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Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia

Published online by Cambridge University Press:  14 October 2020

Atteneri Hernández-Torres ,
Fernando Montón ,
Stephany Hess Medler ,
Érika de Nóbrega  and
Antonieta Nieto Open the ORCID record for Antonieta Nieto [Opens in a new window]
Atteneri Hernández-Torres
Affiliation:
Facultad de Psicología, Universidad de La Laguna (ULL), Campus de Guajara, 38200 La Laguna (Tenerife), España
Fernando Montón
Affiliation:
Departamento de Neurología, Hospital Nuestra Señora de Candelaria (HUNSC), 38010 Santa Cruz de Tenerife, España
Stephany Hess Medler
Affiliation:
Facultad de Psicología, Universidad de La Laguna (ULL), Campus de Guajara, 38200 La Laguna (Tenerife), España
Érika de Nóbrega
Affiliation:
Facultad de Psicología, Universidad de La Laguna (ULL), Campus de Guajara, 38200 La Laguna (Tenerife), España
Antonieta Nieto*
Affiliation:
Facultad de Psicología, Universidad de La Laguna (ULL), Campus de Guajara, 38200 La Laguna (Tenerife), España
*
*Correspondence and reprint requests to: Antonieta Nieto, School of Psychology, University of La Laguna, 38205La Laguna, Tenerife, Spain. E-mail: [email protected]
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Abstract

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.

Keywords

Friedreich’s ataxiaLongitudinal studyCognitionNeuropsychologyCerebellum
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 4 , April 2021 , pp. 343 - 350
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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References

