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Introduction: People with multiple sclerosis and gait impairment are particularly susceptible to facing restrictions in their participation. This study aims to investigate (a) which contextual factors within the framework of the International Classification of Functioning, Disability and Health (ICF) are relevant for participation from the perspective of people with multiple sclerosis and gait impairment who (intend to) use mobility assistive devices, and (b) how these contextual factors shape the subjective facets of participation, including a sense of connection, efficacy and meaning, based on the social identity approach to health and well-being., Methods: We conducted a qualitative analysis on data gathered from four online focus group interviews, each involving four to six people with multiple sclerosis and gait impairment who (intend to) use mobility assistive devices (totalling N = 19), and 12 individual online interviews conducted with participants from the focus group interviews. The analysis followed the qualitative content analysis according to Kuckartz., Results: Mobility assistive devices such as walkers, manual wheelchairs and electric wheelchairs/scooters were seen as facilitators that enabled participation in various life situations and enhanced a sense of efficacy by promoting independence. Challenges were encountered in relation to architectural barriers, pathways, weather conditions, public transportation and the lack of integral accessibility to services and systems. Although instrumental support could ease participation, it was also associated with an impaired sense of efficacy. Attitudes, particularly developing an understanding of the experiences of people with multiple sclerosis and gait impairment from others' perspectives, were considered important but often lacking, and discriminatory attitudes were experienced. On the level of personal factors, acceptance of both the mobility assistive devices and the disease itself were seen as facilitators for maintaining involvement in life situations., Conclusions: This study extends the existing literature by shedding light on the interconnectedness of contextual factors within the ICF and various facets of perceived participation, including a sense of connection, efficacy and meaning. These findings provide valuable insights for stakeholders such as urban planners and policymakers in developing inclusive environments that enhance the overall quality of participation for people with multiple sclerosis and gait impairment., Patient or Public Contribution: This study reports on the lived experiences of people with multiple sclerosis and gait impairment who (intend to) use mobility assistive devices. The research team stood in close exchange with project members of the German Multiple Sclerosis Society Lower Saxony, a group representing the interests of people with multiple sclerosis, to design and conduct the focus group interviews. The results from the focus group interviews were the basis for the design of a participatory future workshop in which people with multiple sclerosis and stakeholders involved in the healthcare process collaboratively developed recommendations for improving the provision of mobility assistive devices., Trial Registration: German Clinical Trials Register number: DRKS00025532., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Background: The World Health Organisation (WHO) reports that morbidity and mortality due to Parkinson's disease (PD) are increasing faster than for other neurodegenerative conditions. People with Parkinson's (PwP) present with a variety of motor symptoms, such as tremor, bradykinesia, and rigidity. Freezing of gait (FoG) is a significant motor symptom that manifests as temporary episodes of inability to move one's feet, despite the intention to walk., Aims: This study examined the impact of FoG on quality of life (QoL) within an Irish cohort of PwP, from the perspectives of both PwP and their carers, using validated questionnaires that had been adapted for online use., Methods: PwP and their carers were recruited by outreach to the Irish Parkinson's Community. Anonymous online questionnaires were distributed, which combined a demographic survey with several clinically validated surveys, including Freezing of Gait Questionnaire (FoG-Q), Parkinson's Disease Questionnaire 8 (PDQ-8), and Parkinson's Disease Carer Questionnaire (PDQ-C)., Results: There was a strong correlation (p < 0.001) between severity of FoG and lower QoL among PwP. Significant correlation was also found between FoG severity and several motor symptoms, such as postural instability and difficulty with balance, and non-motor symptoms, such as cognitive changes and pain/discomfort. FoG severity correlated with disease progression. Significant correlation was also found between FoG and symptoms, as assessed from the perspective of the patients' carers., Conclusions: This study shows that FoG is a significant detriment to the QoL of PwP, from the perspectives of patients and carers. This method of assessing FoG and QoL using online questionnaires has potential to enhance the reach and flexibility of this type of research. These findings will inform future studies on larger cohorts and highlight unmet clinical needs in PwP., (© 2024. The Author(s).)

Background: Quality of life (QOL) and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers are important factors to consider when developing treatment strategies., Objective: To investigate factors associated with QOL in patients with DLB, and to examine factors associated with activities of daily living (ADL) if ADL was associated with QOL., Methods: We previously conducted a questionnaire survey study to investigate the treatment needs of patients with DLB and their caregivers. This pre-specified additional analysis evaluated the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form-8 for QOL, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II total score for ADL., Results: In total, 231 patient- caregiver pairs and 38 physicians were included. Multivariable analysis of QOL showed that the MDS-UPDRS Part II total score (standard regression coefficient [β], - 0.432) was associated with the PCS, and presence of depression (β, - 0.330) was associated with the MCS. The severity of postural instability/gait disorder (PIGD) (β, 0.337) and rigidity (β, 0.266), presence of hallucinations (β, 0.165), male sex (β, 0.157), and use of "short stay" or "small-scale, multifunctional home care" (β, 0.156) were associated with worsened ADL., Conclusions: In patients with DLB, QOL was negatively impacted by severity of ADL disability and depression, and ADL was negatively impacted by severity of PIGD and rigidity, hallucinations, male sex, and use of "short stay" or "small-scale, multifunctional home care."

Background and Purpose:

Stigma is a widespread phenomenon in Parkinson&rsquo;s disease (PD) and has been shown to affect the quality of life of individuals. This study aims to assess the level of stigma and identify the factors contributing to stigma in patients with PD in Turkey.

A total of 142 patients diagno&shy;sed with PD between June 2022 and March 2023 were included in the study. Sociodemographic data including age, gender, marital status, education level, and duration of PD were collected using a sociodemographic information form. Motor symptom severity was assessed using the Unified Parkinson&rsquo;s Disease Rating Scale (UPDRS part III). The disease stage was determined using the Hoehn and Yahr scale. Participants were classified as PIGD (postural instability/gait difficulty) or TD (tremor dominant) based on the UPDRS score. Patients with a UPDRS ratio greater than or equal to 1.5 were classified as TD, while subjects with a ratio less than or equal to 1.0 were classified as PIGD. Ratios between 1.0 and 1.5 were classified as mixed type. Depression was assessed using the Hamilton Depression Rating Scale (HAM-D), while stigma was measured using the Chronic Illness Anticipated Stigma Scale (CIASS) and the stigma sub-scale of the 39-item Parkinson&rsquo;s Disease Questionnaire (PDQ-39 stigma sub-scale).

The mean score on the stigma sub-scale of the PDQ-39 was 7.60&plusmn;4.39, while the mean total stigma score on the CIASS was 1.37&plusmn;0.39. Our results indicated that stigma was more prevalent among patients with PD with the TD motor subtype, younger age, shorter disease duration, higher level of disability, and presence of depression symptoms.

Our study highlights the association between stigma and disease progression, duration, and depressive symptoms in patients with PD in western Turkey.

