Studies highlight potential link between COVID-19 and cognitive impairment

Several studies presented at AAIC 2021 have suggested a possible link between COVID-19 and cognitive impairment.

In the first study, 32 patients (mean age 61.6 years) who had previously been hospitalized for mild-to-moderate COVID-19 were followed up 2 months after hospital discharge. Patients who had been admitted to the intensive care unit or who had undergone intubation, and those with a history of neurodegenerative disease or stroke before COVID-19 diagnosis were excluded.

Cognitive impairment, identified by Montreal Cognitive Assessment score ≤24, occurred in 56.2 percent of patients. The most common patterns of cognitive impairment were short-term memory impairments and multidomain impairment without short-term memory deficits.

Factors associated with a higher risk of cognitive impairment were older age (ρ=-0.513; p=0.003), and greater waist circumference (ρ=-0.388; p=0.028) and waist-to-hip ratio (ρ=-0.361; p=0.042). [AAIC 2021, abstract 57752]

After adjusting for age and sex, a lower level of oxygen saturation (SpO₂) at the 6th minute of the 6-minute walk test (6MWT) was associated with worse cognitive impairment (β=0.579; p=0.001).

“A brain deprived of oxygen is not healthy, and persistent deprivation may very well contribute to cognitive difficulties,” said study author Dr George Vavougios from the University of Thessaly, Volos, Greece.

“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,” he added, highlighting that these findings warrant further investigation.

Elevated levels of neuroinflammation biomarkers

In another study, this time conducted in New York, US, the presence of several serum biomarkers of neuroinflammation was associated with neurogenerative symptoms in patients with COVID-19.

The results were based on analysis of plasma samples from 310 patients aged >60 years hospitalized for COVID-19 within the New York University Langone Health system, of whom 158 and 152 patients did and did not have neurological symptoms, respectively. The most common neurological symptom was confusion due to toxic-metabolic encephalopathy (TME).

Compared with COVID-19 patients without neurological symptoms, those with neurological symptoms had higher levels of neurofilament light (NfL; p=0.0003), glial fibrillary acid protein (GFAP; p=0.0098), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1; p=0.0138), total tau (t-tau; p=0.04), and pTau 181 (p=0.0141). [AAIC 2021, abstract 57892]

There were also significant differences between patients with and without neurological symptoms pertaining to Aβ1-42 levels (p=0.049) and pTau/Aβ42 ratio (p=0.0017), but not Aβ1-40 levels (p=0.33).

“Serum biomarkers of neuronal injury, neuroinflammation, and Alzheimer’s disease such as NfL, t-tau, UCH-L1, GFAP, and pTau-181 correlate strongly with the presence of neurological symptoms in COVID-19 patients,” said Professor Thomas Wisniewski from New York University Grossman School of Medicine, New York, US, and co-authors.

“These findings suggest that patients who had COVID-19 may have an acceleration of Alzheimer’s-related symptoms and pathology,” he continued. “However, more longitudinal research is needed to study how these biomarkers impact [long-term] cognition in individuals who had COVID-19.”

Symptoms persist long term

A separate study from Argentina found that persistent cognitive impairment may occur following recovery from COVID-19, with this impairment tied to persistent anosmia.

These findings were the result of preliminary analysis of The Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2). Participants were 300 individuals aged ≥60 years from the Province of Jujuy, Argentina, who were followed up 3–6 months after clinical recovery from COVID-19 infection (233 infected and 64 controls; mean age 66.7 years). Of these, 44.6 percent had normal cognition, 21 percent memory-only impairment, and 34.4 percent multiple domain impairment (MDI).

Patients with MDI demonstrated severe alterations in short-term memory, semantic memory, naming, executive function, and attention compared with those with memory-only impairment or those with normal cognition. There was a significant association between the severity of cognitive impairment and the severity of olfactory dysfunction (χ² = 13.82; p=0.003), but not with the severity of acute COVID-19. [AAIC 2021, abstract 57897]

“Risk factors for COVID-19 sequelae [such as older age and ApoE4 status] overlap with those for Alzheimer’s disease,” said Dr Gabriel de Erausquin from the University of Texas Health Science Center at San Antonio Long School of Medicine, San Antonio, Texas, US.

“We’re starting to see clear connections between COVID-19 and problems with cognition months after infection,” he continued. “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.”