November 8, 2022 | A recent study revealed that people ages 65 and older who caught COVID-19 were more likely to develop Alzheimer’s disease shortly thereafter. The findings showed that the risk of developing Alzheimer’s almost doubled in this population of older adults over the one-year period following a COVID-19 diagnosis. According to the Case Western Reserve University researchers who conducted the research, it is not yet clear whether COVID-19 sparks the new development of Alzheimer’s disease or speeds along its emergence.
To arrive at their findings, the researchers analyzed data on over 6 million older adults in the United States who had medical encounters with healthcare organizations between February 2020 and May 2021—and no previous Alzheimer’s diagnosis. This population was divided into two groups, a cohort of over 400,000 people who contracted COVID-19 during that same timeframe and another cohort of roughly 5.8 million people with no documented COVID-19 diagnosis.
“The factors that play into the development of Alzheimer’s disease have been poorly understood, but two pieces considered important are prior infections, especially viral infections, and inflammation,” Pamela Davis, one of the study co-authors, said in a news release. Considering SARS-CoV2 infection has been tied to central nervous system issues such as inflammation, she and colleagues wanted to find out if COVID-19 might lead to a surge in Alzheimer’s diagnoses, added the distinguished professor and Arline H. and Curtis F. Garvin research professor at the Case Western Reserve School of Medicine.
In a study published Sept. 13 in the Journal of Alzheimer’s Disease (doi: 10.3233/JAD-220717), Davis and colleagues revealed that people who fell ill with COVID-19 were at a significantly higher risk of being newly diagnosed with Alzheimer’s disease within one year—particularly women and people age 85 or older. According to the findings, the risk of developing Alzheimer’s disease almost doubled (0.35% to 0.68%). “Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer’s disease,” they noted.
If this spike in new Alzheimer’s disease diagnoses continues, Davis cautioned that “the wave of patients with a disease currently without a cure will be substantial” and may exacerbate the existing strain on resources devoted to long-term care. Alzheimer’s is a complex disease, “and we thought we had turned some of the tide on it by reducing general risk factors such as hypertension, heart disease, obesity and a sedentary lifestyle,” she added. But now that such a large number of people have contracted COVID and its long-term effects are still emerging, it will be crucial to keep watch and see how this illness winds up impacting future disability.
The study received support from the National Institute on Aging, the National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative (CTSC) of Cleveland, and the National Cancer Institute Case Comprehensive Cancer Center. Limitations included possible “biases introduced by the observational and retrospective nature of this study,” the researchers acknowledged, as well as the potential for inaccurate Alzheimer’s disease diagnoses.
Surprising Findings, Lingering Unknowns
There were a couple of main reasons why this research group embarked on this particular study, said Rong Xu, one of the co-authors. First of all, in this field, there has always been some debate about the infectious etiology of Alzheimer’s disease, explained the professor of Biomedical Informatics and director of the Center for AI in Drug Discovery at Case Western Reserve School of Medicine. Previous research has suggested that bacterial or viral infections may be associated with risk for Alzheimer’s and that inflammation is one of the primary mechanisms underlying the disease.
Beyond that, she pointed out that prior studies have shown that COVID-19 infections are associated with brain structure changes and neuropsychology disorders such as depression and anxiety. And an earlier study conducted by Xu and colleagues that analyzed the electronic health records of nearly 62 million adult and senior patients in the United States found that people with dementia are at an increased risk of contracting COVID. All of this evidence suggests that there is some sort of bi-directional relationship between COVID-19 and Alzheimer’s disease, she told Diagnostics World.
This set the stage for digging a bit deeper and attempting to learn more about the nature of this relationship. More specifically, Xu and colleagues set out to determine if people who caught COVID-19 have a heightened risk of developing new-onset Alzheimer’s disease. As they dove into the research itself, they were surprised to see such a significant hike in relatable risk among people with COVID-19 compared to people without this illness in such a short timeframe. “We expected to see some increase but not that big of an increase within one year,” she said.
According to Xu, this study “suggests that neuroinflammation is a mechanism for Alzheimer’s disease.” But she said it is not yet understood whether this COVID-associated Alzheimer’s disease, which can involve a rapid onset, differs from the traditional version of the disease, which takes a long time to develop. It is also not clear whether COVID-19 causes Alzheimer’s disease or simply accelerates its emergence. “We don’t know if there is a causal relationship yet,” she said. “Even though it is a large cohort, it is still just an associational study. We don’t know the underlying mechanism.”
