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Journal of Neurology

, Volume 260, Issue 12, pp 3134–3143 | Cite as

Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2

  • Roberto FancelluEmail author
  • Dominga Paridi
  • Chiara Tomasello
  • Marta Panzeri
  • Anna Castaldo
  • Silvia Genitrini
  • Paola Soliveri
  • Floriano Girotti
Original Communication

Abstract

The role of the cerebellum in cognition, both in healthy subjects and in patients with cerebellar diseases, is debated. Neuropsychological studies in spinocerebellar ataxia type 1 (SCA1) and type 2 (SCA2) demonstrated impairments in executive functions, verbal memory, and visuospatial performances, but prospective evaluations are not available. Our aims were to assess progression of cognitive and psychiatric functions in patients with SCA1 and SCA2 in a longitudinal study. We evaluated at baseline 20 patients with SCA1, 22 patients with SCA2 and 17 matched controls. Two subgroups of patients (9 SCA1, 11 SCA2) were re-evaluated after 2 years. We tested cognitive functions (Mini Mental State Examination, digit span, Corsi span, verbal memory, attentional matrices, modified Wisconsin Card Sorting Test, Raven Progressive Matrices, Benton test, phonemic and semantic fluency), psychiatric status (Scales for Assessment of Negative and Positive Symptoms, Hamilton Depression and Anxiety Scales), neurological conditions (Scale for Assessment and Rating of Ataxia), and functional abilities (Unified Huntington Disease Rating Scale–part IV). At baseline, SCA1 and SCA2 patients had significant deficits compared to controls, mainly in executive functions (phonemic and semantic fluencies, attentional matrices); SCA2 showed further impairment in visuospatial and visuoperceptive tests (Raven matrices, Benton test, Corsi span). Both SCA groups had higher depression and negative symptoms, particularly apathy, compared to controls. After 2 years, motor and functional disability worsened, while only attentive performances deteriorated in SCA2. This longitudinal study showed dissociation in progression of motor disability and cognitive impairment, suggesting that in SCA1 and SCA2 motor and cognitive functions might be involved with different progression rates.

Keywords

Spinocerebellar ataxia Cognitive functions Executive functions Apathy Depression 

Notes

Acknowledgments

We thank all the patients, their families, and the control subjects. We also want to thank Drs. L. Nanetti, V. Redaelli, D. Monza, D. Pareyson, F. Taroni, S. Di Donato, and C. Mariotti for their logistic, clinical and intellectual support.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

415_2013_7138_MOESM1_ESM.doc (35 kb)
Supplementary material 1 (DOC 35 kb)

