Abstract
BackgroundIndividuals with premutation alleles of the FMR1 gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition affecting sensorimotor function. Information on quantitative symptom traits associated with aging in premutation carriers is needed to clarify neurodegenerative processes contributing to FXTAS.Materials and Methods26 FMR1 premutation carriers ages 44–77 years and 31 age-matched healthy controls completed rapid (2 s) and sustained (8 s) visually guided precision gripping tasks. Individuals pressed at multiple force levels to determine the impact of increasing the difficulty of sensorimotor actions on precision behavior. During initial pressing, reaction time, the rate at which individuals increased their force, the duration of pressing, and force accuracy were measured. During sustained gripping, the complexity of the force time series, force variability, and mean force were examined. During relaxation, the rate at which individuals decreased their force was measured. We also examined the relationships between visuomotor behavior and cytosine-guanine-guanine (CGG) repeat length and clinically rated FXTAS symptoms.ResultsRelative to controls, premutation carriers showed reduced rates of initial force generation during rapid motor actions and longer durations of their initial pressing with their dominant hand. During sustained force, premutation carriers demonstrated reduced force complexity, though this effect was specific to younger premutation carries during dominant hand pressing and was more severe for younger relative to older premutation carriers at low and medium force levels. Increased reaction time and lower sustained force complexity each were associated with greater CGG repeat length for premutation carriers. Increased reaction time and increased sustained force variability were associated with more severe clinically rated FXTAS symptoms.ConclusionOverall our findings suggest multiple sensorimotor processes are disrupted in aging premutation carriers, including initial force control guided by feedforward mechanisms and sustained sensorimotor behaviors guided by sensory feedback control processes. Results indicating that sensorimotor issues in aging premutation carriers relate to both greater CGG repeat length and clinically rated FXTAS symptoms suggest that quantitative tests of precision sensorimotor ability may serve as key targets for monitoring FXTAS risk and progression.
Highlights
Individuals with premutation alleles of the FMR1 gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition affecting sensorimotor function
maximum voluntary contraction (MVC) was not related to age (β = −2.01, SE = 4.00, p = 0.616, partial R2 = 0.029), and the relationship between age and MVC did not differ between groups
We found that increased reaction time and increased force variability each were associated with more severe clinically rated neuromotor issues in premutation carriers suggesting that quantifiable deficits in precision sensorimotor behaviors may be part of the aging process in FMR1 premutation carriers, or that these issues may reflect early indicators of neurodegeneration associated with FXTAS
Summary
Individuals with premutation alleles of the FMR1 gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition affecting sensorimotor function. Premutations of the FMR1 gene involving 55–200 CGG repeats confer risk for multiple subclinical issues as well as medical, psychiatric, and neurodegenerative conditions (Lozano et al, 2014) including fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS is a neurodegenerative disease in which patients present with a variety of sensorimotor, cognitive, psychiatric and medical issues, as well as cerebellar and cortical degeneration typically beginning at ages 50–70 years (Brunberg et al, 2002; Jacquemont et al, 2003). Symptom presentation is highly variable across patients, and objective, quantitative tools are needed to identify aging premutation carriers most at risk of developing FXTAS, track disease progression, and determine neurobiological mechanisms (Jacquemont et al, 2004; Leehey et al, 2007)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
