Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

The 8-Odorant Barcelona Olfactory Test (BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.

Benralizumab effect on severe chronic rhinosinusitis with nasal polyps (CRSwNP): A randomized double-blind placebo-controlled trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a severe and debilitating disease associated with significant morbidity, loss of smell, sinus pressure and asthma exacerbations. Eosinophils play a role in the majority (85%) of patients. Benralizumab, an afucosylated monoclonal antibody directed against the IL-5 receptor, has powerful apoptotic effects on eosinophils. OBJECTIVE: We sought to investigate the therapeutic benefit of inhibiting the IL-5 receptor using benralizumab to treat severe rhinosinusitis with nasal polyps. METHODS: Patients with severe NP (defined by endoscopic grade 5 or more out of 8) with elevated eosinophils and a history of previous surgical or endoscopic polypectomy met entry criteria and were randomized in a double-blind fashion to receive 30 mg benralizumab SC or placebo. Endoscopic NP score was assessed at baseline and at treatment week 20. CT scan, SNOT-22 survey and UPSIT smell test score changes were also evaluated. RESULTS: Thirty-three patients were screened, and twenty-four (n = 24) were enrolled in the study. Compared with baseline, benralizumab significantly improved NP score (-0.9 ± 0.2, P = 0.004) whereas placebo did not (-0.3 ± 0.3, P = 0.166). Benralizumab induced polyp size reduction compared with placebo did not reach statistical significance (P = 0.103). Five of 12 benralizumab-treated patients (42%) had improvements in all major outcomes (polyp score, CT, SNOT-22 and smell test) versus 2 out of 12 placebo (17%). The ratio of blood eosinophil count to allergen skin test positivity correlated with polyp reduction. CONCLUSION: Benralizumab was well-tolerated and compared with baseline achieved a statistically significant reduction in nasal polyp size, sinus occupancy, symptoms and improved sensation of smell for most patients (83%).

SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss.

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.

Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence.

BACKGROUND: Smell dysfunction has been recognized as an early symptom of SARS-CoV-2 infection, often occurring before the onset of core symptoms of the respiratory tract, fever or muscle pain. In most cases, olfactory dysfunction is accompanied by reduced sense of taste, is partial (microsmia) and seems to normalize after several weeks, however, especially in cases of virus-induced complete smell loss (anosmia), there are indications of persisting deficits even 2 months after recovery from the acute disease, pointing towards the possibility of chronic or even permanent smell reduction for a significant part of the patient population. To date, we have no knowledge on the specificity of anosmia towards specific odorants or chemicals and about the longer-term timeline of its persistence or reversal. METHODS: In this longitudinal study, 70 participants from a community in Lower Austria that had been tested positive for either IgG or IgM SARS-CoV-2 titers in June 2020 and a healthy control cohort (N = 348) underwent smell testing with a 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT). The test was performed in October 2020, i.e. 4 months after initial diagnosis via antibody testing. Results were analyzed using statistical tests for contingency for each smell individually in order to detect whether reacquisition of smell is dependent on specific odorant types. RESULTS: For all odorants tested, except the odor "smoke", even 4 months or more after acute SARS-CoV-2 infection, participants with a positive antibody titer had a reduced sense of smell when compared to the control group. On average, while the control cohort detected a set of 12 different smells with 88.0% accuracy, the antibody-positive group detected 80.0% of tested odorants. A reduction of accuracy of detection by 9.1% in the antibody-positive cohort was detected. Recovery of the ability to smell was particularly delayed for three odorants: strawberry (encoded by the aldehyde ethylmethylphenylglycidate), lemon (encoded by citronellal, a monoterpenoid aldehyde), and soap (alkali metal salts of the fatty acids plus odorous additives) exhibit a sensitivity of detection of an infection with SARS-CoV-2 of 31.0%, 41.0% and 40.0%, respectively. CONCLUSION: Four months or more after acute infection, smell performance of SARS-CoV-2 positive patients with mild or no symptoms is not fully recovered, whereby the ability to detect certain odors (strawberry, lemon and soap) is particularly affected, suggesting the possibility that these sensitivity to these smells may not only be lagging behind but may be more permanently affected.

Is taste and smell impairment irreversible in COVID-19 patients?

