Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes

Abstract

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 olfactorybehavior tests and electrophysiological examination.

Diabetic Peripheral Neuropathy Associated with Cardiovascular Risk Factors and Glucagon-Like Peptide-1 Concentrations Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus

“…It directly leads to changes in sensory function, abnormal feelings, and progressive numbness, and increases the risk of foot ulceration, amputation, cognitive dysfunction, and economic burden. 5,6 Previous studies show that the prevalence of DPN among patients with type 2 diabetes accounts for 2.0-78.8%, depending on the country, duration of diabetes, and examination methods. 1,[7][8][9] Nerve damage not only leads to loss of feeling that allows injuries to go unnoticed and expandable but also causes serious infections and possible amputations.…”

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial

“…Therefore, in persons with diabetes a lower resting state perfusion [ 43 ], worse vasoreactivity and functional connectivity [ 23 , 34 ] were associated with vascular inflammation and microvascular disease [ 36 ], which correlated with worse cognitive performance [ 2 ] and slower walking [ 26 ]. In addition, diabetic peripheral neuropathy was associated with gray matter and cerebellar atrophy, reduced functional connectivity between frontal lobe and motor areas and worse executive function [ 44 , 45 ]. Possible beneficial effects of INI treatment on vasoreactivity in T2DM need confirmation in larger studies.…”

Olfactory Dysfunction: A Complication of Diabetes or a Factor That Complicates Glucose Metabolism? A Narrative Review

“…Finally, Ni et al [ 42 ] included 36 T2DM without DPN, 28 with DPN, and 36 healthy subjects, showing for the first time that T2DM subjects with DPN had worse cognitive function with regard to memory and processing speed as compared with those without DPN. Olfactory identification was a mediating factor between nerve conduction and executive function.…”

“…Olfactory identification was a mediating factor between nerve conduction and executive function. On the basis of these findings, the authors suggested that olfactory status might be indicative of cognitive impairment among people with DPN [ 42 ].…”