References

  1. 1.
    Schmahmann JD (ed) (1997) The cerebellum and cognition. International review of neurobiology, vol 41. Academic Press, San DiegoGoogle Scholar
  2. 2.
    Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579PubMedCrossRefGoogle Scholar
  3. 3.
    Bürk K (2007) Cognition in hereditary ataxia. Cerebellum 6:280–286PubMedCrossRefGoogle Scholar
  4. 4.
    Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, Kolb FP (2010) The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex 46:845–857PubMedCrossRefGoogle Scholar
  5. 5.
    Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG (2011) The cerebellar cognitive profile. Brain 134:3672–3686PubMedCrossRefGoogle Scholar
  6. 6.
    Appollonio IM, Grafman J, Schwartz V, Massaquoi S, Hallett M (1993) Memory in patients with cerebellar degeneration. Neurology 43:1536–1544PubMedCrossRefGoogle Scholar
  7. 7.
    Grafman J, Litvan I, Massaquoi S, Stewart M, Sirigu A, Hallett M (1992) Cognitive planning deficit in patients with cerebellar atrophy. Neurology 42:1493–1496PubMedCrossRefGoogle Scholar
  8. 8.
    Tavano A, Grasso R, Gagliardi C, Triulzi F, Bresolin N, Fabbro F, Borgatti R (2007) Disorders of cognitive and affective development in cerebellar malformations. Brain 130:2646–2660PubMedCrossRefGoogle Scholar
  9. 9.
    Kish SJ, el-Awar M, Stuss D, Nobrega J, Currier R, Aita JF, Schut L, Zoghbi HY, Freedman M (1994) Neuropsychological test performance in patients with dominantly inherited spinocerebellar ataxia: relationship to ataxia severity. Neurology 44:1738–1746PubMedCrossRefGoogle Scholar
  10. 10.
    Trojano L, Chiacchio L, Grossi D, Pisacreta AI, Calabrese O, Castaldo I, De Michele G, Filla A (1998) Determinants of cognitive disorders in autosomal dominant cerebellar ataxia type 1. J Neurol Sci 157:162–167PubMedCrossRefGoogle Scholar
  11. 11.
    Koziol LF, Budding DE, Chidekel D (2012) From movement to thought: executive function, embodied cognition, and the cerebellum. Cerebellum 11:505–525PubMedCrossRefGoogle Scholar
  12. 12.
    Kawai Y, Suenaga M, Watanabe H, Sobue G (2009) Cognitive impairment in spinocerebellar degeneration. Eur Neurol 61:257–268PubMedCrossRefGoogle Scholar
  13. 13.
    Leggio MG, Chiricozzi FR, Clausi S, Tedesco AM, Molinari M (2011) The neuropsychological profile of cerebellar damage: the sequencing hypothesis. Cortex 47:137–144PubMedCrossRefGoogle Scholar
  14. 14.
    Sokolovsky N, Cook A, Hunt H, Giunti P, Cipolotti L (2010) A preliminary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7. Behav Neurol 23:17–29PubMedGoogle Scholar
  15. 15.
    Schmahmann JD (2010) The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev 20:236–260PubMedCrossRefGoogle Scholar
  16. 16.
    Villanueva R (2012) The cerebellum and neuropsychiatric disorders. Psychiatry Res 198:527–532PubMedCrossRefGoogle Scholar
  17. 17.
    Dürr A (2010) Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol 9:885–894PubMedCrossRefGoogle Scholar
  18. 18.
    Whaley NR, Fujioka S, Wszolek ZK (2011) Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis 6:33PubMedCrossRefGoogle Scholar
  19. 19.
    Bird TD (2012) Hereditary ataxia overview. In: Pagon RA, Adam MP, Bird TD (eds) GeneReviews™ [Internet], University of Washington, Seattle, 1993–2013. http://www.ncbi.nlm.nih.gov/books/NBK1138/. Accessed 26 Sept 2013
  20. 20.
    Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, Fetoni V, Mariotti C, Migone N, Di Donato S, Taroni F (2004) Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol 61:727–733PubMedCrossRefGoogle Scholar