OBJECTIVE: It is known that the COVID-19 disease, which has affected the whole world, causes symptoms, such as cough, fever, shortness of breath, muscle pain, fatigue, diarrhea, headache and sore throat, in addition to various clinical findings, such as loss of smell and taste. In this study, we aimed to reveal the loss of sense of taste and smell in COVID-19 patients and to investigate whether these sensory losses are permanent in the healing process of the disease. METHOD: This prospective study included 94 COVID-19 patients. Smell and taste tests were applied to all patients. Ten days after the first test, a second test was applied to the patients with an impaired sense of smell to compare the results. RESULTS: Of the 94 patients, 55.3% were male, and the mean age was 53 ± 19.6 (21-90) years. There were 67 patients with smell and taste impairment, of whom 34 (50.7%) had smell impairment only, 3 (4.4%) had taste impairment only, and 30 (44.7%) had both smell and taste impairment. It was found that the smell scores of 55 patients with smell and taste impairment in the first evaluation were significantly higher at the second measurement; and their tasting period was significantly shortened compared to the first measurement (p˂0.001). CONCLUSION: COVID-19 patients may present to medical centers with a broad variety signs and symptoms. This study shows that impairment in the senses of smell and taste is common in this disease and strongly associated with COVID-19 infection. However, smell and taste impairment is mostly temporary and improves during the recovery period.

A simple method for olfactory rehabilitation following total laryngectomy.

PURPOSE: The aim of the study is to demonstrate the effectiveness of spraying odor particles using sinus rinse kits for olfactory rehabilitation in patients with total laryngectomy. METHODS: Olfactory rehabilitation was performed by applying four different odorant particles orthonasally using a sinus rinse kit pump for 30 min each day for a duration of 6 months. Olfactory function was evaluated by performing olfactory tests before the rehabilitation and at sixth month after the rehabilitation process. RESULTS: The average CCCRC score prior to olfactory rehabilitation was 2.28 ± 0.79 (between 1.50 and 3.75), while it was 4.46 ± 0.5 (between 3.50 and 5.25) out of a maximum score of 7 after 6 months of olfactory rehabilitation (p value < 0.0001) CONCLUSION: Our results suggest that the use of sinus rinse kits is very simple, inexpensive, easy-to-use, and effective in providing passive olfaction to patients requiring olfactory rehabilitation.

Pediatric Barcelona Olfactory Test ̶ 6 (pBOT-6): Validation of a Combined Odor Identification and Threshold Screening Test in Healthy Spanish Children and Adolescents.

BACKGROUND AND OBJECTIVE: Few odor tests have been developed for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test to evaluate odor identification and threshold in a Spanish pediatric population. METHODS: The Pediatric Barcelona Olfactory Test-6 (pBOT-6) consisted of a set of 6 odorants for a forced choice identification test and a 6-dilution phenyl ethyl alcohol geometric series for the threshold test. The pBOT-6 was compared with the Universal Sniff test (a validated international pediatric smell test) in 131 healthy Spanish volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between the 2 tests. Reliability was analyzed in 15 volunteers using the intraclass correlation coefficient. Normative data were obtained, and 8 children diagnosed with subjective loss of smell were tested for validation. RESULTS: The Bland-Altman analysis demonstrated a minimal bias of -1.71% with upper and lower limits of agreement of -31.1% and 27.6%, respectively. The intraclass correlation coefficient was 0.83 (95%CI, 0.6-0.96) for the identification test and 0.73 (95%CI, 0.36-0.9) for the threshold test, with excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers than in patients with loss of smell. Discrimination between normosmia and loss of smell was achieved with a sensitivity of 96.9% and a specificity of 100%. CONCLUSIONS: pBOT-6 offers an effective and fast method that is useful in clinical routine to distinguish, with high sensitivity and specificity, between pediatric patients with normosmia and those with loss of smell.

SMELL-S and SMELL-R: Olfactory tests not influenced by odor-specific insensitivity or prior olfactory experience.

