Association between multi-intensity olfactory test performance and the Montreal Cognitive Assessment score after adjustment for gray matter volume

Previous studies, including ours, have reported that olfactory test scores (OTSs) are associated with gray matter volumes (GMVs) in brain regions including the hippocampus and amygdala, even after adjustment for the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. However, it has not been comprehensively investigated whether decreases in GMV fully explain the association between olfactory and cognitive function test scores. We analyzed the association between OTSs obtained using multiple odor intensities and the MoCA-J score in 1,444 adults (36.1% male) aged 31–91 years using multivariable regression models adjusted separately for (1) whole-brain GMV, (2) total GMV across olfactory limbic (memory-related) regions, and (3) total GMV across brain regions significantly associated with the MoCA-J score. Among participants aged ≥ 65 years, OTSs showed a positive association with the MoCA-J score across all three GMV-adjusted models (standardized β = 0.318, p = 0.001; β = 0.302, p = 0.002; and β = 0.308, p = 0.001, respectively), although effect sizes were small. These findings support the possibility that decreases in GMV may not fully explain the relationship between olfactory and cognitive function in older adults. Longitudinal studies are needed to clarify the causal relationship between olfactory function and cognitive decline.