Language use predicts symptoms of fragile X-associated tremor/ataxia syndrome in men and women with the FMR1 premutation

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an age-related neurodegenerative disorder caused by a premutation of the FMR1 gene on the X chromosome. Despite the pervasive physical and cognitive effects of FXTAS, no studies have examined language in symptomatic males and females, limiting utility as an outcome measure in clinical trials of FXTAS. The goal of this work is to determine (a) the extent to which male and female FMR1 premutation carriers with FXTAS symptoms differ in their language use and (b) whether language production predicts FXTAS symptoms. Thirty-one individuals with the FMR1 premutation (21M, 10F), ages 58-85 years with some symptoms of FXTAS, were recruited from a larger cross-sectional study. Participants completed a five-minute monologic language sample. Language transcripts were assessed for rate of dysfluencies, lexical-semantics, syntax, and speech rate. Multivariable linear and ordinal regressions were used to predict FXTAS-associated symptoms, cognitive functioning, and executive functioning. Males and females did not differ in their language use. Language production predicted FXTAS symptom severity, cognitive functioning, and executive functioning. Language production difficulties may co-occur with FXTAS-associated symptoms and may be a viable outcome measure in future clinical trials, with future research needed.

Keywords: FMR1; Cognition; Executive function; Fragile X-associated tremor/ataxia syndrome; Language.

Fig. 1

Relationship between speech rate and FXTAS-associated symptoms. This figure represents the association between Words per Minute (i.e., speech rate) and predicted FXTAS Stage. FXTAS stage was rated from 0 (no symptoms) to 5 (definite and severe FXTAS symptoms). Fewer words per minute predicted greater FXTAS severity (Estimate = -.045, Wald χ² = 8.20, p=.004; pseudo R² = .38), above and beyond the effects of age and sex.

Fig. 2

Associations between executive functioning and lexical diversity. BDS-2: Behavioral Dyscontrol Scale -2nd edition. This figure represents the association between lexical diversity and executive functioning. Specifically, poorer executive functioning was predicted by lower rates of lexical diversity, above and beyond the effect of age and sex (b = .039, p=.008; R² = .28).