Smell dysfunction is a common and underdiagnosed medical condition that can have serious consequences. It is also an early biomarker of neurodegenerative diseases, including Alzheimer's disease, where olfactory deficits precede detectable memory loss. Clinical tests that evaluate the sense of smell face two major challenges. First, human sensitivity to individual odorants varies significantly, so test results may be unreliable in people with low sensitivity to a test odorant but an otherwise normal sense of smell. Second, prior familiarity with odor stimuli can bias smell test performance. We have developed nonsemantic tests for olfactory sensitivity (SMELL-S) and olfactory resolution (SMELL-R) that use mixtures of odorants that have unfamiliar smells. The tests can be self-administered by healthy individuals with minimal training and show high test-retest reliability. Because SMELL-S uses odor mixtures rather than a single molecule, odor-specific insensitivity is averaged out, and the test accurately distinguished people with normal and dysfunctional smell. SMELL-R is a discrimination test in which the difference between two stimulus mixtures can be altered stepwise. This is an advance over current discrimination tests, which ask subjects to discriminate monomolecular odorants whose difference in odor cannot be quantified. SMELL-R showed significantly less bias in scores between North American and Taiwanese subjects than conventional semantically based smell tests that need to be adapted to different languages and cultures. Based on these proof-of-principle results in healthy individuals, we predict that SMELL-S and SMELL-R will be broadly effective in diagnosing smell dysfunction.

Olfactory and gustatory abnormalities in COVID-19 cases.

PURPOSE: At the time of writing, there is a pandemic affecting virtually every country on Earth. There is considerable discussion amongst clinicians as well as lay people about anosmia and ageusia in COVID-19 sufferers. We aimed to report the results from comprehensive olfactory and gustatory testing in a series of hospital in-patients. METHODS: The prospective study evaluated 81 individuals with a COVID-19 infection, as confirmed by 2019 n-cov Real-Time PCR laboratory testing. The control group consisted of forty individuals with COVID-19 negative. Olfactory and gustatory testings were carried out by an examiner utilizing stringent safety standards and wearing full personal protective equipment. The results obtained in the case group were then compared with those obtained for the controls. RESULTS: In the case group, 41(50.6%) of patients were male and 40 (49.4%) were female, mean age of 54.16 ± 16.98 years (18-95). In the control group, 21 (52.5%) of subjects were male and 19 (47.5%) were female, and mean age was 55 ± 15.39 years (18-90). Fifty (61.7%) COVID-19-positive patients had complaints related to olfaction. The distribution of olfactory symptoms in the case group differed at the level of statistical significance from the control group (p < 0.001). Turning to gustatory abnormalities, within the case group, 22 individuals (27.2%) had taste malfunction. A statistically significant difference was found in the distribution of gustatory abnormalities between cases and controls (p < 0.001). CONCLUSIONS: Olfactory and gustatory dysfunctions are strongly associated with SARS-CoV-2 infection. Hyposmia with or without hypogeusia is potentially a reliable indicator of latent COVID-19.

Olfactory testing in consecutive patients referred with suspected dementia.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia. METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study). RESULTS: The sum of scents detected discriminated patients with probable AD from controls in the cuisine study (n = 40; p < 0.001; area under ROC curve 0.94). In the blinded study (n = 50) the diagnosis was probable AD in 48%, minimal cognitive impairment in 24%, vascular dementia in 8%, alcohol induced impairment in 12%, depression in 4%, and Parkinson's disease and Lewy body dementia in 2%. Area under the ROC-curve was 0.67. The odds ratio for probable AD with 2+ smell errors was 12 (95%-CI: 1.3-101; p = 0.026 (reference 0-1 smell errors)) age adjusted. None in the AD group had zero smell errors (Negative Predictive Value 100%). CONCLUSION: Olfactory testing may support to dismiss the diagnosis of probable AD in the workup of a mixed group of patients referred with cognitive impairment. Still, it had a low sensitivity for probable AD.

Long-term outcomes of endoscopic endonasal approach for skull base surgery: a prospective study.

UNLABELLED: Little is known about the long-term effects of either transnasal transsphenoidal endoscopic approach (TTEA) or expanded endonasal approach (EEA). This study assessed the long-term impact of endoscopic skull base surgery on olfaction, sinonasal symptoms, mucociliary clearance time (MCT), and quality of life (QoL). Patients with pituitary adenomas underwent TTEA (n = 38), while patients with other benign parasellar tumours who underwent an EEA with vascularised septal flap reconstruction (n = 17) were enrolled in this prospective study between 2009 and 2012. Sinonasal symptoms (Visual Analogue Scale), subjective olfactometry (Barcelona Smell Test-24, BAST-24), MCT (saccharin test), and QoL (short form SF-36, rhinosinusitis outcome measure/RSOM) were evaluated before, and 12 months after, surgery. At baseline, sinonasal symptoms, MCT, BAST-24, and QoL were similar between groups. Twelve months after surgery, both TTEA and EEA groups experienced smell impairment compared to baseline. Moreover, EEA (but not TTEA) patients reported increased posterior nasal discharge and longer MCTs compared to baseline. No significant changes in olfactometry or QoL were detected in either group 12 months after surgery. Over the long-term, expanded skull base surgery, using EEA, produced more sinonasal symptoms (including loss of smell) and longer MCTs than pituitary surgery (TTEA). EEA showed no long-term impact on smell test or QoL. LEVEL OF EVIDENCE: IIb.

