Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences

Abstract

The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function.

Fig. 1. The measurement models of LC-dependent function.

LC mean normalized LC signal intensity (LC CR), NA-d NA-dependent factor, NA-in NA_independent factor, Cog single latent factor, EMv emotional source memory—negative valence, EMp emotional implicit memory (priming)—negative valence, EMn emotional object memory—negative valence, SS stop-signal response time (SSRT), ERr emotional reappraisal for negative emotion, ERn negative emotional reactivity, Hotel Hotel task total score, PSQI Pittsburgh Sleep Quality Index total score, Edu years of education, Occ occupational complexity, Verb Spot the Word test as a proxy for verbal intelligence, Int Cattell total score as a proxy for fluid intelligence, Sent sentence comprehension, Fam familiar faces recognition.