University of São Paulo: Study links changes in smell or taste after covid-19 with memory problems

Studies done before the covid-19 pandemic pointed to the loss of smell as a possible early sign of Alzheimer’s disease. There is, in the scientific literature, evidence that this sensory dysfunction can manifest itself years before the first cognitive symptoms appear, which suggests that there is a connection between the brain region responsible for memory and the one that registers and interprets olfactory stimuli.

This hypothesis has just gained strength with a work published by Brazilian researchers in the European Archives of Psychiatry and Clinical Neuroscience . The group followed 701 patients hospitalized with moderate or severe covid-19 at the Hospital das Clínicas da Faculdade de Medicina da USP (FMUSP), between March and August 2020. In evaluations carried out six months after hospital discharge, they observed that individuals who had more post-covid sensory sequelae (reduction or modification of smell and/or taste) performed worse on cognitive tests, particularly on memory. And this result was independent of how severe the condition had been in the acute phase of the disease.

“Smell is an important connection to the external world and is very much related to past experiences. The smell of cake, for example, can remind us of our grandmother. In terms of brain connection, it interacts with memory much more robustly than vision and hearing,” says ENT doctor Fábio Pinna, one of the authors of the article.

Of the 701 volunteers included in the survey, 52.4% were male. The mean age was 55.3 years and the mean length of stay was 17.6 days. Just over half of the sample (56.4%) needed to be admitted to the Intensive Care Unit (ICU) for complications from covid-19, with 37.4% of the volunteers being intubated.

In the analyzes carried out six months after leaving the hospital, the functioning of smell and taste was measured using questionnaires previously standardized for studies of this type, which also assess aspects related to quality of life.

Moderate or severe reduction in taste was the most common sensory sequelae (20%), followed by moderate or severe reduction in smell (18%), concomitant reduction in moderate or severe smell and taste (11%), and parosmia (9%). – term used to describe changes in olfactory perception, for example, when an odor that was previously considered pleasant is now perceived as bad. Twelve volunteers had olfactory hallucinations (smells that other people don’t) and nine people reported gustatory hallucinations (they taste a food without having tasted it). In both cases, most stated that these hallucinations only appeared after infection with the coronavirus. Regarding general health status, 10.1% of the participants described it as “bad or very bad”, 38.5% as “average” and 51.4% as “good or very good”.

Also through standardized questionnaires, the scientists verified the presence of psychiatric symptoms, such as anxiety and depression. And neuropsychological tests were applied to measure so-called cognitive functions, including memory, attention and speed of reasoning.

At the end, all results were analyzed by statistical methods in order to find out if there was a correlation between neuropsychiatric symptoms and sensory dysfunctions. It was observed that volunteers who suffered from parosmia had a greater perception that their memory was poor. Those who had moderate or severe taste impairment did significantly worse on a task that consisted of memorizing a list of words – used to assess so-called episodic memory (short-term, closely related to attention). Volunteers who had concomitant moderate or severe loss of taste and smell also demonstrated significant impairment in episodic memory.

“We did not find any psychiatric symptoms [anxiety or depression, for example] associated with loss of smell and taste. But, as expected, we observed that attention and episodic memory were more impaired in patients with greater chemosensory alterations”, comments Rodolfo Damiano, PhD student at FMUSP with a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) and first author of the article. “This finding supports the hypothesis that covid-19 does, in fact, have an impact on cognition and its damages are not only due to psychosocial or environmental issues”, he evaluates.

the source of the damage
In the case of Alzheimer’s disease, it is believed that the loss of smell may be one of the first consequences of the degenerative process that leads to the progressive loss of neurons. The loss of smell associated with covid-19, according to Pinna, is due to the inflammation triggered by sars-cov-2 in the olfactory mucosa. “This leads to a decrease in olfactory mucus. We have not seen a direct injury to olfactory neurons. They eventually degenerate, but it appears to be a secondary consequence of the loss of olfactory mucus. The mucosa undergoes an atrophy process and may lose this ability to capture odors”, explains the doctor.

As psychogeriatrician Orestes Forlenza, professor at the FMUSP Department of Psychiatry and one of the study coordinators, explains, the cognitive losses observed in Alzheimer’s disease and post-covid syndromes stem from distinct pathogenic processes, but the two processes can overlap. “Particularly in elderly individuals, who already have primary cognitive symptoms and will contract the infection. There is preliminary evidence that this overlapping of pathogenic factors may accelerate or exacerbate the progression of cognitive losses,” he says.

The exact mechanism by which coronavirus infection leads to cognitive damage is not yet known. To try to identify which brain pathways are altered in the acute phase of the disease, the USP group intends to apply new tests in patients who have loss of smell and taste. The idea is that volunteers do the tasks while undergoing a 7-tesla MRI scan, which has a very high resolution image (common equipment has only 3 tesla).

“Our hypothesis is that the virus causes neuroinflammation, which leads to impaired cognition. Whether the damage is permanent remains to be seen. We continue to monitor patients to find out if there is improvement or not”, says Damiano.

The group also intends to investigate whether the relationship between sensory and cognitive loss also occurs in people who contracted covid-19 after vaccination. “We are doing a study similar to the one now released, but considering whether or not the participant was vaccinated and how many doses they took before becoming infected. The aim is to find out whether the vaccine offers protection against neuropsychiatric complications. And also if one type of immunizing agent protects more than another, which would make it more suitable for people with psychiatric illnesses”, says the doctoral student.

More attention to smell
According to the authors, one of the important messages of the article is that olfactory dysfunctions should gain more attention from health professionals and people in general.

“When an elderly person starts to lose their sense of smell, it can be an early sign of dementia. You need to take him to the doctor for an evaluation. People who had moderate or severe olfactory loss after covid-19 should be aware of memory changes in the coming years, as well as their family members”, says Damiano.

Pinna hopes the results will spur doctors and patients with olfactory dysfunction to invest in treatment. “Before Covid-19, this problem was ignored. The treatments were little known, it was believed that there was not much to do. There is now evidence that it is important to treat both to minimize the loss of quality of life caused by sensory dysfunction itself and to prevent other associated health problems. We have an incentive not to give up on treatment,” she says.