Cognitive dysfunction in spinocerebellar ataxias

Teive, Helio Afonso Ghizoni; Arruda, Walter Oleschko

doi:10.1590/S1980-57642009DN30300002

Abstract

Spinocerebellar ataxias (SCAs) comprise a heterogeneous group of complex neurodegenerative diseases, characterized by the presence of progressive cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs, extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia.

Objective:

To verify the presence of cognitive dysfunction among the main types of SCA described in the literature.

Methods:

the review was conducted using the search system of the PUBMED and OMIM databases.

Results:

Cognitive dysfunction occurs in a considerable proportion of SCA, particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA. Mental retardation is a specific clinical feature of SCA 13.

Conclusions:

The role of the cerebellum in cognitive functions has been observed in different types of SCAs which can manifest varying degrees of cognitive dysfunction, dementia and mental retardation.

Key words:
spinocerebellar ataxia; cognitive dysfunction; dementia.

Resumo

Fundamento:

As ataxias espinocerebelares (AECs) compreendem um grupo heterogêneo de enfermidades neurodegenerativas, que se caracterizam pela presença de ataxia cerebelar progressiva, associada de forma avariada com oftalmoplegia, sinais piramidais, extrapiramidais, retinopatia pigmentar, neuropatia periférica, disfunção cognitiva e demência.

Objetivo:

Revisar a presença de disfunção cognitiva entre os principais tipos de AECs publicados na literatura mundial.

Métodos:

A revisão foi realizada através da pesquisa pelo sistema do PUBMED e do OMIM.

Resultados:

Disfunção cognitiva ocorre em uma parcela considerável de AECs, particularmente na AEC 3, que é a forma de AEC mais encontrada em todo o mundo. Demência também tem sido descrita em alguns tipos de AECs como a AEC 2, a AEC 17 e a DRPLA. Retardo mental é característica clínica peculiar da AEC tipo 13.

Conclusões:

O papel do cerebelo nas funções cognitivas vem sendo enfatizado cada vez mais e diferentes tipos de AECs, apresentam graus variados de disfunção cognitiva, demência e também retardo mental.

Palavras-chave:
ataxia espinocerebelar; disfunção cognitiva; demência.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

