Will COVID-19 cause dementia?

Will COVID-19 cause dementia?  In patients with new coronavirus disease, delirium (delirium, an acute and temporary brain dysfunction caused by multiple reasons, is manifested as sudden confusion, inattention, sleep disturbance, and perceptual disturbance, which can affect people, places, Time produces wrong perceptions, and even self-perception disorders) are common. Researchers are exploring whether these temporary insanities can lead to permanent cognitive decline.

Sondra Crosby is a doctor at Boston Medical Center in Massachusetts. She has treated the first COVID-19 patients in the area. Therefore, when she started to feel unwell in April and learned that she was also infected, she was not surprised. At first, her symptoms felt like a bad cold, but by the next day, she was too sick to get out of bed. Crosby struggled to get up to eat, and her husband helped her deliver sports drinks and antipyretics. Then she completely lost the concept of time.

For 5 days, Crosby’s mind was a mess, and he couldn’t remember even the simplest things, such as how to open the phone or what the home address was. She began to hallucinate, seeing lizards on the wall, and smelling a disgusting reptile smell. It was not until later that Crosby realized that she had delirium, a formal medical term to describe her state of insanity.

Crosby stated that she didn’t really treat delirium until later she woke up on her own. Crosby didn’t expect at the time that besides being sick and dehydrated, he had delirium.
Doctors treating COVID-19 hospitalized patients report that a large number of patients have delirium, and the disease has a greater impact in the elderly. A study conducted in Strasbourg, France in April 2020 found that 65% of severely ill patients with new coronavirus disease developed severe confusion, one of the symptoms of delirium.

At the annual meeting of the American College of Chest Physicians last month, scientists from Vanderbilt University Medical Center reported that they tracked critical care Of the 2000 severely ill COVID-19 patients in the laboratory, 55% suffered from delirium. These numbers are much higher than doctors’ previous data: According to a 2015 meta-analysis (Figure “How common is delirium in patients with new coronavirus disease?”), usually, about one-third of critically ill patients will develop delirium.

Delirium is very common in patients with Covid-19, and some researchers have proposed this disease as one of the diagnostic criteria for Covid-19 infection. Sharon Inouye, an expert in geriatrics at the Marcus Institute for Aging and Harvard Medical School in Boston, points out that the pandemic has aroused doctors’ interest in delirium.

When clinicians face the reality of a large number of patients with insanity, Inouye and other researchers are more worried about the future. In the past ten years, long-term studies have shown that an episode of delirium increases the risk of dementia years later and accelerates the decline in cognitive abilities of those who already have the disease. The reverse is also true: dementia makes people more prone to insanity. A simple set of steps, such as ensuring that family members are present to help patients adjust themselves, can reduce the incidence of delirium by 40%, but it is difficult for doctors to follow this advice in the COVID-19 ward.

However, the link between delirium and dementia has been difficult to sort out: Researchers need to follow patients for years to get results. The proliferation of patients with delirium caused by the pandemic has focused attention on the disease and provided scientists with a unique opportunity to follow patients to determine if and how delirium may affect long-term cognition. Researchers have conducted multiple studies to explore the long-term effects of COVID-19 on neurocognition, including dementia. Inouye and others hope that this work will enable researchers to explore the connection between the two diseases in real time.

Inouye said that if the COVID-19n pandemic is beneficial, it is that it has stimulated people’s interest in how delirium causes dementia and how dementia induces delirium. In addition, Catherine Price, a neuropsychologist at the University of Florida in Gainesville, said that the spread of COVID-19 “highlights the fact that the line between delirium and dementia is very blurred, especially in the face of aging The more serious the situation”.

Neglected disease

In 1985, Inouye found her first job as a physician at the Veterans Administration hospital in Connecticut, and she developed an interest in delirium. In the first month there, she treated more than 40 patients with different diseases. Six of them developed delirium during their hospitalization, and none of them seemed to return to their previous physical and mental health. For Inouye, the link between the patient’s delirium and poor prognosis is obvious. However, when she talked to the boss about this topic, they just shrugged, disapproving. Inouye believes that they feel that delirium is just one of the complications of other diseases.
Inouye wondered, why is it acceptable for the elderly to come to the hospital and become unconscious? Answering this question will be a tough battle for Inouye’s entire career.

Soon after, she began a two-year in-depth study. Her research shows that delirium can occur when several types of stress are concentrated. Pre-existing diseases, such as chronic diseases or cognitive impairment, can be combined with precipitating factors such as surgery, anesthesia, or severe infections, leading to sudden confusion, confusion, and difficulty concentrating, especially in the elderly.
According to neurologist Tino Emanuele Poloni of the Golgi Cenci Foundation in Italy, delirium is prone to occur when the brain is unable to compensate for stressful situations. Researchers believe that the underlying biological cause is an imbalance of inflammation and neurotransmitters (chemical messengers such as dopamine and acetylcholine).

Inouye’s accumulated clinical experience tells her that no matter what causes delirium, about 70% of people with symptoms will eventually recover completely. However, the other 30% are unable to recover. Once they have a mental disorder, their cognition will decline in a spiral after a few months, leading to severe cognitive impairment and even symptoms of dementia.

More formal research has strengthened this connection to varying degrees. Inouye surveyed 560 people over 70 who had undergone surgery and found that in the following 36 months, the cognitive decline of patients with delirium was three times faster than that of patients without delirium.

