Pondering a Potential Link Between COVID-19 and Alzheimer’s Disease

Research presented earlier this month discussed a possible link between COVID-19 and long-term cognitive deficits and how it may accelerate the pathology and symptoms of Alzheimer’s disease.

Research presented earlier this month at the Alzheimer’s Association International Conference (AAIC) 2021 discussed a possible link between COVID-19 and long-term cognitive deficits and how it may accelerate the pathology and symptoms of Alzheimer’s disease.

COVID-19 is associated with a broad range of symptoms, not just respiratory and gastrointestinal, but neuropsychiatric symptoms, both short-term and long-term. The neuropsychiatric symptoms include loss of smell and taste, and cognitive and attention deficits, some of which are dubbed “brain fog.” In some individuals, the neurological symptoms remain, and researchers are investigating why these symptoms occur and what the implications are for long-term cognitive health.

“It’s an important thing, really, for us to get a good understanding of our patients and something that people don’t always want to talk about,” said Dr. Christian Gausvik, a family medicine specialist focused on geriatrics.

A Norwegian study published in JAMA Network Open surveyed more than 13,000 people. They had a mean age of 47 and 66% were women. They found that more than one in 10 patients reported memory loss eight months after receiving a positive COVID-19 test, and about 41% reported memory problems several months after infection. They also reported their overall health had been worse.

About 11% of people who tested positive eight months after infection reported memory loss and 12% reported problems concentrating. And the study found that people who tested positive were twice as likely to have cognitive problems.

The researchers said, “Self-reported memory problems are also a risk factor for later mild cognitive impairment or dementia.”

A study from a Greek and Argentinian consortium found that older adults frequently reported lasting cognitive impairment that included persistent lack of smell. They also found that COVID-19 patients with neurological symptoms typically had biological markers in their blood linked to brain injury, neuroinflammation, and Alzheimer’s disease. They also had a higher probability of low blood oxygen levels after short bouts of physical exertion.

“These new data point to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimer’s symptoms,” said Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of Medical and Scientific Relations.

The biomarkers investigated included total tau (t-tau), neurofilament light (NfL), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (IUCH-L1), and certain species of amyloid beta (Abeta40, abeta42) and phosphorylated tau (pTau-181).

The biomarker studies were run by Thomas Wisniewski, M.D., a professor of neurology, pathology and psychiatry at New York University Grossman School of Medicine. Wisniewski and his colleagues collected plasma samples from 310 patients admitted to New York University Langone Health with COVID-19. Of those patients, 158 were positive for COVID-19 with neurological symptoms and 152 were positive without neurologic symptoms. The most common neurological symptom was confusion caused by toxic-metabolic encephalopathy (TME).

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

Gabriel de Erausquin, M.D., Ph.D., a professor of neurology at the University of Texas Health Science Center, who was involved in the Argentina research, noted that, “The severity of the initial disease does not predict who is going to get this. In fact, many of them had minimal symptoms—just a cold or loss of smell.”

He also pointed out that the cognitive symptoms they observed seemed to be separate from the “brain fog” seen with long-term symptoms of COVID-19.

“Brain fog in younger individuals has a different flavor, if you will,” Erausquin said. “They have more attentional problems, more concentration problems, and frequently have more anxiety and depression.”

The National Institutes of Health (NIH) has estimated that as many as 30% of COVID-19 patients suffer from some form of neurological or psychiatric symptoms. But what is even more concerning is that for many the cognitive issues continue for weeks and even months. And in many cases, the people complaining of the brain fog and cognitive issues were never hospitalized with severe disease.

“The expectation was that all these people in the ICU were going to have really long protracted recovery periods,” said Walter Koroshetz, M.D., director of the National Institute of Neurology Disorders and Stroke, part of the NIH, who is co-leading an NIH study on why some patients recover faster than others. “The big surprise was the people who never required hospitalization that are having persistent trouble.”

One of the puzzling aspects of this is there’s little evidence that SARS-CoV-2, the virus that causes COVID-19, infects the brain. There have not been extensive studies on this, but only a few studies have identified the virus in neurons and glia cells, but most researchers don’t find that the virus infects brain cells in large enough amounts to cause neurological damage. A Columbia University study of 40 COVID-19 deaths found no evidence of the virus’s RNA or proteins in brain cells.

The leading theories for why COVID-19 might affect cognition are the infection triggers inflammation in the brain, while a second theory is that the disease may restrict blood flow to the brain and cause oxygen deprivation. Autopsy results have shown evidence of brain tissue being damaged by hypoxia.

Snyder points out that the findings don’t necessarily mean that if you get COVID-19 you’re more likely to develop Alzheimer’s or other dementias. “We’re still trying to understand those association,” she said.

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