Pupillometry as a marker of arousal and in relation to cognition and cortical dynamics in Alzheimer’s disease

Abstract Background Pupil dilation is an established measure of noradrenergic activity. Cortical EEG alpha power, a measure of attentional engagement, can be recorded simultaneously with pupillometry. Dysfunction in the noradrenergic system in Alzheimer’s disease (AD), contributes to the attentional deficits seen in patients. We investigated whether pupillometry recorded at rest can be used to show reduced noradrenergic activity in AD and how this relates to cortical dynamics. Method We recorded simultaneous EEG and pupillometry during 5min of eyes‐open resting‐state in 28 AD patients and 22 age‐matched controls (HC). Pupil dilations – peaks of both pupil diameter and velocity – were identified (Fig. 1A/B). Average pupil diameter and velocity were calculated across all dilations, and compared between groups (Fig. 1 C/D). We plotted EEG power spectra for the 2s pupil dilation‐centred epochs (Fig. 2A). The frequency at which there was the greatest power within the alpha band – the peak alpha frequency (PAF) – was calculated for each individual and compared across groups (Fig. 2B). We then measured the alpha power during the pupil‐dilation epochs and looked at the relationship with the pupils (Fig. 3). Result In HCs, the mean pupil dilations – peaks in diameter and peaks in velocity – were greater than in AD; t = ‐2.62 p = 0.01 and t = ‐2.26 p = 0.03, respectively (Fig. 1C/D). Power spectra for the 2s pupil dilation‐centred epochs showed patients’ PAF was significantly lower than HC’s; t = 2.92 p<0.01 (Fig. 2). There was a corresponding peak in alpha power associated with the pupil dilations, in both groups. Regarding peaks in pupil diameter, the alpha power peaked approximately 0.5sec earlier (Fig. 3A). Regarding peaks in pupil velocity, the alpha power peaked simultaneously with the pupils (Fig. 3B). Conclusion There is a reduction in size and velocity of spontaneous pupil dilations in AD. EEG alpha is shifted to lower frequencies in AD. There is a preserved relationship between pupil dilations and alpha peaks in AD. Pupillometry offers a means of measuring noradrenergic dysfunction in AD that relates to altered cortical dynamics.