The cognitive profile of Friedreich ataxia: a systematic review and meta-analysis

BMC Neurol. 2022 Mar 17;22(1):97. doi: 10.1186/s12883-022-02615-3.


Background: Study the cognitive profile of individuals with Friedreich ataxia (FRDA) and seek evidence for correlations between clinical, genetic and imaging characteristics and neuropsychological impairments.

Methods: Based on PRISMA guidelines, a meta-analysis was realized using the Pubmed and Scopus databases to identify studies (1950-2021) reporting neuropsychological test results in genetically confirmed FRDA and control participants in at least one of the following cognitive domains: attention/executive, language, memory and visuo-spatial functions as well as emotion. Studies using identical outcomes in a minimum of two studies were pooled. Pooled effect sizes were calculated with Cohen's d.

Results: Eighteen studies were included. Individuals with FRDA displayed significantly lower performance than individuals without FRDA in most language, attention, executive function, memory visuospatial function, emotion regulation and social cognitive tasks. Among the included studies, thirteen studies examined the relationship between neuropsychological test results and clinical parameters and reported significant association with disease severity and six studies reviewed the relationship between neuroimaging measures and cognitive performance and mainly reported links between reduced cognitive performance and changes in cerebellar structure.

Conclusions: Individuals with FRDA display significantly lower performances in many cognitive domains compared to control participants. The spectrum of the cognitive profile alterations in FRDA and its correlation with disease severity and cerebellar structural parameters suggest a cerebellar role in the pathophysiology of FRDA cognitive impairments.

Keywords: Cerebellar cognitive affective syndrome; Cerebellum; Cognition; Friedreich ataxia.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cerebellum
  • Cognition / physiology
  • Executive Function
  • Friedreich Ataxia* / complications
  • Friedreich Ataxia* / genetics
  • Humans
  • Neuropsychological Tests