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Persistent Anosmia Due to COVID-19 Linked to Cognitive Impairment

Persistent anosmia for months following infection with SARS-CoV-2 is a stronger predictor of cognitive impairment than the severity of the initial COVID-19 illness, according to a study from Argentina presented at the Alzheimer's Association International Conference.

The prospective, cohort study involved 865 participants, all over the age of 59, whose SARS-CoV-2 test results were maintained in a health registry. Three to six months after infection, the investigators conducted clinical testing on 88.4 percent of infected participants and 11.6 percent of controls who tested negative for the virus, all of whom had been randomly selected. 

The researchers found that two-thirds of participants who had tested positively for SARS-CoV-2 had functional memory impairments. None of the controls has anosmia.

Assessments included an interview with the Schedules for Clinical Assessment in Neuropsychiatry and the Clinical Dementia Rating scale.  A neurocognitive assessment, an emotional reactivity test, and measures of motor function, coordination, and gait were also taken. Anosmia was assessed with a semiquantitative olfactory function test.

“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," said Gabriela Gonzalez-Aleman, LCP, PhD, professor of neuroscience, neuropsychology and biostatistics in the department of psychology at Pontificia Universidad Catolica Argentina in Buenos Aires, who presented the results.

“We used an olfactory function test that evaluated the capacity to correctly identify three different odors," Dr. Gonzalez-Aleman explained. “People who have no olfactory dysfunction can identify them immediately and the test allows [us] to identify mild, moderate, and severe loss of smell." 

Defining impairment as two standard deviations below normal, they found that 545 of the 865 of the cohort (63 percent) had an abnormal cognitive performance, including 234 who tested abnormally on a single cognitive dimension, 181 who demonstrated a decline in both memory and language, and 130 who had a severe cognitive impairment affecting memory, executive functioning and attention.

The cognitive decline “was strongly associated with anosmia, and the severity of the cognitive impairment was linearly predicted by the diagnosis of COVID, age, and anosmia, explaining 22 percent of the variation in the data but not the severity of COVID," Dr. Gonzalez-Aleman told Neurology Today At the Meetings.

Dr. Gonzalez-Aleman said the research suggests that “anosmia represents an early entry point of the infection to the brain through the olfactory bulb; or at least the presence of the virus in the olfactory bulb (even if ever so transiently) triggers a disease process that continues after the resolution of the acute symptoms of the infection."

“If this interpretation is right," she continued, “cognitive performance does not depend on the improvement of smell itself but depends on the underlying processes in the brain."

The researchers are working with the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 Infection.

Avindra Nath, MD, FAAN, clinical director and senior investigator in the section of infections of the nervous system at the National Institute of Neurological Disorders and Stroke, said he found it difficult to interpret the results.

“They say that none of the controls had olfactory dysfunction; that is hard to believe," Dr. Nath said. “Smell testing is very complicated. You have to do a bedside test with a number of different smells and then grade them to determine the degree of loss. Many people have olfactory dysfunction and may not know it. Further, we do not know what the participants' cognitive or olfactory function was prior to developing COVID-19. Hence, there might be limitations to the study, which make it hard to interpret."

The study was funded by the Fundación de Lucha contra los Trastornos Neurológicos y Psiquiátricos en Minorías (FULTRA) and by the Alzheimer's Association.

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AAIC Abstract 66868: Gonzalez-Aleman G, Zamponi HP, Juarez-Aguaysol L, et al. Olfactory dysfunction but not COVID-19 severity predicts severity of cognitive sequelae following SARS-CoV-2 infection in Amerindian older adults