A meta-analysis of 23 studies in 2020 showed that if delirium occurred during hospitalization, the chance of developing dementia was 2.3 times higher than that of the control group (delirium did not occur during hospitalization). A team of scientists in Brazil found that of 309 patients with an average age of 78 years, 32% of patients who developed delirium in the hospital subsequently developed dementia. In contrast, only 16% of people do not develop delirium.

In addition, a 2013 study conducted by Vanderbilt University psychologist James Jackson and others showed that the longer a person’s delirium lasts, the greater the risk of subsequent cognitive impairment. Studies by Inouye, Jackson, and other researchers found that the reverse is true: even after controlling for age, existing symptoms of dementia can increase the risk of delirium.

For patients with delirium (a common symptom of COVID-19), visiting relatives is a comfort.
However, for the sake of controlling the epidemic, many hospitals have strict prohibition policies.

A mess

The link between delirium and dementia only exists in people who will develop dementia anyway? Or even in people who are not prone to dementia, delirium increases the risk of cognitive decline? Scientists have yet to reach a consensus on these issues. They also cannot determine the mechanism by which delirium causes dementia. If researchers can identify these connections, then they may be able to prevent delirium from escalating into dementia.

Price stated that they don’t understand the mechanism of delirium at all-they really don’t. And from a pharmaceutical point of view, there is no successful treatment for delirium.

Scientists have proposed three hypotheses to explain how delirium causes dementia. One view is that the accumulation of toxic cell waste in the brain may cause short-term delirium and cause long-term damage.
The human body usually clears these molecular wastes through the blood and lymphoid system, which is a network of channels filled with cerebrospinal fluid. Acute delirium attacks may continue to damage blood vessels and cause dementia, or brains that have experienced delirium may be more prone to vascular problems in the future.

The second possible mechanism is inflammation. Inflammation often occurs in people hospitalized for infection, respiratory distress, or cardiovascular disease. Surgery and severe infections can cause cell debris to accumulate in the brain, which can trigger more inflammation. This short-term, multi-factorial response protects the brain because it removes harmful debris and inflammation will eventually disappear.

Inouye pointed out that this is not the case for those who develop delirium. Persistent inflammation can trigger the onset of acute delirium and cause damage to neurons and related cells, such as astrocytes and microglia, leading to cognitive impairment.

The third point is the so-called threshold hypothesis. People with dementia (even in the early stages) have fewer connections between neurons, which is manifested as damage to the insulating layer that wraps neurons and helps transmit signals—the white matter as we know it. This loss will reduce the ability of patients to resist inflammation or infection, so that they not only fall into delirium, but also easily develop into a more serious state of dementia.

Although the origin of delirium and its molecular connection with dementia is still unclear, Inouye has managed to find a way to reduce the incidence of delirium during hospitalization. She created a simple strategic project called HELP (Hospital Elder Life Programme), which focused on reducing the use of tranquilizers (even during mechanical ventilation), paying close attention to nutrition and hydration, and ensuring the presence of family members. To help comfort and guide the patient.

A 2015 meta-analysis showed that these steps can reduce delirium symptoms by about 40%. Hospitals across the United States began to develop these simple plans. However, with the outbreak of COVID-19, it has become increasingly impossible to adopt these strategies.

The incidence of dementia soars

While Crosby was suffering from delirium caused by the new coronavirus in his bedroom, Poloni was treating delirium patients with COVID-19 in Lombardy, where the Italian coronavirus originated. Many of Poloni’s patients already suffer from dementia. Like many doctors, he has been observing the common symptoms of respiratory infections, such as fever, cough, and difficulty breathing.

But some of his patients do not have these symptoms at all. Poloni pointed out that instead, most of them became “dull and sleepy”, while others became restless-these are signs of delirium. Delirium in patients with COVID-19 is so common that Poloni believes that delirium should be added to the diagnostic criteria for COVID-19.

Inouye has also put forward this view, and a study she published last month also supports this view. The study showed that 28% of elderly patients with COVID-19 were diagnosed with delirium when they went to the emergency room.

Inouye, Price, and others worry that in the context of an increasingly aging population, the COVID-19 epidemic will cause a surge in the number of dementia patients in the next few decades. Natalie Tronson, a neuropsychologist at the University of Michigan in Ann Arbor, wants to know whether the risk of dementia in people infected with COVID-19 in adult or middle age will increase? What will happen next year?”

To find out, research institutions around the world have funded a series of studies on the long-term cognitive effects of COVID-19, some of which will focus on delirium. The United States is conducting a study to track people treated in hospitals due to COVID-19, many of whom developed delirium during hospitalization.

This study will evaluate the safety and effectiveness of hydroxychloroquine in the treatment of coronavirus, and evaluate the cognitive and mental function of people participating in the trial. At the same time, the United States also plans to conduct an international study to measure the prevalence of delirium among COVID-19 patients in the intensive care unit and determine the factors that predict long-term outcomes. Another study in Germany and the United Kingdom is also tracking the neurocognitive results of COVID-19 patients to determine how delirium affects brain function a few months later.

Another research project led by a team at Vanderbilt University was to find alternatives to commonly used sedatives such as benzodiazepines. It is well known that benzodiazepines can increase the probability of delirium. Researchers are testing a sedative called dexmedetomidine to see if it is a safer option for patients hospitalized with COVID-19.

Inouye and Tronson hope that funding for these long-term studies will trigger a sustained interest in the scientific community in studying the link between delirium and dementia and gain some insights.

Tronson believes that studying how delirium affects dementia risk and how other lifestyle and genetic protection factors affect dementia risk is both worrying and hopeful. Although they are learning quickly, there are still many black boxes.

(source:internet, reference only)

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