REFERENCES

Appollonio, I., Grafman, J., & Schwartz, V. (1993). Memory in patients with cerebellar degeneration. Neurology, 43, 1536–1544.CrossRefGoogle ScholarPubMed
Beck, A., Ward, C., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561–571.CrossRefGoogle ScholarPubMed
Benedet, M.J. & Alejandre, M.A. (1998). TAVEC: Test de Aprendizaje Verbal España-Complutense. Manual. Madrid: TEA ediciones.Google Scholar
Benton, A., Hamsher, K., & Sivan, A. (1989). Multilingual Aphasia Examination. 2nd ed., p. 32. Iowa City: University of Iowa.Google Scholar
Benton, A., Hamsher, S., Varney, O., & Spreen, N. (1983). Contributions to Neuropsychological Assessment: A Clinical Manual. New York: Oxford University Press.Google Scholar
Buckner, R.L. (2013). The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron, 80(3), 807–815.CrossRefGoogle ScholarPubMed
Campuzano, V., Montermini, L., Moltó, M.D., Pianese, L., Cossee, M., & Cavalcanti, F. (1996). Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science, 271(1), 1243–1247.CrossRefGoogle ScholarPubMed
Cocozza, S., Costabile, T., Pontillo, G., Lieto, M., Russo, C., Radice, L., … Saccà, F. (2020). Cerebellum and cognition in Friedreich ataxia: A voxel-based morphometry and volumetric MRI study. Journal of Neurology, 267, 350–358.CrossRefGoogle ScholarPubMed
Cocozza, S., Costabile, T., Tedeschi, E., Abate, F., Russo, C., Liguori, A., … Saccà, F. (2018). Cognitive and functional connectivity alterations in Friedreich’s ataxia. Annals of Clinical and Translational Neurology, 5(6), 677–686.CrossRefGoogle ScholarPubMed
Corben, L.A., Akhlaghi, H., Georgiou-Karistianis, N., Bradshaw, J.L., Egan, G.F., Storey, E., … Delatycki, M.B. (2011). Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task. Brain and Cognition, 76, 140–145.CrossRefGoogle ScholarPubMed
Corben, L.A., Delatycki, M.B., Bradshaw, J.L., Horne, M.K., Fahey, M.C., Churchyard, A.J., & Georgiou-Karistianis, N. (2010). Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction. Journal of Neurology, 257(5), 782–791.CrossRefGoogle ScholarPubMed
Corben, L.A., Klopper, F., Stagnitti, M., Georgiou-Karistianis, N., Bradshaw, J.L., Rance, G., … Delatycki, M.B. (2017). Measuring inhibition and cognitive flexibility in Friedreich ataxia. Cerebellum, 16(4), 757–763.CrossRefGoogle ScholarPubMed
Costabile, T., Capretti, V., Abate, F., Liguori, A., Paciello, F., Paciello, F., … Saccà, F. (2018). Emotion recognition and psychological comorbidity in Friedreich’s ataxia. The Cerebellum, 17, 336–345.CrossRefGoogle ScholarPubMed
Da Silva, C., Yasuda, C., D’Abreu, A., Cendes, F., Lopes-Cendes, I., & França, M. (2013). Neuroanatomical correlates of depression in Friedreich’s ataxia: A voxel-based morphometry study. Cerebellum, 12, 429–436.CrossRefGoogle Scholar
De Nóbrega, E., Nieto, A., Barroso, J., & Montón, F. (2007). Differential impairment in semantic, phonemic, and action fluency performance in Friedreich’s ataxia: Possible evidence of prefrontal dysfunction. Journal of the International Neuropsychological Society, 13, 944–952.CrossRefGoogle ScholarPubMed
Delis, D., Kramer, J., Kaplan, E., & Ober, B. (1987). California Verbal Learning Test: Adult Version Manual (p. 34). San Antonio, TX: Psychological Corporation.Google Scholar
Dogan, I., Tinnemann, E., Romanzetti, S., Mirzazade, S., Costa, A. S., Werner, C., … Reetz, K. (2016). Cognition in Friedreich’s ataxia: A behavioral and multimodal imaging study. Annals of Clinical and Translational Neurology. doi: 10.1002/acn3.315 CrossRefGoogle ScholarPubMed
Dürr, A., Cossee, M., Agid, Y., Campuzano, V., Mignard, C., Penet, C., … Koenig, M. (1996). Clinical and genetic abnormalities in patients with Friedreich’s Ataxia. The New England Journal of Medicine, 335(16), 1169–1175.CrossRefGoogle ScholarPubMed
Erlenmeyer-Kimling, L. & Cornblatt, B.A. (1992). A summary of attentional findings in the New York high-risk project. Journal of Psychiatric Research, 26(4):405–426.CrossRefGoogle ScholarPubMed
Fahey, M.C., Corben, L., Collins, V., Churchyard, A.J., & Delatycki, M.B. (2007). How is disease progress in Friedreich’s ataxia best measured? A study of four rating scales. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 411–413.CrossRefGoogle Scholar
Filla, A., De Michele, G., Cavalcanti, F., Pianese, L., Monticelli, A., Campanella, G., … Cocozza, S. (1996). The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. American Journal of Human Genetics, 59(3), 554–560.Google ScholarPubMed