  21. 21.
    Bürk K, Globas C, Bösch S, Gräber S, Abele M, Brice A, Dichgans J, Daum I, Klockgether T (1999) Cognitive deficits in spinocerebellar ataxia 2. Brain 122:769–777PubMedCrossRefGoogle Scholar
  22. 22.
    Bürk K, Bösch S, Globas C, Zühlke C, Daum I, Klockgether T, Dichgans J (2001) Executive dysfunction in spinocerebellar ataxia type 1. Eur Neurol 46:43–48PubMedCrossRefGoogle Scholar
  23. 23.
    Bürk K, Globas C, Bösch S, Klockgether T, Zühlke C, Daum I, Dichgans J (2003) Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 250:207–211PubMedCrossRefGoogle Scholar
  24. 24.
    Gambardella A, Annesi G, Bono F, Spadafora P, Valentino P, Pasqua AA, Mazzei R, Montesanti R, Conforti FL, Oliveri RL, Zappia M, Aguglia U, Quattrone A (1998) CAG repeat length and clinical features in three Italian families with spinocerebellar ataxia type 2 (SCA2): early impairment of Wisconsin card sorting test and saccade velocity. J Neurol 245:647–652PubMedCrossRefGoogle Scholar
  25. 25.
    Orsi L, D’Agata F, Caroppo P, Franco A, Caglio MM, Avidano F, Manzone C, Mortara P (2011) Neuropsychological picture of 33 spinocerebellar ataxia cases. J Clin Exp Neuropsychol 33:315–325PubMedCrossRefGoogle Scholar
  26. 26.
    Klinke I, Minnerop M, Schmitz-Hübsch T, Hendriks M, Klockgether T, Wüllner U, Helmstaedter C (2010) Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. Cerebellum 9:433–442PubMedCrossRefGoogle Scholar
  27. 27.
    Filla A, De Michele G, Campanella G, Perretti A, Santoro L, Serlenga L, Ragno M, Calabrese O, Castaldo I, De Joanna G, Cocozza S (1996) Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes. J Neurol Sci 142:140–147PubMedCrossRefGoogle Scholar
  28. 28.
    Valis M, Masopust J, Bažant J, Ríhová Z, Kalnická D, Urban A, Zumrová A, Hort J (2011) Cognitive changes in spinocerebellar ataxia type 2. Neuro Endocrinol Lett 32:354–359PubMedGoogle Scholar
  29. 29.
    D’Agata F, Caroppo P, Boghi A, Coriasco M, Caglio M, Baudino B, Sacco K, Cauda F, Geda E, Bergui M, Geminiani G, Bradac GB, Orsi L, Mortara P (2011) Linking coordinative and executive dysfunctions to atrophy in spinocerebellar ataxia 2 patients. Brain Struct Funct 216:275–288PubMedCrossRefGoogle Scholar
  30. 30.
    Le Pira F, Zappalà G, Saponara R, Domina E, Restivo D, Reggio E, Nicoletti A, Giuffrida S (2002) Cognitive findings in spinocerebellar ataxia type 2: relationship to genetic and clinical variables. J Neurol Sci 201:53–57PubMedCrossRefGoogle Scholar
  31. 31.
    Le Pira F, Giuffrida S, Maci T, Marturano L, Tarantello R, Zappalà G, Nicoletti A, Zappia M (2007) Dissociation between motor and cognitive impairments in SCA2: evidence from a follow-up study. J Neurol 254:1455–1456PubMedCrossRefGoogle Scholar
  32. 32.
    Storey E, Forrest SM, Shaw JH, Mitchell P, Gardner RJ (1999) Spinocerebellar ataxia type 2: clinical features of a pedigree displaying prominent frontal-executive dysfunction. Arch Neurol 56:43–50PubMedCrossRefGoogle Scholar
  33. 33.
    Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, van de Warrenburg BP, Dürr A, Klockgether T, Fancellu R (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66:1717–1720PubMedCrossRefGoogle Scholar
  34. 34.
    Klockgether T, Lüdtke R, Kramer B, Abele M, Bürk K, Schöls L, Riess O, Laccone F, Boesch S, Lopes-Cendes I, Brice A, Inzelberg R, Zilber N, Dichgans J (1998) The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 121:589–600PubMedCrossRefGoogle Scholar
  35. 35.
    Huntington Study Group (1996) Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord 11:136–142CrossRefGoogle Scholar
