- Researchers are learning more about how COVID-19 may impact memory.
- In one study, 1 in 10 patients have been reporting memory problems after mild cases of COVID-19 that did not require hospitalization, even 8 months after disease.
- People who have recovered from COVID-19 but presented with cognitive decline are more likely to be in poorer physical health and have low O2 saturation in their blood.
- COVID-19 may heighten the risk of developing Alzheimer’s, and COVID-19 can cause an increase in blood-based molecular biomarkers for Alzheimer’s disease.
COVID-19’s immediate physical effects have been vastly studied, but much remains a mystery regarding long-term complications.
In particular, scientists are scrambling to understand the disease’s long-term effects on neuropsychological health.
Neurological signs of COVID-19, both short and long term, may include symptoms such as the loss of smell and taste and cognitive and attention deficits, known as “brain fog.”
And now, new research shows how COVID-19 continues to affect the brain long after recovery and how some symptoms may be precursors to more serious health problems in the future.
Here is a roundup of the latest studies and newest research presented at the Alzheimer’s Association International Conference (AAIC) on COVID-19 and its neurocognitive effects.
As part of a Norwegian study published in the JAMA Network OpenTrusted Source, scientists reached out to more than 53,000 participants between Feb. 1 and April 15, 2020. These adults included those who tested positive for SARS-CoV-2, those who tested negative, and a sizeable number of untested individuals to represent the general population.
Over 13,000 participants responded to the questionnaire sent out by Arne Søraas, PhD, from Oslo University Hospital in Norway, and his colleagues and around 9,000 followed up.
The mean age of participants was 47, and 66 percent of the participants were women.
Søraas and his team found that more than 1 in 10 patients reported memory loss 8 months after testing positive.
At least 41 percent of those who reported having memory problems months after infection said their overall health had also worsened over the past year.
Of those who tested positive 8 months after infection, approximately 11 percent reported memory loss, and 12 percent had problems concentrating.
Those who tested positive were twice as likely to report cognitive problems.
They also reported more memory problems than those who tested negative or the untested population.
In addition, more than 50 percent of patients experienced persistent fatigue, with 20 percent saying this limited their work and general life activities.
The symptoms reported relatively equally by the three groups were feeling depressed, having less energy, or having pain.
“Self-reported memory problems are also a risk factor for later mild cognitive impairment or dementia,” they said.
Although the self-reported nature of memory problems may not present a 100 percent accurate picture, past studies have listed them as a risk factor for developing dementia or mild cognitive impairment later in life.
The findings, according to the authors, suggest that SARS-CoV-2 may negatively impact memory even 8 months after having a mild case of the disease, and this can be associated with a worsening of health and Post-Acute Sequelae of SARS-CoV-2 infection (PASC), the medical term coined for long COVID in expert circles.
Meanwhile, new research reported at the virtual Alzheimer’s Association International Conference (AAIC) 2021 in Denver found links between COVID-19 and persistent cognitive deficits.
One of the most significant initial findings presented at AAIC 2021 was from a Greece and Argentina consortium, which suggested that:
- Older adults frequently experience lasting cognitive impairment, including persistent lack of smell, after recovering from COVID-19.
The other key findings were:
- COVID-19 patients presenting with neurological symptoms are likely to have biological markers in their blood that indicate brain injury, neuroinflammation, and Alzheimer’s.
- Individuals who experience cognitive decline after COVID-19 are more likely to have low blood oxygen levels after short periods of physical exertion as well as be in an overall poorer physical condition.
“These new data point to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimer’s symptoms,” Heather M. Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said in a statement.
“With more than 190 million cases and nearly 4 million deaths worldwide, COVID-19 has devastated the entire world. It is imperative that we continue to study what this virus is doing to our bodies and brains.”
– Heather M. Snyder, PhD, Alzheimer’s Association VP of medical and scientific relations
Link between cognitive impairment and loss of smell
Another study analyzed 300 older adult Amerindians from Argentina who had COVID-19, 3 and 6 months after initial infection.
