Structural connectivity of the human olfactory network and its relation to aging and olfactory function

Impaired olfactory function in older adults is associated with memory decline and is a biomarker of Alzheimer's disease (AD). However, the structural brain foundation underlying olfactory impairment and its link to memory function remains largely unknown. We address this gap by reconstructing the structural olfactory network, that is, white-matter connections between the primary olfactory cortex (POC) and the whole brain. Through applying multivariate analyses in a population-based sample (n = 137), we investigate the relationships among age, the olfactory network, and olfactory and cognitive function. Our findings reveal that the POC subregions have distinct structural connectivity profiles with the entire brain. Older age was associated with weaker connectivity strength between the POC and nearby regions, suggesting a reorganization of the olfactory network in older adults. Structural connectivity of the olfactory network was associated with behavioral performance in odor identification, episodic memory, and odor threshold, but not processing speed or working memory. Notably, connections including the olfactory tubercle (TUB)-caudate, TUB-amygdala, and olfactory nucleus (AON)-hippocampus were important for both olfaction and episodic memory function, suggesting a common neural basis across cognitive domains. Our study expands on previous research of single brain regions or individual white-matter tracts, uncovering the structural underpinnings of olfactory function at the network level. The results shed light on the common foundation of olfaction and memory dysfunction, an early marker of AD.