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Journal of Neurology

, Volume 265, Issue 7, pp 1563–1572 | Cite as

Executive dysfunction in patients with spinocerebellar ataxia type 3

  • Itaru TamuraEmail author
  • Asako Takei
  • Shinsuke Hamada
  • Hiroyuki Soma
  • Michio Nonaka
  • Sanae Homma
  • Fumio Moriwaka
Original Communication

Abstract

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex–ventral dentate nucleus–thalamus–prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.

Keywords

Spinocerebellar ataxia type 3 Word fluency Verbal working memory Retrieval process Cerebellum 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare that there is no conflict of interest.

Ethical standard statement

The study was performed in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from each subject, and the study was approved by the local ethics committee.

References

  1. 1.
    Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579.  https://doi.org/10.1093/brain/121.4.561 CrossRefPubMedGoogle Scholar
  2. 2.
    Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S et al (1994) CAG expansions in a novel gene for Machado–Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228.  https://doi.org/10.1038/ng1194-221 CrossRefPubMedGoogle Scholar
  3. 3.
    Taniwaki T, Sakai T, Kobayashi T, Kuwabara Y, Otsuka M, Ichiya Y et al (1997) Positron emission tomography (PET) in Machado–Joseph disease. J Neurol Sci 145:63–67.  https://doi.org/10.1016/S0022-510X(96)00242-0 CrossRefPubMedGoogle Scholar
  4. 4.
    Iwabuchi K, Tsuchiya K, Uchihara T, Yagishita S (1999) Autosomal dominant spinocerebellar degenerations. Clinical, pathological, and genetic correlations. Rev Neurol (Paris) 155:255–270Google Scholar
  5. 5.
    Schöls L, Bauer P, Schmidt T, Schulte T, Riess O (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3:291–304.  https://doi.org/10.1016/S1474-4422(04)00737-9 CrossRefPubMedGoogle Scholar
  6. 6.
    D’Abreu A, França MC Jr, Yasuda CL, Campos BA, Lopes-Cendes I, Cendes F (2012) Neocortical atrophy in Machado–Joseph disease: a longitudinal neuroimaging study. J Neuroimaging 22:285–291.  https://doi.org/10.1111/j.1552-6569.2011.00614.x CrossRefPubMedGoogle Scholar
  7. 7.
    Bürk K, Globas C, Bösch S, Klockgether T, Zühlke C, Daum I et al (2003) Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 250: 207–211.  https://doi.org/10.1007/s00415-003-0976-5 CrossRefPubMedGoogle Scholar
  8. 8.
    Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G (2004) Cognitive impairments in Machado–Joseph Disease. Arch Neurol 61:1757–1760.  https://doi.org/10.1001/archneur.61.11.1757 CrossRefPubMedGoogle Scholar
  9. 9.
    Garrard P, Martin NH, Giunti P, Cipolotti L (2008) Cognitive and social cognitive functioning in spinocerebellar ataxia: a preliminary characterization. J Neurol 255:398–405.  https://doi.org/10.1007/s00415-008-0680-6 CrossRefPubMedGoogle Scholar
  10. 10.
    Lopes TM, D’Abreu A, França MC Jr, Yasuda CL, Betting LE, Samara AB,et al (2013) Widespread neuronal damage and cognitive dysfunction in spinocerebellar ataxia type 3. J Neurol 260:2370–2379.  https://doi.org/10.1007/s00415-013-6998-8 CrossRefPubMedGoogle Scholar
  11. 11.
