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

Abstract

Smell dysfunction is a common and underdiagnosed medical condition that can have serious consequences. It is also an early biomarker of Alzheimer's disease that precedes detectable memory loss. Clinical tests that evaluate the sense of smell face two major challenges. First, human sensitivity to individual odorants varies significantly, leading to potential misdiagnosis of people with an otherwise normal sense of smell but insensitivity to the test odorant. Second, prior familiarity with odor stimuli can bias smell test performance. We have developed new nonsemantic tests for olfactory sensitivity (SMELL-S) and olfactory resolution (SMELL-R) that overcome these challenges by using mixtures of odorants that have unfamiliar smells. The tests can be self-administered with minimal training and showed high test-retest reliability. Because SMELL-S uses odor mixtures rather than a single molecule, odor-specific insensitivity is averaged out. Indeed, SMELL-S 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 cannot be objectively calculated. 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 and translated to different populations. We predict that SMELL-S and SMELL-R will be broadly effective in diagnosing smell dysfunction, including that associated with the earliest signs of memory loss in Alzheimer's disease.

Molecularly diverse odors advance olfactory threshold testing

“…Mixture B returned the highest reliability coefficient, suggesting that an optimal number of components for the threshold test stimuli might be in the range of 10 molecules, but that critically depends on the quality of the mixture. This finding is in contrast with former reports suggesting minor differences in the properties of the test based on mixtures of different quality and indicates that results very much depends on the odors used (Hsieh et al, ). Finally, thresholds for Mixture C exhibited modest test–retest reliability, however the coefficient of correlation between test and retest was much lower than that for Mixture B.…”

“…This finding supports the notion that the individual expression of olfactory receptors across the population has a significant impact on olfactory experience and smell abilities (Croy et al, ; Gilbert & Kemp, ; Keller et al, ). Using molecularly varied stimuli makes olfactory threshold assessments relatively independent from an individual variability in sensitivity to specific odorants (Hsieh, Keller, Wong, Jiang, & Vosshall, ; Oleszkiewicz, Pellegrino, Pusch, Margot, & Hummel, ). Nevertheless, this is only true in certain conditions—depending on the number of components and quality of the odors.…”

“…This suggests a variation of the individual results obtained with tests based on single type molecule odorants. Up to date, all studies aimed to introduce mixtures to testing olfactory abilities included normosmic individuals (Oleszkiewicz et al, ) or a small number of individuals with self‐reported olfactory dysfunctions (Hsieh et al, ). It is likely that low variability in the study samples translates into the relatively low test–retest correlation coefficients.…”

Executive Summary of EPOS 2020 Including Integrated Care Pathways

“…The most widely used remain the North American UPSIT (93) , its short version (SIT, B-SIT) and the European Sniffin'Sticks (94) . Although there are many others, all have cultural bias and there have been recent advances to overcome this with culturally unbiased, universally usable smell tests (95) . Nasal obstruction is the most significant of the cardinal symptoms of rhinosinusitis and nasal patency may be objectively evaluated with peak nasal inspiratory flow (PNIF), (active anterior) rhinomanometry (AAR), and acoustic rhinometry (AR) Newer methods such as computational fluid dynamics (96) are presently mainly used for research purposes (97,98) but may be of value in the future.…”

Development of a Korean Culture-Friendly Olfactory Function Test and Optimization of a Diagnostic Cutoff Value

“…The detection threshold, discrimination, and odor identification are affected by low, middle, and high levels of olfactory processing, respectively, and require different levels of cognition [6]. In particular, odor identification may require prior exposure to culturally-specific odor stimuli [7]. Therefore, many culture-friendly odor identification tests have been specifically developed or modified and validated [8].…”