According to a new study, patients admitted to hospital with COVID19 had higher short-term blood protein levels known to increase with neurological damage than non-COVID19 patients diagnosed with Alzheimer disease.
Importantly, the current report, published online today (January 13, 2022) in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, was conducted over a 2 month early in pandemic (March-May 2020). Determining whether patients with COVID19 are at an increased risk of future Alzheimer disease or whether they will recover over time, must await the results of long-term studies.
Led by researchers at NYU Grossman School of Medicine, the new study found higher levels of seven markers of brain damage (neurodegeneration) in COVID19 patients with neurological symptoms than in those without, and much higher levels in patients who died in hospital than those discharged.
A second analysis revealed that a subset of damage markers in hospitalized patients with COVID19, in the short term, was significantly higher than patients diagnosed with Alzheimer disease and in a more double case.
“Our results suggest that patients admitted to hospital with COVID19, and particularly those with neurological symptoms during their acute infection, may have levels of brain injury markers equal to or greater than those seen in patients with of Alzheimer’s disease,” says lead author Jennifer A. Frontera, MD, professor in the Department of Neurology at NYU Langone Health.
The current study identified 251 patients who, despite having an average age of 71, had no history or symptoms of cognitive decline or dementia before being hospitalized for COVID19. These patients were then divided into groups with and without neurological symptoms during their acute infection with COVID19, when the patients recovered & were discharged or died.
The research team also compared marker levels in the COVID19 group to patients in the NYU Alzheimer’s Disease Research Center Clinical Core cohort, an ongoing Long Term study at NYU Langone Health, when possible. None of these 161 control patients (54 normal, 54 with mild cognitive impairment & 53 diagnosed with Alzheimer disease) had COVID19. The brain injury was measured using single molecule array technology, which can track minute blood levels of neurodegeneration markers in picograms per milliliter of blood (pg / ml) where older technologies couldn’t.
3 of the study’s markers (ubiquitin carboxy-terminal hydrolase L1 (UCHL1), total tau, ptau181) are known measures of death or inactivation of neurons, the cells that enable nerve pathways to transmit messages. Neurofilament light chain (NFL) levels increase with damage to axons, extensions of neurons. Glial fibrillary acidic protein (GFAP) is a measure of damage to glial cells that support neurons. Amyloid beta 40 & 42 are proteins known to accumulate in patients with Alzheimer disease. Results from previous studies argue that total tau & phosphorylated tau-181 (ptau) are also specific measures of Alzheimer’s disease, but their role in the disease remains controversial.
Blood markers in the group of Covid patients were measured in blood serum (the liquid portion of the blood which has been made to clot), while those in the Alzheimer’s study were measured in the plasma (the liquid blood fraction that remains when clotting is prevented). For technical reasons, the difference meant that levels of NFL, GFAP & UCHL1 could be compared between the COVID19 group & patients in the Alzheimer’s disease study, but total tau, ptau181, amyloid- beta 40 & amyloid-beta 42 could only be compared within the COVID19 patient group.
In addition, the main measure of neurological damage in COVID19 patients was a toxic metabolic encephalopathy, or TME, with symptoms of confusion to coma & caused during severe infections by toxins generated when the immune system overreacts (sepsis), the kidneys fail (uremia) & the oxygen supply is compromised (hypoxia). Specifically, the average percentage increase in levels of the 7 markers for hospitalized patients with TME compared to those without neurological symptoms (Figure 2 in the study) was 60.5%. For the same markers within the COVID19 group, the average percentage increase when comparing those who managed to return home from hospital to those who died in hospital was 124%.
A secondary set of results came from comparing the levels of NFL, GFAP & UCHL1 in the serum of COVID19 patients with the levels of the same markers in the plasma of non-COVID Alzheimer’s disease patients (Figure 3). The NFL was 179% higher in the short term (73.2 versus 26.2 pg/ml) in patients with COVID19 compared to patients with Alzheimer’s. GFAP was 65% higher (443.5 vs 275.1 pg/mL) in COVID19 patients than in Alzheimer’s patients, while UCHL1 was 13% higher (43 vs 38.1 pg/mL).
“Traumatic brain injury, which is also associated with the increase in these biomarkers, does not mean that a patient will later develop Alzheimer’s disease or related dementia, but it increases their risk,” says the lead author. Thomas M. Wisniewski, Gerald J. and Dorothy R. Friedman Professor in the Department of Neurology and Director of the Center for Cognitive Neurology at NYU Langone. “The question of whether this type of relationship exists in those who survive severe COVID19 is a question that we urgently need to answer with continued monitoring of these patients.