From function to structure: Cortical thickness correlates of olfactory dysfunction across cognitively normal, mild...

Decreased olfactory function occurs in over half of individuals aged 65-80 years, and in 62-80% of those over 80 years of age. Hyposmia is an early symptom and a potential marker for a number of neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD), and can predict the conversion from Mild Cognitive Impairment (MCI) to AD. Building on our previously published resting-state fMRI findings on olfactory network functional connectivity [10], this study examined the same 74 participants categorized as Cognitively Normal (CN), MCI, or PD with cognitive impairment (PD-CogImp) using the Brief Smell Identification Test (B-SIT®). Automated measurements of cortical thickness (CT) and volume for 34 bilateral cortical regions were obtained using FreeSurfer v7.3.2. A moderation analysis based on multiple linear regression was performed to investigate the relationship between B-SIT® scores and cortical measures, controlling for age, education, sex, APOE genotype, and estimated total intracranial volume (eTIV). A significant interaction effect of clinical diagnosis on the olfaction-cortical thickness relationship was identified in 3 out of 68 regions of interest (ROIs): the cuneus bilaterally and the right pericalcarine gyrus, all showing large effect sizes (η² > 0.14). CN individuals showed a significant positive association between B-SIT® and CT in these regions, whereas MCI and PD-CogImp groups showed a negative trend. Cortical volume models yielded no significant findings after correction for multiple comparisons. These results highlight distinct diagnostic group-specific patterns in the olfaction-brain structure relationship, with implications for understanding early pathological aging and neurodegeneration.