Neurocognitive Changes in Spinocerebellar Ataxia Type 3: A Systematic Review with a Narrative Design

Cerebellum. 2022 Apr;21(2):314-327. doi: 10.1007/s12311-021-01282-3. Epub 2021 Jul 7.


Spinocerebellar ataxia type 3 (SCA3), the commonest dominantly inherited ataxia worldwide, is characterized by disruption in the cerebellar-cerebral and striatal-cortical networks. Findings on SCA3-associated cognitive impairments are mixed. The classification models, tests and scoring systems used, language, culture, ataxia severity, and depressive symptoms are all potential confounders in neuropsychological assessments and may have contributed to the heterogeneity of the neurocognitive profile of SCA3. We conducted a systematic review of studies evaluating neurocognitive function in SCA3 patients. Of 1304 articles identified, 15 articles met the eligibility criteria. All articles were of excellent quality according to the National Institutes of Health quality assessment tool for case-control studies. In line with the disrupted cerebellar-cerebral and striatal-cortical networks in SCA3, this systematic review found that the neurocognitive profile of SCA3 is characterized by a core impairment of executive function that affects processes such as nonverbal reasoning, executive aspects of language, and recall. Conversely, neurocognitive domains such as general intelligence, verbal reasoning, semantic aspect of language, attention/processing speed, recognition, and visuospatial perception and construction are relatively preserved. This review highlights the importance of evaluating neurocognitive function in SCA3 patients. Considering the negative impact of cognitive and affective impairment on quality of life, this review points to the profound impairments that existing or future treatments should prioritize.

Keywords: Cerebellar cognitive and affective syndrome; Cerebellar-cerebral network; Neuropsychology; Spinocerebellar ataxia 3.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Ataxia
  • Executive Function
  • Humans
  • Machado-Joseph Disease*
  • Neuropsychological Tests
  • Quality of Life