Noradrenergic signaling in human olfaction assessed by multimodal [11C]yohimbine PET/neuromelanin MRI across sex, healthy aging and Parkinson’s disease

Abstract The role of the noradrenergic system in human olfaction remains to be demonstrated given that, due to the technical limitations of in vivo molecular imaging, most of our knowledge is derived from animal studies. Here, we combine [ 11 C]Yohimbine PET imaging to quantify α2-adrenoceptor availability and neuromelanin-sensitive MRI of the locus coeruleus with behavioral olfactory testing in a cohort of 114 participants encompassing individuals ranging from normosmic to markedly hyposmic across a broad biological continuum. A broad range of olfactory performance was obtained by including 84 healthy controls of both sexes and of various ages and 30 patients with Parkinson’s disease, three major factors known to modulate olfactory processing. In the unadjusted pooled cohort, no significant association was observed between any of the three olfactory performance scores and locus coeruleus MRI signal, but odor identification and discrimination scores showed weak but significant negative correlations with [ 11 C]yohimbine binding in the piriform cortex and amygdala. These correlations were no longer significant after adjustment for age, sex, and diagnostic status and were not detected in within-group analyses. These findings suggest a cohort-level association between α2-adrenoceptor availability in olfactory cortical regions and odor identification/discrimination scores; however, this relationship could not be dissociated from the demographic and clinical factors represented in this cohort.