Intranasal insulin's effects on the sense of smell.

Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and antiapoptotic effects. It prevents energy failure and has regenerative properties, affects neuro-regeneration and counteracts insulin resistance. Hence, insulin has been suggested for various pathological states including neurocognitive disorders, obesity, and as a therapeutic option for smell loss. A sharply increased prevalence of olfactory dysfunction was observed due to the COVID-19 pandemic. The pandemic also emphasized the lack of therapeutic options for smell loss. Intranasal insulin administration has therefore been suggested to serve as potential treatment, influencing the regenerative capacities of the olfactory mucosa. This narrative review summarizes current knowledge on possible effects of intranasal insulin on the sense of smell.

Hedonic perception of odors in children aged 5-8 years is similar across 18 countries: Preliminary data.

OBJECTIVE: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe. METHODS: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors. RESULTS: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants. CONCLUSION: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.

Beyond olfaction: Beneficial effects of olfactory training extend to aging-related cognitive decline.

Studies on olfactory training (OT) outcomes have mostly been limited to olfactory performance, while direct neural connections between olfactory system and amygdala-hippocampal complex allow expecting OT to have psychological effects. To address this hypothesis, we examined olfactory, cognitive and emotional effects of OT in the group of 68 subjects aged between 50 and 88 years (Mage = 62.8 ± 8.9 years; 28 males) who are likely to experience an age-related decline in olfactory and cognitive performance. We diversified stimuli used in the OT to verify whether odor mixtures result in more effective activation of olfactory receptor neurons than single molecule odors. Subjects were randomly assigned to one of the experimental conditions: (a) simple OT utilizing single-molecule odors; (b) mixtures OT using odor mixtures; (c) control group without OT. Results indicate beneficent effects of the simple OT on cognitive assessment, cognitive decline symptoms, and olfactory sensitivity. OT can be adapted from otorhinolaryngological practice to successfully serve neurocognitive research and in supporting the cognitive-related aging process. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

OBJECTIVE: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

BACKGROUND: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult partici- pants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additi- onally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improve- ments after OT.

Consequences of undetected olfactory loss for human chemosensory communication and well-being.

Olfactory perception has implications for human chemosensory communication and in a broader context, it affects well-being. However, most of the studies investigating the consequences of olfactory loss have recruited patients who have already been categorized as having a dysfunctional sense of smell and sought help in an ENT clinic. We revisit these findings by distinguishing subjects with olfactory impairment from a group of subjects who all declared a normal sense of smell when enrolling for this study. In the initial sample of 203 individuals, we found 59 to have impaired olfaction and four with marginal olfactory performance, not useful in daily life. Interestingly, we found a significant between-group difference in cognitive functioning, further supporting the notion of the relationship between cognition and olfactory performance. However, their chemosensory communication and well-being appeared not to be different from subjects with normosmia. Impaired olfactory function certainly has a severe impact on daily life but more so in individuals who are bothered with it and decide to seek treatment. The limited-to-no olfactory perception in the fraction of subjects who neither complain about it nor seek help in ENT clinics does not seem to have a major effect on their social, cognitive, emotional and health functioning. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Updated Sniffin' Sticks normative data based on an extended sample of 9139 subjects.

PURPOSE: To provide up-to-date and detailed normative data based on a large-scale sample, increasing diagnostic validity by reference to narrow age groups as previous normative values were based upon smaller sample sizes-especially in the group of older subjects. METHOD: Data were obtained from 9139 healthy subjects (4928 females aged 5-96 years and 4211 males aged 5-91 years). The standard "Sniffin' Sticks" test was applied, comprising threshold (T), discrimination (D) and identification (I) subtests, and yielding a TDI sum score. RESULTS: Hyposmia was established at a TDI score of less than 30.75. Age-related changes were found in each domain, most pronounced for thresholds. Individuals aged 20-30 years performed best, whereas children below the age of 10 and adults above the age of 71 scored only half as well. Sex-related differences were in favor of women. CONCLUSIONS: Data provide guidance for assessing individual olfactory performance in relation to specific age groups. Significant gender and age effects were observed, with a most pronounced increase of olfactory test scores between age 5 through 20 years and a dramatic decrease at the age of 60 through 71 years.

The confounding effect of background odors on olfactory sensitivity testing.

BACKGROUND: Human olfactory sensitivity is known to vary significantly across subjects. Furthermore, environmental factors such as background noise and odor are known to affect target odor threshold scores but have not yet been fully delineated. We aimed to determine whether congruent and non-congruent background odor impaired target odor threshold scores. NEW METHOD: We performed odor threshold testing in 103 normosmic adults, using phenylethylalcohol (PEA) or linalool as target odors, under three conditions: (a) congruent target and background odors (e.g., PEA in the test and PEA in the background), (b) non-congruent target and background odors (e.g. PEA in the test and Linalool in the background) and (c) no background odor. Background odor was applied to the investigator's glove and testing was performed in an otherwise odorless room. RESULTS: We found that congruent background odors significantly impaired target odor threshold scores. Non-congruent background odors also impaired target odor threshold, but significantly more so with PEA as target and Linalool as background odor. The best threshold scores were obtained with no background odor. Comparison with Existing Method(s). At present, many testing environments may be contaminated with ambient background odors. We have shown that this may negatively affect odor threshold scores, particularly where background and target odors are congruent. CONCLUSIONS: We suggest that investigators performing odor threshold testing do so in well ventilated, odor free environments.

Olfactory deficits decrease the time resolution for trigeminal lateralization.

OBJECTIVES: To date the temporal resolution of the detection of almost simultaneously applied intranasal trigeminal stimuli is unknown. The aim of our study was to examine this temporal resolution in an/hyposmic subjects, who are known to have reduced trigeminal sensitivity and compare it with healthy controls. METHODS: Participants were 20 posttraumatic an/hyposmic patients, and 23 healthy controls (matched with regard to sex and age). Olfactory function was tested psychophysically using the Sniffin´ Sticks test battery. Bilateral trigeminal stimulation was carried out using a birhinal high-precision olfactometer. The trigeminal stimulus used was CO2 60% v/v, the interstimulus interval ranged from 28 to 32s, stimulus duration was 200ms. Time-lags tested between right and left side of stimulation were at 40, 80, 120, 160 and 200ms. Subjects raised their left or right hand to indicate the side on which the stimulus had been perceived first. RESULTS: In both groups the accuracy in the trigeminal lateralization task increased with the time-lag but normosmic subjects significantly outperformed an/hyposmics in the 200ms time-lag condition. Normosmics significantly exceeded 50% chance level at the time-lag of 80ms, whereas an/hyposmics were only able to score above chance starting from 120ms time-lag. Lateralization scores significantly decreased with age. CONCLUSIONS: At a time lag of 200ms intranasal trigeminal stimuli can be lateralized. The reduced trigeminal sensitivity in patients with anosmia or hyposmia leads to an increased time lag required for correct perception of intranasal, almost simultaneously, applied stimuli.