Article In Brief
Electronic health record data suggests that patients with dementia are at an increased risk for contracting COVID-19 and suffering severe outcomes.
Patients with dementia are at significantly increased risk for contracting COVID-19 and suffering severe outcomes, an extensive retrospective case-control analysis of electronic health records (EHRs) indicated.
The findings underscore the importance of protecting high-risk patients amid efforts to curtail the pandemic, according to a report published online on February 9 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
“This is a cautionary tale for the people who are vulnerable, and the vaccines can't come soon enough,” Pamela B. Davis, MD, PhD, a co-author of the report and dean emerita of the Case Western Reserve University School of Medicine in Cleveland, told Neurology Today.
The investigators searched EHRs of 61.9 million adult and senior patients in the United States for a six-month period from July through August 2020, aiming to mitigate the paucity of quantitative analysis predicting risks and outcomes for COVID-19 in individuals with Alzheimer's disease (AD) or other dementias.
The analysis found that patients with dementia were at markedly elevated risk for COVID-19 (p<0.001). The most significant association applied to vascular dementia (p<0.001), followed by presenile dementia (p<0.001), AD (p<0.001), senile dementia (p<0.001), and post-traumatic dementia (p<0.001).
Black people with dementia had a greater likelihood of contracting SARS-CoV2 than Whites with dementia (AOR=2.86), the study authors reported. The investigators observed similar racial disparities for specific types of dementia evaluated in the analysis. “This is consistent with prior data showing that COVID-19 affects African-Americans at a disproportionately high rate,” the authors concluded.
During the pandemic, dementia-related memory deficits may hinder a patient's capability to heed precautions such as social distancing, mask wearing, and frequent hand sanitizing. Taking these factors into account, the authors theorized that patients with dementia had an elevated risk for COVID-19 that exceeds the threat posed by common comorbidities, such as cardiovascular diseases, diabetes, obesity, and hypertension.
“SARS-CoV2 has also been shown to affect the brain directly with reports of encephalitis, thrombotic events, and brain invasion,” the authors wrote, citing loss of taste and smell as an early symptom. Severe infection is characterized by the failure of other organs, such as the heart or lungs, and hypoxemia, which can itself bring on cerebral edema and brain malfunction.”
In light of autopsy results and the prevalence of brain complications, the authors “hypothesized that pre-existing dementia, especially with involvement of the blood vessels in the brain (vascular dementia) predisposes patients to greater risk of morbidity and mortality from COVID-19. Therefore, we tested the hypothesis that patients with dementia, once infected, are at greater risk for adverse outcomes.”
The analysis was funded by grants from the National Institute of Aging and the National Center for Advancing Translational Sciences, as well as the Clinical and Translational Science Collaborative of Cleveland.
Study Design, Findings
Researchers undertook a retrospective case-control study of de-identified population-level EHR data amassed by the IBM Watson Health Explorys. The data from 360 hospitals and 317,000 providers spanned all 50 states and accounted for 20 percent of the US population. A worldwide standard for EHRs, the Systematized Nomenclature of Medicine-Clinical Terms enabled researchers to code disease terminology.
The data represented 61,916,260 adult and senior patients (age 18 years and older). From this total, researchers extrapolated 1,064,960 individuals with dementia, 15,770 with COVID-19, and 810 with both dementia and COVID-19 (5.14 percent of the COVID-19 population).
These 810 individuals included 260 patients with AD (1.65 percent of the COVID-19 population), 70 with post-traumatic dementia (0.44 percent), 40 with presenile dementia (0.25 percent), 140 with senile dementia (0.89 percent), and 170 with vascular dementia (1.08 percent).
The researchers evaluated five dementia types that had adequate COVID-19 sample sizes in the EHRs. They opted not to examine the association between COVID-19 and certain subtypes, such as Lewy body dementia, frontotemporal dementia, and mixed dementia due to the paltry number of COVID-19 cases in the database. They adjusted for age, gender, race, comorbidities, transplantation procedures, and nursing home stay.
National data has demonstrated that the skilled nursing environment is “a hot-spot for COVID-19 infection.” However, “our study showed that patients with dementia were at increased risk for COVID-19 independent of nursing home stay,” corresponding author Rong Xu, PhD, professor of biomedical informatics and director of the Center for Artificial Intelligence in Drug Discovery at Case Medicine Reserve, told Neurology Today.
Researchers analyzed five dementia subtypes separately. They stratified groups demographically to assess how various differentials—age, sex, ethnicity— played a role in COVID-19 risk.
With a COVID-19 diagnosis as the outcome measure, researchers examined if African-Americans with dementia were more susceptible to COVID-19 than Whites with dementia. They adjusted for age, sex, and known COVID-19 risk factors. In addition, they evaluated whether patients with dementia who were older than 65 years old were more likely to get COVID-19 than younger patients with dementia (ages 18-65 years old), after adjusting for race, sex, and known COVID-19 risk factors.
They conducted a separate analysis for dementia in general, and for AD and vascular dementia in particular, since there were adequate numbers of patients with these dementia types (and COVID-19 cases) stratified by age, gender, and race.
The six-month mortality risk for patients with dementia and COVID-19 (20.99 percent) was higher than for patients with the virus but no dementia (4.8 percent; p<0.001) and that of patients with dementia but no COVID-19 (7.6 percent; p<0.001).
