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Abstract
Background and 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 the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 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 ± 5 years, 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 to −0.65] units lower olfaction score per 1 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 with those with normal cognition (e.g., βhippocampus −0.75 [95% CI −1.02 to −0.49] and −0.44 [95% CI −0.63 to −0.26] for MCI and normal cognition, respectively, p interaction = 0.004).
Discussion Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with 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.
Glossary
- AD=
- Alzheimer disease;
- aMCI=
- amnestic MCI;
- ARIC=
- Atherosclerosis Risk in Communities;
- BMI=
- body mass index;
- BP=
- blood pressure;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- FDR=
- Benjamini-Hochberg false discovery rate;
- FWER=
- Bonferroni family-wise error rate;
- GM=
- gray matter;
- JHU=
- Johns Hopkins University;
- MCI=
- mild cognitive impairment;
- MD=
- mean diffusivity;
- MTL=
- medial temporal lobe;
- NCS=
- Neurocognitive Study;
- PD=
- Parkinson disease;
- ROI=
- region of interest;
- SVD=
- small vessel disease;
- WM=
- white matter;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.
- Received January 9, 2023.
- Accepted in final form May 30, 2023.
- © 2023 American Academy of Neurology
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