    Feng L, Chen DB, Hou L, Huang LH, Lu SY, Liang XL,et al (2014) Cognitive impairment in native Chinese with spinocerebellar ataxia type 3. Eur Neurol 71:262–270.  https://doi.org/10.1159/000357404 CrossRefPubMedGoogle Scholar
  12. 12.
    Ma J, Wu C, Lei J, Zhang X (2014) 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 7:5765–5771PubMedPubMedCentralGoogle Scholar
  13. 13.
    Roeske S, Filla I, Heim S, Amunts K, Helmstaedter C, Wüllner U et al (2013) Progressive cognitive dysfunction in spinocerebellar ataxia type3. Move Disord 28:1435–1438.  https://doi.org/10.1002/mds.25512 CrossRefGoogle Scholar
  14. 14.
    Zawacki TM, Grace JG, Friedman JH, Sudarsky L (2002) Executive and emotional dysfunction in Machado–Joseph disease. Move Disord 17:1004–1010.  https://doi.org/10.1002/mds.10033
  15. 15.
    Klinke I, Minnerop M, Schmitz-Hübsch T, Hendriks M, Klockgether T, Wüllner U et al (2010) Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. Cerebellum 9:433–442.  https://doi.org/10.1007/s12311-010-0183-8 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Braga-Neto P, Pedroso JL, Alessi H, Dutra LA, Felício AC, Minett T, et al (2012) Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features. Cerebellum 11:549–556.  https://doi.org/10.1007/s12311-011-0318-6 CrossRefPubMedGoogle Scholar
  17. 17.
    Braga-Neto P, Dutra LA, Pedroso JL, Felício AC, Alessi H, Santos-Galduroz RF et al (2012) Cognitive deficits in Machado–Joseph disease correlate with hypoperfusion of visual system areas. Cerebellum 11:1037–1044.  https://doi.org/10.1007/s12311-012-0354-x CrossRefPubMedGoogle Scholar
  18. 18.
    Tamura I, Takei A, Hamada S, Nonaka M, Kurosaki Y, Moriwaka F (2017) Cognitive dysfunction in patients with spinocerebellar ataxia type 6. J Neurol 264:260–267.  https://doi.org/10.1007/s00415-016-8344-4 PubMedCrossRefGoogle Scholar
  19. 19.
    Gottwald B, Mihajlovic Z, Wilde B, Mehdorn HM (2003) Does the cerebellum contribute to specific aspects of attention? Neuropsychologia 41:1452–1460.  https://doi.org/10.1016/S0028-3932(03)00090-3 CrossRefPubMedGoogle Scholar
  20. 20.
    Gottwald B, Wilde B, Mihajlovic Z, Mehdorn HM (2004) Evidence for distinct cognitive deficits after focal cerebellar lesions. J Neurol Neurosurg Psychiatry 75:1524–1531.  https://doi.org/10.1136/jnnp.2003.018093 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ravizza SM, McCormick CA, Schlerf JE, Justus T, Ivry RB, Fiez JA (2006) Cerebellar damage produces selective deficits in verbal working memory. Brain129:306–320.  https://doi.org/10.1093/brain/awh685
  22. 22.
    Peterburs J, Bellebaum C, Koch B, Schwarz M, Daum I (2010) Working memory and verbal fluency deficits following cerebellar lesions: relation to interindividual differences in patients variables. Cerebellum 9:375–383.  https://doi.org/10.1007/s12311-010-0171-z CrossRefPubMedGoogle Scholar
  23. 23.
    Mak M, Tyburski E, Madany Ł, Sokołowski A, Samochowiec A (2016) Executive function deficits in patients after cerebellar neurosurgery. J Int Neuropsychol Soc 22:47–57.  https://doi.org/10.1017/S1355617715001174 CrossRefPubMedGoogle Scholar
  24. 24.
    Richter S, Gerwig M, Aslan B, Wilhelm H, Schoch B, Dimitrova A et al (2007) Cognitive functions in patients with MR-defined chronic focal cerebellar lesions. J Neurol 254:1193–1203.  https://doi.org/10.1007/s00415-006-0500-9 CrossRefPubMedGoogle Scholar