References

¹
Teive HAG. Spinocerebellar degenerations in Japan. New insights from an epidemiological study. Neuroepidemiology 2009;32:184-185.
²
Duenas AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar ataxias. Brain 2006;129:1357-1370.
³
Schöls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias:clinical features, genetics, and pathogenesis. Lancet Neurol 2004;3:91-304.
⁴
Soong BW, Paulson HL. Spinocerebellar ataxias: an update. Curr Opin Neurol 2007;20:438-446.
⁵
Evidente VGH, Gwinn-Hardy KA, Caviness JN, Gilman S. Hereditary ataxias. Mayo Clin Proc 2000;75:475-490.
⁶
Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4:2-6.
⁷
Durr A, Brice A. Clinical and genetic aspects of spinocerebellar degeneration. Curr Opin Neurol 2000;13:407-413.
⁸
Klockgether T, Lüdtke R, Kramer B, et al. The natural history of degenerative ataxia: a retrospective study of 466 patients. Brain 1998;121:589-600.
⁹
Klockgether T. Recent advances in degenerative ataxias. Curr Opin Neurol 2000;13:451-455.
¹⁰
Pulst SM, Perlman SL. Hereditary ataxias. In: Pulst SM, Editor. Neurogenetics. Oxford: Oxford University Press; 2000:231-264.
¹¹
van de Warremburg BP, Sinke RJ, Verschuuren-Bemelmans CC. Spinocerebellar ataxias in the Netherlands :prevalence and age at onset variance analysis. Neurology 2002;58:702-708.
¹²
Harding AE. The hereditary ataxias and related disorders. New York: Churchill Livingstone; 1984.
¹³
Stevanin G, Durr A, Brice A . Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology. Eur J Hum Genet 2000;8:4-18.
¹⁴
Klockgether T, Wullner U, Spauschus A, Evert B. The molecular biology of the autosomal-dominant cerebellar ataxias. Mov Disord 2000;15:604-612.
¹⁵
Subramony SH, Filla A. Autosomal dominant spinocerebellar ataxias ad infinitum? Neurology 2001;56:287-289.
¹⁶
Margolis RL. The spinocerebellar ataxias: order emerges from chaos. Curr Neurol Neurosci Rep 2002;2:447-456.
¹⁷
Bandmann O, Singleton AB. Yet another spinocerebellar ataxia. The saga continues. Neurology 2008;71:542-543.
¹⁸
Brusse E, Maat-Kievit JA, van Swieten JC. Diagnosis and management of early-and late-onset cerebellar ataxia. Clin Genet 2007;71:12-24.
¹⁹
Stevanin G, Durr A, Brice A. Clinical and genetic aspects of spinocerebellar ataxias with emphasis on polyglutamine expansions. In: Brice A, Pulst S-M. Spinocerebellar degenerations. The ataxias and spastic paraplegias. Philadelphia,USA: Butterworth Heinemann Elsevier; 2007: 113-144.
²⁰
Storey E, Bahlo M, Fahey M, Sisson O, Lueck CJ, Gardner RJM. A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry 2009;80:408-411.
²¹
Pulst S-M. Inherited ataxias: An introduction. In: Pulst S-M. Genetics of Movement Disorders. California, USA: Academic Press, Elsevier Science; 2003:19-34.
²²
Holmes S, O'Hearn EE, McInnis MG, et al. Expansion of a novel CAG trinucleotide repeat in the 5_ region of PPP2R2B is associated with SCA12. Nat Genet 1999;23:391-392.
²³
Silveira I, Lopes-Cendes I, Kish S, et al. Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients. Neurology 1996;46:214-218.
²⁴
Lopes-Cendes I, Teive HAG, Calcagnotto ME, et al. Frequency of the different mutations causing spinocerebellar ataxia (SCA 1, SCA 2, SCA 3/MJD and DRPLA) in a large group of Brazilian patients. Arq Neuropsiquiatr 1997;55:519-529.
²⁵
Teive HAG, Roa B, Raskin S, et al. Clinical phenotype of Brazilian patients with spinocerebellar ataxia 10. Neurology 2004;63:1509-1512.
²⁶
Jardim LB, Silveira I, Pereira ML, et al. A survey of spinocerebellar ataxia in South Brazil - 66 new cases with Machado-Joseph disease, SCA 7, SCA 8, or unidentified disease-causing mutations. J Neurol 2001;248:870-876.
²⁷
Jardim LB, Pereira ML, Silveira I, Ferro A, Sequeiros J, Giugliani R. Neurologic findings in Machado-Joseph disease. Relation with disease duration, subtypes, and (CAG)n. Arch Neurol 2001;58:899-904.
²⁸
Murata Y, Yamaguchi S, Kawakami H. Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol 1998;55:33-37.
²⁹
Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azorean islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 1978;28:703-709.
³⁰
Lima L, Coutinho P. Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-azorean Portuguese family. Neurology 1980;30:319-322.
³¹
Coutinho P. Doença de Machado-Joseph. Tentativa de definição. Tese de Doutorado, Instituto de Ciências Biomédicas, Universidade do Porto, Porto, Portugal, 1992:247.
³²
Sequeiros J, Coutinho P. Epidemiology and clinical aspects of Machado-Joseph disease. Adv Neurol 1993;61:139-153.
³³