“This is a very ambitious study that provides evidence for the heightened vulnerabilities of adults with dementia—especially Black adults with dementia—to COVID-19 infection,” said Sara C. LaHue, MD, assistant professor of clinical neurology at the University of California, San Francisco. The analysis “also offers a glimpse of the tragic, downstream complications faced by these adults following COVID-19 infection.”
Identification of racial disparities in COVID-19 infection risk is a vital step in addressing the pandemic's disproportionate impact on communities of color. “Hopefully,” Dr. LaHue said, “quantification of this important problem will help target resource allocation.”
Access to a large EHR database allows researchers to evaluate hospitalization and mortality in different groups with dementia and COVID-19. “From a public health standpoint, these are useful numbers to understand the social and individual burden,” said Rebecca F. Gottesman, MD, PhD, professor of neurology and epidemiology at the Johns Hopkins University School of Medicine.
Despite the report's major strengths—robust population size and standardized definitions—”there are definite concerns about residual confounding,” she said. As the authors noted, when they adjusted for other COVID-19 risk factors, the observed odds ratios for COVID-19 infection decreased significantly for both groups: individuals with dementia and those without dementia, said Dr. Gottesman, who is also director of research in neurology at Johns Hopkins Bayview Medical Center.
“It is likely there are many other factors which were not evaluated in the study, such as the effect of residing in assisting living or seeking medical care more frequently, which would increase the likelihood of being tested for COVID-19,” she said.
“So, the results presented may still be fairly confounded by these unmeasured factors. In addition, the data looking at mortality is tricky, because decisions made by family and even medical teams about aggressiveness of care may be impacted by underlying dementia status, which makes a measure of mortality difficult to interpret.”
Utilizing pooled data from registries “does not reflect the full spectrum of potential diagnoses that people have” in terms of dementia subtypes, said Gregory A. Jicha, MD, PhD, professor of neurology and director of the Telemedicine Cognitive Clinic at the University of Kentucky in Lexington.
It is unclear from the analysis if patients had been evaluated by neurologists or primary care providers. Considering the nationwide shortage of neurologists, particularly in remote locations, the precise nature of a dementia diagnosis may be undetermined in some cases, Dr. Jicha said.
For instance, even though Lewy body dementia is the second most common form of dementia, early signs often resemble the symptoms of other neurological disorders. “Frequently, clinicians will code for dementia in a generic sense rather than specify the individual or distinct type of dementia that a patient has,” he said.
Nonetheless, the analysis delved into the details of potential vascular repercussions from infection with COVID-19. “It is intriguing to think about these vascular effects,” Dr. Jicha said, raising awareness of not only the risks of transmission, but also the significant complications. “If you have someone who is sitting on the precipice” of becoming seriously ill from the virus, it would take “not much to push them over the edge.”
While the analysis shed light on health disparities affecting African- Americans, the data lacked information about socioeconomic status and living arrangements that may include multigenerational households—factors that contribute to COVID-19 infections, said Claudia H. Kawas, MD, professor of neurology and chair in clinical neuroscience at the University of California, Irvine.
Dr. Kawas, a geriatric neurologist, said the analysis is likely to “severely underrepresent the number of cases” due to the fact that many individuals were tested for COVID-19 at drive-up or pop-in sites that did not record their dementia diagnosis. Even so, she added that this “doesn't take away from the legitimacy of the findings.”
Another reason African-Americans may be at higher risk for COVID-19 and adverse outcomes stems from bearing a disproportionate share of employment in front-line industries—a variable that is not captured in studies based on EHR data, said Mary Sano, PhD, professor of psychiatry and director of Alzheimer's disease research at Mount Sinai School of Medicine.
Meanwhile, the extra burden falling on caregivers has presented unique challenges in dealing with dementia and the risk of COVID-19. They often have to speak loudly and enunciate more clearly because masks muffle sound. It's important for neurologists to recognize the difficulties that families face and listen more to their concerns while congratulating them for faring well in the face of adversity, Dr. Sano said.
Promoting social engagement is essential to caring for patients with dementia. “The data is fairly limited on whether virtual social interaction has the same beneficial effects” as in-person contact, said Bryan K. Woodruff, MD, a neurology consultant to the Mayo Clinic in Scottsdale, AZ.
Frequent repetition in the form of “gentle reminders” about the importance of wearing masks and frequent hand washing is crucial when memory loss interferes with compliance. Patients also may forget that shaking hands with the neurologist at the conclusion of an appointment is no longer a largely innocuous gesture, said Dr. Woodruff, who offers an elbow bump as an alternative. If patients insist on a handshake, he recommends washing hands or using a sanitizing station on the wall afterwards.
Electronic devices, especially with video capabilities, can mitigate social isolation for patients with dementia. However, as Dr. LaHue from the University of California, San Francisco, pointed out, “independent use of these devices is not realistic for many persons with dementia. In these cases, setting devices to automatically accept calls from family, limiting the need for the person to perform complex motor tasks like swiping, can facilitate remote contact with family. This is a technique I find especially useful for hospitalized adults with dementia where visitation remains limited.”
Drs. Davis, Xu, LaHue, Jicha, and Woodruff reported no financial disclosures. Dr. Bergey is compensated for being an associate editor of Neurotherapeutics. Dr. Gottesman received compensation from the AAN as a past associate editor for Neurology.