França, M.C., D’Abreu, A., Yasuda, C.L., Bonadia, L.C., Santos da Silva, M., Nucci, A., … Öz, G. (2009). A combined voxel-based morphometry and 1H-MRS study in patients with Friedreich’s ataxia. Journal of Neurology, 256(7), 1114–1120.CrossRefGoogle ScholarPubMed
Ginestroni, A., Diciotti, S., Cecchi, P., Pesaresi, I., Tessa, C., Giannelli, M., … Mascalchi, M. (2012) Neurodegeneration in Friedreich’s ataxia is associated with a mixed activation pattern of the brain: A fMRI study. Human Brain Mapping, 33, 1780–1791.CrossRefGoogle ScholarPubMed
Golden, C. (1978). Stroop Color and Word Test: A Manual for Clinical and Experimental Uses (p. 29). Chicago: Stoelting Company.Google Scholar
Guell, X., D’Mello, A., Hubbard, N., Romeo, R., Gabrieli, J., Whitfield-Gabrieli, S., … Anteraper, A. (2020) Functional territories of human dentate nucleus. Cerebral Cortex, 30(4), 2401–2417.CrossRefGoogle ScholarPubMed
Harding, A. (1984). The Hereditary Ataxias and Related Disorders. Edinburgh: Churchill Livingstone.Google Scholar
Heaton, R. (1981). A Manual for the Wisconsin card Sorting Test. Odessa: Psychological Assessment Resources.Google Scholar
Koeppen, A.H. (2011). Friedreich’s ataxia: Pathology, pathogenesis, and molecular genetics. Neurological Sciences, 303(1–2), 1–12.CrossRefGoogle ScholarPubMed
Koeppen, A.H. & Mazurkiewicz, J.E. (2013). Friedreich ataxia: Neuropathology revised. Journal of Neuropathology & Experimental Neurology, 72(2), 78–90.CrossRefGoogle ScholarPubMed
Koeppen, A.H. (1998). The hereditary ataxias. Journal of Neuropathology & Experimental Neurology, 57(6), 53143.CrossRefGoogle ScholarPubMed
Koeppen, A.H., Morral, J.A., Davis, A.N., Qian, J., Petrocine, S.V., Knutson, M.D., … Li, D. (2009). The dorsal root ganglion in Friedreich’s ataxia. Acta Neuropathologica, 118, 763–776.CrossRefGoogle ScholarPubMed
Koeppen, A.H., Ramirez, R.L., Becker, A.B., & Mazurkiewicz, J.E. (2016). Dorsal root ganglia in Friedreich ataxia: Satellite cell proliferation and inflammation. Acta Neuropathologica Communications, 4, 46.CrossRefGoogle ScholarPubMed
Koeppen, A.H., Ramirez, R.L., Yu, D., Collins, S.E., Qian, J., Parsons, P.J. … Feustel, P.J. (2010). Friedreich’s ataxia causes redistribution of iron, copper and zinc in the dentate nucleus. Cerebellum, 11, 845.CrossRefGoogle Scholar
Manto, M. & Mariën, P. (2015). Schmahmann’s syndrome – Identification of the third cornerstone of clinical ataxiology. Cerebellum & Ataxias, 2, 2.CrossRefGoogle ScholarPubMed
Mascalchi, M., Toschi, N., Giannelli, M., Ginestroni, A., Della Nave, R., Tessa, C., … Diciotti, S. (2016). Regional cerebral disease progression in Friedreich’s ataxia: A longitudinal diffusion tensor imaging study. Journal of Neuroimaging, 26, 197–200.CrossRefGoogle ScholarPubMed
Nachbauer, W., Bodner, T., Boesch, S., Karner, E., Eigentler, A., Neier, L., … Delazer, M. (2014). Friedreich ataxia: Executive control is related to disease onset and GAA repeat length. Cerebellum, 13, 9–16.CrossRefGoogle ScholarPubMed
Nieto, A., Correia, A., De Nóbrega, E., Montón, F., & Barroso, J. (2013). Cognition in late onset Friedreich ataxia. Cerebellum, 12. doi: 10.1007/s12311-013-0457-z CrossRefGoogle ScholarPubMed
Nieto, A., Correia, R., De Nóbrega, E., Montón, F., Hess, S., & Barroso, J. (2012). Cognition in Friedreich ataxia. Cerebellum, 11, 834–844.CrossRefGoogle ScholarPubMed
Nieto, A., Hernández-Torres, A., Pérez-Flores, J., & Montón, F. (2018). Depressive symptoms in Friedreich ataxia. International Journal of Clinical and Health Psychology, 18(1), 18–26.CrossRefGoogle ScholarPubMed
Nobile-Orazio, E., Baldini, L., & Barbieri, S. (1988). Treatment of patients with neuropathy and anti-MAG IgM M-proteins. Annals of Neurology, 24(1), 93–97.CrossRefGoogle ScholarPubMed
Pagani, E., Ginestroni, A., Della Nave, R., Agosta, F., Salvi, F., DeMichele, G., … Mascalchi, M. (2010). Assessment of brain white matter fiber bundle atrophy in patients with Friedreich ataxia. Radiology, 255(3), 882–889.CrossRefGoogle ScholarPubMed
Patel, M., Isaacs, C.J., Seyer, L., Brigatti, K., Gelbard, S., Strawser, C., Foerster, D., … Lynch, D.R. (2016) Progression of Friedreich ataxia: Quantitative characterization over 5 years. Annals of Clinical and Translational Neurology, 3(9), 684–694.CrossRefGoogle ScholarPubMed
Piatt, A.L, Fields, J.A, Paolo, A.M., & Tröster, A.I. (1999). Action (verb naming) fluency as an executive function measure: convergent and divergent evidence of validity. Neuropsychologia, 37(13), 1499–1503.CrossRefGoogle ScholarPubMed
