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.
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11275-11284. doi: 10.1073/pnas.1711415114. Epub 2017 Oct 10.
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.
嗅觉功能障碍是一种常见且未被充分诊断的医学病症，可能会带来严重后果。它也是神经退行性疾病（包括阿尔茨海默病）的早期生物标志物，在这些疾病中，嗅觉缺陷先于可察觉的记忆丧失。评估嗅觉的临床测试面临两个主要挑战。首先，人类对个别气味的敏感性差异很大，因此对于对测试气味敏感性低但嗅觉正常的人来说，测试结果可能不可靠。其次，对气味刺激物的先前熟悉程度会影响嗅觉测试的表现。我们开发了非语义嗅觉敏感性测试（SMELL-S）和嗅觉分辨力测试（SMELL-R），它们使用具有陌生气味的气味混合物。健康人可以在经过最少培训后自行进行这些测试，并且具有很高的测试-重测可靠性。由于 SMELL-S 使用气味混合物而不是单一分子，因此平均了气味特异性不敏感性，并且该测试可以准确地区分嗅觉正常和功能障碍的人。SMELL-R 是一种辨别测试，其中两个刺激混合物之间的差异可以逐步改变。与目前需要适应不同语言和文化的基于语义的常规辨别测试相比，这是一个进步，因为后者要求测试者辨别其气味无法量化的单分子气味。与需要适应不同语言和文化的传统基于语义的嗅觉测试相比，SMELL-R 在北美和台湾受试者之间的分数差异上表现出的偏差明显较小。基于健康个体的这些原理验证结果，我们预测 SMELL-S 和 SMELL-R 将在诊断嗅觉功能障碍方面具有广泛的有效性。
