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Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11275-11284. doi: 10.1073/pnas.1711415114. Epub 2017 Oct 10.

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

Author information

Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY 10065;
Rhinology-Olfactology Unit, Service of Otorhinolaryngology Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, CH-1211 Geneva 14, Switzerland.
Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY 10065.
Department of Otolaryngology, Taichung Veterans General Hospital, Xitun District, Taichung City, Taiwan 407.
Howard Hughes Medical Institute, New York, NY 10065.
Kavli Neural Systems Institute, The Rockefeller University, New York, NY 10065.


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.


hyposmia; odor-specific insensitivity; olfaction; olfactory dysfunction; smell test

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