Cross-Sectional and Longitudinal Associations Between Olfaction and White-Matter Integrity Across the Lifespan

The loss of smell is common in older age, reducing quality of life and often precedes the onset of cognitive decline and dementia. While age-related olfactory loss has been linked to cortical thinning and volume reductions in key olfactory areas, associations between white-matter (WM) integrity and olfaction are poorly understood. Here, we studied individuals aged 25-85 years from a population-based cohort study with diffusion weighted imaging, together with self-reported olfactory impairment, odor identification and odor threshold measures at baseline (N = 248) and follow-up 5 years later (N = 192). Performance on the odor identification and threshold tests were lower in older adults and declined longitudinally. Older individuals also reported more olfaction complaints, and such complaints increased over time. Results from general linear models showed no cross-sectional associations between WM integrity and olfaction. However, results from non-competitive random forest models identified several tracts as significant contributors to odor identification and subjective olfactory impairment, including the fornix, cingulum and uncinate fasciculus. Moreover, longitudinal analyses showed that olfactory threshold decline was associated with decline in WM integrity in the body of corpus callosum. Taken together, the results support a link between white-matter integrity and olfaction and provide initial evidence for its interplay with age.