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Persistent smell loss after SARS-CoV-2 infection predicted cognitive impairment in older adults, a longitudinal study in Argentina showed.

One year after acute infection, anosmia was more strongly associated with cognitive impairment than severity of SARS-CoV-2 infection, reported Gabriela Gonzalez-Aleman, MSc, PhD, of Pontificia Universidad Católica Argentina in Buenos Aires, at the 2022 Alzheimer's Association International Conference.

"The more insight we have into what causes or at least predicts who will experience the significant long-term cognitive impact of COVID-19 infection, the better we can track it and begin to develop methods to prevent it," Gonzalez-Aleman said.

The findings are part of a of chronic neuropsychiatric sequelae of COVID, a consortium of researchers led by the Alzheimer's Association and representatives from more than 25 countries with technical guidance from the World Health Organization (WHO).

"We're learning more every day about the link between COVID-19 and the brain," noted Claire Sexton, PhD, senior director of scientific programs and outreach at the Alzheimer's Association. "Loss of smell is often a signal of an inflammatory response in the brain. We know inflammation is part of the neurodegenerative process in diseases like Alzheimer's."

"With other viruses, such as SARS and MERS, there have been similar associations between infection and cognition, but there are still big questions about cause and effect," Sexton pointed out.

The Argentina study followed 865 people over age 60 recruited from a provincial health registry that included all SARS-CoV-2 testing data for the region. Researchers randomly invited older adults with a positive PCR COVID test to participate between 3 and 6 months after acute SARS-CoV-2 infection.

Assessments followed the recommendations of the global consortium and included the WHO Schedules for Clinical Assessment in Neuropsychiatry () scale, the Clinical Dementia Rating scale, neurocognitive and emotional reactivity assessments, and evaluations of semi-quantitative olfactory function, motor function, coordination, and gait.

Among the 865 participants, 84.2% had COVID and 15.8% were controls with no history of a positive SARS-CoV-2 test. Median age was 67 and just more than half (56.5%) were female. Participants had a median of 10.35 years of education. Most participants with COVID did not have severe infection, with very few (2% or less) admitted to the ICU.

At 1 year, about one-fourth of the study sample had no cognitive impairment; this group included control participants and about 20% of post-COVID patients, Gonzalez-Aleman said. Scores of remaining participants were normalized to the mean of the cognitively normal group, with impairment defined as z-scores below -2. Remaining participants were clustered into groups based on deficits in memory, attention, executive function, and language, with some people showing impairment in multiple domains.

PCR status and age predicted post-COVID cognitive problems, Gonzalez-Aleman said. Logistic regression analyses showed severity of anosmia, but not severity of SARS-CoV-2 infection, was significantly associated with cognitive impairment.

All anosmia was reported after acute SARS-CoV-2 infection, Gonzalez-Aleman noted. Some people in the control group also had anosmia, but their olfactory dysfunction was much less frequent -- and less severe -- than that of participants with COVID, she added.

The results are part of ongoing research about COVID among older Amerindian adults in Argentina. "It's important to provide the most up-to-date research to the public so we can be aware of the evolving ways this virus impacts us," Sexton said.

"But it's also worth stressing that much more research is needed to paint a more complete picture of what COVID-19 is doing to our bodies and brains," she added. "We also need to study the direct impact that 2 years of pandemic-related isolation has had on our health."

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