Association of Olfaction and Microstructural Integrity of Brain Tissue in Community-Dwelling Adults

Abstract

Objectives: Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. Methods: Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by two diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor-identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor-identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. Results: Among 1,418 participants (mean age: 76±5years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9±2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely, the hippocampus (β: -0.79 (95%CI: -0.94, -0.65) units lower olfaction score per SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared to those with normal cognition (e.g., βhippocampus: -0.75 (95%CI: -1.02, -0.49) and -0.44 (95%CI: -0.63, -0.26) for MCI and normal cognition, respectively, p-interaction=0.004). Conclusions: Neuronal microstructural integrity in multiple brain regions, in particular the MTL (the regions known to be affected in early Alzheimer’s), is associated with odor-identification ability. Differential associations in the MTL regions among cognitively normal individuals compared to those with MCI may reflect the earlier vs. later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.