Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age, Mild Cognitive Impairment and Alzheimer’s Disease: An MRI Structural Study On the Adni Cohort

The Noradrenergic Theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the up-regulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test this theory, a study was conducted on a sample of 686 participants (395 Controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC vol-ume, attentional performance and a biological index of brain maintenance (BrainPAD – a measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic hypothesis. Results showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on upregulation of the noradrenergic system (e.g. attention training, physical exercise and pharmacological intervention) may yield important clin-ical benefits to mitigate cognitive impairment with age and disease.