Zawacki TM, Grace J, Friedman JH, Sudarsky L. Executive and emotional dysfunction in Machado-Joseph disease. Mov Disord 2002;17:1004-1010.
³⁴
Ishikawa A, YamadaM, Makino K, et al. Dementia and delirium in 4 patients with Machado-Joseph disease. Arch Neurol 2002;59:1804-1808.
³⁵
Ikeda K, Kubota S, Isashiki Y, Eiraku N, Osame M, Nakagawa M. Machado-Joseph disease with retinal degeneration and dementia. Acta Neurol Scand 2001;104:402-405.
³⁶
Maruff P, Tyler P, Burt T, Currie B, Burns C, CurrieJ. Cognitive deficits in Machado-Joseph disease. Ann Neurol 1996;40: 421-427.
³⁷
Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G. Cognitive impairment in Machado-Joseph disease. Arch Neurol 2004;61:1757-1560.
³⁸
Rasmunssen A, Matsuura T, Ruano L, et al. Clinical and Genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol 2001;50:234-239.
³⁹
Zu L, Figueroa KP, Grewal R, Pulst S-M. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet 1999;64:594-599.
⁴⁰
Matsuura T, Achari M, Khakavi M, Bachinski LL, Huda ZY, Ashizawa T. Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy. Ann Neurol 1999;45:407-411.
⁴¹
Matsuura T, Yamagata T, Burgess DL, et al. Large expansions of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000;26:191-194.
⁴²
Matsuura T, Ashizawa T. Polymerase chain reaction amplification of expanded ATTCT repeat in spinocerebellar ataxia type 10. Ann Neurol 2002;51:271-272.
⁴³
Matsuura T, Ranum LPW, Volpini V, et al. Spinocerebellar ataxia type 10 is rare in populations other than Mexicans. Neurology 2002;58:983-984.
⁴⁴
Fujigasaki H, Tardieu S, Camuzat A, et al. Spinocerebellar ataxia type 10 in the French population. Ann Neurol 2002;51: 408-409.
⁴⁵
Bürk K, Blobas C, Bösch S, et al. Cognitive deficits in spinocerebellar ataxia 2. Brain1999;122:769-777.
⁴⁶
Ramocki MB, Chapieski L,McDonald RO, Fernandez F, Malphrus AD. Spinocerebellar ataxia type 2 presenting with cognitive regression in childhood. J Child Neurol 2008;23: 999-1001.
⁴⁷
Bürk K, Bösch S, Globas C, Zühlke C, et al. Executive dysfunction in spinocerebellar type 1. Eur Neurol 2001;46:43-48.
⁴⁸
Kawai Y, Suenaga M, Watanabe H, et al. Prefrontal hypoperfusion and cognitive dysfunction correlates in spinocerebellar ataxia type 6. J Neurol Sci 2008;271:68-74.
⁴⁹
Globas C, Bösch S, Zühlke CH, Daum I, Dichgans J, Bürk K. The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6). J Neurol 2003;250:1482-1487.
⁵⁰
Suenaga M, Kawai Y, Watanabe H, et al. Cognitive impairment in spinocerebellar ataxia type 6. J Neurol Neurosurg Psychiatry 2008;79:496-499.
⁵¹
Baba Y, Uitti RJ, Farrer MJ, Wszolek ZK. Sporadic SCA8 mutation resembling corticobasal degeneration. Parkinsonism Relat Disord 2005;11:147-150.
⁵²
Bürk K, Globas C, Bösch S, et al. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 2003;250:207-211.
⁵³
O'Hearn E, Holmes SE, Calvert PC, Ross CA, Margolis RL. SCA-12:Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion. Neurology 2001;56:299-303.
⁵⁴
De Michele G, Malteca F, Carella M, et al. Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17. Neurol Sci 2003;24:166-167.
⁵⁵
Rolfs A, Koeppen AH, Bauer I, et al. Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol 2003;54:367-375.
⁵⁶
Schelhaas HJ,vande Warrenburg BP, Hageman G, Ippel EE, van Hout M, Kremer B. Cognitive impairment in SCA-19. Acta Neurol Belg 2003;103:199-205.
⁵⁷
Delplanque J, Devos D, Vuillaume I, et al. Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). Cerebellum 2008: 179-183.
⁵⁸
Toyoshima Y, Yamada M, Onodera O, et al. SCA 17 homozygote showing Huntington's disease-like phenotype. Ann Neurol 2004;55:281-286.
⁵⁹
Bürk K. Cognition in hereditary ataxia. Cerebellum 2007;6: 280-286.
⁶⁰
Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol 1991;48:1178-1187.
⁶¹
Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. In: Schmahmann JD. The cerebellum and cognition. San Diego: Academic Press; 1997:433-440.
⁶²
Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121:561-579.
⁶³
Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004;16:367-378.
⁶⁴
Timmann D, Daum I. Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 2007;6:159-162
⁶⁵
Garrard P, Martin NH, Giunti P, Cipolotti L. Cognitive and social cognitive functioning in spinocerebellar ataxia: a preliminary characterization. J Neurol 2008;255:398-405.
⁶⁶
Brandt J, Leroi I, O'Hearn E, Rosenblatt A, Margolis RL. Cognitive impairments in cerebellar degeneration: a comparison with Huntington's disease. J Neuropsychiatry Clin Neurosci 2004;16:176-184.

