Much has been learned about SARS-CoV-2, the virus that causes the novel
coronavirus, since the beginning of the COVID-19 pandemic. However,
questions remain about the long-term impact of the virus on our bodies and
brains. New research reported at the Alzheimer’s Association International
Conference® (AAIC®) 2021, held virtually and in Denver found associations
between COVID-19 and persistent cognitive deficits, including the
acceleration of Alzheimer’s disease pathology and symptoms.
In addition to the respiratory and gastrointestinal symptoms that accompany
COVID-19, many people with the virus experience short- and/or long-term
neuropsychiatric symptoms, including loss of smell and taste, and cognitive
and attention deficits, known as “brain fog.” For some, these neurological
symptoms persist, and researchers are working to understand the mechanisms
by which this brain dysfunction occurs, and what that means for cognitive
health long term.
Scientific leaders, including the Alzheimer’s Association and
representatives from nearly 40 countries — with technical guidance from the
World Health Organization (WHO) — are part of an international,
multidisciplinary consortium to collect and evaluate the long-term
consequences of COVID-19 on the central nervous system, as well as the
differences across countries. Initial findings from this consortium
presented at AAIC 2021 from Greece and Argentina suggest older adults
frequently suffer persistent cognitive impairment, including persistent lack
of smell, after recovery from SARS-CoV-2 infection.
Other key results reported at AAIC 2021 include:
- Biological markers of brain injury, neuroinflammation and Alzheimer’s correlate strongly with the presence of neurological symptoms in COVID-19 patients.
- Individuals experiencing cognitive decline post-COVID-19 infection were more likely to have low blood oxygen following brief physical exertion as well as poor overall physical condition.
Cognitive Impairment Correlates with Persistent Loss of Smell in Recovered COVID-19 Patients
Gabriel de Erausquin, M.D., Ph.D., M.Sc., of the University of Texas Health
Science Center at San Antonio Long School of Medicine, along with colleagues
from the Alzheimer’s Association-led global SARS-CoV-2 consortium, studied
cognition and olfactory senses in a cohort of nearly 300 older adult
Amerindians from Argentina who had COVID-19.
Participants were studied between three and six months after COVID-19
infection. More than half showed persistent problems with forgetfulness, and
roughly one in four had additional problems with cognition including
language and executive dysfunction. These difficulties were associated with
persistent problems in smell function, but not with the severity of the
original COVID-19 disease.
“We’re starting to see clear connections between COVID-19 and problems with
cognition months after infection,” Erausquin said. “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.”
COVID-19 Infection Associated with Uptick in Alzheimer’s Biomarkers in the Blood
Certain biological markers in blood — including 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) — are indicators of injury in the
brain, neuroinflammation and Alzheimer’s disease.
To study the presence of these blood biomarkers, neurodegeneration and
neuroinflammation in older patients who were hospitalized with COVID-19,
Thomas Wisniewski, M.D., a professor of neurology, pathology and psychiatry
at New York University Grossman School of Medicine, and colleagues took
plasma samples from 310 patients who were admitted to New York University
Langone Health with COVID-19. Of the patients, 158 were positive for
SARS-CoV-2 with neurological symptoms and 152 were positive for SARS-CoV-2
without neurologic symptoms. The most common neurological symptom was
confusion due to toxic-metabolic encephalopathy (TME).
In patients who were initially cognitively normal with and without TME
related to COVID-19 infection, 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 with
Aβ1-40, but the pTau/Aβ42 ratio showed significant differences in patients
with TME. Additionally, t-tau, NfL, UCH-L1 and GFAP significantly correlated
with markers of inflammation such as C-reactive peptide, which may suggest
inflammation-related blood-brain barrier disruption accompanying
neuronal/glial injury.
“These findings suggest that patients who had COVID-19 may have an
acceleration of Alzheimer’s-related symptoms and pathology,” Wisniewski
said. “However, more longitudinal research is needed to study how these
biomarkers impact cognition in individuals who had COVID-19 in the long
term.”
Individuals Recovered from COVID-19 Who Experience Cognitive Decline More Likely to Have Poor Physical Condition, Low Oxygen Saturation
George Vavougios, M.D., Ph.D., postdoctoral researcher for the University of
Thessaly (UTH), and colleagues studied cognitive impairment and related
health measures in 32 previously hospitalized mild to moderate COVID-19
patients two months after discharge from the hospital. Among them, 56.2%
presented with cognitive decline. Short-term memory impairments and
multidomain impairment without short-term memory deficits were the
predominant patterns of cognitive impairment.
Worse cognitive test scores correlated with higher age, waist circumference
and waist-to-hip ratio. After adjusting for age and sex, worse memory and
thinking scores were independently associated with lower levels of oxygen
saturation during the 6-minute walk test, which is commonly used to assess
the functional capacity of people with cardiopulmonary disease.
“A brain deprived of oxygen is not healthy, and persistent deprivation may
very well contribute to cognitive difficulties,” Vavougios said. “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.”
This cohort is also part of the global SARS-CoV-2 consortium.