The Association between HbA1c Levels, Olfactory Memory and Cognition in Normal, Pre-Diabetic and Diabetic Persons

Abstract

Background and Aim: Recent data have shown that olfactory dysfunction is strongly related to Alzheimer’s Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes. Methods: We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT). Results: We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction. Conclusion: To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.

Mechanisms Linking Olfactory Impairment and Risk of Mortality

“…Of note, a recent study involving type 2 diabetic patients demonstrated not only increased OI in this population compared to controls but also diminished abilities in specific cognitive tests. Besides, once again, they found a strong association between OI and specific memory impairment in this population (Yulug et al, 2019). As for smoking, which is known to interfere with olfactory performance, the effect is equivocal or weak and mostly seen in long-standing heavy smokers (Mackay-Sim et al, 2006).…”

“…Indeed, a recent study found that older adults with high insulin resistance (quantified by the HOMA-IR test) had an approximately 2-fold increased odds of OI compared with subjects with low insulin resistance (Min and Min, 2018). This could explain, at least in part, the independent association found between type 2 diabetes mellitus (in which insulin resistance represents the key mechanism) and OI (Gopinath et al, 2012;Gouveri et al, 2014;Yulug et al, 2019). OI in type 2 diabetes mellitus might also be due to microvascular injury since OI was mainly found in diabetic patients already suffering from the microvascular complications of this disease (Gouveri et al, 2014).…”

International consensus statement on allergy and rhinology: Olfaction

“…Autoimmune diseases have long been associated with smell loss 1709,1710 . Specifically, patients with Sjögren syndrome and SLE have been found to commonly exhibit olfactory deficits.…”

“…1708 Treatment of OD related to autoimmune diseases Autoimmune diseases have long been associated with smell loss. 1709,1710 Specifically, patients with Sjögren syndrome and SLE have been found to commonly exhibit olfactory deficits. Schonfeld et al 1711 reported that the odor threshold and odor discrimination scores decreased in patients with SLE, and that OD correlated with disease severity and CNS involvement.…”

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

“…Recent studies have confirmed that there was an interplay between diabetes mellitus, olfaction, and dysfunction of the central nervous system. In a prospective study of 15 normal, 16 prediabetic, and 15 T2DM subjects, a strong association between olfactory dysfunction and specific memory impairment was observed among subjects with prediabetes and diabetes [ 39 ]. Moreover, among 151 older Japanese T2DM subjects, those with olfactory dysfunction at baseline developed dementia more frequently after 3 years than those without smell impairment [ 40 ].…”