Locus coeruleus (LC) integrity in cognitively normal older adults is a potentially important preclinical marker in dementia. Our study establishes a link between variability in LC integrity and cognitive decline related to noradrenergic modulation in old age. We find that in older adults, reduced LC integrity explains lower memory performance. This effect was more pronounced for memory related to negative events, and accompanied by increased pupil diameter size in response to negative events. The study provides a strong motivation for future research investigating the role of LC integrity in healthy, as well as in pathological, aging.Abstract
The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.
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