Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

Normative database of postural sway measures using inertial sensors in typically developing children and young adults.

OBJECTIVE: Reference values utilizing the APDM MobilityLab® inertial sensor system have not been established in children and young adults ages 5-30. These values are necessary for clinicians and researchers to compare to children with balance impairments. METHODS: A group of 144 typically developing children and young adults from age 5-30 years completed the instrumented SWAY test during 6 test conditions: normal stance, firm surface, eyes open (EO) and closed (EC); normal stance, foam surface, EO and EC; and tandem stance, firm surface, EO and EC. Selected variables for normative outcomes included total sway area, and the mean, sagittal and coronal values for RMS sway, jerk, sway velocity and path length. Sex differences were examined within age groups via t tests. The effect of age on postural sway variables was analyzed using a one-way ANOVA for the mean values of total sway area, RMS sway, velocity and jerk, followed by post-hoc pairwise comparisons. RESULTS: All sway parameters decreased significantly with age (p < 0.0001). Adult-like total sway area and jerk were achieved by ages 9-10 except for jerk during EC on foam. RMS sway and sway velocity reached adult levels by ages 11-13 during all EO and tandem stance conditions, and 14-21 with EC during normal stance on firm and foam surfaces for RMS sway and EC on firm surfaces for velocity. Females ages 5-6 performed more poorly during EO firm and EC foam for certain variables, but better during EO tandem and females ages 7-13 outperformed males when sex differences were found. SIGNIFICANCE: These reference values can now be used by clinicians and researchers to evaluate abnormal postural sway and response to interventions in children and young adults.

The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a genetic neurodegenerative disorder characterized by cerebellar ataxia, tremor, and cognitive dysfunction. We examined the impact of dual-task (DT) cognitive-motor interference and fast-paced (FP) gait on gait and turning in FXTAS. Thirty participants with FXTAS and 35 age-matched controls underwent gait analysis using an inertial sensor-based 2-min walk test under three conditions: (1) self-selected pace (ST), (2) FP, and (3) DT with a concurrent verbal fluency task. Linear regression analyses were performed to assess the association between FXTAS diagnosis and gait and turn outcomes. Correlations between gait variables and fall frequency were also calculated. FXTAS participants had reduced stride length and velocity, swing time, and peak turn velocity and greater double limb support time and number of steps to turn compared to controls under all three conditions. There was greater dual task cost of the verbal fluency task on peak turn velocity in men with FXTAS compared to controls. Additionally, stride length variability was increased and cadence was reduced in FXTAS participants in the FP condition. Stride velocity variability under FP gait was significantly associated with the number of self-reported falls in the last year. Greater motor control requirements for turning likely made men with FXTAS more susceptible to the negative effects of DT cognitive interference. FP gait exacerbated gait deficits in the domains of rhythm and variability, and increased gait variability with FP was associated with increased falls. These data may inform the design of rehabilitation strategies in FXTAS.

The effects of dual-task cognitive interference on gait and turning in Huntington's disease.

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.

The Effects of Dual-Task Cognitive Interference and Environmental Challenges on Balance in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is characterized by chorea, balance and gait impairments, and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. Furthermore, the impact of cognitive deficits on balance dysfunction and falls in HD is unknown. OBJECTIVE: To determine the impact of DT interference, sensory feedback, and cognitive performance on balance and falls in HD. METHODS: Seventeen participants with HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative balance testing with APDM inertial sensors. Postural sway was assessed during conditions of manipulated stance, vision, proprioception, and cognitive demand. The DT was a concurrent verbal fluency task. Neuropsychological assessments testing multiple cognitive domains were also administered. RESULTS: HD participants exhibited significantly greater total sway area, jerk, and variability under single-task (ST) and DT conditions compared to controls (P = 0.0002 - < 0.0001). They also demonstrated greater DT interference with vision removed for total sway area (P = 0.01) and variability (P = 0.02). Significantly worse postural control was observed in HD with vision removed and reduced proprioception (P = 0.001 - 0.01). Decreased visuospatial performance correlated with greater total sway and jerk (P = 0.01; 0.009). No balance parameters correlated with retrospective falls in HD. CONCLUSIONS: HD participants have worse postural control under DT, limited proprioception/vision, and greater DT interference with a narrowed base and no visual input. These findings may have implications for designing motor and cognitive strategies to improve balance in HD.