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

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

The big question for researchers now is whether Covid-related loss of smell can also be associated with cognitive decline. Around 5 percent of Covid patients worldwide – around 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, although experts caution that more research is needed.

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Previous research has found that some Covid patients go on to develop cognitive impairment after the infection. 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 impairment if they had an 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, and adds that it is too early to say whether the cognitive failure is permanent.

The study tracked 766 adults aged 55 to 95 for a year after the infection. Almost 90 percent had a confirmed case of Covid and all completed standard physical, cognitive and neuropsychiatric tests within a year.

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

The researchers did not have hard data on the state of cognitive function of the patients before they got Covid to compare with the findings at the end, but they asked the 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, professor of psychology at the University of Stockholm who studies the connection between the sense of smell and dementia risk – and was not involved in the new research, loss of smell is a well-established precursor to cognitive decline. It is also well established that Covid can lead to permanent loss of smell, he said.

“The question is whether these two lines of research intersect,” Olofsson said. “This study is quite tempting, 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 exactly how they connect.”

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

Using data from Rush University’s Memory and Aging Project, the researchers tracked the loss of smell in 515 older adults over the age of 22. They also measured gray matter volume in parts of the brain related to dementia and those related to smell.

They found that people whose sense of smell declined faster over time ended up with smaller amounts of gray matter in both of these areas of the brain. The same did not apply to parts of the brain linked to vision, which suggests that the sense of smell has a unique link to 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 the brain regions that are important,” said study leader Dr. Jayant Pinto, director of rhinology and allergy at UChicago Medicine.

Smell “critical” for cognition

Covid is not the first virus to cause loss of smell, but virus-related smell loss was a rare occurrence before the pandemic, Pinto said. This means that it is only recently that scientists are able to carry out large-scale studies on how loss of smell caused by a virus can affect cognition.

“The sense of smell is extremely critical for cognition, especially for the brain to handle 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 Covid-related loss of smell can cause cognitive decline remains unclear.

“It is an open question – does the damage to the olfactory system from SARS-CoV-2 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—connects to parts of the brain that process memory. While it is possible that Covid disrupts the olfactory bulb and then the brain deteriorates around it, Olofsson said this is unlikely.

“There are a number of other ways these two things could be related. The cause could be a pathology unrelated to the Covid effect,” he said.

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

“It could be that the olfactory function was maintained despite being atrophied, but when Covid came it wiped it out,” he said.

If it turns out that Covid loss of smell can cause cognitive impairment, understanding the link could help doctors intervene with loss of smell early and potentially prevent cognitive decline in high-risk people.

“We want to deal with the endemic circulation of a virus that is not going away,” Pardo said. “If we learn more ways that we are able to restore smell quickly, we may be able to minimize the damage that loss of smell can cause with cognitive problems in people who are susceptible.”

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