Publication Dates

Publication in this collection
Jul-Sep 2009

History

Received
10 Apr 2009
Accepted
26 June 2009

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Teive HAG. Spinocerebellar degenerations in Japan. New insights from an epidemiological study. Neuroepidemiology 2009;32:184-185.

[2] ²
Duenas AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar ataxias. Brain 2006;129:1357-1370.

[3] ³
Schöls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias:clinical features, genetics, and pathogenesis. Lancet Neurol 2004;3:91-304.

[4] ⁴
Soong BW, Paulson HL. Spinocerebellar ataxias: an update. Curr Opin Neurol 2007;20:438-446.

[5] ⁵
Evidente VGH, Gwinn-Hardy KA, Caviness JN, Gilman S. Hereditary ataxias. Mayo Clin Proc 2000;75:475-490.

[6] ⁶
Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4:2-6.

[7] ⁷
Durr A, Brice A. Clinical and genetic aspects of spinocerebellar degeneration. Curr Opin Neurol 2000;13:407-413.

[8] ⁸
Klockgether T, Lüdtke R, Kramer B, et al. The natural history of degenerative ataxia: a retrospective study of 466 patients. Brain 1998;121:589-600.

[9] ⁹
Klockgether T. Recent advances in degenerative ataxias. Curr Opin Neurol 2000;13:451-455.

[10] ¹⁰
Pulst SM, Perlman SL. Hereditary ataxias. In: Pulst SM, Editor. Neurogenetics. Oxford: Oxford University Press; 2000:231-264.

[11] ¹¹
van de Warremburg BP, Sinke RJ, Verschuuren-Bemelmans CC. Spinocerebellar ataxias in the Netherlands :prevalence and age at onset variance analysis. Neurology 2002;58:702-708.

[12] ¹²
Harding AE. The hereditary ataxias and related disorders. New York: Churchill Livingstone; 1984.

[13] ¹³
Stevanin G, Durr A, Brice A . Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology. Eur J Hum Genet 2000;8:4-18.

[14] ¹⁴
Klockgether T, Wullner U, Spauschus A, Evert B. The molecular biology of the autosomal-dominant cerebellar ataxias. Mov Disord 2000;15:604-612.

[15] ¹⁵
Subramony SH, Filla A. Autosomal dominant spinocerebellar ataxias ad infinitum? Neurology 2001;56:287-289.

[16] ¹⁶
Margolis RL. The spinocerebellar ataxias: order emerges from chaos. Curr Neurol Neurosci Rep 2002;2:447-456.

[17] ¹⁷
Bandmann O, Singleton AB. Yet another spinocerebellar ataxia. The saga continues. Neurology 2008;71:542-543.

[18] ¹⁸
Brusse E, Maat-Kievit JA, van Swieten JC. Diagnosis and management of early-and late-onset cerebellar ataxia. Clin Genet 2007;71:12-24.

[19] ¹⁹
Stevanin G, Durr A, Brice A. Clinical and genetic aspects of spinocerebellar ataxias with emphasis on polyglutamine expansions. In: Brice A, Pulst S-M. Spinocerebellar degenerations. The ataxias and spastic paraplegias. Philadelphia,USA: Butterworth Heinemann Elsevier; 2007: 113-144.

[20] ²⁰
Storey E, Bahlo M, Fahey M, Sisson O, Lueck CJ, Gardner RJM. A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry 2009;80:408-411.