Rao, S.M., Leo, G.J., Bernardin, L., & Unverzagt, F. (1991). Cognitive dysfunction in multiple sclerosis: I. Frequency, patterns, and prediction. Neurology, 41(5), 685–691.CrossRefGoogle ScholarPubMed
Reetz, K., Dogan, I., Costa, A.S., Dafotakis, M., Fedosov, K., Giunti, P., … Schulz, J.B. (2015). Biological and clinical characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) cohort: A cross-sectional analysis of baseline data. The Lancet Neurology, 14(2), 174–182. CrossRefGoogle ScholarPubMed
Reetz, K., Dogan, I., Hilgers, R., Giunti, P., Mariotti, C., Durr, A., … Schulz, J.B. (2016). Progression characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS): A 2 year cohort study. The Lancet Neurology, 15, 1346–1354. CrossRefGoogle ScholarPubMed
Rezende, T.J.R., Martinez, A.R.M., Faber, I., Girotto, K., Pedroso, J.L., Barsottini, O.G., … França, M.C. (2017). Structural signature of classical versus late-onset Friedreich’s ataxia by multimodality brain MRI. Human Brain Mapping, 38, 4157–4168.CrossRefGoogle ScholarPubMed
Rezende, T.J.R., Silva, C.B., Yasuda, C.L., Campos, B.M., D’Abreu, A., Cendes, F., … França, M.C. (2016). Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich’s ataxia. Movement Disorders, 31(1), 70–78.CrossRefGoogle ScholarPubMed
Saccà, F., Costabile, T., Abate, F., Liguori, A., Paciello, F., Pane, C., … Filla, A. (2017). Normalization of timed neuropsychological tests with the PATA rate and nine-hole pegboard tests. Journal of Neuropsychology, 12(3), 471–483.CrossRefGoogle ScholarPubMed
Sayah, S., Rotgé, J.Y., Francisque, H., Gargiulo, M., Czernecki, V., Justo, D., … Durr, A. (2018). Personality and neuropsychological profiles in Friedreich ataxia. Cerebellum, 17(2), 204–212.CrossRefGoogle ScholarPubMed
Schmahmann, J. (2013). Cerebellar cognitive affective syndrome and the neuropsychiatry of the cerebellum. In Manto, M., Gruol, D.L., Schmahmann, J.D., Koibuchi, N, Rossi, F (Eds.), Handbook of the cerebellum and cerebellar disorders (pp. 1717–1750). Dordrecht: Springer Science+Business Media.CrossRefGoogle Scholar
Schmucker, S. & Puccio, H. (2010). Understanding the molecular mechanisms of Friedreich’s ataxia to develop therapeutic approaches. Human Molecular Genetics, 19, R103–R110.CrossRefGoogle ScholarPubMed
Schuhfried, G. (1992). Vienna Reaction Unit. Manual. Vienna: Schuhfried Ges.m.b.H.Google Scholar
Selvadurai, L., Corben, L., Delatycki, M., Storey, E., Egan, G., Georgiou-Karistianis, N., & Harding, I. (2020). Multiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE-FRDA study. Human Brain Mapping, 41(7), 1920–1933.CrossRefGoogle ScholarPubMed
Selvadurai, L., Harding, I., Corben, L., & Georgiou-Karistianis, N. (2018). Cerebral abnormalities in Friedreich ataxia: A review. Neuroscience and Biobehavioral Reviews, 84, 394–406.CrossRefGoogle ScholarPubMed
Selvadurai, L.P., Harding, I.H., Corben, L.A., Stagnitti, M.R., Storey, E., Egan, G.F., … Georgiou-Karistianis, N. (2016). Cerebral and cerebellar grey matter atrophy in Friedreich ataxia: The IMAGE-FRDA study. Journal of Neurology, 263(11), 2215–2223.CrossRefGoogle ScholarPubMed
Solbach, K., Kraff, O., Minnerop, M., Becke, A., Schölsf, L., Gizewskii, E. R. … Timmann, D. (2014). Cerebellar pathology in Friedreich´s ataxia: Atrophied dentate nuclei with normal iron content. NeuroImage: Clinical, 6, 93–99.CrossRefGoogle Scholar
Strick, P., Dum, R., & Fiez, J. (2009). Cerebellum and nonmotor function. Annual Review of Neuroscience, 32, 413–434.CrossRefGoogle ScholarPubMed
Tsou, A.Y., Paulsen, E.K., Lagedrost, S.J., Perlman, S.L., Mathews, K.D., Wilmot, G.R., … Lynch, D.R. (2011). Mortality in Friedreich ataxia. Journal of the Neurological Sciences, 307(1), 46–49.CrossRefGoogle ScholarPubMed
Vankan, P. (2013). Prevalence gradients of Friedreich’s ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge. Journal of Neurochemistry, 126(Suppl. 1), 11–20.CrossRefGoogle ScholarPubMed
Wechsler, D. (1997). Wechsler Adult Intelligence Scale—Administration and Scoring Manual. 3rd ed. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D. (1997). Wechsler Memory Scale. 3rd ed. (p. 30). Technical manual. San Antonio, TX: Psychological Corporation.Google Scholar
Zalesky, A., Akhlaghi, H., Corben, L., Bradshaw, J., Delatycki, M., Storey, E., …, Egan, G. (2014). Cerebello-cerebral connectivity deficits in Friedreich ataxia. Brain Structure and Function, 219, 969–981.CrossRefGoogle ScholarPubMed