  25. 25.
    Petrides M, Alivisatos B, Evans AC (1995) Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information. Proc Natl Acad Sci 92:5803–5807.  https://doi.org/10.1073/pnas.92.13.5803
  26. 26.
    Cabeza R, Kapur S, Craik F, McIntosh AR (1997) Functional neuroanatomiy of recall and recognition: a PET study of episodic memory. J CogNeurosci 9:254–265.  https://doi.org/10.1162/jocn.1997.9.2.254 CrossRefGoogle Scholar
  27. 27.
    Schlösser R, Hutchinson M, Joseffer S, Rusinek H, Rusinek H, Saarimaki A et al (1998) Functional magnetic resonance imaging of human brain activity in a verbal fluency task. J Neurol Neurosurg Psychiatry 64:492–498.  https://doi.org/10.1136/jnnp.64.4.492 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gourovitch ML, Kirkby BS, Goldberg TE, Weinberger DR, Gold JM, Esposito G et al (2000) A comparison of rCBF patterns during letter and semantic fluency. Neuropsychology 14:353–360.  https://doi.org/10.1037/0894-4105.14.3.353 CrossRefPubMedGoogle Scholar
  29. 29.
    Jansen A, Flöel A, Randenborgh JV, Konrad C, Rotte M, Förster AF et al (2005) Crossed cerebro-cerebellar language dominance. Hum Brain Mapp 24:165–172.  https://doi.org/10.1002/hbm.20077 CrossRefPubMedGoogle Scholar
  30. 30.
    Bellebaum C, Daum I (2007) Cerebellar involvement in executive control. Cerebellum 6:184–192.  https://doi.org/10.1080/14734220601169707 CrossRefPubMedGoogle Scholar
  31. 31.
    Baddeley A (2003) Working memory: looking back and looking forward. Nat Rev Neurosci 4:829–839.  https://doi.org/10.1038/nrn1201 CrossRefPubMedGoogle Scholar
  32. 32.
    Chen A, Desmond J (2005) Cereberocerebellar network during articulatory rehearsal and verbal working memory task. Neuroimage 24:332–338.  https://doi.org/10.1016/j.neuroimage.2004.08.032 CrossRefPubMedGoogle Scholar
  33. 33.
    Stuss D, Bisschop S, Alexander M, Levine B, Katz D, Izukawa D (2001) The trail making test: a study in focal lesion patients. Psychol Assess 13:230–239.  https://doi.org/10.1037//1040-3590.13.2.230 CrossRefPubMedGoogle Scholar
  34. 34.
    Miyake K (1923) The clinical study on memory. Shinkeigaku-zassi 24:12–45Google Scholar
  35. 35.
    Mohs RC, Rosen WG, Davis KL (1983) The Alzheimer’s disease assessment scale; an instrument for assessing treatment efficacy. Psycho-Pharmacol Bull 19:448–450Google Scholar
  36. 36.
    Homma A, Fukuzawa K, Tsukada Y, Ishii T, Hasegawa K, Mohs RC (1992) Development of a Japanese version of Alzheimer’s disease assessment scale (ADAS). Jpn J Geriatr Psychiatry 3:647–655 (in Japanese) Google Scholar
  37. 37.
    Imamura Y (1998) Manual on Neuropsychology. Shinkouigaku syuppansya, Tokyo (in Japanese) Google Scholar
  38. 38.
    Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a frontal assessment battery at bedside. Neurology 55:1621–1626.  https://doi.org/10.1212/WNL.55.11.1621 CrossRefPubMedGoogle Scholar
  39. 39.
    Takagi R, Kajimoto Y, Kamiyoshi S, Miwa H, Kondo T (2002) The frontal assessment battery at bedside (FAB) in patients with Parkinson’s disease. No To Shinkei 54:897–902 (in Japanese) PubMedGoogle Scholar
  40. 40.
    Watanabe J, Sugiura M, Sato K, Sato Y, Maeda Y, Matsue Y et al (2002) The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study. Neuroimage 17:1207–1216.  https://doi.org/10.1006/nimg.2002.119 CrossRefPubMedGoogle Scholar
