Abstract
BackgroundFragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative movement disorder characterized by tremor, ataxic gait, and balance issues resulting from a premutation of the Fragile X Mental Retardation 1 (FMR1) gene. No biomarkers have yet been identified to allow early diagnosis of FXTAS, however, recent studies have reported subtle issues in the stability of younger premutation carriers, before disease onset. This study investigates the efficacy of multiscale entropy analysis (MSE) in detecting early changes in the motor system of premutation carriers without FXTAS.MethodsSway complexity of 12 female Premutation carriers and 15 healthy Controls were measured under four conditions: eyes open, closed, and two dual-task conditions. A Sustained Attention Response Task (SART) and a working memory based N-Back task were employed to increase cognitive load while standing on the forceplate. A Complexity Index (Ci) was calculated for anterior-posterior (AP) and mediolateral (ML) sway. Independent t-tests were used to assess between-group differences and Oneway repeated measures ANOVA were used to assess within group differences with Bonferroni corrections to adjust for multiple comparisons.ResultsGroup performances were comparable with eyes open and closed conditions. The Carrier group’s Ci was consistent across tasks and conditions while the Control group’s AP Ci increased significantly during the cognitive dual-task (p = 0.001). There was also a strong correlation between CGG repeat length and complexity for the Carrier group (p = 0.004).SignificanceIncreased sway complexity is believed to stem from reallocation of attention to facilitate the increased cognitive demands of dual-tasks. Carriers’ complexity did not change during dual-tasks, possibly indicating capacity interference and inefficient division of attention. Lower sway complexity in carriers suggests diminished adaptive capacity under stress as well as degradation of motor functioning. Therefore, sway complexity may be a useful tool in identifying early functional decline in FMR1 premutation carriers as well as monitoring progression towards disease onset.
Highlights
Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a late-onset neurodegenerative movement disorder characterized by progressive cognitive decline, intention tremor, ataxic gait as well as impaired postural control and balance, which subsequently leads to increased risk of falls
There was no significant difference between Premutation Carriers and Controls in terms of their performance during either Sustained Attention Response Task (SART) or Nback task (Table 1)
Classical parameters There were no differences between groups in path length, sway area, or velocity in either ML or AP direction, during the eyes open (EO) and eyes closed (EC) conditions (p > 0.05)
Summary
Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a late-onset neurodegenerative movement disorder characterized by progressive cognitive decline, intention tremor, ataxic gait as well as impaired postural control and balance, which subsequently leads to increased risk of falls. FXTAS has been associated with neurophysiological changes such as reduced cerebellar volume, and aberrant structural connectivity among the superior and middle cerebellar peduncles [3,4,5]. Such regions are heavily involved in the cortico-ponto-cerebellar feedback loop, imperative for adaptive postural control [6]. Emerging evidence has shown carriers both male and female carriers with FXTAS and those younger than the typical age of onset to exhibited subtle changes in postural stability [7] and that such changes were mediated by reduced cerebellar volume and disruption in vulnerable cerebellar circuits [8]. This study investigates the efficacy of multiscale entropy analysis (MSE) in detecting early changes in the motor system of premutation carriers without FXTAS
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