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Cognitive impairment was correlated with persistent anosmia in older adults recovering from SARS-CoV-2 infection, initial findings from a showed.

Severity of cognitive impairment was significantly correlated with severity of olfactory dysfunction (χ²=13.82, P=0.003) but not with the severity of acute COVID-19, Gabriel de Erausquin, MD, PhD, MSc, of the University of Texas Health Science Center at San Antonio, reported at the 2021 Alzheimer's Association International Conference (AAIC), held virtually and in Denver.

In other research presented at AAIC, biological markers of brain injury, neuroinflammation, and Alzheimer's disease correlated strongly with the presence of neurological symptoms in COVID-19 patients, reported Thomas Wisniewski, MD, of New York University Grossman School of Medicine.

In addition, people experiencing cognitive decline after SARS-CoV-2 infection were more likely to have low oxygen saturation after brief physical exertion, as well as poor overall physical condition, according to George Vavougios, MD, PhD, of the University of Thessaly in Greece.

"We don't know anything about the course of illness with COVID-19," de Erausquin told 麻豆传媒.

"It may progress as a dementia, stay stable over time, or even improve," he said. "The studies are intended to answer this question."

In their study, de Erausquin and co-researchers evaluated olfactory dysfunction and chronic cognitive impairment after SARS-CoV-2 infection in 233 older adults from the Andes mountains of Argentina, comparing them with 64 matched controls with no history of COVID. Participants were studied between 3 and 6 months after SARS-CoV-2 infection. Mean participant age was 67 and mean education was 9.35 years of formal learning.

More than half of people showed persistent, severe problems with forgetfulness. Roughly a quarter had additional problems with cognition, including language and executive dysfunction. The only predictor of cognitive impairment was anosmia that persisted for at least 3 to 6 months, de Erausquin said.

"In this study, we are looking at just one age group, people over 60," he pointed out. "So far, we have not looked at biomarkers of brain inflammation or injury, though we have the plasma samples to do it. We are looking at one specific ethnic group, Amerindians. We don't have imaging data, and we don't have longitudinal data yet, though we will be following up with the same people in 1 year."

"We're starting to see clear connections between COVID-19 and problems with cognition months after infection," de Erausquin noted. "It's imperative we continue to study this population, and others around the world, for a longer period of time to further understand the long-term neurological impacts of COVID-19."

Uptick in Alzheimer's Biomarkers

Wisniewski and colleagues evaluated plasma biomarkers total tau (t-tau), neurofilament light (NfL), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and species of amyloid beta (Aβ40, Aβ42) and phosphorylated tau (ptau-181) -- indicators of injury in the brain, neuroinflammation, and Alzheimer's disease -- in COVID-19 patients.

The researchers assessed plasma samples from 310 patients admitted to New York University Langone Health. All were positive for SARS-CoV-2: 158 people had neurological symptoms and 152 did not. People with new neurologic symptoms were older (median age 71 versus 63).

The most common neurological symptom was confusion due to toxic-metabolic encephalopathy (TME), which accounted for 51% of new neurologic diagnoses.

Among people who initially were cognitively normal, the researchers found higher levels of t-tau, NfL, GFAP, ptau-181, and UCH-L1 in COVID-19 patients with TME compared to COVID-19 patients without TME. There were no significant differences in Aβ1-40, but the ptau/Aβ42 ratio showed significant differences in patients with TME.

Tau, NfL, UCH-L1, and GFAP also significantly correlated with inflammation markers, including C-reactive peptide. This may suggest inflammation-related blood-brain barrier disruption accompanying neuronal or glial injury, Wisniewski noted.

"These findings indicate that patients who had COVID-19 may have an acceleration of Alzheimer's-related symptoms and pathology, but that clearly needs longer follow-up," he said.

Post-COVID Cognitive Decline and Health

In the study from Vavougios's group, which also was part of the global SARS-CoV-2 consortium, researchers studied cognitive impairment and health measures in 32 previously hospitalized mild to moderate COVID-19 patients 2 months after discharge. Participants had a mean age of 62 and no history of neurodegenerative disease or stroke before SARS-CoV-2 infection.

More than half (56.2%) of participants presented with cognitive decline, as indicated by a under 24. Predominant patterns of cognitive impairment were short-term memory impairments or multi-domain impairment without short-term memory deficits.

Worse cognitive test scores correlated with higher age, waist circumference, and waist-to-hip ratio. Worse memory and thinking scores were independently associated with lower oxygen saturation levels during a 6-minute walk test, after adjusting for age and sex.

"A brain deprived of oxygen is not healthy, and persistent deprivation may very well contribute to cognitive difficulties," Vavougios observed. "These data suggest some common biological mechanisms between COVID-19's dyscognitive spectrum and post-COVID-19 fatigue that have been anecdotally reported over the last several months."

"These new data point to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimer's symptoms," noted Heather Snyder, PhD, the Alzheimer's Association vice president of medical and scientific relations.

"We're only starting to put together pieces of this very important puzzle," Snyder told 麻豆传媒. "With more time, and more longitudinal data, we will have a better understanding of how COVID-19 impacts the brain, including risk for dementia. Studies are underway in populations around the world, including the United States."