# Noradrenergic Locus Coeruleus Hyperactivity Alters Attention in Cognitively Healthy Older Adults

## TL;DR

This study shows that older adults have increased brain activity in a region linked to attention, which may affect how they process distractions.

## Contribution

The study provides empirical evidence of locus coeruleus-noradrenaline system hyperactivity in older adults using multimodal measures.

## Key findings

- Older adults showed weaker behavioral and physiological responses to arousal compared to young adults.
- Arousal differentially modulated attentional control to distractors between age groups.
- Findings suggest aging is linked to locus coeruleus-noradrenaline system hyperactivity.

## Abstract

Animal models of Alzheimer’s disease have shown that neuropathology in the locus coeruleus (LC) leads to increased neuronal firing, while human studies demonstrate that age-related dysregulation of the LC-noradrenaline (LC-NA) system is associated with cognitive decline. However, due to limitations in directly measuring LC function in vivo, it remains unclear whether age-related alterations in humans reflect tonic LC-NA system hyperactivity. In this study, we tested the hypothesis that cognitively healthy older adults sustain tonic LC hyperactivity, by acquiring electrophysiological, pupillometric, and behavioral measures during a passive and active auditory oddball paradigm. We capitalized on the LC-NA system’s role in arousal regulation and manipulated state arousal using the threat of electric shock. We hypothesized that if older adults maintain elevated LC activity compared with young adults, task-evoked noradrenergic responses would be less responsive to arousal in older adults. Consistent with this hypothesis, arousal elicited weaker behavioral responses, pupil dilation responses, and P300 event-related potentials in older adults compared with young adults. Linear mixed models revealed an arousal by modality interaction and revealed that arousal differentially modulated attentional control to salient but task-irrelevant distractors between both age groups. Collectively, these findings support the hypothesis that aging is associated with tonic LC-NA system hyperactivity in humans, with downstream consequences for mechanisms of attentional control. These multimodal findings underscore the potential of non-invasive physiological markers to assess LC-NA system function throughout aging and identify individuals at elevated risk for neurodegenerative progression prior to the emergence of clinical biomarkers.