Task-evoked pupillary responses as potential biomarkers of mild cognitive impairment.

Introduction: Eye movement alterations are effective biomarkers for Alzheimer's disease (AD). This study examines task-evoked pupillary responses (TEPRs) as potential biomarkers of the mild cognitive impairment (MCI), the symptomatic stage preceding AD.

Methods: The prospective cohort study included 213 MCI patients and 514 cognitively normal controls (CNs). Participants performed a prosaccade (PS) or antisaccade (AS) task while their eye movements were tracked using a Tobii Pro Spectrum system.

Results: The CNs showed unique TEPRs linked to better performance, characterized by larger baselines, greater PS target-onset variability, and smaller AS target-onset variability. Conversely, for MCI patients, better performance was linked to larger AS target-onset sizes. Furthermore, MCI patients displayed reduced dilation during the cue and target-onset periods compared to CNs.

Discussion: MCI patients showed altered pupillary response patterns associated with cognitive task performance, highlighting the potential of oculomotor changes as a biomarker for early cognitive decline.

Highlights: MCI patients displayed markedly smaller pupil dilation than CNs in response to cue and target stimuli.For MCI patients, larger pupil size upon target appearance during antisaccades correlated with better performance.Faster and more consistent prosaccades were linked to better performance in both groups.For MCI patients, the association between longer AS latencies and better performance was more pronounced than in CNs.Combined analysis of TEPRs and saccade performances in a sizeable cohort strengthens the generalizability of our findings to the broader MCI population.