Valid olfactory impairment tests can help identify mild cognitive impairment: an updated meta-analysis.

Background: Olfactory testing is emerging as a potentially effective screening method for identifying mild cognitive impairment in the elderly population. Objective: Olfactory impairment is comorbid with mild cognitive impairment (MCI) in older adults but is not well-documented in subdomains of either olfactory or subtypes of cognitive impairments in older adults. This meta-analysis was aimed at synthesizing the differentiated relationships with updated studies. Methods: A systematic search was conducted in seven databases from their availability to April 2023. A total of 38 publications were included, including 3,828 MCI patients and 8,160 healthy older adults. Two investigators independently performed the literature review, quality assessment, and data extraction. The meta-analyses were conducted with Stata to estimate the average effects and causes of the heterogeneity. Results: Compared to normal adults, MCI patients had severe impairments in olfactory function and severe deficits in specific domains of odor identification and discrimination. Olfactory impairment was more severe in patients with amnestic mild cognitive impairment than in patients with non-amnestic MCI. Diverse test instruments of olfactory function caused large heterogeneity in effect sizes. Conclusion: Valid olfactory tests can be complementary tools for accurate screening of MCI in older adults.

Evaluation of Olfactory Dysfunction Among COVID-19 Patients in Baghdad, Iraq.

Background SARS­CoV­2 (COVID-19) causes olfactory dysfunction which is characterized by anosmia or hyposmia. Characterization of olfactory dysfunction has added value to the diagnosis and prognosis of the disease. Nevertheless, scarce information exists about COVID-19 patients suffering from olfactory dysfunction in Iraq. This study aimed to identify olfactory dysfunction (anosmia or hyposmia) in Iraqi COVID-19 patients and examine their response to smell exercise at Baghdad Medical City Complex, Baghdad, Iraq. Methodology This case series prospective study involving 300 patients (160 males and 140 females) with COVID-19 infection was conducted from June 1, 2020, to October 1, 2021. We recorded signs and symptoms of COVID-19 among patients by examining olfactory dysfunction, n-butanol olfaction test, and smell test exercise. Results Anosmia and hyposmia were found in 69.3% and 30.7% of the patients, respectively; of these, 65.7% were of sudden onset. The association between olfactory dysfunction and smoking was not significant. The most frequent signs and symptoms of COVID-19 were fatigue, fever, loss of taste, myalgia, headache, sore throat, cough, depressed appetite, dyspnea, nausea, abdominal pain, and diarrhea. The highest frequencies of occurrence of anosmia (30.7%) and hyposmia (13.3%) were in the age group of 31-40 years. The majority (47.7%) of patients with olfactory dysfunction recovered within one month of COVID-19 onset. The rest of the patients recovered within one month to 16 months. The most commonly encountered ear, nose, and throat symptoms were nasal obstruction, rhinorrhea, and facial/ear pain. The percentages of patients with anosmia and hyposmia recovering with smell exercise were significant at 64.7% and 25.3%, respectively. Conclusions The prognosis of olfactory dysfunction in COVID-19 patients was good as most cases recovered within a short period with concomitant smell exercise. Olfactory dysfunction in the majority of COVID-19 patients was self-limiting in young age groups, albeit in association with the non-severity of the disease. Being an important public health issue, examining olfactory dysfunction aspects should be considered in the diagnosis, prognosis, and treatment protocols of COVID-19 patients. In-depth exploration is needed to examine olfactory and gustatory dysfunction in patients suffering from severe COVID-19.

Low to moderate genetic influences on the rapid smell test SCENTinel™.

SCENTinel™ - a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™ was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™ test performance is unknown, which could affect the test's validity. This study assessed performance of SCENTinel™ in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™ test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™ test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™ test on each of the festival's two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™ test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™ subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™ is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.

