Attenuated pupillary response during visual search in preclinical Alzheimer's disease

The locus coeruleus is among the earliest brain regions affected by tau pathology in Alzheimer's disease (AD), but the functional impact is difficult to measure in vivo. Task-evoked pupil dilation provides an index of locus coeruleus-norepinephrine function that might be altered in cognitively normal older adults with underlying AD pathology.

Cognitively normal older adults identified as AD biomarker positive (N = 25) or negative (N = 36) based on plasma phosphorylated tau (p-tau) levels completed a conjunctive visual search task that manipulated attentional load by varying set size. Pupil dilation responses during the task were analyzed using mixed-effects models and time-resolved regression.

Despite comparable accuracy and reaction times, biomarker-positive adults showed reduced load-dependent modulation of pupil dilation during target-present trials. Weaker modulation was associated with higher p-tau levels and poorer executive and memory function.

Attenuated task-evoked modulation of pupil dilation during visual search reveals locus coeruleus-norepinephrine dysfunction in preclinical AD.