Skip to main content
SpringerLink
Log in

Selective Procedural Memory Impairment but Preserved Declarative Memory in Spinocerebellar Ataxia Type 3

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominant neurodegenerative disorder that affects mainly the cerebellum and less other brain areas. While the ataxic/motor features of the disease have been well described, the cognitive consequences of the degeneration require additional testing. The aim of this study was to evaluate learning abilities in SCA3. We tested 13 SCA3 patients and 14 age-matched healthy controls, all of Yemenite origin, on a neuropsychological battery of procedural and declarative memory tests. SCA3 patients demonstrated impaired sequence learning on the procedural Serial Reaction Time test (SRTt) but normal learning on the procedural Weather Prediction Probabilistic Classification test (WPPCt). SCA3 patients showed normal learning on the declarative Rey Auditory Verbal Learning test (Rey-AVLt). The correlations between the learning measures of the SRTt, WPPCt, and Rey-AVLt tests in SCA3 and controls separately were not significant. These results imply that the cerebellar degeneration in SCA3 causes selective impairment in procedural sequence learning while the procedural probabilistic learning and declarative memory were mostly preserved. These findings support the assumption that procedural learning is not a homogeneous function and could be dissociated in cerebellar neurodegenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bettencourt C, Lima M. Machado-Joseph Disease: from first descriptions to new perspectives. Orphanet J of Rare Diseases. 2011;6(1):35–47.

    Article  Google Scholar 

  2. Schmahmann JD. An emerging concept: the cerebellar contribution to higher function. Arch Neurol. 1991;48(11):1178–87.

    Article  CAS  PubMed  Google Scholar 

  3. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain : A J of Neurology. 1998;121(4):561–79.

    Article  Google Scholar 

  4. Goldberg-Stern H, D’jaldetti R, Melamed E, Gadoth N. Machado-Joseph (Azorean) disease in a Yemenite Jewish family in Israel. Neurology. 1994;44(7):1298–301.

    Article  CAS  PubMed  Google Scholar 

  5. Zaltzman R, Sharony R, Klein C, Gordon CR. Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation. J Neurol. 2016;263(11):2207–14.

    Article  PubMed  Google Scholar 

  6. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 1994;8(3):221–8.

    Article  CAS  PubMed  Google Scholar 

  7. Soong B, Paulson HL. Spinocerebellar ataxias: an update. Curr Opin Neurol. 2007;20(4):438–46.

    Article  CAS  PubMed  Google Scholar 

  8. Teive H, Arruda W. Cognitive dysfunction in spinocerebellar ataxias. Dementia and Neuropsychologia. 2009;3(3):180–7.

    Article  PubMed  PubMed Central  Google Scholar 

  9. de Rezende TJR, D’Abreu A, Guimaraes RP, Lopes TM, Lopes-Cendes I, Cendes F, et al. Cerebral cortex involvement in Machado−Joseph disease. Eur J Neurol. 2015;22(2):277–83.

    Article  PubMed  Google Scholar 

  10. Klockgether T, Skalej M, Wedekind D, Luft AR, Welte D, Schulz JB, et al. Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3. Brain : A J of Neurology. 1998;121(9):1687–93.

    Article  Google Scholar 

  11. Pedroso JL, Franca MC, Braga-Neto P, D’Abreu A, Saraiva-Pereira ML, Saute JA, et al. Nonmotor and extracerebellar features in Machado-Joseph disease: a review. Mov Disord. 2013;28(9):1200–8.

    Article  PubMed  Google Scholar 

  12. Rub U, Brunt E, Deller T. New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado–Joseph disease). Curr Opin Neurol. 2008;21(2):111–6.

    Article  PubMed  Google Scholar 

  13. Koeppen AH. The hereditary ataxias. J Neuropathol Exp Neurol. 1998;57(6):531–43.

    Article  CAS  PubMed  Google Scholar 

  14. Sequeiros J, Coutinho P. Epidemiology and clinical aspects of Machado-Joseph disease. Adv Neurol. 1993;61:139–53.

    CAS  PubMed  Google Scholar 

  15. Burt T, Blumbergs P, Currie B. A dominant hereditary ataxia resembling Machado-Joseph disease in Arnhem Land, Australia. Neurology. 1993;43(9):1750–2.

