Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3

Ye, Zhi-Xian; Bi, Jin; Qiu, Liang-Liang; Chen, Xuan-Yu; Li, Meng-Cheng; Chen, Xin-Yuan; Qiu, Yu-Sen; Yuan, Ru-Ying; Yu, Xin-Tong; Huang, Chun-Yu; Cheng, Bi; Lin, Wei; Chen, Wan-Jin; Hu, Jian-Ping; Fu, Ying; Wang, Ning; Gan, Shi-Rui; ,

doi:10.1007/s00415-023-12042-0

Cited by 2 publications

(1 citation statement)

References 65 publications

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“…The CAG repeat size typically falls within the range of 10 to 44 in normal individuals; however, in SCA3 patients, there is a notable expansion, ranging from 56 to 87 [2]. Onset of SCA3 usually occurs in adulthood, and clinical symptoms are notably diverse, including gait ataxia, pyramidal, extrapyramidal, and oculomotor system disorders, as well as cognitive impairment [3,4].…”

Section: Introductionmentioning

confidence: 99%

Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study

Ye,

Chen,

et al. 2024

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Background: Spinocerebellar ataxia type 3 (SCA3) is a hereditary polyglutamine disease, caused by abnormally expanded cytosine–adenine–guanine (CAG) repeats in ATXN3 gene. It is classically characterized by cerebellar and spinal cord atrophy and presents with progressive ataxia. we here investigated the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in SCA3. Methods: In this prospective cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) score were investigated using partial correlation and mediation analyses. Sample sizes of potential markers were calculated. Results:Compared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. CAG repeat size was associated with right cerebellar lobule IV volume (r = -0.423, P < 0.001) and cervical spinal cord area (r = -0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cordmeasures. Conclusions: CAG repeat size influenced cerebellar lobule IV and cervical spinal cord volume loss. Our results indicated the potential of cervical spinal cord area as a marker for disease progression and sample size estimations in future SCA3 clinical studies.

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Section: Introductionmentioning

confidence: 99%

Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study

Ye,

Chen,

et al. 2024

Preprint

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Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3

Chen,

Lin,

et al. 2024

Euro J of Neurology

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BackgroundThe regulatory role of the apolipoprotein E (APOE) ε4 allele in the clinical manifestations of spinocerebellar ataxia type 3 (SCA3) remains unclear. This study aimed to evaluate the impact of the APOE ε4 allele on cognitive and motor functions in SCA3 patients.MethodsThis study included 281 unrelated SCA3 patients and 182 controls. APOE genotypes were analyzed using PCR amplification combined with Sanger sequencing. Additionally, 96 SCA3 patients were prospectively recruited for neuropsychological and motor function assessments. Neuropsychological phenotypes were evaluated using the modified Chinese version of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). Motor function was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS).ResultsThe frequency of the APOE ε4 allele was increased in SCA3 patients compared to the control group. The APOE ε4 allele was associated with better performance in language and visual memory, but also with more severe speech disturbances in SCA3 patients. Furthermore, in SCA3, the expanded CAG repeat length was correlated with poorer language memory performance and slower information processing speed, as well as more severe gait disturbances, fast alternating hand movements, speech disturbance, and oculomotor disorders.ConclusionsThe APOE ε4 allele may serve as a disease‐modifying factor in SCA3, influencing both cognitive and motor functions.

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Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3

Cited by 2 publications

References 65 publications

Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study

Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study

Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3

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