Top

BMC Neurology

Published in:

Open Access 01-12-2022 | Research article

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

Authors: Gilles Naeije, Jörg B Schulz, Louise A Corben

Published in: BMC Neurology | Issue 1/2022

Abstract

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.

Anheim M, et al. Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: Implications for clinical management. Neurogenetics. 2010. https://doi.org/10.1007/s10048-009-0196-y.CrossRefPubMed

Campuzano V, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271:1423–7.PubMed

Gottesfeld JM. Molecular mechanisms and therapeutics for the GAA·TTC expansion disease friedreich ataxia. Neurotherapeutics. 2019. https://doi.org/10.1007/s13311-019-00764-x.CrossRefPubMedPubMedCentral

Durr A, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med. 1996;335:1169–75.PubMed

Montermini L, et al. Phenotypic variability in friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann Neurol. 1997. https://doi.org/10.1002/ana.410410518.CrossRefPubMed

Koeppen AH, Mazurkiewicz JE. Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol. 2013;72:78–90.PubMed

Reetz K, et al. Nonataxia symptoms in Friedreich Ataxia. Neurology. 2018;91(10):e917-e930.

Pandolfo M. Neurologic outcomes in Friedreich ataxia. Neurol Genet. 2020;6:e415.PubMedPubMedCentral

Naeije G, Rovai A, Pandolfo M, De Tiège X, Pandolfo M. Hand dexterity and pyramidal dysfunction in Friedreich Ataxia, a finger tapping study. Mov Disord Clin Pract. 2020. https://doi.org/10.1002/mdc3.13126.CrossRefPubMedPubMedCentral

10.

Baumann O, et al. Consensus paper: the role of the cerebellum in perceptual processes. Cerebellum. 2015;14:197–220.PubMed

11.

Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46:831–44.PubMedPubMedCentral

12.

Davies DL. The intelligence of patients with Friedreich’s ataxia. J Neurol Neurosurg Psychiatry. 1949;12(1):34-8. https://doi.org/10.1136/jnnp.12.1.34.

13.

Fehrenbach RA, Wallesch CW, Claus D. Neuropsychologic findings in Friedreich’s ataxia. Arch Neurol. 1984;41:306–8.PubMed

14.

Nachbauer W, et al. Friedreich ataxia: executive control is related to disease onset and GAA repeat length. Cerebellum. 2014;13:9–16.PubMed

15.

Hernández-Torres A, Montón F, Hess Medler S, de Nóbrega É, Nieto A. Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia. J Int Neuropsychol Soc. 2021;27(4):343-50. https://doi.org/10.1017/S1355617720000958.

16.

de Nóbrega E, Nieto A, Barroso J, Montón F. Differential impairment in semantic, phonemic, and action fluency performance in Friedreich’s ataxia: possible evidence of prefrontal dysfunction. J Int Neuropsychol Soc. 2007;13:944–52.PubMed

17.

Wollmann T, Nieto-Barco A, Montón-Alvarez F, Barroso-Ribal J. Friedreich’s ataxia: analysis of magnetic resonance imaging parameters and their correlates with cognitive and motor slowing. Rev Neurol. 2004;38:217–22.PubMed

18.

Nieto A, et al. Cognition in friedreich ataxia. Cerebellum. 2012;11:834–44.PubMed

19.

Ciancarelli I, Cofini V, Carolei A. Evaluation of neuropsychological functions in patients with Friedreich ataxia before and after cognitive therapy. Funct Neurol. 2010;25:81–5.PubMed

20.

Corben LA, et al. Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction. J Neurol. 2010;257:782–91.PubMed

21.

Dogan I, et al. Structural characteristics of the central nervous system in Friedreich ataxia: an in vivo spinal cord and brain MRI study. J Neurol Neurosurg Psychiatry. 2019;90:615–7.PubMed

22.

Costabile T, et al. Emotion recognition and psychological comorbidity in Friedreich’s ataxia. Cerebellum. 2018;17:336–45.PubMed

23.

Moher D, Liberati A, Tetzlaff J, Altman DG, & PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535.

24.

