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 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.

Self-Administered Testing of Odor Threshold and Discrimination Using Sniffin’ Sticks—Reviving the “Odor-Curves-On-Paper” Method

“…Another issue in olfactory testing is the individual sensitivity level to single-molecule odors (Keller et al 2012) and diverse odor discrimination abilities based on familiarity (Jehl et al 1995). Recently, usage of more complex odors in terms of odor mixtures seems to overcome these confounding factors and to be more reliable than single-molecule testing, as presently used in the Sniffin' Sticks testing battery (Oleszkiewicz et al 2017;Hsieh et al 2017).…”

European position paper on diagnostic tools in rhinology

“…Other, more rarely used techniques are the odour memory test (156) that specifically addresses the capacity to memorize previously presented odorants, and the sniff magnitude test (157) or olfactory respirometry (158) (159)(160)(161)(162) . Two very recent publications have addressed the biases that the classical psychophysical tests have, such as the genetic variability of odour sensitivity and cultural influences (163,164) . The authors propose the use of mixtures instead of single odours for both identification and threshold testing, suggesting that this can overcome these biases.…”

Störungen des Geruchssinns: Psychiatrisch-neurologische Bezüge und Diagnostik

“…So muss eine geringe Sensitivität für einen bestimmten Geruch nicht zwingend ein Indikator für eine Riechstörung sein. Die Verwendung von Geruchsmischungen statt einzelner Gerüche kann den Einfluss molekülabhängiger Sensitivitätsunterschiede verringern [57,58].…”

“…Auf diese Weise werden vermeintliche Leistungsunterschiede, welche nur auf der Ansprechbarkeit einzelner Geruchsrezeptoren beruhen, minimiert und es wird eher als bei anderen Tests die allgemeine Geruchsleistung erfasst. Das Prinzip, bei Geruchstests eher Geruchsmischungen als Einzelsubstanzen einzusetzen, ist in der Geruchsforschung hochaktuell [58] und wurde mit den DODT bereits stark fokussiert. Bisher liegen Testgüte-Maße zur Reliabilität und internen Validität vor, an dieser Stelle sollen außerdem erste klinische Validierungsdaten vorgestellt werden.…”