    Article  CAS  PubMed  Google Scholar 

  16. Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands. Neurology. 1978;28(7):703–9.

    Article  CAS  PubMed  Google Scholar 

  17. Fowler HL. Machado-Joseph-Azorean disease. A ten-year study. Arch Neurol. 1984;41(9):921–5.

    Article  CAS  PubMed  Google Scholar 

  18. Rosenberg RN, Nyhan WL, Bay C, Shore P. Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. Neurology. 1976;26(8):703–14.

    Article  CAS  PubMed  Google Scholar 

  19. Maruff P, Tyler P, Burt T, Currie B. Cognitive deficits in Machado-Josephs disease. Ann Neurol. 1996;40(3):421–7.

    Article  CAS  PubMed  Google Scholar 

  20. Burk K, Globas C, Bosch S, Klockgether T, Zuhlke C, Daum I, et al. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol. 2003;250(2):207–11.

    Article  CAS  PubMed  Google Scholar 

  21. Lopes TM, D’Abreu A, Franca MC, Yasuda CL, Betting LE, Samara AB, et al. Widespread neuronal damage and cognitive dysfunction in spinocerebellar ataxia type 3. J Neurol. 2013;260(9):2370–9.

    Article  CAS  PubMed  Google Scholar 

  22. Moriarty A, Cook A, Hunt H, Adams ME, Cipolotti L, Giunti P. A longitudinal investigation into cognition and disease progression in spinocerebellar ataxia types 1, 2, 3, 6, and 7. Orphanet J of Rare Diseases. 2016;11(1):82–90.

    Article  Google Scholar 

  23. Wang R, Tan S, Song B, Wang J, Ge F, Sun S, et al. Cognitive impairments in patients with spinocerebellar ataxia type 3 (SCA3) in China. Life Sci J. 2013;10(1):1655–9.

    Google Scholar 

  24. Ma J, Wu C, Lei J, Zhang X. Cognitive impairments in patients with spinocerebellar ataxia types 1, 2 and 3 are positively correlated to the clinical severity of ataxia symptoms. Int J Clin Exp Med. 2014;7(12):5765–71.

    PubMed  PubMed Central  Google Scholar 

  25. Schacter DL, Tulving E. Memory systems. 1st ed. Cambridge: MIT Press; 1994.

    Google Scholar 

  26. Lum JAG, Conti-Ramsden G, Page D, Ullman MT. Working, declarative and procedural memory in specific language impairment. Cortex. 2012;48(9):1138–54.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cohen NJ, Squire LR. Preserved learning and retention of pattern-analyzing skill in amnesia: dissociation of knowing how and knowing that. Science. 1980;210(4466):207–10.

    Article  CAS  PubMed  Google Scholar 

  28. Vakil E, Hoffman Y. Dissociation between two types of skill learning tasks: the differential effect of divided attention. J Clin Exp Neuropsychol. 2004;26(5):653–66.

    Article  PubMed  Google Scholar 

  29. Doyon J, Gaudreau D, Laforce R, Castonguay M, Bedard PJ, Bedard F, et al. Role of the striatum, cerebellum, and frontal lobes in the learning of a visuomotor sequence. Brain Cogn. 1997;34(2):218–45.

    Article  CAS  PubMed  Google Scholar 

  30. Gomez-Beldarrain M, Garcia-Monco JC, Rubio B, Pascual-Leone A. Effect of focal cerebellar lesions on procedural learning in the serial reaction time task. Exp Brain Res. 1998;120(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  31. Nissen MJ, Bullemer P. Attentional requirements of learning: evidence from performance measures. Cogn Psychol. 1987;19(1):1–32.

    Article  Google Scholar 

  32. Shin JC, Ivry RB. Spatial and temporal sequence learning in patients with Parkinson’s disease or cerebellar lesions. J Cogn Neurosci. 2003;15(8):1232–43.

    Article  PubMed  Google Scholar 

  33. Grafman J, Litvan I, Massaquoi S, Stewart M, Sirigu A, Hallett M. Cognitive planning deficit in patients with cerebellar atrophy. Neurology. 1992;42(8):1493–6.

