Aim: Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction.
Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters.
Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior.
Conclusion: Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactory-behavior tests and electrophysiological examination.
Keywords: type 2 diabetes mellitus, peripheral neuropathy, cognitive dysfunction, olfactory behavior, odor-induced brain activation