Upton G, Cook I. A Dictionary of Statistics. A Dictionary of Statistics. 2014. https://doi.org/10.1093/acref/9780199679188.001.0001.CrossRef

25.

Higgins JPT, Green G. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 . The Cochrane Collaboration (2011). https://handbook-5-1.cochrane.org25.

26.

Morris SB, DeShon RP. Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychol Methods. 2002. https://doi.org/10.1037/1082-989X.7.1.105.CrossRefPubMed

27.

Cohen J. statistical power analysis for the behavioral sciences. Stat Power Anal Behav Sci. 2013. https://doi.org/10.4324/9780203771587.CrossRef

28.

Beeldman E, et al. The cognitive profile of ALS: A systematic review and meta-analysis update. J Neurol Neurosurg Psychiatry. 2016;87(6):611–9. https://doi.org/10.1136/jnnp-2015-310734.CrossRefPubMed

29.

Reetz K, et al. Biological and clinical characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data. Lancet Neurol. 2015;14:174–82.PubMed

30.

Sayah S, et al. Personality and neuropsychological profiles in Friedreich Ataxia. Cerebellum. 2018;17:204–12.PubMed

31.

Naeije G, et al. Cerebellar cognitive disorder parallels cerebellar motor symptoms in Friedreich ataxia. Ann Clin Transl Neurol. 2020;7:1050–4.PubMedPubMedCentral

32.

Harding IH, et al. Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: The IMAGE-FRDA study. Hum Brain Mapp. 2016;37:338–50.PubMed

33.

Cocozza S, et al. Cognitive and functional connectivity alterations in Friedreich’s ataxia. Ann Clin Transl Neurol. 2018;5:677–86.PubMedPubMedCentral

34.

Dogan I, et al. Cognition in Friedreich’s ataxia: a behavioral and multimodal imaging study. Ann Clin Transl Neurol. 2016;3:572–87.PubMedPubMedCentral

35.

Saccà F, et al. Normalization of timed neuropsychological tests with the PATA rate and nine-hole pegboard tests. J Neuropsychol. 2018;12:471–83.PubMed

36.

Cocozza S, et al. Cerebellum and cognition in Friedreich ataxia: a voxel-based morphometry and volumetric MRI study. J Neurol. 2020;267:350–8.PubMed

37.

Mantovan MC, et al. Exploring mental status in Friedreich’s ataxia: a combined neuropsychological, behavioral and neuroimaging study. Eur J Neurol. 2006;13:827–35.PubMed

38.

Vavla M, et al. Functional and structural brain damage in Friedreich’s Ataxia. Front Neurol. 2018;9:747.PubMedPubMedCentral

39.

Corben LA, et al. measuring inhibition and cognitive flexibility in Friedreich Ataxia. Cerebellum. 2017;16:757–63.PubMed

40.

Shishegar R, et al. Longitudinal increases in cerebral brain activation during working memory performance in Friedreich Ataxia: 24-Month Data from IMAGE-FRDA. Cerebellum. 2020;19:182–91.PubMed

41.

Reitan RM. Manual for administration of neuropsychological test batteries for adults and children. Tucson, AZ: Neuropsychology Laboratory. 1979.

42.

Corben LA, et al. The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity? Neuroscience. 2011;192:382–90.PubMed

43.

Corben LA, et al. Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task. Brain Cogn. 2011;76:140–5.PubMed

44.

Golden CJ, Freshwater SM. Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Chicago, IL: Stoelting Co; 2002.

45.

Akhlaghi H, et al. Cognitive deficits in Friedreich ataxia correlate with micro-structural changes in dentatorubral tract. Cerebellum. 2014;13:187–98.PubMed

46.

Klopper F, et al. The test of everyday attention reveals significant sustained volitional attention and working memory deficits in friedreich ataxia. J Int Neuropsychol Soc. 2011;17:196–200.PubMed

47.

Costabile T, et al. Emotion recognition and psychological comorbidity in Friedreich’s Ataxia. Cerebellum. 2018. https://doi.org/10.1007/s12311-018-0918-5.CrossRefPubMed

48.

