Olfactory Loss and Alzheimer’s Disease
Commercialized smell testing could pay off big time.
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As a general rule, aging brings with it a gradual loss of sensory acuity. High frequency sounds become harder to hear, visual acuity declines, and our sense of smell becomes weaker. While the overall trends are unmistakable, people age differently—there are older perfumers, vintners, brew masters, and chefs who run circles around their younger colleagues.
On a group level, age-related declines in smell ability emerge in the fifth decade of life, both in smell identification ability and in odor detection threshold. The smell tests in most common clinical use are age-normed: the results tell you where you stand in relation to people of similar age.
An accelerated loss of smell in late middle age can be an early sign of Alzheimer’s disease (AD). The pathological hallmark of AD is the appearance in the brain of extracellular amyloid plaques and intracellular tangles of tau protein—features that can only be confirmed with tissue sampling or at autopsy. This pathology develops early on in the olfactory bulb, the first relay point for the sensory nerves leaving the nose.
Naturally, this has led to much interest in smell testing as a means of early diagnosis for AD. There is a large literature on the topic, going back decades. It can be summarized easily: as the disease progresses, smell loss more or less tracks the degree of cognitive impairment. Thus, smell ability could be a rough indicator of AD status.
New smell tests for use in AD evaluation keep popping up. Why? Because the number of AD cases is large and continues to rise as worldwide populations age. Also because a smell test could be less expensive and time-consuming than a full cognitive examination by a neuropsychologist or psychiatrist. The ultimate prize? A self-administered or even fully automated test.
The latest entry into the fray is a group from Harvard Medical School/Massachusetts General Hospital. Jobin, et al. published results from an at-home, self-administered smell test that can separate people diagnosed with mild cognitive impairment (MCI) from those who are cognitively normal (CN) or who merely have subjective cognitive complaints (SCC). The paper makes a lot of noise about the need for noninvasive testing for AD, but no actual AD patients were tested. This is probably why the smell test is dubbed the AROMHA Brain Health Test. Another reason is that author Mark W. Albers, a faculty member at Harvard Medical School, is co-founder of a startup company called Aromha, Inc.
To be fair, Albers is an established Alzheimer’s expert and the study’s experimental design is pretty tight. However, the samples sizes (CN = 127, SCC = 34, MCI = 19) are relatively small for a test validation study. [No kidding—the MCI group has barely twice as many patients as there are authors on the paper.—Ed.]
AROMHA is attempting to enter a crowded marketplace. The USPIT Smell Identification Test has been around for decades. Also well established are the Sniffin’ Sticks smell test kits which assess odor threshold as well as identification. Thomas Hummel, a German MD/PhD with an extensive list of clinical studies on olfaction, helped create these products. Like Albers, he is interested in smell as a biomarker for brain aging.
Hummel, along with a Finnish research team, recently published a paper on the functionality of a prototype device called AutomOT, short for Automated Olfactory Threshold Test. [Meh. Needs a better name.—Ed.] The device looks promising: AutomOT results correlated with Sniffin’ Sticks results, and the device scored well on formal measures of usability.
With the future of a lucrative AD testing market at stake, it looks like the battle for early market dominance has commenced.
Benoît Jobin, Colin Magdamo, Daniela Delphus, Andreas Runde, Sean Reineke, Alysa Alejandro Soto, Beyzanur Ergun, Sasha Mukhija, Alefiya Dhilla Albers and Mark W. Albers, The AROMHA brain health test is a remote olfactory assessment to screen for cognitive impairment. Scientific Reports 15: 9290, 2025.
Veikko Surakka, Marko Björkbacka, Jani Lylykangas, Jussi Rantala, Timo Salpavaara, Jarmo Verho, Oleg Spakov, Venla Kamppari, Philipp Müller, Antti Vehkaoja, Pasi Kallio, Divesh Thaploo, and Thomas Hummel, A new method for automated olfactory threshold testing. Chemical Senses 50:29, 2025