Determinant of the cerebellar cognitive affective syndrome in Friedreich's ataxia

Individuals with Friedreich's ataxia (FRDA) display significantly lower performances in many cognitive domains with a pattern of impairment that falls within the cerebellar cognitive affective syndrome (CCAS).

To assess in a large cohort of individuals with FRDA, the main determinant of the CCAS using multiple variable regression models.

This is a monocentric observational study that included 39 individuals with FRDA. Ataxic motor symptoms were evaluated with the SARA and cognitive functions with the CCAS-Scale (CCAS-S). Age, SARA, GAA1, Age of symptoms onset (ASO), Age and disease duration (DD) were chosen as covariates in a linear regression model to predict CCAS-S failed items and covariates in a logistic regression model to predict definite CCAS.

Patients mean age, SARA score, ASO, DD and GAA1 were respectively of 29 ± 14, 22 ± 10, 14 ± 11, 15 ± 9 and 712 ± 238 (4 point-mutations). Mean CCAS-S raw score was of 86 ± 16, mean number of failed items was 2.9 ± 1.6. Twenty-three individuals had definite CCAS. The multiple linear regression model with age, SARA, ASO, DD & GAA1 as covariates was statistically significant to predict CCAS-S failed items. The SARA was the only significant coefficient in regression models for predicting CCAS-S failed items number and the definite CCAS occurrence.

CCAS is highly prevalent in adult individuals with FRDA. CCAS is predicted by ataxic motor symptoms severity. This finding supports common core cerebellar pathophysiology in both cognitive and motor symptoms in FRDA and warrants screening for CCAS, especially in patients with SARA > 20.