  41. 41.
    Ng HB, Kao K-L, Chan YC, Chew E, Chuang KH, Chen SH (2016) Modality specificity in the cerebro-cerebellar neurocircuitry during working memory. Behav Brain Res 305:164–173.  https://doi.org/10.1016/j.bbr.2016.02.027 CrossRefPubMedGoogle Scholar
  42. 42.
    Gerton BK, Brown TT, Meter-Lindenberg A, Kohn P, Holt JL, Olsen RK et al (2004) Shared and distinct neuropsychological components of the digits forward and backward tasks as revealed by functional neuroimaging. Neurospychologia 42:1781–1787.  https://doi.org/10.1016/j.neuropsychologia CrossRefGoogle Scholar
  43. 43.
    Marvel C, Desmond J(2010) The contributions of cerebro-cerebellar circuitry to executive verbal working memory. Cortex 46:880–895.  https://doi.org/10.1016/j.cortex.2009.08.017 CrossRefPubMedGoogle Scholar
  44. 44.
    Thüring M, Hautzel H, Küper M, Stefanescu R, Maderwald S, Ladd ME et al (2012) Involvement of the cerebellar cortex and nuclei in verbal and visuospatial working memory: a 7 T fMRI study. Neuroimage 62:1537–1550.  https://doi.org/10.1016/j.neuroimage.2012.05.037 CrossRefGoogle Scholar
  45. 45.
    Küper M, Kaschani P, Thüring M, Stefanescu MR, Burciu RG, Göricke S et al (2016) Cerebellar fMRI activation increases with increasing working memory demands. Cerebellum 15:322–335.  https://doi.org/10.1007/s12311-015-0703-7 CrossRefPubMedGoogle Scholar
  46. 46.
    Thüring M, Küper M, Stefanescu R, Maderwald S, Gizewski ER, Ladd ME et al (2011) Activation of the dentate nucleus in a verb generation task: a 7 T MRI study. Neuroimage 57:1184–1191.  https://doi.org/10.1016/j.neuroimage.2011.05.045 CrossRefGoogle Scholar
  47. 47.
    Dum PR, Strick PL (2003) An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol 89:634–639.  https://doi.org/10.1152/jn.00626.2002 CrossRefPubMedGoogle Scholar
  48. 48.
    Saab CY, Willis WD (2003) The cerebellum: organization, functions and its role in nociception. Brain Res Rev 42(03):85–95.  https://doi.org/10.1016/S0165-017300151-6 CrossRefPubMedGoogle Scholar
  49. 49.
    Mariën P, Ackermann H, Adamaszek M, Barwood CHS, Beaton A, Desmond J et al (2014) Consensus paper: language and the cerebellum: an ongoing enigma. Cerebellum 13:386–410.  https://doi.org/10.1007/s12311-013-0540-5 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Etchebehere EC, Cendes F, Lopes-Cendes I, Pereira JA, Lima MC, Sansana CR et al (2001) Brain single-photon emission computed tomography and magnetic resonance imaging in Machado–Joseph disease. Arch Neurol 58:1257–1263.  https://doi.org/10.1001/archneur.58.8.1257 CrossRefPubMedGoogle Scholar
  51. 51.
    Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG (2011) The cerebellar cognitive profile. Brain 134:3672–3686.  https://doi.org/10.1093/brain/awr266 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Itaru Tamura
    • 1
    Email author
  • Asako Takei
    • 2
  • Shinsuke Hamada
    • 2
  • Hiroyuki Soma
    • 2
  • Michio Nonaka
    • 2
  • Sanae Homma
    • 2
  • Fumio Moriwaka
    • 2
  1. 1.Department of Communication Disorders, School of Rehabilitation SciencesHealth Sciences University of HokkaidoIshikari-TobetsuJapan
  2. 2.Hokuyukai Neurology HospitalSapporoJapan

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