Oculomotor Behaviors and Integrative Memory Functions in the Alzheimer's Clinical Syndrome

Background: Biological information drawn from eye-tracking metrics is providing evidence regarding drivers of cognitive decline in Alzheimer's disease. In particular, pupil size has proved useful to investigate cognitive performance during online activities. Objective: To investigate the oculomotor correlates of impaired performance of patients with mild Alzheimer's Clinical Syndrome (ACS) on a recently developed memory paradigm, namely the Short-Term Memory Binding Test (STMBT). Methods: We assessed a sample of eighteen healthy controls (HC) and eighteen patients with a diagnosis of mild ACS with the STMBT while we recorded their oculomotor behaviors using pupillometry and eye-tracking. Results: As expected, a group (healthy controls versus ACS) by condition (Unbound Colours versus Bound Colours) interaction was found whereby behavioral group differences were paramount in the Bound Colours condition. Healthy controls' pupils dilated significantly more in the Bound Colours than in the Unbound Colours condition, a discrepancy not observed in ACS patients. Furthermore, ROC analysis revealed the abnormal pupil behaviors distinguished ACS patients from healthy controls with values of sensitivity and specify of 100%, thus outperforming both recognition scores and gaze duration. Conclusion: The biological correlates of Short-Term Memory Binding impairments appear to involve a network much wider than we have thought to date, which expands across cortical and subcortical structures. We discuss these findings focusing on their implications for our understanding of neurocognitive phenotypes in the preclinical stages of Alzheimer's disease and potential development of cognitive biomarkers that can support ongoing initiatives to prevent dementia.