Factors that influence the decision of voluntary driving cessation in patients living with Parkinson's disease (PD) are still unclear. We aimed to reveal the factors affecting the decision of voluntary driving cessation in patients with PD. This hospital-based cross-sectional study recruited consecutive outpatients with PD. Data on sociodemographic and clinical characteristics and medication use were collected from the patients using semistructured interviews. Cognitive function was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). We excluded patients with dementia or motor impairment (Hoehn - Yahr stage > 3). We divided the patients into two groups, with and without voluntary driving cessation (D: driver; RD: retired driver), and conducted investigations using multivariate logistic regression analyses. Of the 40 patients, 8 (20.0%) voluntarily retired from driving. Patients who decided on driving cessation had a higher prevalence of freezing of gait (FOG) (D vs. RD, 25.0% vs. 87.5%; P = 0.001) and tended to have lower scores for attention in the MoCA-J (D vs. RD, 5.0 ± 1.2 vs. 4.1 ± 1.4; P = 0.086). Multivariable analysis showed that FOG was independently associated with driving cessation (odds ratio: 14.46, 95% confidence interval: 1.91-303.74). FOG was associated with voluntary driving cessation in patients with PD without dementia or severe motor impairment. Physicians should consider providing extensive social support to maintain patients' mobility and independence, especially if the patients have these clinical factors., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hidetada Yamada et al.)

Introduction: The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes., Methods: Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity., Results: Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance., Conclusions: The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This investigation examined whether aspects of attention and executive functioning differed between Parkinson's Disease (PD) patients with freezing of gait (FOG) based on responsiveness to dopamine. We also explored association of cognition with FOG severity and gait metrics., Methods: Fifty-four individuals with PD completed the study protocol: 17 without freezing (PDC), 23 with dopa-responsive FOG (RFOG), and 14 with dopa-unresponsive (URFOG). Standardized neuropsychological tests assessed attention (focused and sustained), psychomotor speed, and set-switching (time and errors). FOG severity was measured using the new FOG Questionnaire (nFOG-Q). Metrics from timed up and go (TUG) tasks were obtained while "on" and "off" dopamine, with and without dual cognitive tasks., Results: After controlling for clinical and demographic factors, analysis of covariance revealed a significant between-group difference for set-switching errors; planned contrasts revealed increased set-switching errors in URFOG relative to RFOG and PD control groups. Groups were not different in other cognitive domains. FOG severity was modestly associated with set-switching errors in RFOG but not URFOG. TUG performances while "on" were associated with set-switching errors in PD controls, and with focused attention in RFOG., Conclusion: PD patients with dopa-unresponsive FOG are more prone to set-switching errors than those who respond to treatment. Furthermore, executive function appears relevant to FOG severity only in patients who show dopamine response. Together, these findings suggest disruption of a common dopamine-mediated pathway for FOG and ability to monitor rules while alternating cognitive processes. Consideration of dopa-response could be useful in characterizing cohorts and treating FOG in PD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To identify homogeneous subsets of survivors of chronic stroke who share similar characteristics across several domains and test if these groups differ in real-world walking activity. We hypothesized that variables representing the domains of walking ability, psychosocial, environment, and cognition would be important contributors in differentiating real-world walking activity in survivors of chronic stroke., Design: Cross-sectional, secondary data analysis., Setting: University/laboratory., Participants: A total of 283 individuals with chronic (≥6mo) stroke (N=238)., Interventions: Not applicable., Main Outcome Measures: Thirteen variables representing 5 domains were included: (1) walking ability: 6-minute walk test (6MWT), self-selected speed (SSS) of gait; (2) psychosocial: Patient Health Questionnaire-9, Activities-specific Balance Confidence (ABC) scale; (3) physical health: low-density lipoprotein cholesterol, body mass index, Charlson Comorbidity Index (CCI); (4) cognition: Montreal Cognitive Assessment (MoCA); and (5) environment: living situation and marital status, work status, Area Deprivation Index (ADI), Walk Score. Mixture modeling was used to identify latent classes of survivors of stroke. After identifying the latent classes, walking activity, measured as steps per day (SPD), was included as a distal outcome to understand if classes were meaningfully different in their real-world walking RESULTS: A model with 3 latent classes was selected. The 6MWT, SSS, ABC scale, and Walk Score were significantly different among all 3 classes. Differences were also seen for the MoCA, ADI, and CCI between 2 of the 3 classes. Importantly, the distal outcome of SPD was significantly different in all classes, indicating that real-world walking activity differs among the groups identified by the mixture model., Conclusions: Survivors of stroke with lower walking ability, lower self-efficacy, lower cognitive abilities, and greater area deprivation had lower SPD. These results demonstrate that the physical and social environment (including socioeconomic factors) and cognitive function should also be considered when developing interventions to improve real-world walking activity after stroke., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Individuals with Parkinson's disease (PD) who report freezing of gait (FOG) have poorer sleep quality than those without FOG. Cognitive, anxiety, and mobility disability are components of the FOG phenotype, however, no study has investigated if poor sleep quality is associated with all three components that underlie FOG in PD., Research Question: Are there associations among sleep quality and all three components of the FOG phenotype?, Methods: Forty and 39 individuals with and without FOG (PD + FOG and PD-FOG), respectively, and 31 age-matched healthy controls (HC) participated in this study. Self-reported FOG (new-FOG questionnaire-NFOGQ), sleep quality (Pittsburgh Sleep Quality Index-PSQI), cognitive function (Montreal Cognitive Assessment-MoCA), anxiety (subscale from Hospital Anxiety and Depression Scale-HADS-A), and mobility (timed-up-and-go test-TUG) were assessed., Results and Significance: PSQI scores were correlated with the scores of NFOGQ, MoCA, HADS-A, and TUG time in PD + FOG (P ≤ 0.0038). The multiple regression analysis identified the PSQI scores as the only predictor of the variance of the NFOGQ scores (R 2  = 0.46, P < .0001). The variance in the PSQI scores were explained (69 %) by MoCA scores, NFOGQ scores, TUG time, and HADS-A scores (P ≤ 0.05). Although PD + FOG had a higher disease severity compared to PD-FOG (P < 0.001), disease severity did not enter in the regression model to explain PSQI scores and NFOGQ scores. We also observed associations of PSQI scores with the MoCA scores and TUG time for HC (P ≤ 0.0038), whereas there was no association between PSQI scores and any variable in PD-FOG (P > 0.05). Finally, PD + FOG presented worse scores of PSQI, MoCA, HADS-A, and TUG time than PD-FOG and HC (P < 0.05). Thus, poor sleep quality is associated with FOG and all three components that underlie FOG, regardless of the disease severity. Therefore, treatments useful to decrease FOG should be targeted to ameliorate sleep quality, cognition, anxiety, and mobility., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hui-xian Yu et al.)

