Multimodal oculomotor assessment reveals prodromal markers of Parkinson’s disease in non-manifesting LRRK2 G2019S mutation carriers

Abstract

Oculomotor behaviour changes in patients with Parkinson’s disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk. Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition—less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite—higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers.