The first quick olfactory test specific for Alzheimer's disease and French culture.

PURPOSE: Olfactory identification disorder is considered a promising early biomarker of Alzheimer's disease (AD). The QUICK TODA2 can be used as a short olfactory screening tool specific for French AD patients. The selection of AD specific odorants and the design of this screening were the main objectives of this twofold study. METHODS: In study 1, the TODA2 olfactory test was administered to 43 mild-AD patients and 45 healthy controls (HC) in five memory centres in France. The selection of AD specific odorants was based on the differences in the proportion of correct answers and in the threshold means between AD and HC groups. In study 2, another set of 19 mild-AD patient were included at the memory centre of Nice Hospital. All participants completed the olfactory assessment pipeline including the QUICK TODA2, TODA2 and Sniffin' Sticks Identification sub-Test (SST-i). The individual scores of the three tests were correlated. RESULTS: In study 1, ten TODA2 odorants could significantly differentiate AD participants from controls. We selected the six most AD-sensitive items to design the QUICK TODA2. In study 2, we reported strong significant correlations between QUICK TODA2 and TODA2 (ρ(17) = 0.68, p = 0.001**), SST-i and QUICK TODA2 (ρ(17) = 0.65, p = 0.002**), SST-i and TODA2 (ρ(17) = 0.57, p = 0.01*). CONCLUSION:  QUICK TODA2 is a 5-min non-invasive olfactory AD screening tool dedicated to French culture. Its results converge with those of longer, validated olfactory tests. It could be used as a quick screening tool in the general daily practice before an extensive assessment in memory centres.

Propriety of various examinations for subjective symptoms of olfactory disorders.

PURPOSE: In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on patients with olfactory disorders. This study examined the validity of these olfactory tests and whether psychophysical or morphological tests are more helpful in evaluating olfactory disorders. METHODS: We evaluated patients who visited our department and underwent two types of olfaction tests and sinus computed tomography (CT). Data regarding the age, sex, peripheral blood eosinophil percentage, presence of bronchial asthma, diagnoses, olfactory symptom score, results of the two olfactory tests, and CT findings in eligible patients were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and sixty-three patients underwent all tests during the study period. The results of the T&T olfactometry and intravenous olfactory tests were significantly correlated. However, only the results of T&T olfactometry and olfactory cleft opacification on CT were statistically significant predictors of the olfactory symptom scores. CONCLUSION: T&T olfactometry and CT evaluations of olfactory cleft opacification helped evaluate olfactory dysfunction. It is important to note that intravenous olfactory tests are best performed with careful control and not blindly to assess olfactory disorders.

Vitamin D levels and olfactory dysfunction in multiple sclerosis patients.

OBJECTIVE: The objective was to explore the possible relationship between the serum vitamin D level and olfactory impairment in a population of multiple sclerosis (MS) patients in Guizhou, China. METHODS: We included 25 patients with MS and 18 healthy controls (HCs) who were recruited from the Affiliated Hospital of Guizhou Medical University from February 2021 to September 2021. The University of Pennsylvania Smell Identification Test (UPSIT) was used to test the patients' sense of smell, and the level of serum 25-hydroxyethylene polyprotein D was measured. RESULTS: Serum vitamin D levels and UPSIT scores were significantly different between the MS group and the control group (both p < 0.001). Moreover, a significant positive correlation emerged between vitamin D levels and UPSIT scores in MS patients (r = 0.537, p = 0.021). CONCLUSIONS: The serum vitamin D level may be involved in the regulation of olfactory dysfunction in MS patients in Guizhou, China.

Multiple sclerosis is a rare disease in China.Compared with that of healthy controls, the olfactory function of MS patients was severely impaired.Compared with healthy controls, MS patients had low vitamin D levels.A significant positive correlation emerged between vitamin D levels and UPSIT scores in MS patients.The vitamin D levels of MS patients may be associated with olfactory impairment, which may have implications for future mechanistic studies.

Development of parallel forms of a brief smell identification test useful for longitudinal testing.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study.

INTRODUCTION: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. METHODS: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. RESULTS: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. CONCLUSIONS: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

First recognized n-butanol concentration may be simple and useful index for assessing olfactory dysfunction in geriatric patients.

The KVSSII is widely used to evaluate olfactory function in the Korean population. We evaluated the usefulness of the first recognized n-butanol concentration, which is obtained at the beginning part of KVSS II, in predicting olfactory dysfunction. Three hundred seventy two subjects were enrolled in our study. The results of KVSS II and the demographic characteristics were statistically analyzed. The first recognized n-butanol concentration was positively correlated with the result of KVSS II. The mean value of first recognized n-butanol concentration was 5.59 ± 1.42 in normosmia, 4.10 ± 1.40 in hyposmia, and 0.84 ± 1.68 in the anosmia group. By ROC curve, cut-off value of 2.5 showed sensitivity of 85.9% and specificity of 90.6% for anosmia, and cut-off value of 4.5 showed sensitivity of 77.6% and specificity of 69.8% for hyposmia. Consequently, we suggest that it may be useful in assessing olfactory function, in geriatric patients who are not able to tolerate conventional KVSS II.

Correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery.

PURPOSE: To investigate the correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS). METHODS: This was a cross-sectional study including 40 patients with a history of ESS for CRSwNP recruited consecutively. Visual analog scale score and the Lund-Kennedy endoscopic score were recorded. Biopsies of the ethmoidal sinus mucosal were performed and evaluated. Chemosensory functions were measured by Sniffin' Sticks and chemosensory event-related potentials (CSERP). The associations between chemosensory functions and tissue eosinophil count were analyzed using Spearman correlation and partial correlation after adjusting the confounding factors. Kendall's tau-b correlation was performed between sneezing score and CSERP with ethyl alcohol (EAL) stimulation. RESULTS: Olfactory and trigeminal nerve function was successfully evaluated using CSERP. Postoperative tissue eosinophil count was correlated with threshold (T) score (partial correlation coefficient r = - 0.460, p = 0.012) and CSERP peak latency for olfactory (N1: partial r = 0.471, p = 0.010; P2: partial r = 0.487, p = 0.007) and mixed olfactory-trigeminal (N1: partial r = - 0.516, p = 0.008; P2: partial r = - 0.590, p = 0.002). There were also correlations between T score and N1 latency with phenyl ethyl alcohol (PEA) (partial r = - 0.560, p < 0.001), between sneezing score and N1 latency with EAL (Kendall's tau-b = - 0.40, p = 0.005). CONCLUSIONS: Postoperative tissue eosinophilia is significantly associated with postoperative olfactory disorders as assessed by Sniffin' Sticks and CSERP peak latency. Furthermore, olfaction as measured by T score correlates with olfactory ERP latency in inflammation-associated olfactory dysfunction. Trigeminal sensitivity also appears to relate to tissue eosinophilia, indicating mucosal inflammation can affect both sensory systems in the nose.

Development and Validation of a Food-Associated Olfactory Test (FAOT).

Olfactory tests are an important tool in human nutritional research for studying food preferences, yet comprehensive tests dedicated solely to food odors are currently lacking. Therefore, within this study, an innovative food-associated olfactory test (FAOT) system was developed. The FAOT comprises 16 odorant pens that contain representative food odors relating to different macronutrient classes. The test underwent a sensory validation based on identification rate, intensity, hedonic value, and food association scores. The accuracy of the test was further compared to the accuracy of the established Sniffin' Sticks identification test. The identification rates and intensities of this new FAOT were found to be comparable to the Sniffin' Sticks olfactory identification test. The odorant pens were also assessed chemo-analytically and were found to be chemically stable for at least 24 weeks. Overall, this new identification test for use in assessing olfaction in a food-associated context is valid both in terms of its use in sensory perception studies and its chemical stability. The FOAT is particularly suited to examinations of the sense of smell regarding food odors.

A Cross-Cultural Adaptation of the Sniffin' Sticks Olfactory Identification Test for US children.

Disorders associated with smell loss are common in adolescents. However, current odor identification tests focus on children from age 6 and older and no cross-cultural test has to date been validated and fully implemented. Here, we aimed to investigate how 3-to-11-year-old US children performed to an adapted and shortened (11 odors instead of 14) version of a European odor identification test-the Sniffin' Kids (Schriever VA, Mori E, Petters W, Boerner C, Smitka M, Hummel T. 2014. The "Sniffin'Kids" test: a 14-item odor identification test for children. Plos One. 9:e101086.). Results confirmed that cued odor identification performance increases with age and revealed little to no differences between girls and boys. Scores below 3 and below 6 may raise hyposmia concerns in US children aged 3-7 years and 8-10 years, respectively. Even though the completion rate of the task reached the 88%, suggesting that children below age 5 were able to finish the test, their performance was relatively poor. In comparing the overall identification performance of US children with that of German children, for whom the test was specifically developed, significant differences emerged, with higher scores obtained by the German sample. Analysis of errors indicated that a lack of semantic knowledge for the olfactory-presented objects may be at the root of poor identification skills in US children and therefore constitutes a problem in the development of an odor identification test for younger children valid across cultures.

Odor-cued taste avoidance: a simple and robust test of mouse olfaction.

In odor-cued taste avoidance (OCTA), thirsty mice, offered either an odorized nonaversive fluid (S+) or an odorized aversive fluid (S-), quickly learn to use odor to avoid drinking the S-. Acquisition of both odor detection and odor discrimination tasks is very rapid with learning evidenced in most cases by either long response times or total avoidance on the second presentation of the S- stimulus. OCTA is perhaps one of the simplest conditioning procedures for assessing olfaction in mice; it requires only a test box, drinkometer circuit, and thirsty mice accustomed to drinking in the apparatus. Its advantages over the most commonly used alternatives, habituation-dishabituation, and the mouse dig test, are discussed.

The relationship between survey-based subjective olfactory awareness and objective olfactory function.

KEY POINTS: Correlation between symptom-based surveys and objective olfactory testing is variable. For diagnosis and symptom monitoring, surveys should correlate with objective testing. The Odor Awareness Scale (OAS) and Affective Importance of Odor Scale (AIO) showed significant but moderate positive correlations with University of Pennsylvania Scent Identification Test (UPSIT) score.

Evaluating olfactory function and quality of life in patients with traumatic brain injury.

KEY POINTS: Patients with traumatic brain injury (TBI) had worse olfactory quality of life (QoL) and Sino-Nasal Outcome Test-22 scores compared to a normal cohort. A worse olfactory QoL correlated with concussion symptom burden. Olfactory dysfunction among TBI patients should be addressed to improve overall outcomes.

Reliability and validity of the Arabic version of the brief version of the Questionnaire of Olfactory Disorders.

Background: An accessible self-assessment questionnaire is needed to evaluate quality of life in olfactory dysfunction. The need to address this gap led to the development of the brief version of the Questionnaire of Olfactory Disorders (brief QOD), which holds particular value in the context of telemedicine. Objectives: The aim of this study is to examine the reliability and validity of the Arabic brief QOD. Methods: This study included 307 patients suffering from olfactory dysfunction as well as a control group filled a questionnaire including demographic information, the olfaction Visual Analog Scale (VAS), the Sino-nasal Outcome Test 22 (SNOT-22) questionnaire, and the Arabic version of the brief QOD. The Arabic brief QOD's reliability was assessed using Cronbach's α to measure internal consistency. To evaluate test-retest reliability, the intraclass correlation coefficient (ICC) was employed. The discriminative ability: score differences between the two groups were analyzed. The validity Arabic brief QOD was evaluated by comparing it to the olfaction VAS. Results: The Cronbach's α coefficients were 0.757 for Questionnaire of Olfactory Disorders-Parosmia (QOD-P), 0.832 Questionnaire of Olfactory Disorders-quality of life (QOD-QoL), and 0.817 Questionnaire of Olfactory Disorders-visual analog scale (QOD-VAS). The reliability of the overall brief QOD was 0.93. The ICC exceeded the acceptable threshold of 0.7, indicating strong test-retest reliability. The highest correlation was observed between the SNOT-22 and QOD total scores (r = 0.552 and p < .001) as well as between SNOT-22 and QOD VAS (r = 0.512 and p < .001). Conclusion: Excellent validity and reliability have been shown for the Arabic brief QOD as a self-assessment tool assessing quality of life among olfactory dysfunction patients. Level of evidence: NA.

How accurate is the human olfactory system in detecting peanuts?

KEY POINTS: This is the first study to quantify the accuracy, sensitivity, and specificity of the human olfactory system in detecting peanuts in common food items. With more competing sensory input, the human olfactory sensitivity to peanuts decreases; this is especially evident when peanuts are mixed in sauces. Metrics established in this study can be used to develop standards for determining the clinical utility of allergen detecting devices that are currently under development.

The "Sniffin' Kids-PT" test: A smell test variant for Portuguese children.

OBJECTIVE: Olfactory tests tailored for children are essential, as diagnosing olfactory dysfunction at these ages can be challenging. The 16-item "Sniffin' Sticks" is reliable and easy to perform. To the best of our knowledge, there is currently no validated olfactory test for the Portuguese pediatric population. This study aimed to adapt and validate the "Sniffin' Sticks" olfactory test for the Portuguese pediatric population. METHODS: Between August 2020 and September 2021, 354 children aged between 6 and 17years old enrolled in the study, 336 healthy children with a normal sense of smell, and 18 anosmic children with Kallmann syndrome. The study consisted of two parts. Firstly, the "Sniffin' Sticks" olfactory identification test was applied to healthy children and the odors with statistically significant low identification rates were excluded. A modified version of "Sniffin' Sticks" was defined and named "Sniffin' Kids-PT" test. Secondly, normative data were assessed and test-retest and validation tests were performed. RESULTS: Apple and Cloves odors were identified with a low rate and were excluded from the "Sniffin' Sticks" olfactory test. In the modified 14-item "Sniffin' Kids-PT", scoring <6 (from 6-8years old), <7 (from 9-11years old) or <8 (from 12-14years old and 15-17years old) was indicative of olfactory dysfunction. The test-retest reliability was good (r=0.81; P<0.001) and the differences between scores of healthy children and anosmic children were statistically significant (U213=13.00; P<0.001). CONCLUSION: The modified "Sniffin' Kids-PT" is a reliable test to discriminate between normosmia and olfactory dysfunction in Portuguese children over 5years old.

Development of a Digital Olfactory Function Test: A Preliminary Study.

Olfactory dysfunction is associated with conditions such as neurodegenerative diseases, diabetes, obesity, autoimmune diseases, mental illnesses, and upper-airway-related diseases. The COVID-19 pandemic necessitated the development of an examiner-independent olfactory function test. We recently developed a digital olfactory function test called Digitalscent (DIGITAL SCENT), which is a kiosk-type device with an integrated hardware system. The protocol follows conventional psychophysical olfactory function protocols, including threshold, discrimination, and identification test subsets. Eight healthy participants without olfactory dysfunction volunteered for the suitability test and completed both the YSK olfactory function and Digitalscent tests. Pearson correlations were determined between the YSK olfactory function and Digitalscent tests. Digitalscent could be implemented as a conventional olfactory function test, and all participants followed the Digitalscent test protocols. Limitations in the threshold and identification test subsets included unfamiliarity of the patients to the digital test and incompleteness in the sophisticated release of odorants. A strength of the identification test subset was the dual sensory stimulation of vision and olfaction. Digitalscent could-without facilitating viral transmission-enable early diagnosis of olfactory dysfunction during respiratory viral pandemics. Future studies with larger sample sizes are warranted to facilitate wider use of this digital olfactory function test.

Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial.

OBJECTIVES: Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. METHODS: This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. RESULTS: A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p = 0.000), olfactory threshold (p = 0.000), identification score (p = 0.000) and VAS score (p = 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p = 0.63), olfactory threshold (p = 0.50), identification score (p = 0.96) and VAS score (p = 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. CONCLUSIONS: Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. LEVEL OF EVIDENCE: Level 2.

Dataset on assessing olfactory function in the residents of Central Russia using the University of Pennsylvania Smell Identification Test.

Data were acquired via sensory testing of olfactory function in 252 adult residents of Central Russia (18-87 years old), including groups from urban and rural areas. The 40-item North American version of the University of Pennsylvania Smell Identification Test (UPSIT) was used. The test alternatives were initially translated into Russian by the authors with minor adaptations. We followed the test procedure recommended by the manufacturer and introduced additional tasks. Familiarity with odor names and consistency with the pre-existing concepts for the test odor items were determined using multiple response questions. Intensity ratings for the UPSIT odorants were obtained using 4-point categorical scale for a subset of the participants. Demographic data and other relevant characteristics of the study population were collected using an adapted translation of the questionnaire included with the test. Descriptive statistics of the collected data are presented in this article. The dataset may be reused for evaluating the impact of various factors, such as cultural context, age, sex, environment, and smoking habits, on the perception of specific odorants as well as on general olfactory function (determined by the number of recognized test items). The data may find its application in the clinical practice of otolaryngologists and neurologists who work with the ethno-cultural group in Russia and all over the world. The dataset can also be used for development of new diagnostic tools for olfactory dysfunction.

Olfactory Dysfunction and Glaucoma.

BACKGROUND: Olfactory dysfunction is a well-known phenomenon in neurological diseases with anosmia and hyposmia serving as clinical or preclinical indicators of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. Since glaucoma is a neurodegenerative disease of the visual system, it may also entail alterations in olfactory function, warranting investigation into potential sensory interconnections. METHODS: A review of the current literature of the last 15 years (from 1 April 2008 to 1 April 2023) was conducted by two different authors searching for topics related to olfaction and glaucoma. RESULTS: three papers met the selection criteria. According to these findings, patients with POAG appear to have worse olfaction than healthy subjects. Furthermore, certain predisposing conditions to glaucoma, such as pseudoexfoliation syndrome and primary vascular dysregulation, could possibly induce olfactory changes that can be measured with the Sniffin Stick test. CONCLUSIONS: the scientific literature on this topic is very limited, and the pathogenesis of olfactory changes in glaucoma is not clear. However, if the results of these studies are confirmed by further research, olfactory testing may be a non-invasive tool to assist clinicians in the early diagnosis of glaucoma.