AbstractBackgroundThe eye adapts to the demands of our behavior [1], its motor activity has proven to be a feasible method for measuring cognition in both health and disease [2]. This study assessed the sensitivity of oculo‐motor features in a benign cognitive challenge model with the purpose of identifying objective efficacy readouts for clinical drug trials in early Alzheimer’s disease (AD).MethodFifty participants, aged 60 to 80 years, performed a reading task in two sessions conducted the same day, morning and evening (i.e. the “cognitive challenge”), with an average inter‐session period of 9.28h, during which participants were not allowed to take naps or consume stimulating beverages. Participants were distributed across four cohorts corresponding to progressive stages of early AD [3]: 1) amyloid negative, cognitively healthy (control group), 2) amyloid positive pre‐symptomatic AD, 3) Mild Cognitive Impairment (MCI) due to AD (pre‐dementia group) and 4) mild AD (mild‐dementia group). ViewMind technology was used to track the oculo‐motor activity [4].ResultNone of the four cohorts reported increased levels of sleepiness during the challenge. However, cohorts showed significantly different oculo‐motor responses during the cognitive challenge (Table 1). The control group showed evidence of learning effects on the reading during the challenge reflected in no change in pupil size, longer saccades, less fixations and shorter gaze. Within the pre‐symptomatic group, however, a negative impact of the challenge was observed in a decrease in pupil size and increase in fixations. However, some learning effects were nevertheless seen in this cohort, in shorter gaze and longer saccades. In pre‐dementia group the learning effects were lost and participants demonstrated difficulty performing the task reflected in decreased pupil size and longer gaze. Finally, the mild‐AD participants showed an increase in fixations, longer gaze and no change in pupil size indicating a pattern of poor reading performance during the challenge.ConclusionOur preliminary results demonstrate that oculo‐motor activity may reflect changes in cognitive resources induced by a benign challenge in progressive clinical stages of early AD. These promising results support continued investigation into the potential of eye‐tracking during reading as a sensitive and objective measure .