α7 nicotinic acetylcholine receptor (α7 nAChR) is an extensively validated target for several neurological and psychiatric conditions namely, dementia and schizophrenia, owing to its vital roles in cognition and sensorimotor gating. Positive allosteric modulation (PAM) of α7 nAChR represents an innovative approach to amplify endogenous cholinergic signaling in a temporally restricted manner in learning and memory centers of brain. α7 nAChR PAMs are anticipated to side-step burgeoning issues observed with several clinical-stage orthosteric α7 nAChR agonists, related to selectivity, tolerance/tachyphylaxis, thus providing a novel dimension in therapeutic strategy and pharmacology of α7 nAChR ion-channel. Here we describe a novel α7 nAChR PAM, LL-00066471, which potently amplified agonist-induced Ca 2+ fluxes in neuronal IMR-32 neuroblastoma cells in a α-bungarotoxin (α-BTX) sensitive manner. LL-00066471 showed excellent oral bioavailability across species (mouse, rat and dog), low clearance and good brain penetration (B/P ratio > 1). In vivo, LL-00066471 robustly attenuated cognitive deficits in both procognitive and antiamnesic paradigms of short-term episodic and recognition memory in novel object recognition task (NORT) and social recognition task (SRT), respectively. Additionally, LL-00066471 mitigated apomorphine-induced sensorimotor gating deficits in acoustic startle reflex (ASR) and enhanced antipsychotic efficacy of olanzapine in conditioned avoidance response (CAR) task. Further, LL-00066471 corrected redox-imbalances and reduced cortico-striatal infarcts in stroke model. These finding together suggest that LL-00066471 has potential to symptomatically alleviate cognitive deficits associated with dementias, attenuate sensorimotor gating deficits in schizophrenia and correct redox-imbalances in cerebrovascular disorders. Therefore, LL-00066471 presents potential for management of cognitive impairments associated with neurological and psychiatric conditions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The goal of this study was to analyze how depression associated with Parkinson's disease (PD) affected gait variability in these patients using a dual-task paradigm. Additionally, the dependency of the executive functions and the impact of depression on gait variability were analyzed., Patients and Methods: Three subject groups were included: patients with PD, but no depression (PD-NonDep; 14 patients), patients with both PD and depression (PD-Dep; 16 patients) and healthy controls (HC; 15 subjects). Gait was recorded using the wireless sensors. The participants walked under four conditions: single-task, motor dual- task, cognitive dual-task, and combined dual-task. Variability of stride length, stride duration, and swing time was calculated and analyzed using the statistical methods., Results: Variability of stride duration and stride length were not significantly different between PD-Dep and PD-NonDep patients. The linear mixed model showed that swing time variability was statistically significantly higher in PD-Dep patients compared to controls (p = 0.001). Hamilton Disease Rating Scale scores were significantly correlated with the swing time variability (p = 0.01). Variability of all three parameters of gait was significantly higher while performing combined or cognitive task and this effect was more pronounced in PD-Dep group of patients., Conclusions: Depression in PD was associated with swing time variability, and this effect was more prominent while performing a dual-task., Significance: Diagnosing and treating depression might be important for gait improvement and fall reduction in PD patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Stroke is the leading cause of disability among the elderly in the industrialized world. No more than 40% of stroke survivors walk independently, and only after receiving appropriate rehabilitation treatment; many stroke patients have also non-motor symptoms. The aim of this pilot study is to evaluate the effects of Ekso-training on non-motor outcomes, including gastrointestinal function and psychological well-being, in post stroke patients. We enrolled 30 post-stroke subjects, which were randomized into two groups in order of recruitment: 15 patients were trained with the overground exoskeleton Ekso-GT (experimental group, EG), whereas 15 patients were submitted to a standard gait training (control group, CG). Both the groups underwent the same amount of physiotherapy. At the end of the training, only in the EG we observed a significant improvement in constipation, mood, and coping strategies, with regard to social support, as well as in the perception of quality of life (as per SF-12). According to these preliminary data, overground robotic gait training can be considered a valuable tool in improving non-motor symptoms, including constipation and behavioral disorders in patients with chronic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Gait initiation and turning are common triggers for Freezing of Gait (FOG) in people with Parkinson's disease (PD). Recently, it has been shown that closed-loop tactile feedback (CLTF) can be effective to improve turning performance in people with FOG., Research Question: Does CLTF change the preparation and execution of the first step during gait initiation?, Methods: People (n = 36) with PD with FOG (PD + FOG) (n = 18) and without FOG (PD-FOG) (n = 18) were included in the study and performed self-initiated gait with or without CLTF under single and dual task conditions. Anticipatory postural adjustments (APAs) and step kinematics were quantified with inertial measurement units (IMUs). Muscle activity of the right and left tensor fasciae latae (TFL) was measured via EMG recordings., Results: PD + FOG and PD-FOG did not differ in age, gender and disease duration and severity (p > 0.05). PD + FOG performed smaller APAs (F = 4.559, p = 0.04) with a higher amount of TFL co-contraction (F = 6.034, p = 0.02) compared to PD-FOG. CLTF had no effect on APAs but led to an increase in first step duration (F = 7.921, p = 0.008)., Conclusions: PD + FOG had smaller APAs and higher left and right TFL co-contraction during gait initiation. CLTF did not impact preparation of the first step but led to a slower execution of the first step. We speculate that, similarly to findings from turning, CLTF might result in the participant attending more closely to the first step compared to without CLTF. Whether increased attention on gait initiation is beneficial in diminishing FOG should be investigated in more detail., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report., (Copyright © 2020. Published by Elsevier B.V.)

Background: We investigated the gait characteristics of patients with Parkinson's disease (PD), under free-living conditions, using a wearable device, and assessed their relationships with global cognitive function and motor abnormalities., Methods: The study subjects comprised patients with PD aged < 80 years, with a Mini-Mental State Examination (MMSE) score of ≥20, free of any motor complications. A wearable sensor with a built-in tri-axial accelerometer was waist-mounted on each patient, and continuous, 24-h records were obtained. The mean gait cycle duration and mean gait acceleration amplitude, under free-living conditions, were computed and analyzed to determine their relationship with disease duration, MMSE score, Unified Parkinson's Disease Rating Scale (UPDRS) Part III score, and postural instability and gait difficulty (PIGD) score., Results: The study included 106 consecutive patients with PD. The mean gait cycle duration was 1.18 ± 0.12 s, which was similar to that of the normal controls. However, the mean gait acceleration amplitude of PD patients (1.83 ± 0.36 m/s 2 ) was significantly lower than that of the control (p < 0.001). In PD patients, the mean gait acceleration amplitude correlated with the MMSE (β = 0.197, p = 0.028), UPDRS Part III (β = - 0.327, p < 0.001), and PIGD (β = - 0.235, p = 0.008) scores., Conclusions: The gait rhythm of PD patients is preserved at levels similar to those of normal subjects. However, the mean gait acceleration amplitude was significantly reduced in patients with PD. The results indicate that gait acceleration amplitude correlates with the severity of motor disorders and global cognitive function.

Huntington's disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). However, the impact of gait "stress tests" on HD individuals needs further investigation. Therefore, the aims of this study were to investigate whether: 1) fast-paced and dual-task walking uncover deficits in gait and turning not seen under single-task, 2) cognitive and gait outcomes relate to fall incidence, and 3) gait deficits measured with wearable inertial sensors correlate with motor symptom severity in HD as measured by the Unified Huntington's disease Rating Scale-total motor score (UHDRS-TMS). Seventeen HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative gait testing via a 25m, two-minute walk test with APDMTM inertial sensors. Gait was assessed under a 1) ST, self-selected pace, 2) fast-as-possible (FAP) pace, and 3) verbal fluency DT. The UHDRS-TMS and a cognitive test battery were administered, and a retrospective fall history was obtained. During ST, DT, and FAP conditions, HD participants demonstrated slower gait, shorter stride length, and greater lateral step and stride length variability compared to controls (p<0.00001 to 0.034). Significant dual-task costs (DTC) were observed for turns; HD participants took more time (p = 0.013) and steps (p = 0.028) to complete a turn under DT compared to controls. Higher UHDRS-TMS correlated with greater stride length variability, less double-support, and more swing-phase time under all conditions. Decreased processing speed was associated with increased gait variability under ST and FAP conditions. Unexpectedly, participant's self-reported falls did not correlate with any gait or turn parameters. HD participants demonstrated significantly greater DTC for turning, which is less automatic than straight walking, requiring coordination of body segments, anticipatory control, and cortical regulation. Turn complexity likely makes it more susceptible to cognitive interference in HD., Competing Interests: The authors have declared no competing interest exist.

Objectives: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801., Methods: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task., Key Findings: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3β expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg)., Conclusions: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3β signalling pathways., (© 2019 Royal Pharmaceutical Society.)

Background. Context-dependent behavior is a phenomenon in which people demonstrate superior performance in the context where a motor task was originally learned, but show poorer performance in an unfamiliar context. Previous studies found that people with Parkinson's disease (PD) demonstrated greater context-dependency than nondisabled adults. Moreover, the frontostriatal circuit appeared to play a role in mediating context-dependent behavior. Neuroimaging studies showed that people with PD and freezing of gait (FoG) had difficulty recruiting the frontostriatal circuit when performing a set-shifting task, known to be mediated by this neural network. Objective. This study aimed to investigate whether individuals with PD and FoG (PD + FoG) would be more context-dependent than those without FoG (PD - FoG). Furthermore, the association between context-dependent behavior and set-shifting ability would be determined. Methods . Sixteen individuals with PD + FoG, 15 participants with PD - FoG, and 15 nondisabled adults (Control) were recruited. The participants practiced 3 numerical sequences, each associated with a specific context. One day following practice, the participants were tested under 2 conditions: the sequence-context associations remained the same as practice or were changed. Set-shifting ability was measured by the Trail Making Test (TMT). Results. Compared to the PD - FoG group, the PD + FoG group showed a greater decrement in normalized motor performance when the sequence-context associations were changed. Context-dependency correlated with the TMT in the PD - FoG group but not in the PD + FoG or Control groups. Conclusion. While people with PD + FoG appeared to be more context-dependent than individuals without FoG, a relationship between context-dependent behavior and set-shifting existed only in those without FoG.

Prior literature has proposed that the coexistence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling, and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, 15 studies including 11,213 participants met criteria for inclusion in this study. The triad's existence was supported by 12 of the 15 studies (80%), including 4 longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacologic and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities and the triad, with one study finding a significant longitudinal relationship with periventricular white matter hyperintensities. Vascular risk factors were also commonly associated with this triad. Taken together, the relationship between this triad, the vascular depression hypothesis, and frontal-subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this concomitant prescence oflate-life depression, executive dysfunction and impaired gait speed., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Gait of people with unilateral stroke is characterized by pronounced asymmetry. The aim of the study was to investigate the effect of cognitive and motor tasks on asymmetry of gait in people with stroke., Materials and Methods: Nine individuals with stroke walked over the GAITRite walkway while performing motor (holding a cup with water) or cognitive (reciting the alphabet) tasks or walked with no additional task. Gait velocity, cadence, and symmetry indexes for the stance phase, swing phase, and single support phase of a gait cycle were calculated., Results: The motor and cognitive tasks negatively affected gait velocity (P < .05) and cadence (P < .05). Walking and performing additional tasks resulted in the increase of the asymmetry of gait. The cognitive task had a greater effect on gait asymmetry than the motor task., Conclusions: The study outcome revealed that gait of individuals with stroke could be affected by simultaneous performance of additional tasks. The outcome provides a basis for future investigation of the ways of improving symmetry of gait in people with stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The effectiveness of dual-task training has been reported in individuals with cognitive impairments. To date, there is no clear evidence on the incorporation of dual-task training in ambulatory individuals with spinal cord injury (SCI) who have intact cognitive functions but have various degrees of sensorimotor dysfunction. Objectives: To compare the immediate effects of dual-task obstacle crossing (DTOC) and single-task obstacle crossing (STOC) training on functional and cognitive abilities in chronic ambulatory participants with SCI. Methods: This is a randomized 2 × 2 crossover design with blinded assessors. Twenty-two participants were randomly trained using a 30-minute DTOC and STOC training program with a 2-day washout period. Outcomes, including 10-Meter Walk Tests (single- and dual-task tests), percent of Stroop Color and Word Test task errors, Timed Up and Go Test (TUG), and five times sit-to-stand test, were measured immediately before and after each training program. Results: Participants showed significant improvement in all outcomes following both training programs ( p < .05), except percent of Stroop Color and Word Test task errors after STOC training. Obvious differences between the training programs were found for the percent of Stroop task errors and TUG ( p s = .014 and .06). Conclusion: Obstacle crossing is a demanding task, thus the obvious improvement was found immediately after both training programs in participants with long post-injury time (approximately 5 years). However, the findings primarily suggest the superior effects of DTOC over STOC on a complex motor task and cognitive activity. A further randomized control trial incorporating a complex dual-task test is needed to strengthen evidence for the benefit of DTOC for these individuals., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest.

Objectives: To review intervention programs that measure gait to investigate what features of the intervention may contribute to improving gait in older adults with cognitive impairment or dementia., Design: Systematic review using Medline, Cinahl, Scopus, PsychInfo, Amed, Embase, Web of Science, and PubMed for original research published in English between January 1, 2000, and July 23, 2018, to identify interventional controlled trials. Narrative synthesis was undertaken., Results: Of 6,379 citations, 36 articles met inclusion criteria. Interventions were categorized as medication or medical devices (8 studies), exercise (19 studies), and exercise plus cognitive training (9 studies). Antidementia medication may improve gait variability in people with Alzheimer's disease. Exercise programs focusing on strength and balance training, especially when combined with functional mobility training, improve gait in people with mild cognitive impairment or dementia. Exercise plus cognitive training programs combining strength and balance training, functional mobility training, and training on attention and executive function also improve gait., Conlusion: Physical and cognitive factors affect gait performance, and both should be addressed in intervention programs. Physical exercises including functional mobility training, especially walking, have better results than physical programs with only static, resistance, and flexibility training. Cognitive intervention should be concomitant with physical exercises rather than separate, with a focus on attention and executive function. Combining physical training with cognitive training in a functional context may assist older adults with cognitive impairment generalize from training to everyday activity. J Am Geriatr Soc 67:381-391, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: Falls represent one of the main complications of Parkinson's disease (PD), significantly lowering quality of life. Cardiovascular autonomic neuropathy (cAN) is one of the key contributing factors to PD-associated falls. However, a direct quantification of its impact on the risk of falling in PD is still lacking. In this 12-month prospective study, we sought to evaluate the association between cAN and falls., Methods: Fifty consecutive patients were evaluated with a standardized battery of autonomic testing, Unified Parkinson's Disease Rating Scale, push and release (P&R) test, timed up and go test, freezing of gait (FOG) questionnaire, Montreal cognitive assessment (MoCA). Dyskinesia severity and presence of REM sleep behavioral disorder (RBD) were additionally considered. Patients were followed-up for 12 months., Results: We observed a 38% prevalence of cAN. At baseline, 36% of patients reported at least one fall in the previous 6 months. This figure increased to 56% over the follow-up. After adjusting for age, disease duration, axial symptoms, MoCA and dopaminergic treatment, cAN was significantly associated with a 15-fold (OR 15.194) higher probability of falls; orthostatic hypotension (OH), the most common expression of cAN, with a 10-fold probability (OR 10.702). In addition P&R test (OR 14.021), RBD (OR 5.470) and FOG (OR 1.450) were independently associated with greater probability of falls., Conclusions: cAN, including but not limited to OH, is a strong independent predictor of falls in PD. Future research endeavors clarifying to what extent pharmacological and non-pharmacological treatments targeting autonomic dysfunctions might reduce the risk of falls are warranted.