Disparity of smell tests in Alzheimer's disease and other neurodegenerative disorders: a systematic review and meta-analysis.

Background: There are discrepancies of olfactory impairment between Alzheimer's disease (AD) and other neurodegenerative disorders. Olfactory deficits may be a potential marker for early and differential diagnosis of AD. We aimed to assess olfactory functions in patients with AD and other neurodegenerative disorders, to further evaluate the smell tests using subgroup analysis, and to explore moderating factors affecting olfactory performance. Methods: Cross-sectional studies relating to olfactory assessment for both AD and other neurodegenerative disorders published before 27 July 2022 in English, were searched on PubMed, Embase and Cochrane. After literature screening and quality assessment, meta-analyses were conducted using stata14.0 software. Results: Forty-two articles involving 12 smell tests that evaluated 2,569 AD patients were included. It was revealed that smell tests could distinguish AD from mild cognitive impairment (MCI), Lewy body disease (LBD), depression, and vascular dementia (VaD), but not from diseases such as frontotemporal dementia (FTD). Our finding indicated that in discriminating AD from MCI, the University of Pennsylvania Smell Identification Test (UPSIT) was most frequently used (95%CI: -1.12 to -0.89), while the Brief Smell Identification Test (B-SIT), was the most widely used method in AD vs. LBD group. Further subgroup analyses indicated that the methods of smell test used contributed to the heterogeneity in olfactory threshold and discrimination scores in group AD vs. MCI. While the moderating variables including age, MMSE scores, education years in AD vs. LBD, were account for heterogeneity across studies. Conclusion: Our finding suggests smell tests have potential value in early differential diagnosis of AD. UPSIT and its simplified variant, B-SIT, are widely used methods in the analyses. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID = 357970 (PROSPERO, registration number CRD42022357970).

The 8-item NHANES pocket smell test®: Normative data.

This study provides normative data useful for interpreting scores from the Pocket Smell Test® (PST®), a brief "scratch & sniff" neuropsychological olfactory screening test comprised of 8 items from the 40-item University of Pennsylvania Smell Identification Test (UPSIT®). We combined 3,485 PST® scores from the 2013 to 2014 National Health and Nutrition Survey (NHANES) of persons 40 years of age and older with equivalent PST® items extracted from an UPSIT® database of 3,900 persons ranging in age from 5 to 99 years. Decade-related age- and gender-adjusted percentile normative data were established across the entire age spectrum. Cut-points for defining clinically useful categories of anosmia, probable microsmia, and normosmia were determined using receiver operating characteristic (ROC) curve analyses. An age-related decline in test scores was evident for both sexes after the age of 40 years, with women outperforming men. Based on the ROC analyses, subjects scoring 3 or less (AUC = 0.81) defines anosmia. Regardless of sex, a score of 7 or 8 on the N-PST® signifies normal function (AUC of 0.71). Probable microsmia is classified as scores extending from 3 to 6. These data provide an accurate means for interpreting PST® scores within a number of clinical and applied settings.

On the relationship between neurocognitive measures and olfactory dysfunction in COVID-19 patients with and without anosmia.

One of the predominant symptoms of the COVID-19 virus is the complete (anosmia) or partial (hyposmia) loss of smell. Anosmia may be a critical neurocognitive symptom because there is an empirically demonstrated association of anosmia with neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, etc. The present study assessed the neurocognitive disorder patterns in recovered COVID-19 patients who either self-reported anosmia or its absence. Of the 60 adult participants (n = 32 males, n = 28 females; Mage = 20.78 years, range = 18-31 years), 15 reported COVID-19 induced anosmia, 15 reported COVID-19 without anosmia, and 30 reported not having contracted COVID-19. The participants were first administered a 10-item smell test, and analysis of variance revealed significantly better scores for the control group than the other two groups. Further, there was no significant difference in smell scores between the patients who self-reported anosmia or denied it. This statistical pattern was consistent across all neuropsychological tests: short- and long-term verbal memory, digit span, Trail Making, and a self-report 46-item neurocognitive scale. Regardless of the self-report of anosmia or denial, all thirty COVID-19 patients scored significantly poorer than the control group on all of the tests and neurocognitive scale. In summary, the self-report of anosmia appears to be unreliable, and the COVID-19 patients who were found to be anosmic on the initial objective smell test demonstrated poorer neuropsychological performance than controls.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19 related olfactory disorders.

It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.