Longitudinal Study of Cognitive Functioning in Friedreich's Ataxia.

OBJECTIVE: Friedreich's ataxia (FRDA) is the most common hereditary ataxia. It is a neurodegenerative disorder, characterized by progressive ataxia. FRDA is also associated with cognitive impairments. To date, the evolution of cognitive functioning is unknown. Our aim was to investigate the changes in the cognitive functioning of FRDA patients over an average eight-year timeframe. In addition, we aimed to study the relationship between cognitive changes and clinical variables. METHODS: Twenty-nine FRDA patients who had been part of the sample of a previous study participated in the present study. The mean average time between the two assessments was 8.24 years. The participants completed an extensive battery of neuropsychological tests chosen to examine cognitive functioning in various cognitive domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions and language. RESULTS: At follow-up, cerebellar symptoms had worsened, and patients presented greater disability. Differences between baseline and follow-up were observed in motor and cognitive reaction times, several trials of the Stroop test, semantic fluency, and block designs. No other cognitive changes were observed. Deterioration in simple cognitive reactions times and block designs performance correlated with the progression of cerebellar symptoms. CONCLUSIONS: Our study has demonstrated for the first time that patients with FRDA experience a significant decline over time in several cognitive domains. Specifically, after an eight-year period, FRDA patients worsened in processing speed, fluency, and visuoconstructive skills. This progression is unlikely to be due to greater motor or speech impairment.

Cognition in late-onset Friedreich ataxia.

Friedreich ataxia (FRDA) is the most common hereditary ataxia. Since the discovery of the genetic cause of this disease, the phenotypic spectrum seems to be wider, including late-onset forms such as late-onset Friedreich ataxia--LOFA (25-39 years at onset). The neuropathological and clinical patterns in patients with LOFA are similar to those in patients with typical FRDA, but LOFA patients tend to have an overall milder, slowly evolving disease. Given the lack of data about cognitive performance of LOFA, we aimed to investigate whether differences in age at disease onset may be related also to differences at a cognitive level. Twenty-nine typical FRDA and seven LOFA patients were administered a comprehensive neuropsychological battery measuring multiple domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language. There were no significant differences in disease duration between the two groups of patients. Every patient group was matched in gender, age, years of education, and estimated IQ with a healthy-participant control group. Results indicate that both patient groups shared slowed motor processing speed and impaired conceptual thinking and verbal fluency. However, only typical FRDA patients showed a diminished cognitive processing speed and impaired visuoperceptive and visuoconstructive abilities. This pattern indicates that a later disease onset is associated to a milder cognitive impairment. Thus, our findings are in concordance with those related to clinical differences between typical FRDA and LOFA.

Cognition in Friedreich ataxia.

Friedreich ataxia (FRDA) is the most frequent of the inherited ataxias. However, very few studies have examined the cognitive status of patients with genetically defined FRDA. Our aim was to study cognitive performance of FRDA patients taking into account the motor problems characteristic of this clinical population. Thirty-six FRDA patients were administered a comprehensive neuropsychological battery measuring multiple domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language. Thirty-one gender, age, years of education, and estimated IQ-matched healthy participants served as control subjects. All participants were native Spanish speakers. Patients showed decreased motor and mental speed, problems in conceptual thinking, a diminished verbal fluency, deficits in acquisition of verbal information and use of semantic strategies in retrieval, visuoperceptive and visuoconstructive problems, and poor action naming. Scores on the depression inventory were significantly higher in patients than controls, but depression did not account for group differences in cognitive performance. The observed pattern of neuropsychological impairment is indicative of executive problems and parieto-temporal dysfunction. Neuropathological and neuroimaging studies with FRDA patients have reported only mild anomalies in cerebral hemispheres. Thus, cognitive impairment in FRDA is probably caused by the interruption of the cerebro-cerebellar circuits that have been proposed as the anatomical substrate of the cerebellar involvement in cognition.

Differential impairment in semantic, phonemic, and action fluency performance in Friedreich's ataxia: possible evidence of prefrontal dysfunction.

This study examined phonemic (letters), semantic (animals) and action verbal fluency cues in twenty-four patients with FRDA, and twenty matched healthy control subjects. The Action Fluency Test (AFT) is a newly-developed verbal fluency cue that consists in asking the subject to rapidly generate verbs. Given the high presence of dysarthria and cognitive slowness in FRDA patients, control tasks were administered in order to dissociate motor/articulatory impairment and cognitive slowness from verbal fluency deficit. Results showed that patients and control subjects performed similarly on the semantic fluency task. In contrast, patients performed significantly poorer on phonemic and action fluency tests. Correlational analyses showed that the deficits cannot be attributed to dysarthria or cognitive slowness. Although executive processes are necessary for initiating and monitoring all verbal fluency tasks, phonemic and action fluency may place a greater burden on strategic processes, given that they require a more unusual type of lexicon search. Thus, the deficits found occur in tasks that require greater executive/prefrontal control. This impairment might be the result of an affectation of cerebellum-prefrontal cortex connections, although the possibility of a primary prefrontal dysfunction remains to be investigated.