Alzheimer's and COVID: Is There a Link?

Older adults with COVID-19 were more likely to have a new diagnosis of Alzheimer's disease a year later than non-infected people, an analysis of electronic medical record (EMR) data showed.

The risk for a new diagnosis of Alzheimer's disease in older COVID patients within 360 days after SARS-CoV-2 infection was 0.68%, according to Rong Xu, PhD, of Case Western Reserve University in Cleveland, Ohio, and colleagues.

In a matched group of older adults without SARS-CoV-2 infection, the risk for a new Alzheimer's diagnosis was 0.47% (HR 1.69, 95% CI 1.53-1.72), Xu and co-authors wrote in a brief communication published in the Journal of Alzheimer's Disease.

"It's possible that persons who already had declining cognitive function were tipped over into frank Alzheimer's disease by the viral infection, the stress of the infection, the inflammation that accompanied it, or the accompanying anxiety," co-author Pamela Davis, MD, PhD, also of Case Western Reserve, told MedPage Today. "Longer follow-up and continued monitoring of the elderly population would be important to help sort this out."

There could be several explanations for the findings, observed Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer's Association, who wasn't involved in the study.

"First, the pandemic presented serious delays for individuals seeking out medical diagnoses like Alzheimer's, meaning these results could be driven by those who already had Alzheimer's when they were infected but had not yet sought out a formal diagnosis," Snyder told MedPage Today.

"Alternatively, COVID-19 infection -- which is linked to immune changes, including inflammation -- may impact the onset of brain changes that are linked to Alzheimer's and other dementia," she continued. "However, because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research."

Alzheimer's disease takes years to develop and long-term studies to determine whether COVID plays a role in dementia are underway. "The Alzheimer's Association's International SARS-CoV-2 Study is a network of studies aimed at answering some of these open questions but because this virus is still relatively new, longitudinal research examining COVID-19 and dementia risk will take some time," Snyder said.

Previous research has linked COVID with cognitive changes. In Wuhan, China, long-term cognitive decline was common a year after older adults were hospitalized with SARS-CoV-2 infection. Preliminary studies also showed COVID patients had an uptick in the same biomarkers as Alzheimer's patients and persistent cognitive problems.

In their analysis, Xu and co-authors examined electronic health records for 6,245,282 people ages 65 and older who had medical encounters with healthcare organizations from February 2020 through May 2021 and no prior diagnosis of Alzheimer's disease.

The population was divided into two cohorts. In the COVID-19 cohort, 410,748 people had SARS-CoV-2 infection during the study period. In the non-COVID-19 cohort, 5,834,534 people had no documented SARS-CoV-2 infection but had medical encounters with healthcare organizations during the course of the study.

At baseline, the COVID cohort was more likely to have depression, hypertension, type 2 diabetes, tobacco smoking (all P<0.001), and other comorbidities.

The researchers matched the two groups on demographics; adverse socioeconomic determinants of health including problems with education, occupational exposure, and physical, social, and psychosocial environment; and known risk factors for Alzheimer's disease.

The study methodology left open opportunities for bias, including imbalances in who received cognitive testing during the study period and who did not. "It is possible that more intensive evaluation occurred in those who had COVID compared to those who had visits for other reasons," Davis said. "We cannot tell from the information available to us in the EMR."

It also meant that other disorders, including persistent long COVID brain fog, or cognitive problems stemming from medications, hospitalization, or depression, may have been misdiagnosed as Alzheimer's disease. "Not all of these patients would necessarily have had definitive testing," Davis added.

While the database encompassed more than 25% of the U.S. population, it may not be entirely representative, she acknowledged. "Also, we studied patients prior to emergence of the newer variants," Davis noted.

"Only the latter months of the study included vaccinated patients, and potent antiviral drugs were not available during that time period," she said. "Vaccination data in our database may not be complete because many people were vaccinated at pharmacies and centers outside of the health systems recording the clinical data, so we could not comment on the impact of vaccination."

Comment