    Article  CAS  PubMed  Google Scholar 

  34. Topka H, Valls-Solé J, Massaquoi SG, Hallett M. Deficit in classical conditioning in patients with cerebellar degeneration. Brain : A J of Neurology. 1993;116(4):961–9.

    Article  Google Scholar 

  35. Witt K, Nuhsman A, Deuschl G. Dissociation of habit-learning in Parkinson’s and cerebellar disease. J Cogn Neurosci. 2002;14(3):493–9.

    Article  CAS  PubMed  Google Scholar 

  36. Vakil E, Kahan S, Huberman M, Osimani A. Motor and non-motor sequence learning in patients with basal ganglia lesions: the case of serial reaction time (SRTt). Neuropsychologia. 2000;38(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  37. Vakil E, Herishanu-Naaman S. Declarative and procedural learning in Parkinson’s disease patients having tremor or bradykinesia as the predominant symptom. Cortex. 1998;34(4):611–20.

    Article  CAS  PubMed  Google Scholar 

  38. Knowlton BJ, Mangels JA, Squire LR. A neostriatal habit learning system in humans. Science. 1996;273(5280):1399–402.

    Article  CAS  PubMed  Google Scholar 

  39. Squire LR, Zola SM. Episodic memory, semantic memory, and amnesia. Hippocampus. 1998;8(3):205–11.

    Article  CAS  PubMed  Google Scholar 

  40. Knowlton, B. J., & Moody, T. D. (2008). Procedural learning in humans. In: J. H. Bryne (ed.), Learning and memory: a comprehensive reference (vol. 3): Memory systems, pp. 321-340. Oxford: academic press/Elsevier.

  41. Eichenbaum, H., & Cohen, N. (2004). From conditioning to conscious recollection: memory systems of the brain. Oxford Psychology Series, 35, Oxford University Press.

  42. Manns JR, Hopkins RO, Reed JM, Kitchener EG, Squire LR. Recognition memory and the human hippocampus. Neuron. 2003;37(1):171–80.

    Article  CAS  PubMed  Google Scholar 

  43. Wechsler D. Wechsler adult intelligence scale. 4th ed. San Antonio, TX: Psychological Corporation; 2008.

    Google Scholar 

  44. D’Abreu A, Franca MC Jr, Yasuda CL, Campos BAG, Lopes-Cendes I, Cendes F. Neocortical atrophy in Machado-Joseph disease: a longitudinal neuroimaging study. J Neuroimaging. 2012;22(3):285–91.

    Article  PubMed  Google Scholar 

  45. Schmitz-Hubsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006a;66(11):1717–20.

    Article  CAS  PubMed  Google Scholar 

  46. Schmitz-Hubsch T, Tezenas du Montcel S, Baliko L, Boesch S, Bonato S, Fancellu R, et al. Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients. Mov Disord. 2006b;21(5):699–704.

    Article  PubMed  Google Scholar 

  47. Beck A, Steer R, Brown G. Beck depression inventory-II. San Antonio. 1996;78(2):490–8.

    Google Scholar 

  48. Shapira-Lichter I, Vakil E, Litinsky I, Oren N, Glikmann-Johnston Y, Caspi, et al. Learning and memory-related brain activity dynamics are altered in systemic lupus erythematosus: a functional magnetic resonance imaging study. Lupus. 2013;22(6):562–73.

    Article  PubMed  Google Scholar 

  49. Vakil E, Blachstein H. Rey AVLT: developmental norms for adults and the sensitivity of different memory measures to age. Clin Neuropsychol. 1997;11(4):356–69.

    Article  Google Scholar 

  50. McMinn MR, Wiens AN, Crossen JR. Rey Auditory-Verbal Learning Test: development of norms for healthy young adults. Clin Neuropsychol. 1988;2(1):67–87.

    Article  Google Scholar 

  51. Lezak MD. Neuropsychological assessment. USA: Oxford University Press; 2004.

    Google Scholar 

  52. Paran D, Litinsky I, Shapira-Lichter I, Navon S, Hendler T, Caspi D, et al. Impaired memory and learning abilities in patients with systemic lupus erythematosus as measured by the Rey Auditory Verbal Learning Test. Ann Rheum Dis. 2009;68(6):812–6.