Background: Stroke patients have a lower quality of life than other people., Objective: The purpose of this study was to examine the effect of balance and gait function of stroke patients on their quality of life., Methods: Twenty-seven subjects participated in the experiment. Balance ability was assessed using a SpaceBalance 3D and a Berg Balance Scale (BBS). Gait function was measured with a Biodex Gait Trainer 2 treadmill system. The quality of life of the subjects was assessed through the Stroke specific Quality of Life Scale (SS-QOL)., Results: Correlation analysis between balance and quality of life showed that weight bearing distribution and BBS are positive correlated with quality of life. In addition, gait speed, step length of the paretic limb, and step length of the non-paretic limb were also found to be correlated with quality of life., Conclusion: Balance and gait function must all be considered in order to improve the quality of life of stroke patients.

Gait variability is associated with cognitive performance in people with central neurologic damage illnesses, which includes multiple sclerosis. However, presently, there have been no data available as to whether this association exists in adolescents with multiple sclerosis. Therefore, our objective was to investigate the association between gait variability and cognition in adolescents with multiple sclerosis encompassing 48 recently diagnosed adolescents with multiple sclerosis (26 girls; 22 boys), average age of 16.0 years (SD = 2.2), and an Expanded Disability Status Scale (EDSS) score of 1.6 (SD = 1.3). Walking speed and gait variability expressed by the coefficient of variation of the mean step time was studied using an electronic walkway. A computerized cognitive battery of tests evaluated cognition. Cognitive outcome measurements included verbal and nonverbal memory, executive function, visual spatial processing, verbal function, attention, information processing speed, and motor skills. Mean walking speed was 76.9 cm/s (SD = 57.6); mean step time variability was 3.5 (SD = 1.3) and the global cognitive score was 93.9 (SD = 12.5). According to linear regression analysis, a significant association was found between step time variability, cognitive subdomains of attention, and information processing speed. After incorporating walking speed into the model, the association remained significant. Increased gait variability, not walking speed, is suggested as a clinical marker of cognitive performance in minimally disabled adolescents with multiple sclerosis.

ABSTRACTBackground:Walking ability recently emerged as a sub-clinical marker of cognitive decline. Hence, the relationship between baseline gait and future cognitive decline was examined in geriatric patients. Because a "loss of complexity" (LOC) is a key phenomenon of the aging process that exhibits in multiple systems, we propose the idea that age- and cognition-related LOC may also become manifested in gait function. The LOC theory suggests that even healthy aging is associated with a (neuro)physiological breakdown of system elements that causes a decline in variability and an overall LOC. We used coordination dynamics as a conceptual framework and hypothesized that a LOC is reflected in dynamic gait outcomes (e.g. gait regularity, complexity, stability) and that such outcomes could increase the specificity of the gait-cognition link., Methods: 19 geriatric patients (age 80.0±5.8) were followed for 14.4±6.6 months. An iPod collected three-dimensional (3D) trunk accelerations while patients walked for 3 minutes. Cognition was evaluated with the Mini-Mental State Examination (MMSE) and the Seven-Minute screen (7MS) test. The Reliable Change Index (RCI) quantified the magnitude of cognitive change. Spearman's Rho coefficients (ρ) indexed correlations between baseline gait and future cognitive change., Results: Seven patients showed reliable cognitive decline ("Cognitive Decline" group), and 12 patients remained cognitively stable ("Cognitive Stable" group) over time. Future cognitive decline was correlated with a more regular (ρ = 0.579*) and predictable (ρ = 0.486*) gait pattern, but not with gait speed., Conclusions: The increase in gait regularity and predictability possibly reflects a LOC due to age- and cognition-related (neuro)physiological decline. Because dynamic versus traditional gait outcomes (i.e. gait speed and (variability of) stride time) were more strongly correlated with future cognitive decline, the use of wearable sensors in predicting and monitoring cognitive and physical health in vulnerable geriatric patients can be considered promising. However, our results are preliminary and do require replication in larger cohorts.

Background: Disturbance of gait is a key feature of Parkinson's disease (PD) and has a negative impact on quality of life. Deficits in cognition and sensorimotor processing impair the ability of people with PD to walk quickly, efficiently and safely. Recent evidence suggests that emotional disturbances may also affect gait in PD., Research Question: We explored if there were relationships between walking ability, emotion and cognitive impairment in people with PD., Methods: The literature was firstly reviewed for unimpaired individuals. The recent experimental evidence for the influence of emotion on gait in people with PD was then explored. The contribution of affective disorders to continuous gait disorders was investigated, particularly for bradykinetic and hypokinetic gait. In addition, we investigated the influence of emotional processing on episodic gait disturbances, such as freezing of gait. Potential effects of pharmacological, surgical and physical therapy interventions were also considered., Results: Emerging evidence showed that emotional disturbances arising from affective disorders such as anxiety and depression, in addition to cognitive impairment, could contribute to gait disorders in some people with PD. An analysis of the literature indicated mixed evidence that improvements in affective disorders induced by physical therapy, pharmacological management or surgery improve locomotion in PD., Significance: When assessing and treating gait disorders in people with PD, it is important to take into the account non-motor symptoms such as anxiety, depression and cognitive impairment, in addition to the motor sequalae of this progressive neurological condition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Older adults with Type 2 diabetes (DM2) and hypertension (HTN) often experience cognitive weaknesses. Growing evidence suggests that such weaknesses place patients at risk for gait disturbance and falls. The current systematic review evaluated (a) the impact of DM2 and HTN on cognition and gait and (b) the association between cognition and gait in the context of DM2 and HTN., Methods: PubMed was searched to identify studies published in English before 15 April 2017 that evaluated both cognition and gait among non-demented older adults either as a function of DM2 or HTN status or as a function of continuous variables that indicate disease severity and/or management (e.g. blood pressure, HbA1C). Risk of bias was assessed by examining the method of verifying HTN/DM2 and excluding dementia as well as included covariates., Results: In the majority of studies reviewed (n = 17), both DM2 and HTN status were associated with poorer cognitive and/or gait functioning (8 out of 10 studies). In addition, in 10 out of 11 studies cognition was reliably associated with gait. For continuous variables, higher systolic blood pressure (measured with ambulatory methods) was consistently related to poorer cognition and slower gait, but other continuous variables (e.g. HbA1C) were studied inconsistently with inconclusive results., Conclusions: Cognitive and gait decrements are not only common in the context of HTN and DM2, but also are related to each other. This suggests that clinical neuropsychologists should address cognitive contributions to gait disturbance and falls in their clinical work and research with these patient populations.