Over half of the patients showed persistent problems with forgetfulness. At the same time, 1 in 4 had additional problems with cognition, including issues with language and executive dysfunction, such as difficulty organizing, misplacing items, and not being able to deal with frustration.
These setbacks, the research found, were associated with persistent problems in the 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,” said Dr. Gabriel de Erausquin of the University of Texas Health Science Center at San Antonio Long School of Medicine.
“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,” he said.
COVID-19 and Alzheimer’s risk
All of this research points to a potential for long COVID-19 to impact dementia risk.
In another study published this year, researchers studied patients to understand the risks of developing neurological symptoms after having COVID-19.
After analyzing plasma samples from 310 COVID-19 patients admitted to New York University Langone Health, scientists classified them into two categories: those with and those without neurological symptoms.
Out of these, 158 patients tested positive with neurological symptoms, and 152 tested positive without neurological symptoms.
The most common neurological symptom they observed was confusion due to toxic-metabolic encephalopathy (TME). TME occurs when the electrolytes, hormones, or other body chemicals are off-balance, impacting the brain’s function. It is found after more severe or critical cases of COVID-19.
As part of the study, researchers checked for changes in levels of biological markers of proteins, including tau, and others that may indicate signs of inflammation or injury in the brain.
These involve proteins and other biomarkers, 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).
Researchers found that patients who experienced neurologic symptoms had elevated levels of certain biological markers. Likewise, people with TME had higher amounts of these markers than people without TME.
The study also suggested a significant correlation between levels of these biomarkers with other inflammation markers, including C-reactive peptide (CRP), a sign of inflammation in artery walls.
Researchers think this could indicate a blood-brain barrier disruption caused by COVID-19-related inflammation and possible damage to the brain.
“These findings suggest that patients who had COVID-19 may have an acceleration of Alzheimer’s-related symptoms and pathology,” said Dr. Thomas Wisniewski, a professor of neurology, pathology and psychiatry at New York University Grossman School of Medicine.
“However, more longitudinal research is needed to study how these biomarkers impact cognition in individuals who had COVID-19 in the long term,” he said.
Wisniewski and his team declined to comment further until the data is published in a peer-reviewed journal.
Commenting on the research, Dr. John Raimo, chair of medicine at Long Island Jewish Forest Hills in Queens, New York, said the findings of higher levels of proteins previously linked to Alzheimer’s disease in patients with COVID-19 and neurological symptoms compared with those without neurological symptoms were particularly interesting.
Nevertheless, he noted that though people have been investigating blood biomarkers to diagnose Alzheimer’s disease more easily, researchers are still trying to understand their relationship to Alzheimer’s disease risk.
“Although these biomarkers are being actively studied and have shown some encouraging results, their role in clinical practice is still being established. [T]he long-term impact of these blood biomarkers on cognition is not yet known and warrants further investigation,” he said.
Raimo also warned that such long-term neurological symptoms in COVID-19 recoverees “will stress our healthcare system further.”
“Although the full magnitude of the long-term effects is still to be determined, the pandemic has already had a tremendous impact on healthcare,” he said.
Recoverees with cognitive decline likely to be in worse overall health
Another study looked at 32 previously hospitalized patients with mild to moderate COVID-19 and followed up 2 months after discharge from the hospital.
Researchers found that about 56 percent of the patients presented with cognitive decline. The predominant patterns were short-term memory impairments and multidomain impairment (i.e., having at least one other domain of thinking impaired in addition to memory) without short-term memory deficits.
Researchers found that those who had lower cognitive test scores after recovering from COVID-19 also had a higher waist circumference and waist-to-hip ratio. These patients were also older.
The subjects then were made to take a 6-minute walk test. Those with lower oxygen saturation levels had worse memory and thinking scores, researchers found.
“A brain deprived of oxygen is not healthy, and persistent deprivation may very well contribute to cognitive difficulties,” said Dr. George Vavougios, a postdoctoral researcher for the University of Thessaly in 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 said.