The cerebellar cognitive affective syndrome scale reveals early neuropsychological deficits in SCA3 patients

Abstract

Background: The cerebellar cognitive affective syndrome scale (CCAS-S) was recently developed to detect specific neuropsychological deficits in patients with cerebellar diseases in an expedited manner.

Objectives: To evaluate the discriminative ability of the CCAS-S in an etiologically homogeneous cohort of spinocerebellar ataxia type 3 (SCA3) patients and to examine relationships between cognitive deficits and motor symptom severity.

Methods: The CCAS-S was administered to twenty mildly to moderately affected SCA3 patients and eighteen healthy controls matched for age, sex, and educational level. Disease severity was measured by the Scale for the Assessment and Rating of Ataxia (SARA), Inventory of Non-Ataxia Signs (INAS), 8 m walk test, nine-hole peg test (9HPT), and Patient Health Questionnaire-9 (PHQ-9).

Results: SCA3 patients had a lower total CCAS-S score (p < 0.001) and higher number of failed tests (p = 0.006) than healthy controls. Patients displayed impairments in semantic fluency, phonemic fluency, category switching, cube drawing, and affect regulation. Total CCAS-S score showed high discriminative ability (area under the curve [AUC]: 0.96) and was associated with disease duration, SARA score, walking speed, and dominant hand 9HPT performance. No correlations were observed with INAS count, repeat length, and PHQ-9 score. Discriminative capacity of the number of failed tests was moderate (AUC: 0.76).

Conclusion: Essentially all SCA3 patients exhibited some form of cognitive impairment. The CCAS-S differentiates SCA3 patients from healthy controls, detects neuropsychological deficits early in the disease course, and correlates with relevant ataxia severity measures.

Keywords: Cerebellar cognitive affective syndrome; Cerebellum; Cognition; Spinocerebellar ataxia type 3.

Fig. 1

Global performance of the cerebellar cognitive affective syndrome scale in SCA3 patients and healthy controls

Fig. 2

Discriminative ability of total cerebellar cognitive affective syndrome scale score and number of failed tests. Receiver operating characteristic curves illustrate the high discriminative performance of the former (a) and the moderate discriminative performance of the latter (b). To determine if the phonemic fluency task negatively affected CCAS-S’s overall ability to differentiate SCA3 patients from healthy controls, a separate analysis was conducted without this item (red line)

Fig. 3

Dot plots displaying individual neuropsychological test scores in SCA3 patients and healthy controls. The dashed red lines represent previously assigned cut-offs that indicate if a participant passed or failed the task [14]

Fig. 3

Dot plots displaying individual neuropsychological test scores in SCA3 patients and healthy controls. The dashed red lines represent previously assigned cut-offs that indicate if a participant passed or failed the task [14]

Fig. 4

Associations between total cerebellar cognitive affective syndrome (CCAS) scale score and relevant disease severity measures in SCA3 patients. SARA Scale for the Assessment and Rating of Ataxia; 9HPT nine-hole peg test