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives., (© 2018 John Wiley & Sons, Ltd.)

Objectives: To assess rhythm abilities, to describe their relation to clinical presentation, and to determine if rhythm production independently contributes to temporal gait asymmetry (TGA) poststroke., Design: Cross-sectional., Setting: Large urban rehabilitation hospital and university., Participants: Individuals (N=60) with subacute and chronic stroke (n=39) and data for healthy adults extracted from a preexisting database (n=21)., Interventions: Not applicable., Main Outcome Measures: Stroke group: National Institutes of Health Stroke Scale (NIHSS), Chedoke-McMaster Stroke Assessment (CMSA) leg and foot scales, Montreal Cognitive Assessment (MoCA), rhythm perception and production (Beat Alignment Test [BAT]), and spatiotemporal gait parameters were assessed. TGA was quantified with the swing time symmetry ratio. Healthy group: age and beat perception scores assessed by the BAT. Rhythm perception of the stroke group and healthy adults was compared with analysis of variance. Spearman correlations quantified the relation between rhythm perception and production abilities and clinical measures. Multiple linear regression assessed the contribution of rhythm production along with motor impairment and time poststroke to TGA., Results: Rhythm perception in the stroke group was worse than healthy adults (F 1,56 =17.5, P=.0001) Within the stroke group, rhythm perception was significantly correlated with CMSA leg (Spearman ρ=.33, P=.04), and foot (Spearman ρ=.49, P=.002) scores but not NIHSS or MoCA scores. The model for TGA was significant (F 3,35 =12.8, P<.0001) with CMSA leg scores, time poststroke, and asynchrony of rhythm production explaining 52% of the variance., Conclusions: Rhythm perception is impaired after stroke, and temporal gait asymmetry relates to impairments in producing rhythmic movement. These results may have implications for the use of auditory rhythmic stimuli to cue motor responses poststroke. Future work will explore brain responses to rhythm processing poststroke., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Freezing of gait (FOG) is a motor disturbance usually appearing in advanced Parkinson's disease (PD). Cognitive and executive function seems to play an important role in this phenomenon., Aim: To investigate if cognitive and kinematic parameters correlate with FOG in PD patients without dementia., Patients and Methods: We conducted an observational cross-sectional study. Participants were classified in two groups: freezers and non-freezers. Clinical information was obtained by Hoehn and Yahr scale, Unified Parkinson's Disease Rating Scale and balance test of Short Physical Performance Battery. Cognitive function was evaluated using Minimental Examination and the Fuld Object Memory Evaluation; executive function was assessed with the Frontal Assessment Battery test. Battery kinematic parameters were assessed by means of gait speed, cadence, stride length and stride time., Results: Twenty-five participants with PD without dementia completed the evaluation. Statistical significant differences between freezers and non-freezers were found in global cognition (p = 0,02), memory (p = 0,04), executive function (p = 0,04), cadence (p = 0,02), stride length (p = 0,04) and stride time (p = 0,01)., Conclusion: Cognitive parameters may have an important contribution to the manifestation of freezing of gait in PD. These results may have important clinical implications for developing future non-pharmacological and cognitive interventions strategies targeted to PD patients with FOG.

Functional (psychogenic) gait disorders are a common presentation of functional neurological disorder - one of the commonest diagnoses made in neurology practice. People with functional neurological disorder are as disabled and experience as poor a quality of life as patients with multiple sclerosis and Parkinson's disease. People with functional neurological disorder, including gait disorder, are often perceived as being challenging to diagnose and manage, and as a result attitudes of health professionals towards them are often negative. However, a rapid positive diagnosis of functional gait disorder can often be made, and with a specific approach to diagnostic explanation and treatment, many patients experience improvement in symptoms and disability, with such improvements sustained in the long term. Here I review current evidence regarding the diagnosis, pathophysiology and management of functional gait disturbance with an emphasis on how to make a positive diagnosis and how to select the most appropriate treatment approach. Rehabilitative treatments, with an emphasis on specific physiotherapy interventions, have increasing evidence for benefit, particularly if carried out following a comprehensive explanation of the diagnosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, adult mice were assigned to five groups, and administered vehicle (distilled water), or aspartame (20, 40, 80 and 160mg/kg body weight) for 28days. Behavioural tests to assess motor-balance and gait were conducted on day 28, following which animals were sacrificed. Sections of the cerebellar cortex and pons were processed, for general histology and Bielschwosky's silver staining protocol. Glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) immunoreactivity were assessed. Antioxidant status and aspartic acid/cysteine-aspartic acid protease (caspase)-3 levels were also assessed using homogenates of the cerebellum and pons. Body weight-gain decreased significantly following aspartame consumption; while no significant changes in gait and balance were observed. Histological changes suggestive of neuronal injury were observed at 80 and 160mg/kg/day; however, no obvious neuritic plaques were seen. GFAP-reactive astrocytes and NSE-reactive neurons increased at 20, 40 and 80mg/kg, but decreased at 160mg/kg. There was derangement of oxidative status and increased caspase-3 concentration with increasing doses of aspartame; although no significant difference in aspartate level was observed. The study concluded that repeated oral administration of the higher doses of aspartame was associated with morphological alterations suggestive of neuronal injury, and derangement of antioxidant status., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinson's disease (PD)., Methods: One hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up., Results: During the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (-52.9%, p < 0.001) and PD-D (-24.2%, p < 0.001) with a significant difference in the change of FOG in favor of PD-ND (p = 0.001). Similarly, there was an improvement in the axial score for both PD-ND (-66.1%, p < 0.001) and PD-D (-45.3%, p < 0.001) at 12-month with a significant difference between the groups. (p = 0.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups., Conclusions: Our findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Behavioural symptoms and gait disorders are very common in patients with multiple sclerosis., Objective: To evaluate the association between fear of falling and gait instability at one year in patients with multiple sclerosis., Methods: Thirty-five multiple sclerosis patients were included. Fear of falling was assessed by the Fall Efficacy Scale-International and gait variability with stride time variability under single and dual-task conditions at baseline and at one year., Results: Baseline fear of falling score was associated with increased stride time variability at one year during dual-task condition even after adjustment on covariates., Conclusion: Fear of falling is associated with gait variability at one year, especially under dual-task condition., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Impaired motor function in children with histories of prenatal exposure to alcohol has been previously reported but, to date, no studies using quantitatively based analyses have been performed to assess gait in these children., Methods: Gait of children with (n = 18) or without (n = 26) prenatal alcohol exposure was assessed using an electronically instrumented walkway. Children completed blocks of trials traversing the walkway with different combinations of walking condition (increased, self-paced, and decreased cadence) and direction (forward and backward). Gait velocity, cadence, stride length, step width, foot angle, and double support time, as well as the variability of these temporal-spatial markers, were used to assess gait., Results: Results indicated that, in comparison with typically developing children, alcohol-exposed children produced exaggerated foot angle and increased step width. Additionally, alcohol-exposed children produced greater intrasubject variability of gait velocity and walking cadence while walking forward and backward, and greater variability in step width when walking backward and for all 3 walking conditions., Conclusions: The results indicate that selected gait markers are adversely affected by prenatal exposure to alcohol. Clinicians and front-line personnel (e.g., teachers) should provide movement enriched experiences to help ameliorate these alcohol-related deficits., (Copyright © 2017 by the Research Society on Alcoholism.)

