title: Widespread neuronal damage and cognitive dysfunction in spinocerebellar ataxia type 3.
abstract: Previous studies demonstrated cognitive impairments in spinocerebellar ataxia type 3 (SCA3/MJD); however, there is no consensus about the cognitive domains affected and the correlation with structural brain abnormalities. We investigated the neuropsychological profile and 3T-MRI findings, including high-resolution T1-images, diffusion tensor imaging and magnetic resonance spectroscopy of 32 patients with SCA3/MJD and 32 age-, gender- and educational level-matched healthy controls. We reviewed patients' clinical history and CAG repeat length, and performed assessment and rating of ataxia (SARA)-Brazilian version and the neuropsychiatric inventory. Patients presented worse performance in episodic and working memory and Beck inventories (depression and anxiety). SCA3/MJD patients had a reduction of gray matter volume (GM) in the cerebellum, putamen, cingulum, precentral and parietal lobe. A positive correlation was identified between the cognitive findings and GM of temporal, frontal, parietal, culmen and insula. We observed positive correlation between the brainstem's fractional anisotropy and digit span-forward. The following cerebellar metabolite groups (measured relative to creatine) were reduced in patients: N-acetyl-aspartate (NAA), NAA + N-acetyl-aspartate-glutamate and glutamate + glutamine (Glx). We found a positive correlation between Corsi's block-tapping task forward with Glx; semantic verbal fluency with phosphorylcholine and glycerophosphorylcholine; digits span-forward with NAA. The cognitive impairments in SCA3/MJD are associated not only with cerebellar and brainstem abnormalities, but also with neuroimaging evidence of diffuse neuronal and axonal dysfunction, particularly in temporal, frontal, parietal and insular areas.
authors.affiliation: Laboratory of Neuroimaging, Department of Neurology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Tátila Martins
authors.initials: TM
authors.lastname: Lopes
authors.forename: Anelyssa
authors.initials: A
authors.lastname: D'Abreu
authors.forename: Marcondes Cavalcante
authors.initials: MC
authors.lastname: França
authors.forename: Clarissa Lin
authors.initials: CL
authors.lastname: Yasuda
authors.forename: Luiz Eduardo
authors.initials: LE
authors.lastname: Betting
authors.forename: Adriana Bastos
authors.initials: AB
authors.lastname: Samara
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castellano
authors.forename: Júlio César
authors.initials: JC
authors.lastname: Somazz
authors.forename: Marcio Luiz Figueredo
authors.initials: ML
authors.lastname: Balthazar
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
authors.forename: Fernando
authors.initials: F
authors.lastname: Cendes
mesh_terms: D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D017827:Machado-Joseph Disease / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D009483:Neuropsychological Tests