  36. 36.
    Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  37. 37.
    Measso G, Cavarzeran F, Zappalà G, Lebowitz BD, Crook TH, Pirozzolo FJ, Amaducci LA, Massari D, Grigoletto F (1993) The mini-mental state examination: normative study of an Italian random sample. Dev Neuropsychol 9:77–95CrossRefGoogle Scholar
  38. 38.
    Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G (1987) Verbal and spatial immediate memory span: normative data from 1355 adults and 112 children. Ital J Neurol Sci 8:539–548PubMedCrossRefGoogle Scholar
  39. 39.
    Spinnler H, Tognoni G (1987) Standardizzazione e taratura italiana di test psicometrici. Ital J Neurol Sci 8(Suppl. 6):7–120Google Scholar
  40. 40.
    Novelli G, Papagno C, Capitani E, Laiacona M, Cappa SF, Vallar G (1986) Tre test clinici di memoria verbale a lungo termine. Taratura su soggetti normali. Archivio di Psicologia Neurologia e Psichiatria 2:278–296Google Scholar
  41. 41.
    Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex 12:313–324PubMedCrossRefGoogle Scholar
  42. 42.
    Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2004) Modified card sorting test: normative data. J Clin Exp Neuropsychol 26:246–250PubMedCrossRefGoogle Scholar
  43. 43.
    Raven JC (1962) Coloured progressive Matrices Sets A, Ab, B. HK Lewis, LondonGoogle Scholar
  44. 44.
    Basso A, Capitani E, Laiacona M (1987) Raven’s coloured progressive matrices: normative values on 305 adult normal controls. Funct Neurol 2:189–194PubMedGoogle Scholar
  45. 45.
    Benton AL, Sivan AB, Des Hamsher K, Varney NR, Spreen O (1994) Contribution to neuropsychological assessment: a clinical manual, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  46. 46.
    Ferracuti S, Cannoni E, Sacco R, Hufty AM (2000, ristampa 2007) Contributi per un assessment neuropsicologico. Manuale clinico. Giunti Organizzazioni Speciali, FirenzeGoogle Scholar
  47. 47.
    Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62PubMedCrossRefGoogle Scholar
  48. 48.
    Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55PubMedCrossRefGoogle Scholar
  49. 49.
    Andreasen NC (1982) Negative symptoms in schizophrenia. Arch Gen Psychiatry 39:784–788PubMedCrossRefGoogle Scholar
  50. 50.
    Andreasen NC (1990) Methods for assessing positive and negative symptoms. Mod Probl Pharmacopsychiatry 24:73–88PubMedGoogle Scholar
  51. 51.
    Stoodley CJ, Schmahmann JD (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46:831–844PubMedCrossRefGoogle Scholar
  52. 52.
    Berent S, Giordani B, Gilman S, Trask CL, Little RJ, Johanns JR, Junck L, Kluin KJ, Heumann M, Koeppe RA (2002) Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy. Brain Cogn 50:194–206PubMedCrossRefGoogle Scholar
  53. 53.
    Fratkin JD, Vig PJ (2012) Neuropathology of degenerative ataxias. Handb Clin Neurol 103:111–125PubMedCrossRefGoogle Scholar
  54. 54.
    Jacobi H, Hauser TK, Giunti P, Globas C, Bauer P, Schmitz-Hübsch T, Baliko L, Filla A, Mariotti C, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Fancellu R, Rola R, Depondt C, Schöls L, Zdzienicka E, Kang JS, Ratzka S, Kremer B, Stephenson DA, Melegh B, Pandolfo M, Tezenas du Montcel S, Borkert J, Schulz JB, Klockgether T (2012) Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings. Cerebellum 11:155–166PubMedCrossRefGoogle Scholar
  55. 55.
    Brandt J, Leroi I, O’Hearn E, Rosenblatt A, Margolis RL (2004) Cognitive impairments in cerebellar degeneration: a comparison with Huntington’s disease. J Neuropsychiatry Clin Neurosci 16:176–184PubMedCrossRefGoogle Scholar
