Friedreich ataxia: executive control is related to disease onset and GAA repeat length.

ABSTRACT

Friedreich ataxia (FRDA) is the most frequent inherited ataxia. Neuropsychological studies suggest that FRDA may be associated with specific cognitive impairment. Very little is known about the relation between cognitive performance, demographics and disease-related parameters, such as GAA repeat size, age of onset and disease duration. The present investigation aimed at assessing cognitive functions in a representative sample of FRDA patients and at identifying the most relevant disease-related parameters. Twenty-nine adult FRDA patients underwent neuropsychological tests assessing executive functions, attention, memory and visual perception. Performance was compared with 28 age- and education-matched controls as well as with standardized norms. The relation between neuropsychological outcome, demographical variables and disease-related parameters was assessed. Cognitive impairment affected only a subgroup of patients and mostly concerned attentional and executive functions. Good cognitive performance was associated with a later disease onset, shorter GAA repeat length and lower burden of disease. Age at disease onset has been found to be a good predictor when a cut-off of 14 years was chosen. No correlation was found between cognitive performance and education, age or disease duration. The present study extends earlier findings in FRDA showing that performance in attentional and executive function tasks is best predicted by the age at disease onset. Moreover, executive functions show a clear relationship to disease severity and repeat size of the shorter GAA allele. These findings therefore have important implications for patient counselling regarding education and career choices.