The effects of vestibular rehabilitation on poststroke patients are unknown. This study aimed to investigate whether or not vestibular rehabilitation would improve both the vestibulo-ocular reflex and gait performance of patients with poststroke hemiparesis. Twenty-eight patients with stroke were assigned randomly to either an experimental group (N=14) or a control group (N=14). The experimental group performed the conventional physical therapy for 40 min and vestibular rehabilitation for 20 min, as a 60 min session, during the first 3 weeks and then completed only the conventional intervention for 60 min for the following 3 weeks. The control group performed only the 60 min conventional physical therapy for 6 weeks. Both groups were measured using the gaze stabilization test, the 10 m walking test, the timed up and go test, and the dynamic gait index. Patients were assessed at baseline, and at 3 and 6 weeks. Although the control group showed no significant difference in any outcome measures, the experimental group showed an improvement in gaze stabilization test scoring, which increased significantly after 3 weeks compared with the baseline (P=0.030). The dynamic gait index was also significantly increased after 3 and 6 weeks compared with the baseline (P=0.049 and 0.024, respectively). This study indicated that vestibular rehabilitation might improve poststroke patients' vestibulo-ocular reflex. Moreover, patients might show improved gait performance at least up to 3 weeks after the vestibular intervention by the sensory reweight to coordinate vestibular input.

Objective: To explore whether the cognitive impairment is correlated with freezing of gait (FOG) in patients with Parkinson disease (PD)., Methods: A total of 186 patients with Parkinson disease (104 patients with FOG and 82 patients with no clinical history of freezing behavior) and 125 healthy individuals were selected for this study. Neuropsychological assessments, including the scales for outcomes in Parkinson disease cognition, unified Parkinson's disease rating scale, and Hamilton depression/anxiety rating scale etc., were applied to evaluate the patients'cognitive functioning., Results: We found that the scores of Unified Parkinson's Disease Rating Scale (UPDRS) were significantly higher among PD patients with FOG, compared with non-FOG group. We also showed that Mini-Mental State Examination score (MMSE) was lower among subjects with FOG than in patients without FOG. Patients with FOG displayed lower Scales for OUTCOMES: in Parkinson's Disease Cognition (SCOPA-COG) score than non-FOG patients. In addition, significant higher Hamilton Anxiety Rating Scale (HAMD) scores were found in patients with FOG than patients without FOG. Moreover, disease duration, stage of the disease, the severity of motor symptom, increased depressive and anxiety complaints measured by FOG questionnaire were significantly associated with severity of FOG. Meanwhile, we also found that the score of Freezing of Gait Questionnaire (FOGQ) score was negatively correlated with MMSE., Conclusion: Our results demonstrated that FOG is related to impaired cognitive functions in PD patients with FOG. The understanding of impaired cognitive functions in PD patients with FOG can provide evidences for possible therapeutic interventions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A detailed gait analysis (e.g., measures related to speed, self-affinity, stability, and variability) can help to unravel the underlying causes of gait dysfunction, and identify cognitive impairment. However, because geriatric patients present with multiple conditions that also affect gait, results from healthy old adults cannot easily be extrapolated to geriatric patients. Hence, we (1) quantified gait outcomes based on dynamical systems theory, and (2) determined their discriminative power in three groups: healthy old adults, geriatric patients with- and geriatric patients without cognitive impairment., Methods: For the present cross-sectional study, 25 healthy old adults recruited from community (65 ± 5.5 years), and 70 geriatric patients with (n = 39) and without (n = 31) cognitive impairment from the geriatric dayclinic of the MC Slotervaart hospital in Amsterdam (80 ± 6.6 years) were included. Participants walked for 3 min during single- and dual-tasking at self-selected speed while 3D trunk accelerations were registered with an IPod touch G4. We quantified 23 gait outcomes that reflect multiple gait aspects. A multivariate model was built using Partial Least Square- Discriminant Analysis (PLS-DA) that best modelled participant group from gait outcomes., Results: For single-task walking, the PLS-DA model consisted of 4 Latent Variables that explained 63 and 41% of the variance in gait outcomes and group, respectively. Outcomes related to speed, regularity, predictability, and stability of trunk accelerations revealed with the highest discriminative power (VIP > 1). A high proportion of healthy old adults (96 and 93% for single- and dual-task, respectively) was correctly classified based on the gait outcomes. The discrimination of geriatric patients with and without cognitive impairment was poor, with 57% (single-task) and 64% (dual-task) of the patients misclassified., Conclusions: While geriatric patients vs. healthy old adults walked slower, and less regular, predictable, and stable, we found no differences in gait between geriatric patients with and without cognitive impairment. The effects of multiple comorbidities on geriatric patients' gait possibly causes a 'floor-effect', with no room for further deterioration when patients develop cognitive impairment. An accurate identification of cognitive status thus necessitates a multifactorial approach.

Cueing or feedback provided when gait deviates from a predefined goal (intelligent input) can now be provided with wearable technology for Parkinson's disease (PD). As people with and without freezing of gait (FOG) have distinct cognitive profiles, they may respond differently to various types of input. This study compared the effects of four input modalities during prolonged walking and explored the relationship with cognition, subjective preference, and FOG. Participants (15 with and 13 without FOG) walked 30 min while exposed to continuous cueing; intelligent cueing; intelligent feedback; or no input. Cueing consisted of metronome beats matched to comfortable cadence. Intelligent input represented bouts of ten beats indicating comfortable cadence (intelligent cueing) or an instruction to adapt gait speed (intelligent feedback) when cadence deviated from the comfortable target. Preference for one condition over the other was gathered. Freezers produced most stable gait under continuous cueing, but the majority favored intelligent feedback. Non-freezers showed no differences between conditions, but gait was more stable under intelligent input than in freezers. Interestingly, lower cognitive scores were related to worse gait during intelligent input, most prominently seen in freezers. These results suggest that cognitive ability is an aspect to take into account when deciding on the most appropriate cueing modality in different PD subgroups.

