Mov Disord

Background

Fragile X premutation carriers are at increased risk for fragile X-associated tremor ataxia syndrome (FXTAS), but to date we know little about prediction of onset and rate of progression, and even less about treatment of this neurodegenerative disease. Thus, longitudinal study of carriers, and identification of potential biomarkers and prodromal states, is essential. Here, we present results of baseline assessments from an ongoing longitudinal project.

Methods

The cohort consisted of 73 males, 48 with the fragile X mental retardation 1 (FMR1) premutation (55–200 cytosine-cytosine-guanine, CGG repeats) and 25 well-matched controls (< 40 repeats) between 40 and 75 years. At enrollment, none met criteria for FXTAS or had any clinically-significant tremor or ataxia by blinded neurological examination. The battery consisted of measures of visual memory, spatial working memory, response inhibition, motor speed and control, planning and problem solving, sustained attention, and a standardized movement disorder evaluation.

Results

Contrary to expectations, there were no significant differences between premutation carriers and controls on any measure of executive function. However, premutation carriers had significantly longer manual movement and reaction times than controls, and the significant interaction between CGG repeat and age revealed the slowest movement times among older carriers with higher CGG repeat alleles. A subset of premutation carriers had marginally lower scores on the ataxia evaluation, and they performed no differently from controls on the parkinsonism assessment.

Conclusion

Early-developing cerebellar or fronto-motor tract white matter changes, previously documented in MRI studies, may underlie motor slowing that occurs before clinically observable neurological symptoms.

29389022

PMC5889332

Journal Article

CDC Public Access