Cognitive vergence and pupil response during oddball task are associated with Alzheimer´s disease cerebrospinal fluid neurodegenerative biomarkers

Abstract

Alzheimer’s disease (AD) can be diagnosed using cerebrospinal fluid (CSF) biomarkers reflecting amyloid and tau pathology. However, they provide no information about functional network status. We aimed to determine whether CSF biomarkers (Aβ42, p-Tau, t-Tau, and Aβ42/p-Tau ratio) are associated with altered stimulus differentiation in vergence and pupil responses during an oddball task, and to evaluate oculomotor metrics as exploratory correlates of CSF biomarkers at MCI stage. Thirty-eight participants with abnormal CSF core AD biomarkers at MCI stage completed a visual oddball task while oculomotor responses were recorded. Linear mixed-effects models examined condition × biomarker interactions, controlling for sex, age, and MMSE. Temporal and magnitude features were examined using linear regression. Higher p-Tau levels were negatively associated with target-distractor differentiation in cognitive vergence (β = -0.035, p < 0.001) and pupil responses (β = -0.060, p < 0.001). Higher Aβ42 and Aβ42/p-Tau showed positive associations with vergence differentiation but opposite effects on pupil responses. Exploratory linear regression indicated that oculomotor features were associated with p-Tau variability (R² = 0.20–0.21). Oculomotor metrics show associations consistent with functional signatures of tau-related network dysfunction and may complement CSF measures in characterizing attention network status at MCI stage.