Why Loss of Smell Can Be an Early Sign of Brain Diseases Like Alzheimer’s.

It’s summer in San Diego, California, where I live. When I walk down the street, I can smell the delirious musk of jasmine clinging to the air. My nose picks up the languid smokiness of briquets burning on barbecues, taking me back to decades of yard parties. But given the heat wave descending on the city, the garbage is also throwing off a sickly stench, hinting at decay. These odors are all good signs.

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We have long known that smell has potent connections to memory and emotion, as the endurance of Proust’s proverbial madeleine moment attests. In fact, the limbic system, including the amygdala and the hippocampus, is responsible for processing not just memory and emotion, but also smell. While Western culture has generally relegated the sense of smell to the lowest rank since the time of Plato, some hunter-gatherer groups such as the Semaq Beri of the Malay peninsula have more words for smells than for color hues. Now, researchers are learning that the sense of smell is critical as a marker of brain disease and health.

Over the past decade, loss of smell—known as hyposmia—has emerged as an early indicator of several neurodegenerative disorders, according to a recent International Journal of Molecular Science review of 20 papers. The high prevalence and early onset of smell loss, along with the development of sensitive olfactory tests, has raised interest in it as a diagnostic tool for Parkinson’s disease and Alzheimer’s disease, in particular. But loss of smell also afflicts people with Huntington’s disease, multiple sclerosis, and mild cognitive impairment. Catching these diseases early by testing for powers of smell could give patients a head start on neuroprotective and disease-modifying therapies.

The power of the nose peaks in middle age, around age 40.

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The connection between odor detection and brain health makes sense. Our sense of smell begins in the nose and then proceeds directly to the olfactory bulb at the base of the brain. It’s the first sensory structure we have that provides direct contact with sensory stimuli and environmental pathogens in the air. Experimental evidence suggests olfactory bulb neurons play a key role not just in the loss of smell but also in the early stages of brain disease.

Some researchers at the University of Padova in Italy are looking at how the sudden smell loss characteristic of COVID-19 connects with Parkinson’s disease. Viral infections, like COVID-19, and regional inflammatory processes may trigger defective proteins to aggregate, a feature of Parkinson’s, and lead neurons to subsequently degenerate, the researchers hypothesize. Certain psychiatric diseases are also associated with smell dysfunction: Schizophrenia patients have shallower nasal cavities and smaller olfactory bulbs than healthy individuals, as well as other nasal abnormalities that Alzheimer’s patients also experience.

Not everyone with smell loss will develop brain disease. The acuity of our sense of smell declines as we age but follows a different trajectory from that of some other cognitive and perceptual abilities. While short-term memory peaks at age 25, for example, the power of the nose peaks in middle age, around age 40, and then gradually begins to slip. Age-related loss of smell is greater in men than women, and women have a higher total number of olfactory bulb cells than men—at least 50 percent more, on average, research suggests.

Aside from its connection to neurodegeneration, smell is also a powerful marker of overall health and mortality risk. In one longitudinal study of 1,162 healthy older people (without dementia) the mortality rate over a four-year period was 45 percent for those with the lowest baseline olfactory test scores, compared to 18 percent for those with the highest scores, even after controlling for age and other factors.

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It is surprisingly difficult to know when we have lost our sense of smell: About 70 percent of people living with a loss of smell don’t realize it until they’re tested. (If you’re curious, you can take a simple scratch and sniff smell test to find out how well your nose performs, and depending on the results, you could receive an invite to join a research study sponsored by the Michael J. Fox Foundation.) There may be more truth than we realized to the saying, “Follow your nose.”