Lower cognitive function affects gait and functional mobility in those with fragile X-associated tremor/ataxia syndrome (FXTAS), a study has found. Linking quantitative gait assessment with neuropsychological tests may help explain the complex interplay between cognitive and motor function and history of falls in these patients. The study, “Cognitive function impacts gait, functional mobility and falls in fragile X- associated tremor/ataxia syndrome” was published in Gait & Posture. Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disease that affects many people who carry the fragile X premutation. A premutation carrier (PMC) is a person who has anywhere from 55 to 200 CGG repeats in the fragile X gene FMR1. The full mutation is defined as more than 200 CGG repeats, and results in fragile X syndrome. A significant percentage of fragile X syndrome patients are affected by FXTAS. Most are men, usually in their early 70s. FXTAS patients may show symptoms including gait ataxia, balance problems, tremor, parkinsonism, and cognitive deficits. The main cognitive characteristic affecting people with FXTAS is impairment in executive function. These include working memory, attention control, response inhibition and self-regulation, verbal fluency, and information processing speed. These cognitive deficits may progress to dementia in advanced stages. Executive function allows people to plan, organize, and complete tasks. They are usually divided into three skills: working memory (being able to memorize something and use it afterward); cognitive flexibility (being able to think about something in more than one way); and inhibitory control (being able to ignore distractions; this includes self-control). Deficits in executive function also have been observed in FMR1 premutation carriers without FXTAS. Researchers now investigated the associations between executive function and information processing speed and gait, turning, and falls in male and female premutation carriers with and without FXTAS. This information is crucial "to determine fall risk in patients with FXTAS and may lead to the development of therapies tailored to their individual cognitive and gait deficits," researchers said. Patients were recruited from the Fragile X-Associated Disorders Program at Rush University Medical Center (RUMC) and divided into three experimental groups: premutation carriers with FXTAS (nine men and nine women), premutation carriers without FXTAS (four men and 11 women), and 27 healthy controls (14 men and 13 women). Participants were given gait testing — quantitative and mobility tests (gait speed, rhythm, and stride length, among others) — and neuropsychological tests to assess cognitive function (processing speed, verbal fluency and other factors). Oral tests were favored over written ones to prevent potential tremor limb ataxia from affecting individuals' performance. Subjects were also asked to self-report their number of falls within the previous year. There were no sex differences in demographic, cognitive function, clinical and molecular data among the three groups, except the number of falls in the past year, which was higher in men with FXTAS than women. Due to the nature of the disease, participants with FXTAS were significantly older than those without FXTAS and therefore presented with increased disease severity. The retrospective number of falls was significantly greater in the FXTAS group, which also presented with lower balance and increased overall disability. Gait speed, rhythm and cadence variability were significantly worse in premutation carriers with FXTAS compared to those without FXTAS and healthy controls. Lower information processing speed was significantly associated with shorter stride length, reflecting slower gait speed, in premutation carriers with FXTAS but not those without FXTAS or controls. Lower processing speed and working memory were strongly correlated with the high number of self-reported falls in the past year in FXTAS patients. “This cognitive information may be useful in identifying predictors for heightened fall risk in patients with FXTAS,” researchers said. Another interesting finding was the increased stride length variability in premutation carriers without FXTAS compared to healthy controls, which did not differ from those with FXTAS. “This suggests that some “asymptomatic” carriers could be developing the ataxic phenotype, which is characterized by increased gait variability. This potential marker of disease onset needs to be confirmed in prospective longitudinal studies," researchers concluded.