Saccades, eye-hand movement and cognition in Huntington's disease: a 12 month study

Abstract

Huntington’s disease (HD), a genetically inherited neurodegenerative disease caused by CAG trinucleotide repeat expansion, is characterised by movement disorders, cognitive impairment, and behavioural disorders. Saccadic and manual dexterity abnormalities are established deficits in manifest HD but short-term changes (i.e. 12 months) in saccades and eye-hand coordination have not been well-explored.

Given the progressive nature of cognitive, saccadic, and manual dexterity abnormalities, it is hypothesized that measurement of these abnormalities can be useful progression markers for monitoring short-term longitudinal disease changes in manifest HD. The overarching aim of the thesis work is to identify potentially objective biomarkers for measuring HD status and short-term progression that could be employed in clinical research, therapeutic trials, and clinics.

Saccades and eye-hand coordination in 22 manifest HD patients (stage 1 – 4) and 22 demographically-matched controls were measured using high-speed video-oculography and an electromagnetic motion detection system at baseline and after 12 months. Saccadic and eye-hand coordination tasks consisted of a series of visually-guided reflexive, rhythmical, and complex movement tasks. A comprehensive neuropsychological battery was used to assess cognition in both groups whereas the HD group alone was also assessed using the full Unified Huntington’s Disease Rating Scale (UHDRS) at both time points. The relationships between saccades and eye-hand coordination, and current disease status in the HD group were also examined.

Linear mixed-effect models showed that, in general, there was a strong effect of HD upon almost all cognitive measures, and saccadic and eye-hand parameters at baseline. This study also revealed that there was an impairment in the predictive behaviour of oculomotor and somatomotor movements in HD. Most of the saccadic and eye-hand parameters correlated well with cognitive status and motor scores of HD patients. Performance of reflexive saccades in a 2D (combined horizontal and vertical) task and self-paced eye-hand movement were sensitive measures of disease severity and progression over 12 months. The basal ganglia are involved in regulating rhythmical movement and the decline in performance in self-paced eye-hand task at follow-up may reflect short-term neuropathological changes in the basal ganglia in HD. There were no significant differences, in terms of 12 month longitudinal changes, in a majority of the other saccadic and eye-hand parameters, between the HD and control group after 12 months. These findings suggest that there is a slow and heterogeneous disease progression and also a compensating mechanism to maintain behavioural performance over short-time intervals in HD.

Saccades may provide a better measurement of disease severity and short-term disease changes than somatomotor parameters in manifest HD. In summary, this study provided novel perspectives on eye-hand coordination in HD. Several potential useful markers for monitoring short-term disease changes, which could be easily adapted for use in longitudinal research studies, clinical trials, and clinics, were also identified. Due to the exploratory nature of this research, results should be confirmed in future studies.