Roger Fredenburg always looked forward to the scent of freshly baked bread wafting from a bakery near the hair salon he owned in Bellevue, NE. Then one morning in the late 1990s, as he approached the bakery, he was puzzled when he couldn't detect any aroma. “I wondered if they were closed or something,” he says. But as he passed the shop, he saw lights on and staff bustling about inside. For some strange reason, he just couldn't smell their wares that day. “I thought my nose was stuffed up, maybe allergies,” he says.
Gradually, however, Fredenburg, who is now 56, began losing his sense of smell almost entirely. “It got to the point where I couldn't smell pancakes being cooked or garlic and onions being fried,” he says. “If I put a candy bar in my mouth, I could taste that it was sweet, but I couldn't really experience the chocolate flavor of it,” he adds.
A year or so after his sense of smell began to fade, Fredenburg noticed small tremors in his right hand. “My ring finger would start shaking, then eventually my whole hand, and then it moved on to my left hand, too,” he says. “Clients started asking me if I was okay, and I'd say I had low blood sugar. Doctors told me it was stress.”
A client became so concerned about Fredenburg that she brought her physician son to see him. “By then I was walking hunched over, shuffling my feet, and taking very small steps,” he says. “Her son took one look at me and said, ‘You're walking like you're 85. You need to see a neurologist.’” After imaging scans and other diagnostic tests, Fredenburg was diagnosed with young-onset Parkinson's disease in February 2000, a week before he turned 32.
That Fredenburg's diminished sense of smell was a precursor to Parkinson's disease is supported by research, which finds that it also may be an early symptom of Alzheimer's disease. “Studies have demonstrated that between 75 percent and 95 percent of people with Parkinson's have an impaired sense of smell—a deficit that can develop several years before the classic motor symptoms of Parkinson's appear and is now considered one of the earliest signs of the disorder,” says neuroscientist Richard Doty, PhD, FAAN, who directs the Smell and Taste Center at the Perelman School of Medicine at the University of Pennsylvania. “Low olfactory test scores also have been associated with cognitive decline and an increased probability of Alzheimer's disease over the next few years,” he adds.
People lose their sense of smell when any part of the pathway that enables smell—including the nasal passages, the olfactory nerve, and the brain—is damaged by aging, disease, or trauma. Impairment can range from a decreased sense of smell (hyposmia) to complete loss of smell (anosmia). Because the ability to taste is linked to smell, changes in taste often accompany changes in smell. This happens even though the taste buds that tell us whether something is salty, sweet, sour, bitter, or savory usually continue to function. (That's why Fredenburg could detect the sweetness of the candy but could not identify its chocolate flavor.)
Causes of Smell Loss
“We all lose our sense of smell to some degree as we age, due to a combination of factors,” Dr. Doty explains. “The foramina—the holes between the nasal cavity and the brain cavity through which the olfactory axons project—harden with age. An old skull won't have as many of those openings as a young skull. And as we go through life, we accumulate areas of damage—from microparticles, pollution, viruses, bacteria, and so on—in the olfactory region. More cells are damaged or lost, and we may not notice these changes until some threshold is reached.”
That lifelong damage can be exacerbated by various neurologic conditions. “Our research has found that dysfunction in certain neurotransmitters [the chemical messengers of the brain], particularly acetylcholine, is involved in the association between smell loss and conditions such as Parkinson's and Alzheimer's,” Dr. Doty says. In a study in Lancet Neurology, Dr. Doty and his colleagues looked at the size of a brain region called the nucleus basalis, the source of these neurotransmitters, and found that it correlated with the amount of smell loss that occurs in neurodegenerative disorders.
The abnormally folded proteins associated with Parkinson's disease (alpha-synuclein) and Alzheimer's disease (amyloid-beta and tau) accumulate first in the olfactory bulb, says Daniel Wesson, PhD, chair and associate professor of pharmacology and therapeutics at the University of Florida College of Medicine and a lead investigator with the UF Center for Smell and Taste. Everyone has two olfactory bulbs, one above each nasal passage, and they are the first processing centers for smell input from the nose. “So even before other symptoms are detectable, those pathogens are influencing normal communication in the olfactory system,” says Dr. Wesson. “We still don't know for certain why accumulation happens here first, but it may be because this area is uniquely exposed to the environment as an entry point to the brain.”
A diminished sense of smell can occur for other reasons as well, says Dr. Wesson. “Some people are born without a sense of smell. Others may lose their sense of smell, temporarily or permanently, as a result of head trauma or damage from smoking or allergies. It also can be caused by nasal sprays, new medications, dietary changes, or infection.”
