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Cognitive Deficits in Machado–Joseph Disease Correlate with Hypoperfusion of Visual System Areas

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Abstract

Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease (MJD)—SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin’ Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.

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Acknowledgments

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). We would like to thank the patients, their families, and the health volunteers for participating in this study.

Conflict of interest

Information concerning all sources of financial support and funding for the preceding 12 months is disclosed below, regardless of relationship to the current manuscript, submitted under the following suggested categories. Rodrigo A. Bressan was a consultant and a member of the advisory board of AstraZeneca and Janssen-Cilag; had partnerships with FAPESP, CNPq, and Instituto Albert Einstein de Ensino e Pesquisa; received honoraria from Eli Lilly, AstraZeneca, Janssen-Cilag, and Novartis; and received grants from FAPESP, CNPq, and Instituto Albert Einstein de Ensino e Pesquisa.

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Authors and Affiliations

  1. Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil

    Pedro Braga-Neto, Lívia Almeida Dutra, José Luiz Pedroso, André C. Felício & Orlando Graziani Povoas Barsottini

  2. Behavior Neurology Section, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil

    Pedro Braga-Neto, Lívia Almeida Dutra, Helena Alessi & Paulo Henrique F. Bertolucci

  3. Center of Mathematics, Computer and Cognition–Universidade Federal do ABC, UFABC, São Paulo, Brazil

    Ruth F. Santos-Galduroz

  4. Institute of Biosciences, UNESP, Rio Claro, São Paulo, Brazil

    Ruth F. Santos-Galduroz

  5. Section of Nuclear Medicine, Department of Radiology, Universidade Federal de São Paulo, São Paulo, Brazil

    Mário Luiz V. Castiglioni

  6. Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil

    Rodrigo Affonseca Bressan & Andrea Jackowski

  7. Western Australian Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Crawley, Australia

    Griselda Esther Jara de Garrido

  8. 650 Pedro de Toledo st, Vila Clementino, São Paulo, SP, 04039-002, Brazil

    Pedro Braga-Neto

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  1. Pedro Braga-Neto
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  2. Lívia Almeida Dutra
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Correspondence to Pedro Braga-Neto.

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Braga-Neto, P., Dutra, L.A., Pedroso, J.L. et al. Cognitive Deficits in Machado–Joseph Disease Correlate with Hypoperfusion of Visual System Areas. Cerebellum 11, 1037–1044 (2012). https://doi.org/10.1007/s12311-012-0354-x

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