Akhlaghi H, et al. Cognitive deficits In Friedreich Ataxia Correlate with micro-structural changes in dentatorubral tract. The Cerebellum. 2014;13:187–98.PubMed

49.

50.

Reetz K, et al. Progression characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS): a 2 year cohort study. Lancet Neurol. 2016;15:1346–54.PubMed

51.

Gibilisco P, Vogel AP. Friedreich ataxia. BMJ. 2013;347:f7062. https://doi.org/10.1136/bmj.f7062.

52.

Hoche F, Guell X, Vangel MG, Sherman JC, Schmahmann JD. The cerebellar cognitive affective/Schmahmann syndrome scale. Brain. 2018;141:248–70.PubMed

53.

Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121(Pt 4):561–79.PubMed

54.

Whiteside D, et al. Verbal Fluency: Language or Executive Function Measure? Appl Neuropsychol Adult. 2016;23(1):29–34.PubMed

55.

Morris JC, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). part I. clinical and neuropsychological assessment of Alzheimer’s disease. Neurology. 1989;39(9):1159–65.PubMed

56.

Amunts J, Camilleri JA, Eickhoff SB, Heim S, Weis S. Executive functions predict verbal fluency scores in healthy participants. Sci Rep. 2020;10:11141.PubMedPubMedCentral

57.

Shao Z, Janse E, Visser K, Meyer AS. What do verbal fluency tasks measure? predictors of verbal fluency performance in older adults. Front Psychol. 2014;5:772.PubMedPubMedCentral

58.

King M, Hernandez-Castillo CR, Poldrack RA, Ivry RB, Diedrichsen J. Functional boundaries in the human cerebellum revealed by a multi-domain task battery. Nat Neurosci. 2019;22:1371–8.PubMedPubMedCentral

59.

Price CJ. A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading. Neuroimage. 2012;62:816–47.PubMed

60.

Stoodley CJ, MacMore JP, Makris N, Sherman JC, Schmahmann JD. Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke. NeuroImage Clin. 2016;12:765–75.PubMedPubMedCentral

61.

Stoodley CJ, Schmahmann JD. The cerebellum and language: evidence from patients with cerebellar degeneration. Brain Lang. 2009;110:149–53.PubMed

62.

De Smet HJ, Paquier P, Verhoeven J, Mariën P. The cerebellum: its role in language and related cognitive and affective functions. Brain Lang. 2013;127:334–42.PubMed

63.

Ahmadian N, van Baarsen K, van Zandvoort M, Robe PA. The cerebellar cognitive affective syndrome—a meta-analysis. Cerebellum. 2019. https://doi.org/10.1007/s12311-019-01060-2.CrossRefPubMedPubMedCentral

64.

Kaplan, R. M. (Robert M. & Saccuzzo, D. P. Psychological testing : principles, applications, 8th issues. (Wadsworth, Cengage Learning, 2013)

65.

Benussi A, et al. Motor and cognitive outcomes of cerebello-spinal stimulation in neurodegenerative ataxia. Brain. 2021. https://doi.org/10.1093/brain/awab157.CrossRefPubMed

66.

Georgiou-Karistianis N, et al. Decreased functional brain activation in Friedreich ataxia using the Simon effect task. Brain Cogn. 2012;79:200–8.PubMed

67.

Vavla M, et al. Functional and structural brain damage in Friedreich’s Ataxia. Front Neurol. 2018;9:747.PubMedPubMedCentral

Title: The cognitive profile of Friedreich ataxia: a systematic review and meta-analysis
Authors: Gilles Naeije
Jörg B Schulz
Louise A Corben
Publication date: 01-12-2022
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-022-02615-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

Autoimmune encephalitis after BBIBP-CorV (Sinopharm) COVID-19 vaccination: a case report

Covid-19 threat and coping: application of protection motivation theory to the pandemic experiences of people affected by amyotrophic lateral sclerosis

Birth prevalence of neural tube defects in eastern Africa: a systematic review and meta-analysis

A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports

Development of a patient decision aid for discharge planning of hospitalized patients with stroke

Recurrent headache and visual symptoms in a young man: a rare neuronal intranuclear inclusion disease case report