Could Covid-19 Increase The Risk Of Memory Loss?

September 17, 2020

Of all the terrifying ways the SARS-COV-2 virus affects the body, the effects of COVID-19 on the brain are one of the more insidious.

It is now clear that many COVID-19 patients exhibit neurological symptoms ranging from loss of smell, to delirium, to an increased risk of stroke. There are also longer-lasting effects on the brain, including myalgic encephalomyelitis/chronic fatigue syndrome and Guillain-Barré syndrome.

These effects may be caused by direct viral infection of brain tissue. However, there is growing evidence that additional indirect effects, either through viral infection of epithelial cells and the cardiovascular system, or through immune system and inflammatory triggers, contribute to the lasting neurological changes after COVID-19.

I am a neuroscientist who specializes in how memories are formed, the role of immune cells in the brain, and how memories are persistently destroyed following disease and immune activation. As I survey the emerging scientific literature, my question is: will there be a future wave of COVID-19-related cases of memory loss, cognitive decline, and dementia?

The immune system and the brain
Many of the symptoms we attribute to infections are actually due to the protective response of the immune system. A runny nose during a cold is not a direct result of the virus, but rather a result of the immune system’s response to the cold virus. This is also true when you are feeling unwell. General weakness, fatigue, fever and social withdrawal are caused by specific immune cells in the brain (called neuroimmune cells) and the activation of signals in the brain.

These brain and behavioral changes, while annoying to our daily lives, are highly adaptive and hugely beneficial. By resting, you can allow the immune response that needs energy to do its thing. Fever makes the body less susceptible to viruses and increases the efficiency of the immune system. Social withdrawal may help reduce the spread of the virus.

In addition to changing behavior and regulating physiological responses during illness, the specific immune system in the brain plays a number of other roles. It has recently become clear that neuroimmune cells located at the junctions (synapses) between brain cells, which provide energy and trace amounts of inflammatory signals, are essential for normal memory formation.

Unfortunately, this also provides a way in which diseases like COVID-19 can cause both acute neurological symptoms as well as long-term problems in the brain.

During disease and inflammation, specialized immune cells in the brain are activated, spewing out a flood of inflammatory signals and modifying the way they communicate with neurons. For one type of cell, the microglia, this means changing shape, retracting their slender arms and becoming thick, mobile cells that wrap up potential pathogens or pieces of cells in their path. But in doing so, they also disrupt and eat away at neuronal connections that are important for memory storage.

Another type of neuroimmune cell, called an astrocyte, typically wraps the connections between neurons during disease-induced activation and dumps inflammatory signals on those connections, effectively preventing changes in the connections between neurons that store memories.

Because COVID-19 involves a massive release of inflammatory signals, the impact of this disease on memory is of particular interest to me. This is because there are both short-term effects on cognition (delirium) and potentially long-term changes in memory, attention and cognition. The risk of cognitive decline and dementia, including Alzheimer’s disease, also increases during the aging process.

How does inflammation have long-term effects on memory?
If the activation of neuroimmune cells is limited to the duration of the disease, how can inflammation cause lasting memory loss or increase the risk of cognitive decline?

Both the brain and the immune system have evolved specifically to change with experience to neutralize danger and maximize survival. In the brain, changes in connections between neurons allow us to store memories and quickly change behavior to escape threats or seek food or social opportunities. The immune system has evolved to fine-tune the inflammatory response and the production of antibodies to fight previously encountered pathogens.

However, long-term changes in the brain following disease are also strongly associated with age-related cognitive decline and increased risk of Alzheimer’s disease. The disruptive and destructive effects of neuroimmune cells and inflammatory signaling can permanently impair memory. This can occur through permanent damage to neuronal connections or to the neurons themselves, or through more subtle changes in neuronal function.

The potential link between COVID-19 and persistent effects on memory is based on observations of other disorders. For example, many patients recovering from heart attacks or bypass surgery report persistent cognitive deficits that become exaggerated during the aging process.

Another major disease with similar cognitive complications is sepsis-an inflammation-induced multi-organ dysfunction. In animal models of these diseases, we have also seen memory impairment and changes in neuroimmune and neuronal function that persist for weeks and months after the disease.

Even mild inflammation, including chronic stress, is now considered a risk factor for Alzheimer’s disease and cognitive decline.

In my own laboratory, my colleagues and I have also observed that triggering inflammatory signals in the short term, even in the absence of a bacterial or viral infection, can lead to long-term changes in neuronal function and memory-related impairment in brain regions associated with memory.

Does COVID-19 increase the risk of cognitive decline?
It will be many years before we know whether COVID-19 infection leads to cognitive decline or an increased risk of Alzheimer’s disease. But with prevention and treatment of COVID-19, this risk may be reduced or mitigated.

Both prevention and treatment rely on the ability to reduce the severity and duration of disease and inflammation. Interestingly, very new research suggests that common vaccines, including influenza and pneumonia vaccines, may reduce the risk of Alzheimer’s disease.

In addition, some of the emerging treatments for COVID-19 are drugs that suppress excessive immune activation and inflammatory states. Potentially, these treatments will also reduce the impact of inflammation on the brain and reduce the impact on long-term brain health.

COVID-19 will continue to impact health and well-being long after the end of the epidemic. Therefore, it will be critical to continue to assess the impact of COVID-19 disease on later cognitive decline and vulnerability to dementia.

In doing so, researchers will likely gain critical new insights into the role of inflammation in age-related cognitive decline across the lifespan. This will help to develop more effective strategies for the prevention and treatment of these debilitating diseases.