Loss of smell is a warning sign of Alzheimer’s. What if you lose your sense of smell from Covid?

One of the strange symptoms of Covid – the loss of smell – is a symptom that, long before the pandemic, was considered a warning sign of dementia.

The big question for researchers now is whether the loss of smell associated with Covid may also be associated with cognitive decline. About 5 percent of Covid patients worldwide – about 27 million people – have reported a loss of smell lasting more than six months.

New preliminary findings presented Sunday at the Alzheimer’s Association International Conference in San Diego suggest there may be a link, though experts caution more research is needed.

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Previous research has found that some Covid patients go on to develop cognitive impairment after being infected. In the new study – which has not been published in a peer-reviewed journal – researchers in Argentina found that loss of smell during Covid may be a stronger predictor of cognitive decline, regardless of the severity of the disease.

“Our data strongly suggest that adults over 60 are more vulnerable to post-Covid cognitive decline if they have had olfactory dysfunction, regardless of the severity of Covid,” said study co-author Gabriela Gonzalez-Aleman, professor at the Pontificia Universidad Catolica Argentina in Buenos Aires, adding that it is too early to tell if the cognitive decline is permanent.

The study followed 766 adults aged 55 to 95 for a year after they became infected. Almost 90 percent had a confirmed case of Covid and all completed regular physical, cognitive and neuropsychiatric tests over the course of a year.

Two-thirds of those infected had some kind of cognitive impairment by the end of that year. In half of the participants, the damage was severe.

The researchers did not have hard data on the patients’ cognitive status before they contracted Covid to compare with the findings at the end, but they asked participants’ families about their cognitive function before infection and did not include people who had clear cognitive impairment before the study.

According to Jonas Olofsson, a professor of psychology at Stockholm University who studies the link between smell and dementia risk — and was not involved in the new research, loss of smell is an established precursor to cognitive decline. It is also well documented that Covid can lead to permanent loss of smell, he said.

“The question is whether these two lines of inquiry intersect,” Olofsson said. “This study is quite enticing, although the information I have seen so far does not allow for any strong conclusions. “

The smell-brain connection

According to Dr. Claire Sexton, senior director of scientific programs and outreach at the Alzheimer’s Association, “loss of smell is a signal of an inflammatory response in the brain.”

“We know that inflammation is part of the neurodegenerative process in diseases like Alzheimer’s,” Sexton said. But we need to dig deeper into how exactly they are connected.”

A separate study – unrelated to Covid – published last Thursday in the journal Alzheimer’s & Dementia further explores this connection. Researchers from the University of Chicago have found that not only can a decline in smell over time predict cognitive decline, but loss of smell can also be a warning sign of structural changes in areas of the brain that are important for Alzheimer’s disease and dementia.

Using data from Rush University’s Memory and Aging Program, researchers tracked smell loss in 515 seniors over the age of 22. They also measured gray matter volume in parts of the brain associated with dementia and those associated with smell.

They found that people whose sense of smell declined more quickly over time ended up with smaller amounts of gray matter in both of these brain regions. The same was not true for parts of the brain associated with vision, suggesting that the sense of smell has a unique relationship with cognition in terms of structural differences.

“Not only can change in olfactory function over time predict the development of dementia, but it can also predict the size of those brain regions that are important,” said study leader Dr. Jayant Pinto, director of Rhinology and of Allergy at UChicago Medicine.

Smell is “critical” to cognition

Covid is not the first virus to cause smell loss, but virus-related smell loss was a rare occurrence before the pandemic, Pinto said. This means that only recently have scientists been able to conduct large studies of how the loss of smell caused by a virus can affect cognitive function.

“Olfaction is extremely critical for cognition, especially for the brain that processes information about the environment. If you close that channel of communication with the brain, it will suffer,” said Dr. Carlos Pardo, a professor of neurology at Johns Hopkins University who was not involved in either study.

But whether the loss of smell associated with Covid can cause cognitive decline remains unclear.

“This is an open question –– does SARS-CoV-2 injury to the olfactory system lead to problems not only in the olfactory system, but also in the brain itself?” Pinto said.

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According to Olofsson, the olfactory system — the parts of the brain related to smell, including the olfactory bulb, the part of the brain that processes smell — is connected to parts of the brain that process memory. While it’s possible that Covid disrupts the olfactory bulb and then the brain deteriorates around it, Olofsson said that’s not likely.

“There are many other ways in which these two things can be related. The cause may be a pathology unrelated to the Covid phenomenon,” he said.

Or Covid may simply amplify existing olfactory loss or cognitive decline that went unnoticed before the infection, Olofsson said. Patients may have already experienced some cognitive impairment when they contracted Covid, or they may have already had mild impairment of the olfactory system, which made them more susceptible to the loss of smell associated with Covid.

“Olfactory function could be preserved despite it being atrophied, but when Covid came along, it took it away,” he said.

If it turns out that Covid olfactory loss can cause cognitive decline, understanding the connection could help doctors intervene early on olfactory loss and potentially prevent cognitive decline in high-risk people.

“We’re going to be dealing with the endemic circulation of a virus that’s not going away,” Pardo said. “If we learn more about how we can quickly regain our sense of smell, we may be able to minimize the damage that cognitively impaired smell loss can do to people who are susceptible.”

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