Conference Coverage

COVID-19 tied to acceleration of Alzheimer’s disease pathology


 

From AAIC 2021

Certain plasma biomarkers of neuronal damage and neuroinflammation are markedly elevated in hospitalized COVID-19 patients with neurologic symptoms compared with hospitalized COVID-19 patients without such symptoms, a new study shows.

These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.

The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.

Strong correlation

There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.

He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.

Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.

The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.

Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.

“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.

However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.

Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.

The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).

Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.

There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.

“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”

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