Two-year decline in performance on the Cerebellar Cognitive Affective Syndrome Scale in spinocerebellar ataxias

Cognitive deficits are observed in a subset of individuals with spinocerebellar ataxias (SCAs); however, there is limited research on the longitudinal trajectory of such deficits. We investigated longitudinal cognitive performance amongst individuals with SCAs relative to controls, and the relationship of change in cognitive performance with change in self-reported function.

Individuals with symptomatic SCA1, SCA2, SCA3, and SCA6 as well as unaffected controls were administered the Cerebellar Cognitive Affective Syndrome Scale (CCAS-S) at yearly intervals for up to two years. Participants with SCA self-reported day-to-day cognitive and motor function via annual completion of the Patient-Reported Outcome Measure of Ataxia.

Significant two-year decline in CCAS-S performance was observed in individuals with SCA (n = 25). In a larger cohort of individuals who completed 1-year follow-up (n = 45 SCA), greater decline was observed among individuals with better baseline performance, and, at a trending level, those with milder motor ataxia severity. Greater one-year decline on the CCAS-S was significantly associated with greater decline in self-reported day-to-day cognitive function. In contrast, one-year CCAS-S change was not related to change in self-reported motor function.

The CCAS-S indexes functionally relevant cognitive change over time in SCAs, with this decline apparent in at least a subset of individuals with SCAs. Decline in cognitive performance may be particularly pronounced in early/mild disease stages. Our results motivate larger and longer-term studies of the CCAS-S in SCAs, including investigating cognitive change across the pre-symptomatic and symptomatic disease course, and identifying risk factors for cognitive decline, to inform appropriate clinical support.