The lateralized smell test for detecting Alzheimer's disease: failure to replicate

Abstract

Objectives: A widely publicized study by Stamps, Bartoshuk and Heilman (2013) reported that a simple measure of left:right naris differences in the ability to detect the odor of peanut butter is a sensitive marker of Alzheimer's disease (AD). AD patients were said to have abnormal smell function on the left side of the nose and normal function on right side of the nose. In light of its implications for medical practice and the world-wide publicity that it engendered, we sought to replicate and expand this work.

Methods: Two studies were performed. In the first, 15 AD patients were tested according to the procedures described by Stamps et al. in which the nostril contralateral to the tested side was occluded by the patient using lateral pressure from the index finger. Since this can potentially distort the contralateral naris, we repeated the testing using tape for naris occlusion. In the second, 20 AD patients were administered 20 odors of the University of Pennsylvania Smell Identification Test (UPSIT) to each side of the nose, with the contralateral naris being closed with tape. In both studies, the order of the side of testing was systematically counterbalanced.

Results: No evidence of a left:right asymmetry on any test measure was observed.

Conclusion: Although hyposmia is well-established in AD, no meaningful asymmetry in smell perception is apparent. If olfactory function on the right side of the nose was normal as claimed, then AD patients should exhibit normal function when tested bilaterally, a phenomenon not seen in dozens of AD-related olfactory studies.

Keywords: Alzheimer's disease; Laterality; Neurodegeneration; Olfaction; Psychophysics; UPSIT.