A respiratory infection is one of the most common causes, and the COVID-19 virus is associated with significantly more severe smell loss than other viruses, according to several European studies in 2020. “Viruses in general damage the olfactory epithelium, the specialized tissue inside the nasal passages that contains the olfactory neurons,” says Dr. Doty.
For Kimberly Montgomery, 65, the director of the annual Macy's Thanksgiving Day Parade in New York City, losing her sense of smell was a hint that she might have COVID-19. The Sunday before the parade in November 2020, she and her family ordered Italian food to eat while she worked to get ready for the event. “I took one bite of my ravioli and thought it tasted terrible,” says Montgomery, who lives in Teaneck, NJ.
Later that day, she remembers, she sprayed surfaces in her home with Lysol and realized that she wasn't smelling its strong odor. “Then it hit me: Nothing was wrong with the ravioli earlier; I just couldn't smell it, so the taste was off too. I thought ‘Uh-oh.’” Sure enough, Montgomery tested positive for COVID-19. Her sense of smell gradually returned after about six months.
COVID-19 appears to do more damage to the sense of smell than other viruses because of its effect on certain types of cells that support the olfactory sensory neurons and ensure that they work in a way that allows us to perceive and identify smells. “COVID-19 kills these cells quickly, and the debris generated by their deaths leads to an overwhelming immune response,” says Benjamin tenOever, PhD, professor of microbiology at NYU Langone Health. “Instead of processing smells and making smell-related receptors, which is their primary function, the olfactory sensory neurons are busy launching antiviral activity and being diverted from olfaction.” A few days or weeks later, the system returns to normal and the sense of smell comes back.
“In some cases, there may be damage to the neurites, the long receptors that extend from the cell body, and it can take longer for those to grow again,” says Dr. tenOever. “Those people may lose their sense of smell for months. In extreme cases, damage can kill those neurite outgrowths, and people can lose their sense of smell permanently.”
Chances of Recovery
About one-third to one-half of patients in Dr. Doty's clinic ultimately regained some of their sense of smell, according to a study published in Annals of Neurology. “Of those who came in with total smell loss, only about 11 percent regained enough smell function to be ‘normal,’” he says. “But for those who still had some ability to smell, about 23 percent returned to an age-adjusted normal range of olfactory function, although there is a lot of variability.”
A study published in the American Journal of Otolaryngology in 2022 found that most people who lost their sense of smell due to COVID-19 recovered it about three weeks after being infected, and 81 percent saw their sense of smell return to normal by six months. People with more severe initial loss of smell were less likely to recover fully.
Montgomery can taste and smell again but not as she once could. “Certain flavors taste or smell completely different,” she says. “Anything with cinnamon, nutmeg, or cloves, like pumpkin pie—I don't really taste that. And the other day my husband had a Coke, and I asked if I could smell it. It smelled like I remember, but when I tasted it, it tasted like garlic water.”
Other people who had COVID-19, like James Rahill of Schwenksville, PA, still can't smell. He was first diagnosed in November 2020 and realized he'd lost the ability to smell when his wife took horseradish out of the refrigerator and he couldn't smell it. “We've both had COVID-19 more than once, and my wife did have some impaired smell the first time, but hers has come back and mine hasn't.” The loss is particularly devastating for 65-year-old Rahill, a former chef and restaurant owner, who has since retired.
The inability to smell was the least of Fredenburg's problems. He was so debilitated by Parkinson's disease that he stopped working and moved in with his parents in 2007. Then five years later, he underwent deep brain stimulation (DBS) and experienced a remarkable physical recovery. “I have no visible tremors anymore. I'm still on medication, and I get Botox every few months because I get dystonia in one leg, but if you looked at me today, you wouldn't think I had ever had Parkinson's,” he says. “I've moved into my own place again. I mow and shovel snow and do yard work and walk my dog.”
A possible and unexpected benefit of DBS has been the occasional return of his sense of smell. “Sometimes if I'm baking apple pie, I can smell the cinnamon,” says Fredenburg.
It's possible that DBS could have jump-started at least some of Fredenburg's long-lost sense of smell, says Michael S. Okun, MD, FAAN, medical adviser to the Parkinson's Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health. He cites a large study in the Journal of Clinical Neuroscience that found a link between DBS and improved olfactory function. “Many interconnected regions of the brain contribute to the ability to detect aroma and fragrance. Neural network modulation induced by DBS could possibly reestablish important networks for smell for some patients,” he says, adding that DBS is not recommended as a treatment for loss of or reduced smell.
Still, for people like Fredenburg, the procedure has had a positive impact. One morning, he says, “I walked into my mom's house, and she was cooking bacon, and I could smell it!”
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