COVID Smell Loss Tops Disease Severity as a Predictor of Long-term Cognitive Impairment

Pauline Anderson

July 31, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires, told Medscape Medical News.

The more information that can be gathered on factors increasing risks for this cognitive impact, "the better we can track it and begin to develop methods to prevent it," she said.

The findings were presented at the Alzheimer's Association International Conference (AAIC) 2022.

Memory, Attention Problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer's disease (AD), and the two conditions may share risk factors and blood biomarkers.

Dr Gabriela Gonzalez-Alemán

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19's impact on the brain allows consortium members to compare study results, said Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

Investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction (PCR) testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as Z-scores below - 2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

"Our participants showed a predominance of memory impairment as would be seen in Alzheimer's disease," noted Gonzalez-Alemán. "And a large group showed a combination of memory and attention problems."

About 40% of the study sample — but no controls — had olfactory dysfunction.

"All the subjects that had a severe cognitive impairment also had anosmia [loss of smell]," said Gonzalez-Alemán. "We established an association between olfactory dysfunction and cognitive performance and impairment."

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. "So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection," said Gonzalez-Alemán.

For individuals over 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. Some 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.

Longest Follow-Up to Date

Commenting on the research for Medscape Medical News, Heather Snyder, PhD, vice president, medical & scientific relations at the Alzheimer's Association, noted the study is "the longest follow-up we've seen" looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a "fairly large" sample size and was "unique" in that it was set up in a part of the country with centralized testing, said Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Snyder.

Members of this Alzheimer's Association consortium, said Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are "because no one group will be able to do this on their own," she said.

"We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there's a connection to the brain."

However, she added, "there's still a lot we don't know" about this connection.

The study was funded by Alzheimer's Association and FULTRA. Gonzalez-Alemán reports no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2022. Abstract 66868. Presented July 31, 2022.

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