HAI Book 2025 - Flipbook - Page 109
Grube, Jill
5
APOE ε4 carriers exhibit attenuated habituation in pupil size and
practice effects on a repeated auditory oddball task
Jill A.E. Grube1,2, Marina Rodríguez Alonso3, Nina Engels-Domínguez1,2,4, Heidi I.L. Jacobs1,2,4,
Joost M. Riphagen1,2
1
The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General
Hospital, Boston, MA, US
2
Harvard Medical School, Boston, MA, US
3
Baylor College of Medicine, Houston, TX, US
4
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre
Limburg, Maastricht University, Maastricht, NL
Introduction: The locus coeruleus (LC), an area of early Alzheimer9s disease (AD) pathology, plays a key role in
regulating arousal and attention. We have previously shown that lower LC integrity is associated with attenuated
practice effects in learning. Pupillometry has emerged as a reliable method for assessing LC function. Here, we
compared APOE ε4 and non-ε4 carriers on changes in pupil dilation and reaction time during repeated exposure to
an oddball task.
Methods: Older participants from the WALLe study (n=19, mean age: 67y (sd=4.70), 53% female, 32% APOE ε4carrier) performed an auditory oddball task on day 1-5-10 of a two-week period (Fig. 1). Pupillometry data was
simultaneously recorded with a EyeLink-1000. Habituation in pupillometry was defined as a decrease in peak
height of pupil size and a faster time-to-peak pupil dilation after the target tone across visits. Practice effects in
behavior was defined as faster reaction time across 3 timepoints. Linear mixed models tested pupil dilation peak
height (DPH), time to peak pupil dilation (TTP), or reaction time over time (age and sex as covariates) within ε4 or
non-ε4 carriers.
Results: Non-ε4 carriers showed a decrease in pupil DPH between Visit 1-5 (p=0.06) and Visit 1-10 (p=0.05), while
ε4 carriers only exhibited a decreased pupil DPH between Visit 1-10 (p=0.05) (Fig. 2a). ε4 carriers showed no
significant change in TTP, while non-ε4 carriers showed a decrease of their TTP between Visit 1-5 (p=0.01) and
between Visit 1-10 (p=0.02; Fig. 2b). ε4-carriers showed no significant change in reaction times, while non-ε4
carriers displayed faster reaction times between Visit 1-5 (p=0.05; Fig. 3).
Conclusion: Individuals with the APOE ε4 allele exhibit decreased practice effects in performance and habituation
in pupillometry during an oddball task. These findings can be important for early detection of cognitive decline in
individuals at genetic risk for AD.
HAI2025 - 109