[21] ²¹
Pulst S-M. Inherited ataxias: An introduction. In: Pulst S-M. Genetics of Movement Disorders. California, USA: Academic Press, Elsevier Science; 2003:19-34.

[22] ²²
Holmes S, O'Hearn EE, McInnis MG, et al. Expansion of a novel CAG trinucleotide repeat in the 5_ region of PPP2R2B is associated with SCA12. Nat Genet 1999;23:391-392.

[23] ²³
Silveira I, Lopes-Cendes I, Kish S, et al. Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients. Neurology 1996;46:214-218.

[24] ²⁴
Lopes-Cendes I, Teive HAG, Calcagnotto ME, et al. Frequency of the different mutations causing spinocerebellar ataxia (SCA 1, SCA 2, SCA 3/MJD and DRPLA) in a large group of Brazilian patients. Arq Neuropsiquiatr 1997;55:519-529.

[25] ²⁵
Teive HAG, Roa B, Raskin S, et al. Clinical phenotype of Brazilian patients with spinocerebellar ataxia 10. Neurology 2004;63:1509-1512.

[26] ²⁶
Jardim LB, Silveira I, Pereira ML, et al. A survey of spinocerebellar ataxia in South Brazil - 66 new cases with Machado-Joseph disease, SCA 7, SCA 8, or unidentified disease-causing mutations. J Neurol 2001;248:870-876.

[27] ²⁷
Jardim LB, Pereira ML, Silveira I, Ferro A, Sequeiros J, Giugliani R. Neurologic findings in Machado-Joseph disease. Relation with disease duration, subtypes, and (CAG)n. Arch Neurol 2001;58:899-904.

[28] ²⁸
Murata Y, Yamaguchi S, Kawakami H. Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol 1998;55:33-37.

[29] ²⁹
Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azorean islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 1978;28:703-709.

[30] ³⁰
Lima L, Coutinho P. Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-azorean Portuguese family. Neurology 1980;30:319-322.

[31] ³¹
Coutinho P. Doença de Machado-Joseph. Tentativa de definição. Tese de Doutorado, Instituto de Ciências Biomédicas, Universidade do Porto, Porto, Portugal, 1992:247.

[32] ³²
Sequeiros J, Coutinho P. Epidemiology and clinical aspects of Machado-Joseph disease. Adv Neurol 1993;61:139-153.

[33] ³³
Zawacki TM, Grace J, Friedman JH, Sudarsky L. Executive and emotional dysfunction in Machado-Joseph disease. Mov Disord 2002;17:1004-1010.

[34] ³⁴
Ishikawa A, YamadaM, Makino K, et al. Dementia and delirium in 4 patients with Machado-Joseph disease. Arch Neurol 2002;59:1804-1808.

[35] ³⁵
Ikeda K, Kubota S, Isashiki Y, Eiraku N, Osame M, Nakagawa M. Machado-Joseph disease with retinal degeneration and dementia. Acta Neurol Scand 2001;104:402-405.

[36] ³⁶
Maruff P, Tyler P, Burt T, Currie B, Burns C, CurrieJ. Cognitive deficits in Machado-Joseph disease. Ann Neurol 1996;40: 421-427.

[37] ³⁷
Kawai Y, Takeda A, Abe Y, Washimi Y, Tanaka F, Sobue G. Cognitive impairment in Machado-Joseph disease. Arch Neurol 2004;61:1757-1560.

[38] ³⁸
Rasmunssen A, Matsuura T, Ruano L, et al. Clinical and Genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol 2001;50:234-239.

[39] ³⁹
Zu L, Figueroa KP, Grewal R, Pulst S-M. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet 1999;64:594-599.

[40] ⁴⁰
Matsuura T, Achari M, Khakavi M, Bachinski LL, Huda ZY, Ashizawa T. Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy. Ann Neurol 1999;45:407-411.

[41] ⁴¹
Matsuura T, Yamagata T, Burgess DL, et al. Large expansions of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000;26:191-194.

[42] ⁴²
Matsuura T, Ashizawa T. Polymerase chain reaction amplification of expanded ATTCT repeat in spinocerebellar ataxia type 10. Ann Neurol 2002;51:271-272.

