Interrogating the role of the noradrenergic locus coeruleus in memory encoding in aging

Abstract

AbstractBackgroundThe locus coeruleus‐norepinephrine system (LC‐NE system) supports the process of encoding of emotionally salient events. LC integrity varies in healthy elderly and is associated with altered cognitive functions in aging. Post‐mortem as well as structural indicators suggest that the modulation of the LC‐NE system is reduced in elderly. This reduction in ageing is also of note as it might be one of the earliest pre‐symptomatic indicators of dementia‐related brain pathology. Indeed, LC neuron degeneration is already observable in early stages of tau pathology before any cognitive symptoms are clinically notable in Alzheimer´s disease (AD). The main aim of this study was to investigate age differences in functional activations of the LC during (emotionally) salient events.MethodA total of 50 people (28 younger, 22 older healthy adults) participated in the experiment. A reversal learning task has been chosen as it provokes the release of NE. The study used neuromelanin (NM) ‐ sensitive magnetic resonance imaging (MRI) and high‐resolution functional MRI (fMRI) to visualise age differences in LC structure and function. Functional indicators can add sensitivity over structural indicators, which is important considering the fact of neuronal function loss before cell death occurs.ResultReduced LC integrity was related to lower memory performance for negative emotional events in elderly only. Moreover, unexpectedly, stronger functional responses of dopaminergic and noradrenergic midbrain structures to (emotionally) salient events during memory encoding were observed in older adults.ConclusionThese results are discussed in light of age differences in adapting to high and low levels of task difficulty. The study has shown the feasibility of investigating age differences in neuromodulatory nuclei. Therefore, the observed reduction in LC integrity might be a typical sign of healthy ageing or a sign of mild cognitive impairment (MCI) and thus also for AD.