There are many older adults who have contracted COVID-19, she explained, and aging is a significant risk factor for Alzheimer’s disease. This newly published study suggests that COVID-19 is another risk factor, Xu added, so we probably ought to be on the lookout for COVID-associated Alzheimer’s disease moving forward.
Added Perspective on COVID-19 / Alzheimer’s Relationship
Along with his staff at the Wein Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach, Medical Director Ranjan Duara has encountered plenty of patients who have fallen ill with COVID-19 and later been diagnosed with Alzheimer’s disease. Duara, who was not involved with the Journal of Alzheimer’s Disease study, does not necessarily see a causal relationship between COVID-19 and Alzheimer’s disease. From his vantage point, COVID essentially “unmasks the symptoms of Alzheimer’s,” often before those symptoms would otherwise be noticeable.
Currently, Duara is working with the National Institutes of Health (NIH) on the development of a blood test to diagnose Alzheimer’s disease and envisions utility among patients experiencing long COVID-related brain health issues, such as memory disorders and confusion.
Harold Hong, a psychiatrist at New Waters Recovery in North Carolina (who was not involved with the Journal of Alzheimer’s Disease study but is a Case Western Reserve alum), noted that there are a variety of factors that play into the development of Alzheimer’s disease in relation to COVID infections but emphasized how inflammation and viral infections can wind up leading to long-term cognitive decline.
“Lung function and cognitive impairment are linked, and studies have found that individuals with Alzheimer’s are more likely to experience respiratory problems,” Hong told Diagnostics World. “Given that COVID-19 is a respiratory illness, it’s not surprising that there would be a connection between the two.”
When the lungs become inflamed, it can result in respiratory issues such as low oxygen levels in the blood. So when a person contracts COVID-19 and experiences this form of inflammation, it can lead to oxygen deficiency. “This affects brain function because brain cells die when they don’t get enough oxygen,” Hong noted. “In turn, this can cause long-term cognitive impairment and increase the risk of developing Alzheimer’s disease.”
There is also a possibility that COVID-19 could spark a cytokine storm, or an over-reaction on the part of the immune system. “When this happens, it can lead to the uncontrolled release of cytokines and widespread tissue damage and has been linked to cognitive decline in other studies,” Hong added. “This reaction aggravates respiratory problems and can cause acute respiratory distress syndrome (ARDS), one of the most notable clinical conditions associated with cytokine storms. ARDS has accounted for a significant number of immediate deaths from SARS-CoV-2.”
During his career in the biotech industry, Raymond Tesi has focused on the development of therapies that intersect with the biology of inflammation and immunology. Before that, he was a transplant surgeon for roughly a decade. We know elderly patients have a heightened risk of death from COVID-19 infection, noted the president, CEO, and acting CMO of INmune Bio (who was not involved with the Journal of Alzheimer’s Disease study). But the effects of COVID-19 on elderly patients with Alzheimer’s disease remain mysterious for now.
“Do they die faster?” he wonders. “Is there a significant worsening of their cognition?” Tesi thinks we will continue to learn more about this COVID/Alzheimer’s dynamic “once health care professionals can stop manning the ramparts” and consider the pandemic’s impact on health and society. Some data has revealed that COVID patients in the ICU have shown signs of an accelerated cognitive decline following discharge. “As a surgeon, the data is not convincing as any elderly patient who is sick in the ICU comes out with cognitive defects,” he continued. “I will be more convinced when we have compelling data on patients who had COVID-19 and did not end up in the ICU but do have an increased risk of cognitive decline.”
Tesi thinks that COVID-19 infections do pose “a very real risk” of increased Alzheimer’s disease over the next several decades. “I hope I am wrong,” he told Diagnostics World, “but time will tell.”
Plans to Learn More, Explore Treatment Possibilities
According to Case Western’s Xu, her work looking into the intersection of COVID-19 and Alzheimer’s disease isn’t finished. Looking ahead, she and her colleagues intend to continue studying this relationship. They would like to follow people for a longer stretch of time because she said it isn’t yet known if the increase observed in their recent research is a short spike or if it will be persistent.
Other next steps include studying the relationship between COVID-19 and other forms of dementia as well as exploring the relationship between COVID-19 and other neurodegenerative disorders, such as Parkinson’s disease. Beyond that, Xu intends to determine whether any currently available FDA-approved drugs could be helpful. “We really want to see the treatment options—to see if existing drugs can be repurposed to treat COVID-19-associated dementia,” she added.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.