  56. 56.
    Wolf U, Rapoport MJ, Schweizer TA (2009) Evaluating the affective component of the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 21:245–253PubMedCrossRefGoogle Scholar
  57. 57.
    Schmitz-Hübsch T, Coudert M, Giunti P, Globas C, Baliko L, Fancellu R, Mariotti C, Filla A, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Rola R, Depondt C, Schöls L, Zdzienicka E, Kang JS, Ratzka S, Kremer B, Schulz JB, Klopstock T, Melegh B, du Montcel ST, Klockgether T (2010) Self-rated health status in spinocerebellar ataxia—results from a European multicenter study. Mov Disord 25:587–595PubMedCrossRefGoogle Scholar
  58. 58.
    Schmitz-Hübsch T, Coudert M, Tezenas du Montcel S, Giunti P, Labrum R, Dürr A, Ribai P, Charles P, Linnemann C, Schöls L, Rakowicz M, Rola R, Zdzienicka E, Fancellu R, Mariotti C, Baliko L, Melegh B, Filla A, Salvatore E, van de Warrenburg BP, Szymanski S, Infante J, Timmann D, Boesch S, Depondt C, Kang JS, Schulz JB, Klopstock T, Lossnitzer N, Löwe B, Frick C, Rottländer D, Schlaepfer TE, Klockgether T (2011) Depression comorbidity in spinocerebellar ataxia. Mov Disord 26:870–876PubMedCrossRefGoogle Scholar
  59. 59.
    Leroi I, O’Hearn E, Marsh L, Lyketsos CG, Rosenblatt A, Ross CA, Brandt J, Margolis RL (2002) Psychopathology in patients with degenerative cerebellar diseases: a comparison to Huntington’s disease. Am J Psychiatry 159:1306–1314PubMedCrossRefGoogle Scholar
  60. 60.
    Liszewski CM, O’Hearn E, Leroi I, Gourley L, Ross CA, Margolis RL (2004) Cognitive impairment and psychiatric symptoms in 133 patients with diseases associated with cerebellar degeneration. J Neuropsychiatry Clin Neurosci 16:109–112PubMedCrossRefGoogle Scholar
  61. 61.
    Krishnamoorthy A, Craufurd D (2011) Treatment of apathy in Huntington’s disease and other movement disorders. Curr Treat Options Neurol 13:508–519PubMedCrossRefGoogle Scholar
  62. 62.
    Park KM, Kim JJ, Seok JH, Chun JW, Park HJ, Lee JD (2009) Anhedonia and ambivalence in schizophrenic patients with fronto-cerebellar metabolic abnormalities: a fluoro-d-glucose positron emission tomography study. Psychiatry Investig 6:72–77PubMedCrossRefGoogle Scholar
  63. 63.
    Andreasen NC, Paradiso S, O’Leary DS (1998) “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull 24:203–218PubMedCrossRefGoogle Scholar
  64. 64.
    Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, Dürr A, Marelli C, Globas C, Linnemann C, Schöls L, Rakowicz M, Rola R, Zdzienicka E, Schmitz-Hübsch T, Fancellu R, Mariotti C, Tomasello C, Baliko L, Melegh B, Filla A, Rinaldi C, van de Warrenburg BP, Verstappen CC, Szymanski S, Berciano J, Infante J, Timmann D, Boesch S, Hering S, Depondt C, Pandolfo M, Kang JS, Ratzka S, Schulz J, Tezenas du Montcel S, Klockgether T (2011) The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology 77:1035–1041PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Roberto Fancellu
    • 1
    • 4
    Email author
  • Dominga Paridi
    • 2
  • Chiara Tomasello
    • 1
  • Marta Panzeri
    • 1
  • Anna Castaldo
    • 1
  • Silvia Genitrini
    • 1
  • Paola Soliveri
    • 2
  • Floriano Girotti
    • 3
  1. 1.SOSD Genetics of Neurodegenerative and Metabolic DiseasesIRCCS Foundation Neurological Institute Carlo BestaMilanItaly
  2. 2.Unit of Movement DisordersIRCCS Foundation Neurological Institute Carlo BestaMilanItaly
  3. 3.Unit of NeuropathologyIRCCS Foundation Neurological Institute Carlo BestaMilanItaly
  4. 4.Unit of NeurologyVilla Scassi Hospital, ASL3GenoaItaly

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