[43] ⁴³
Matsuura T, Ranum LPW, Volpini V, et al. Spinocerebellar ataxia type 10 is rare in populations other than Mexicans. Neurology 2002;58:983-984.

[44] ⁴⁴
Fujigasaki H, Tardieu S, Camuzat A, et al. Spinocerebellar ataxia type 10 in the French population. Ann Neurol 2002;51: 408-409.

[45] ⁴⁵
Bürk K, Blobas C, Bösch S, et al. Cognitive deficits in spinocerebellar ataxia 2. Brain1999;122:769-777.

[46] ⁴⁶
Ramocki MB, Chapieski L,McDonald RO, Fernandez F, Malphrus AD. Spinocerebellar ataxia type 2 presenting with cognitive regression in childhood. J Child Neurol 2008;23: 999-1001.

[47] ⁴⁷
Bürk K, Bösch S, Globas C, Zühlke C, et al. Executive dysfunction in spinocerebellar type 1. Eur Neurol 2001;46:43-48.

[48] ⁴⁸
Kawai Y, Suenaga M, Watanabe H, et al. Prefrontal hypoperfusion and cognitive dysfunction correlates in spinocerebellar ataxia type 6. J Neurol Sci 2008;271:68-74.

[49] ⁴⁹
Globas C, Bösch S, Zühlke CH, Daum I, Dichgans J, Bürk K. The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6). J Neurol 2003;250:1482-1487.

[50] ⁵⁰
Suenaga M, Kawai Y, Watanabe H, et al. Cognitive impairment in spinocerebellar ataxia type 6. J Neurol Neurosurg Psychiatry 2008;79:496-499.

[51] ⁵¹
Baba Y, Uitti RJ, Farrer MJ, Wszolek ZK. Sporadic SCA8 mutation resembling corticobasal degeneration. Parkinsonism Relat Disord 2005;11:147-150.

[52] ⁵²
Bürk K, Globas C, Bösch S, et al. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 2003;250:207-211.

[53] ⁵³
O'Hearn E, Holmes SE, Calvert PC, Ross CA, Margolis RL. SCA-12:Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion. Neurology 2001;56:299-303.

[54] ⁵⁴
De Michele G, Malteca F, Carella M, et al. Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17. Neurol Sci 2003;24:166-167.

[55] ⁵⁵
Rolfs A, Koeppen AH, Bauer I, et al. Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol 2003;54:367-375.

[56] ⁵⁶
Schelhaas HJ,vande Warrenburg BP, Hageman G, Ippel EE, van Hout M, Kremer B. Cognitive impairment in SCA-19. Acta Neurol Belg 2003;103:199-205.

[57] ⁵⁷
Delplanque J, Devos D, Vuillaume I, et al. Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). Cerebellum 2008: 179-183.

[58] ⁵⁸
Toyoshima Y, Yamada M, Onodera O, et al. SCA 17 homozygote showing Huntington's disease-like phenotype. Ann Neurol 2004;55:281-286.

[59] ⁵⁹
Bürk K. Cognition in hereditary ataxia. Cerebellum 2007;6: 280-286.

[60] ⁶⁰
Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol 1991;48:1178-1187.

[61] ⁶¹
Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. In: Schmahmann JD. The cerebellum and cognition. San Diego: Academic Press; 1997:433-440.

[62] ⁶²
Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121:561-579.

[63] ⁶³
Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004;16:367-378.

[64] ⁶⁴
Timmann D, Daum I. Cerebellar contributions to cognitive functions: a progress report after two decades of research. Cerebellum 2007;6:159-162

[65] ⁶⁵
Garrard P, Martin NH, Giunti P, Cipolotti L. Cognitive and social cognitive functioning in spinocerebellar ataxia: a preliminary characterization. J Neurol 2008;255:398-405.

[66] ⁶⁶
Brandt J, Leroi I, O'Hearn E, Rosenblatt A, Margolis RL. Cognitive impairments in cerebellar degeneration: a comparison with Huntington's disease. J Neuropsychiatry Clin Neurosci 2004;16:176-184.

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