Brain metabolic correlates of Locus Coeruleus degeneration in Alzheimer's disease: a multimodal neuroimaging study

Locus Coeruleus (LC) degeneration occurs early in Alzheimer’s disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investi- gate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were sub- mitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LC CR ) and LC-belonging voxels (LC VOX ). Both LC CR and LC VOX were significantly lower in patients compared to HCs, and were directly associ- ated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.0 01, kE > 10 0). These results suggest a possible association between LC degeneration and cortical hy- pometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.