The Association Between Saccadic Eye Movement Parameters and Mild Cognitive Impairment: the Nagahama Study

Purpose The early identification of mild cognitive impairment (MCI) is crucial in preventing dementia progression, making reliable cognitive screening tools essential. This study was conducted to examine the relationship between saccadic eye movement parameters and MCI using a novel eye-tracking device, the gaze-analyzing perimeter (GAP) screener, which records saccadic eye movements precisely without large equipment or dark rooms. Design Cross-sectional study. Participants We used the dataset from the Nagahama Prospective Cohort for Comprehensive Human Bioscience conducted between 2017 and 2023. A total of 1,202 participants aged ≥59 years who completed both the cognitive assessment using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and the gaze-tracking assessment using GAP were included. Methods Saccadic parameters such as reaction time, latency, the number of saccades, and gain were analyzed, and participants were divided into the MCI and non-MCI groups based on a MoCA-J score threshold of 25. Logistic regression models adjusted for possible confounders were used to evaluate the association between MCI and saccadic eye movement parameters as measured using GAP. Genome-wide association study was performed for reaction time. Main Outcome Measures The association between MCI and saccadic eye movement parameters obtained using GAP. Results The average age of participants was 70.9±5.6 years. The MCI group included 557 (46.3%) participants. When the participants were divided into three groups based on reaction time tertiles, the percentage of individuals with MCI was 34% in Tertile 1, 47% in Tertile 2, and 59% in Tertile 3, with a higher proportion in groups with longer mean reaction times (P<0.001). Multivariable logistic regression analysis revealed that longer reaction time, longer latency, and smaller end gain were associated with MCI ( P =1.04×10 -4 , 0.03, and 0.045, respectively). Rs1991348 near RALYL , which is reportedly a hub gene for Alzheimer's disease reserve, was significantly associated with reaction time (P = 3.25 × 10 -8 ). Conclusions The MCI group exhibited longer reaction times, longer latencies, and smaller end gains in saccadic movements than the non-MCI group, even after adjusting for possible confounders. These findings suggest that saccadic eye movement parameters, particularly mean reaction time, may serve as biomarkers for identifying MCI.