Abstract
AIMS: This study investigates the relationship between multisensory (visual, somatosensory, and olfactory) dysfunction and cognitive decline in Type 2 diabetes (T2D), with a particular focus on the mediating role of olfactory dysfunction. METHODS: We used resting-state fMRI to assess seed-based functional connectivity from the primary sensory cortices (visual, somatosensory, and olfactory) and whole-brain regional activity metrics in 152 patients with T2D and 50 controls. A Multisensory Dysfunction Index (MSDI) was constructed to quantify integrated sensory dysfunction, and moderated mediation analysis was performed to examine the impact of sensory complications on cognitive function. RESULTS: The MSDI was correlated with sensory complication burden and associated with worse global cognitive performance (Montreal Cognitive Assessment, MoCA). Mediation analysis showed that odour identification mediated the relationship between MSDI and MoCA in T2D. This indirect effect was absent in diabetic peripheral neuropathy (DPN)+ individuals but remained significant in DPN- individuals. Additionally, olfactory dysfunction had both direct and indirect effects on cognition in DPN- patients. CONCLUSIONS: Our findings highlight the central role of olfactory dysfunction in linking multisensory impairment to cognitive decline in T2D. The results emphasize the need for personalized management strategies based on sensory complications and suggest that preserving sensory network integrity may help maintain olfactory and cognitive health in T2D.