    Article  PubMed  Google Scholar 

  53. Vakil E, Greenstein Y, Blachstein H. Normative data for composite scores for children and adults derived from the Rey Auditory Verbal Learning Test. Clin Neuropsychol. 2010;24(4):662–77.

    Article  PubMed  Google Scholar 

  54. Zadka H. The dopaminergic system is involved in trial-and-error learning in uncertain environments and enables flexible learning strategies. Thesis: Unpublished M.Sc; 2013.

    Google Scholar 

  55. Knowlton BJ, Squire LR, Gluck MA. Probabilistic classification learning in amnesia. Learn Mem. 1994;1(2):106–20.

    Article  CAS  PubMed  Google Scholar 

  56. Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G. Cognitive impairments in Machado-Joseph disease. Arch Neurol. 2004;61(11):1757–60.

    Article  PubMed  Google Scholar 

  57. Zawacki TM, Grace J, Friedman JH, Sudarsky L. Executive and emotional dysfunction in Machado-Joseph disease. Mov Disord. 2002;17(5):1004–10.

    Article  PubMed  Google Scholar 

  58. Schols L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3(5):291–304.

    Article  PubMed  Google Scholar 

  59. Braga-Neto P, Pedroso JL, Alessi H, Dutra LA, Felício AC, Minett T, et al. Cerebellar cognitive affective syndrome in Machado-Joseph disease: core clinical features. Cerebellum. 2012;11(2):549–56.

    Article  PubMed  Google Scholar 

  60. Cecchin CR, Pires AP, Rieder CR, Monte TL, Silveira I, Carvalho T, et al. Depressive symptoms in Machado-Joseph disease (SCA3) patients and their relatives. Community Genetics. 2007;10(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  61. Klinke I, Minnerop M, Schmitz-Hubsch T, Hendriks M, Klockgether T, Wullner U, et al. Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. Cerebellum. 2010;9(3):433–42.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4(1):2–6.

    Article  CAS  PubMed  Google Scholar 

  63. Pascual Leone A, Grafman J, Clark K, Stewart M, Massaquoi S, Lou JS, et al. Procedural learning in Parkinson’s disease and cerebellar degeneration. Ann Neurol. 1993;34(4):594–602.

    Article  CAS  PubMed  Google Scholar 

  64. Rub U, Schols L, Paulson H, Auburger G, Kermer P, Jen JC, et al. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7. Prog Neurobiol. 2013;104:38–66.

    Article  PubMed  CAS  Google Scholar 

  65. Gobel EW, Blomeke K, Zadikoff C, Simuni T, Weintraub S, Reber PJ. Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson’s disease. Neuropsychology. 2013;27(3):314–21.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Knopman D, Nissen MJ. Procedural learning is impaired in Huntington’s disease: evidence from the serial reaction time task. Neuropsychologia. 1991;29(3):245–54.

    Article  CAS  PubMed  Google Scholar 

  67. Molinari M, Chiricozzi FR, Clausi S, Tedesco AM, De Lisa M, Leggio MG. Cerebellum and detection of sequences, from perception to cognition. Cerebellum. 2008;7(4):611–5.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the patients and families that participated in the study and the Israeli Machado-Joseph disease Association for their support.

Author information

Authors and Affiliations

  1. School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel

    Zohar Elyoseph & Matti Mintz

  2. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Matti Mintz & Carlos R. Gordon

  3. Department of Psychology, Bar Ilan University, Ramat Gan, Israel

    Eli Vakil

  4. Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel

    Eli Vakil

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Roy Zaltzman & Carlos R. Gordon

  6. Department of Neurology, Meir Medical Center, Kfar Saba, Israel

    Roy Zaltzman & Carlos R. Gordon

Authors
  1. Zohar Elyoseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matti Mintz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eli Vakil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roy Zaltzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlos R. Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos R. Gordon.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elyoseph, Z., Mintz, M., Vakil, E. et al. Selective Procedural Memory Impairment but Preserved Declarative Memory in Spinocerebellar Ataxia Type 3. Cerebellum 19, 226–234 (2020). https://doi.org/10.1007/s12311-019-01101-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-019-01101-w

Keywords

Search

Navigation