P3‐078: Pupil dilation during a cognitive task: A psychophysiological biomarker differentiating early MCI and normal cognitive function

Early identification of mild cognitive impairment (MCI) and Alzheimer's disease is of substantial public health importance. Using the Jak/Bondi approach, we identified MCI in community-dwelling midlife adults. Pupil dilation during a cognitive task is a validated psychophysiological biomarker of effortful brain resource allocation. We examined whether this biomarker can differentiate early MCI from normal cognition. 980 Vietnam Era Twin Study of Aging participants underwent testing covering 6 neuropsychological domains at waves 1 (ages 51-60) and 2 (ages 56-65). Multiple-domain MCI was defined as 2+ domains impaired (>2SDs below mean normative values on 2 measures in a domain) (Kremen et al, 2014). At wave 2 participants underwent pupillometry, measuring increase in pupil dilation—controlling for maximum span length outside pupillometry conditions—while recalling spans of 3, 6, and 9 digits. As expected, dilation during pupillometry decreased as maximum span increased (consistent with less effort required when cognitive ability is higher), and dilation increased with increasing cognitive load but decreased when load was well beyond capacity (Figure 1). Most of the multiple-domain MCI group had stable MCI (i.e., at both timepoints). Amnestic and non-amnestic multi-domain MCI groups had similar pupil responses and were combined. They had significantly less dilation than other groups at 6 and 9 digits (effect sizes: d=.62-.65 at 6 digits), and no increased dilation in response to increased cognitive load (Figure 2). Task-evoked pupillary response differentiates multi-domain MCI from normal cognition in late midlife. When capacity is overwhelmed, the system fails and dilation decreases. Individuals with multiple-domain MCI seem unable to increase resource allocation and modulate in response to changing cognitive demands. Pupil responses are unlikely to reflect low effort because most recalled 6 digits, despite impairment on more challenging neuropsychological tests. A conservative (e.g., multi-domain) threshold may be important because this is a relatively young, community-dwelling (non-clinic) sample. However, although single-domain MCI participants increased dilation at 6 digits, their significant drop-off at 9 digits compared to normal suggests risk for further decline at follow-up. This simple 5-minute pupil dilation task provides a novel psychophysiological biomarker for MCI identified relatively early in adulthood.