Objective: To assess saccadic paradigms in asymptomatic Huntington disease mutation carriers.

Background: Huntington’s disease (HD) is characterized by motor, cognitive and behavioural abnormalities, such as depression, apathy, and irritability. However, impaired decision making (1) as well as impairment in saccadic inhibition, using the antisaccade task, has been also described in asymptomatic HD mutation carriers far from disease onset (2).

Method: A total of 17 asymptomatic HD mutation carriers (pre-HD) were prospectively enrolled. All participants had a total motor score of 5 or lower. Participants were further split into those near to the predicted disease onset (<15 years; NEAR) and far from predicted disease onset (>15 years; FAR). Demographic characteristics were collected and all participants performed a Mini-Mental state examination (MMSE), and an eye tracking assessment battery consisting of a delayed prosaccade task, an antisaccade task, a Go-/NoGo-task, and a countermanding task.

Results: We included 8 FAR (5 females) and 9 NEAR (5 females) participants. There were no differences in education, age or on the MMSE. However, we found a significant group difference in the error rate on the antisaccade task (FAR: 8.47 ±8.56%; NEAR: 25.3 ±10.4; p = 0.004). The group difference in the prosaccade task just reached trend levels (FAR: 16.3 ±5.5%; NEAR: 26.0 ±11.8%; p = 0.065). There were no differences in the error rate of the Go-/NoGo task, or the countermanding task (all p values > 0.1). When we analysed the pro- and antisaccades of the countermanding task separately, we found a significant difference in error rate of the antisaccade task (FAR: 14.3 ±13.0%; NEAR: 37.9 ±19.9%; p = 0.027). There was no difference in the reaction times of the saccadic paradigms (all p values > 0.1).

Conclusion: In line with one previous study (2), we found that HD carriers close to predicted disease onset performed worse on an antisaccade task compared to HD carriers far from predicted disease onset. These results highlight a dysfunction of the frontal-striatal top down inhibitory control in asymptomatic HD carriers. Interestingly, we did not find group differences on other saccadic paradigms. However, it is possible that a larger sample size would have revealed further group differences.
Our preliminary results suggest that the antisaccade task is a sensitive tool to detect early cognitive impairment in HD mutation carriers near to disease onset.

References: 1. Heim, B, Peball, M, Saft, C, et al. Time will tell: Decision making in premanifest and manifest Huntington’s disease. Brain Behav. 2020; 10:e01843. https://doi.org/10.1002/brb3.1843 2. Wiecki TV, Antoniades CA, Stevenson A, et al. A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease. PLoS One. 2016;11(2):e0148409. Published 2016 Feb 12. doi:10.1371/journal.pone.0148409

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impaired-saccadic-inhibition-in-huntington-mutation-carriers/