Cognitive Vergence and Pupil Response During Oddball Task are Associated With Alzheimer’s Disease Cerebrospinal Fluid Neurodegenerative Biomarkers

Abstract Background Alzheimer’s disease (AD) can be diagnosed using cerebrospinal fluid (CSF) biomarkers reflecting amyloid and tau pathology. However, it provides 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 predictors of CSF core AD biomarkers in patients at mild cognitive impairment (MCI) stage. Methods 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 tested as predictors using linear regression. Results 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. Oculomotor features predicted p-Tau levels (R 2 = 0.20–0.21). Conclusion Oculomotor differentiation metrics capture functional signatures of tau-related network dysfunction, positioning them as accessible biomarkers complementing CSF measures for detecting network disruption at MCI stage.