Neuroplasticity of the sensorimotor neural network associated with walking aid training in people with multiple sclerosis.

The objective of this pilot study was to identify neural descriptors and correlates of participation in a multicomponent walking aid program, the Assistive Device Selection, Training and Education Program (ADSTEP), in people with multiple sclerosis, as reflected by resting state functional MRI. Fourteen people with multiple sclerosis who used a walking aid at baseline and reported falling at least once in the prior year were recruited from the multiple sclerosis clinic in a Veterans Affairs and the surrounding community to participate in a trial of ADSTEP, a multicomponent program of walking aid selection, fitting and six weekly progressive task-oriented walking aid training sessions and undergo resting state functional brain MRI. The functional MRI was performed at baseline and at program completion to assess for changes in neural connectivity of the sensorimotor neural network. Compared to baseline, following ADSTEP participation, functional connectivity between the supplementary motor areas and both the primary somatosensory cortices and the putamen was increased; whereas functional connectivity between the supplementary motor areas and the cerebellum was decreased. This study provides preliminary support for supraspinal sensorimotor neuroplasticity in response to rehabilitation interventions such as task-oriented walking aid training, suggests specific neural targets for future mobility interventions, and supports the need for full-scale randomized controlled trials in this area.

Overview of the cholinergic contribution to gait, balance and falls in Parkinson's disease.

Mobility deficits, including gait disturbance, balance impairments and falls, are common features of Parkinson's disease (PD) that negatively impact quality of life. Mobility deficits respond poorly to dopaminergic medications, indicating a role for additional neurotransmitters. Due to the critical role of cortical input to gait and balance, acetylcholine-an essential neurotransmitter system for attention-has become an area of interest for mobility. This review aimed to identify the role of cholinergic function on gait, balance, and falls in PD using three techniques; pharmacological, imaging, and electrophysiological. Studies supported the role of the cholinergic system for mobility in PD, with the most promising evidence indicating a role in falls. Imaging studies demonstrated involvement of anterior cholinergic (basal forebrain) systems in gait, and posterior (brainstem) systems in balance. However, this review identified a small number of studies which used varying protocols, making comparisons difficult. Further studies are warranted, measuring comprehensive gait and balance characteristics as well as gold standard falls detection to further quantify the relationship between ACh and mobility in PD.

ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.

OBJECTIVE: To evaluate the effect of the Assistive Device Selection, Training and Education Program (ADSTEP) on falls and walking and sitting activity in people with multiple sclerosis (PwMS). DESIGN: Randomized controlled trial. SETTING: Veterans affairs medical center. PARTICIPANTS: PwMS (N=40) using a walking aid at baseline who had fallen in the previous year. INTERVENTIONS: Participants were randomly assigned to ADSTEP or control. ADSTEP had 6 weekly, 40-minute, 1-on-1 sessions with a physical therapist, starting with walking aid selection and fitting, followed by task-oriented progressive gait training. Control was usual medical care with the option of ADSTEP after the study. MAIN OUTCOME MEASURES: The following were assessed at baseline, intervention completion, and 3 months later: falls, timed Up and Go, timed 25-foot walk, 2-minute walk, Four Square Step Test, International Physical Activity Questionnaire, Quebec User Evaluation of Satisfaction with Assistive Technologies, Multiple Sclerosis Walking Scale-12, Activities-Specific Balance Confidence Scale, and Multiple Sclerosis Impact Scale-29. Effect on these outcomes was estimated by a 2-by-2 repeated measures general linear model. RESULTS: Fewer ADSTEP than control participants fell (χ2=3.96, P<.05. number needed to treat =3.3). Time spent sitting changed significantly differently with ADSTEP than with control from baseline to intervention completion (F=11.16, P=.002. ADSTEP: reduced 87.00±194.89min/d; control: increased 103.50±142.21min/d; d=0.88) and to 3-month follow-up (F=9.25, P=.004. ADSTEP: reduced 75.79±171.57min/d; control: increased 84.50±149.23min/d; d=0.79). ADSTEP yielded a moderate effect on time spent walking compared to control at 3-month follow-up (P>.05. ADSTEP 117.53±148.40min/d; control 46.43±58.55min/d; d=0.63). CONCLUSIONS: ADSTEP prevents falls, reduces sitting, and may increase walking in PwMS.