Turning has been implicated as a complex task that requires both motor and cognitive resources. Accumulating evidence shows that patients with Parkinson's disease (PD) require more steps and more time to complete a turn, however, the role of the prefrontal cortex during turning is not clear. Forty nine patients with PD without freezing of gait (mean age 71.7 ± 1.0 years; 67% men, disease duration 9.7 ± 1.3 years) performed motor and cognitive tests. Prefrontal activation, specifically in Brodmann area 10 (BA10), during turning and usual walking was measured using functional near infrared spectroscopy (fNIRS). The patients with PD were further divided into two subgroups with high and low functional status based on limitations in community ambulation. General Linear Model analysis adjusted for age, gender, disease duration and turn duration was used to assess differences between tasks and subgroups of patients with PD. In addition, Pearson's correlation was performed to assess association between BA10 activation and motor and cognitive scores. Activation in BA10 increased during walking (p < 0.001), while it decreased during turning (p = 0.006). A comparison between the two subgroups of patients with PD revealed that patients with relatively better ambulation decreased prefrontal activation during turning, as compared to patients with relatively worse ambulation (p < 0.001). These findings are the first to show that BA10 plays a different role during turning and walking and that ambulation status may alter BA10 activation during turning. Higher prefrontal activation during turning in the subgroup of patients with relatively worse ambulation may reflect a compensatory attempt at improving performance.

Background and Purpose: Individuals with Parkinson disease exhibit decreased axial head-pelvis rotation. Consequently, they turn more en bloc than healthy controls, which may contribute to freezing during turning. We wanted to understand the influence of auditory cueing and an attentional strategy on turning and how this related to freezing of gait (FOG)., Methods: Fifteen participants with Parkinson disease and FOG were asked to turn 180° during baseline condition, unilateral cueing, and an attentional strategy prompting to start the turn with head rotation first. FOG occurrence, axial rotation, center of mass (COM) deviation, knee-flexion amplitude, and total turn velocity were measured using 3D motion analysis while off-medication. Normal reference values were obtained from 14 age-matched controls., Results: Thirty-nine FOG episodes occurred in 5 participants. FOG occurred in 52.8% of baseline trials compared with 34.6% of trials using the head-first strategy, and 3.8% of the auditory cueing trials. During the head first strategy, the initiation of head, trunk, and pelvic rotation as well as the head-pelvis separation resembled turning patterns of healthy controls, but the COM shift to the inside of the turn was exaggerated. By contrast, during cueing, turning became more en bloc, with decreased head-pelvis separation and knee-flexion amplitude., Discussion and Conclusions: Cueing reduced FOG but did not correct axial movement deficits. The head-first strategy improved head-pelvis dissociation but had only limited effects on FOG. These results suggest that axial and COM deviation impairments are not directly related to FOG but may rather indicate a compensatory mechanism. Cueing reinforced the en-bloc movement and might as such help prevent FOG by triggering an alternative neural mechanism for movement generation.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A163).

Objective: Explore and describe experiences and perceptions of falls, risk of falling, and fall-related consequences in individuals with incomplete spinal cord injury (SCI) who are still walking., Design: A qualitative interview study applying interpretive content analysis with an inductive approach., Setting: Specialized rehabilitation hospital., Subjects: A purposeful sample of 15 individuals (10 men), 23 to 78 years old, 2-34 years post injury with chronic incomplete traumatic SCI, and walking ⩾75% of time for mobility needs., Methods: Individual, semi-structured face-to-face interviews were recorded, condensed, and coded to find themes and subthemes., Results: One overarching theme was revealed: "Falling challenges identity and self-image as normal" which comprised two main themes "Walking with incomplete SCI involves minimizing fall risk and fall-related concerns without compromising identity as normal" and "Walking with incomplete SCI implies willingness to increase fall risk in order to maintain identity as normal". Informants were aware of their increased fall risk and took precautions, but willingly exposed themselves to risky situations when important to self-identity. All informants expressed some conditional fall-related concerns, and a few experienced concerns limiting activity and participation., Conclusion: Ambulatory individuals with incomplete SCI considered falls to be a part of life. However, falls interfered with the informants' identities and self-images as normal, healthy, and well-functioning. A few expressed dysfunctional concerns about falling, and interventions should target these.

Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signaling in the brainstem. We investigated how long-term loss of cholinergic signaling from mesopontine nuclei influence motor behaviors. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT E n1-Cre-flox/flox ). VAChT E n1-Cre-flox/flox mice did not show any gross health or neuromuscular abnormality on metabolic cages, wire-hang and grip-force tests. Young VAChT E n1-Cre-flox/flox mice (2-5 months-old) presented motor learning/coordination deficits on the rotarod; moved slower, and had smaller steps on the catwalk, but showed no difference in locomotor activity on the open field. Old VAChT E n1-Creflox/flox mice (13-16 months-old) showed more pronounced motor learning/balance deficits on the rotarod, and more pronounced balance deficits on the catwalk. Furthermore, old mutants moved faster than controls, but with similar step length. Additionally, old VAChT-deficient mice were hyperactive. These results suggest that dysfunction of cholinergic neurons from mesopontine nuclei, which is commonly seen in PD, has causal roles in motor functions. Prevention of mesopontine cholinergic failure may help to prevent/improve postural instability and falls in PD patients. Read the Editorial Highlight for this article on page 688., (© 2016 International Society for Neurochemistry.)

Background: In patients affected by multiple sclerosis (MS) the disabilities increase during the progression of the disease, with a negative impact on quality of life. Rehabilitation improves motor performances, but remains unclear the role of psychological variables on motor recovery., Aim: The aim of this study was to investigate the role of the psychological well‑being during a rehabilitation care in MS patients with moderate to severe disability., Design: Longitudinal study., Setting: Outpatients in a Neurorehabilitation Unit of Pisa and Ferrara University Hospital., Population: 93 subjects affected by MS with moderate to severe degree of impairment were recruited (43 male, 50 female; mean age 53±11.19 years). In relation to the Expanded Disability Status Scale (EDSS) score the sample was divided in two group: Group 1 with moderate impairment (EDSS 4-5.5) and Group 2 with severe impairment (EDSS 6-7)., Methods: Psychological and functional status was assessed before and after a motor rehabilitative treatment, appropriate to their clinical needs. Parameters collected were: Short Form 36, Patient Health Questionnaire, Fatigue Severity Scale, 6-minute walking test and 10-meter walking test., Results: Mood disorders, low quality of life (QoL) and high perceived fatigue are characteristic symptoms in our sample. Results do not show a direct correlation with motor impairment. Mood improves in both groups, while walking endurance and speed ability recovers only in Group 1, on the contrary QoL improves only in Group 2. Regression analysis show that in Group 1 a better QoL predicts a higher motor recovery, whereas in Group 2 the improvement of walking endurance influences the subjective well‑being at the discharge., Conclusions: Subjective well‑being is related with the perception of the new condition of life. In less impaired patients psychological status can influence the liability toward rehabilitation treatment, while in more impaired patients motor recovery affect well‑being. Therefore, the psychological counselling should be provided during the rehabilitation treatment in order to achieve a successful patients' care., Clinical Rehabilitation Impact: Our approach contributes to bring out the role of subjective factors on motor rehabilitation outcome and the functional recovery effect on the psychological well‑being. The knowledge of subjective needs related to disability degree should be used to customize an appropriate care in MS patients.